Current knowledge on genus Bassia All.: a comprehensive review on traditional use, phytochemistry, pharmacological activity, and nonmedical applications

Bassia All. is a genus from the Amaranthaceae family, which was created by merging selected species belonging to the former Bassia and Kochia genera with those classified to Chenolea, Londesia, Kirilowia and Panderia. The reorganised Bassia genus currently comprises around 20 species, which are annual herbs or perennial subshrubs native to Eurasia and Africa. Bassia plants are well known for their therapeutic applications in folk medicine and traditional medical systems, and they are also used for nonmedical purposes. Some members of this genus, such as Bassia scoparia (syn. Kochia scoparia) is of great medical importance and economic value. The plant is cultivated in some regions of Asia as a crop to collect Kochiae fructus, which is used for both curative and food purposes. Phytochemical studies carried out on Bassia species indicate that these plants synthesize metabolites belonging to different groups of compounds (e.g., triterpene saponins, sterols, flavonoids, fatty acids, lignanamides, alkaloids, organic acids). Some of the structures are rarely found in the plant kingdom. Biological activity studies carried out on Bassia plants revealed various effects exerted by extracts and isolated compounds, including anti-inflammatory, cytotoxic, antioxidant, antimicrobial, hypoglycemic, anti-obesity, etc. Modern research explained some of the mechanisms of action. This review covers literature from 1935 to 2022, and assembles and discusses data on phytochemistry, biological activity, as well as medical and nonmedical use of the representatives of the genus Bassia. In this review we present the current state of knowledge about the plants of the genus.


Introduction
The genus Bassia All. is one of the genera found in the Amaranthaceae family.The taxonomy of these plants is problematic, but according to a new reclassification, the genus Bassia comprises circa 20 species (Kaderit and Freitag 2011).Bassia plants are annual herbs or perennial subshrubs native to Eurasia and Africa.As members of the Amaranthaceae family, these species operate C4 photosynthesis, which evolved in dicots to facilitate their growth in arid ecosystems.Therefore, Bassia plants can be found in semideserts or dry steps, and, as halophytes, can exist also in habitats characterized by high salinity.Due to adaptation to different environmental conditions, Bassia species have attracted attention as plants that can be cultivated in regions where other plant species cannot be planted (Al-Ahmadi et al. 2007;Kaderit and Freitag 2011;Orlovsky et al. 2011;Shelef et al. 2012;Abideen et al. 2015).Today, as can be seen in Fig. 1 scoparia, a year after introduction, work on the eradication of this plant species began.The elimination process proved successful, and no B. scoparia have been observed in Australia since 2000.In turn, there are some records that B. hyssopifolia still occurs in southeastern Australia, but only in a small area of north-western Victoria state (POWO 2022;Panetta 2015).
In Asia, B. scoparia (syn.Kochia scoparia) has great medical importance and economic value.At present, it is cultivated in China and Japan as a crop for both curative and food purposes (Tashiro et al. 2019;Chen et al. 2021;Zou et al. 2021).B. scoparia is a plant recorded in the Chinese Pharmacopeia (Chen et al. 2021), which provides dried fruits (Kochiae fructus, Di-Fu-Zi) which is a TCM product very popular in different parts of Asia.Currently, due to globalization, Kochiae fructus is commercially available worldwide.Given that B. scoparia has welldocumented pro-health effects and is also used as a food, some authors suggest that its fruit should be Fig. 1 The distribution range of plants in the genus Bassia considered for the development of functional foods (Chen et al 2017).
Apart from B. scoparia, other Bassia species have also been recommended in traditional medical systems, especially in regions where they grow as wild plants (Hammiche and Maiza 2006;Khare 2007;Altundag and Ozturk 2011;Youssef 2013;Moein et al. 2015;Umair et al. 2017).In addition to the therapeutic value of these plants, they have also been used for nonmedical purposes.For example, some plants of the genus Bassia are being appreciated as human food and livestock feed because of their nutritional value.(Nadelcheva et al. 2007;El Shaer 2010;Khan et al. 2013;Youssef 2013;Akhtar et al. 2018).
In recent years, several studies have provided new data on the chemistry and biological activity of Bassia species (Xiae et al. 2018;Houlihan et al. 2019;Abd-ElGawad et al. 2020;Gancheva et al. 2020;Othman et al. 2021a;2021b;Othman et al. 2022;Said et al. 2021;Petruk et al. 2021).It is noteworthy that not only B. scoparia but also other hitherto unexplored Bassia species attracted scientific attention.
To the best of our knowledge, there are no papers reviewing available scientific data on the Bassia genus.Although there are some reviews devoted to B. scoparia, they focused exclusively on one part of this plant, namely Kochiae fructus (Al-Sanafi et al. 2018;Zou et al. 2021).Therefore, the main objective of the current review is to provide the first comprehensive overview of the Bassia genus, including the latest information on its phytochemistry, biological activity, as well as its medical and nonmedical use.

Methods
The search of scientific literature was carried out in various databases including PubMed, Scopus, Google Scholar, Science Direct, and Embase, and covered the period up to 2022 June 17.The key words (as individuals and their different combinations) used to search were: Bassia, Kochia, "phytochemistry", "phytochemical", "taxonomic", "distribution", "saponins", "phenolics", "triterpenes", "fatty acids", "flavonoids", "quantification", "sterol", "alkaloid", "terpenes", "compound", "nitrates", "organic acid", "oil", "essential oil", "monosaccharides", "carotenoids", "activity", "pharmacological", "extract", "anti-inflammatory", "inflammatory", "oedema", "anti-allergic", "psoriasis", "eczema", "wound healing", "traditional medicine", "food", "ethnobotany", "TCM", "animal model", "antibacterial", "antifungal", "antiparasitic", "phytoremediation", "gastric", "hypoglycemic", "antioxidant", "toxicity", "cytotoxicity", "cancer cell", "mechanism".As key words, the full Latin name of representatives of the genus Bassia (according to the new classification proposed by Kaderit and Freitag (2011), as well as their synonyms and former Latin name (according to the previous taxonomic classification) (as individual or in combination with the above-mentioned keywords) were used.According to the rules of the specific databases, Boolean operators were also used.No filters or time restrictions were applied for publications during the search.Furthermore, the reference lists of all selected reports were searched to identify potentially eligible publications.Only publications that had available full texts were included.Conference communications, posters, and the thesis were excluded.The available information on Bassia species has been divided into several sections, i.e. taxonomy, distribution, phytochemistry, biological activity, medical use, nonmedical use, and toxicology.Publications outside the scope of these thematic sections were rejected.Moreover, publications on the phytochemistry of Bassia species were thoroughly checked, and articles that contained information on preliminary phytochemical analyses of extracts, based only on characteristic reactions of groups of compounds (e. g. foam test), which are not specific, were excluded from the phytochemistry section.
ChemDraw 19.0 software was used to draw the chemical structures of compounds.The graphs were performed using Excel 365 software (Microsoft Office) software.The illustrations were made with CorelDraw 2021.5 software.
Despite the new classification and nomenclature proposed by Kaderit and Freitag, both new names and their synonyms coexist in the scientific literature.Interestingly, for some species, such as Bassia scoparia, the term Kochia scoparia is used even more frequently.This may be related to the fact that K. scoparia is a plant commonly used in TCM, and according to Flora of China records, Kochia and Bassia were not merged but are still treated as separate genera (Chen et al. 2021).
Therefore, in order to avoid any confusion, in the current review, the new terminology according to Kadereit and Freitag (2011) is used for all species of the genus Bassia.

The importance of plants of the genus Bassia
Numerous ethnobotanical surveys carried out in different regions of Asia and Europe, records found in herbal books referring to traditional medicinal systems, and scientific literature reports, all underline that Bassia plants have been intensively used by humans for therapeutic purposes and as nonmedical products (Hammiche and Maiza 2006;Khare 2007;Nadelcheva et al. 2007;Altundag and Ozturk 2011;Umair et al. 2017;Lin et al. 2021) (see Table 1).It should be mentioned that modern research revealed some new potential applications of Bassia plants, which are currently being investigated.

Medical uses of Bassia species
Representatives of the genus Bassia have been used in traditional medicine to treat various aliments (see Table 1).One of the most important species from the therapeutic point of view is B. scoparia.The dried fructus of B. scoparia, known as Di-Fu-Zi, has been valued in Traditional Chinese Medicine (TCM).Its application is based on ethnopharmacological data, and modern scientific research (Zou et al. 2021).Today, Kochiae fructus is recommended for urinary system disorders, such as frequent urination or  urinary incontinence, and as a remedy in vaginal discharge.Kochiae fructus is also applied in skin, eyes, and ear diseases (Im et al. 2016;Lin et al. 2021;Zou et al. 2021).Recent studies have shown that Di-Fu-Zi is one of the most prescribed single herbal preparations in traditional Chinese medicine to treat dermatological problems such as eczema, urticaria, psoriasis, and pediatric atopic dermatitis (Chien et al. 2013;Chen et al. 2015Chen et al. , 2016;;Weng et al. 2016).The fruit is also used as a key ingredient in herbal formulas to reduce itching, swelling, and sores (Chien et al. 2013;Chen et al. 2015;Weng et al. 2016).In China, the fruits and leaves of B. scoparia have been known as cardiac tonics (Kirtikar and Basu 1935).People in Armenia and Uzbekistan have also used B. scoparia as a breath stimulator and hypotensive agent (Akopian et al. 2020).In addition to B. scoparia, other species of the genus have also been valued as medicinal plants.In the Middle East, as well as in India, the decoction of the entire plant of B. indica has been recommended as a cardiac stimulant (Khare 2007;Youssef 2013;Umair et al. 2017).Ethnobotanical surveys revealed that aerial parts of B. muricata, and B. prostrata have been used by inhabitants of Saudi Arabia and Turkey to treat kidney diseases and as antirheumatic agents (Altundag and Ozturk 2011;Youssef 2013).Furthermore, B. muricata leaves poultices have been applied to the skin as a remedy for boils, ulcers, dermatosis, pustules, and infected wounds in folk medicine of different regions of North Africa and Saudi Arabia (Hammiche and Maiza 2006;Abouri et al. 2012;Al-Harbi 2017).B. eriophora has traditionally been used in Iran as an infusion of leaves or twigs in the treatment of gingivitis, hair loss, and the symptoms of Alzheimer's disease (Moein et al. 2015).Furthermore, recent research has revealed some new applications for Bassia species.B. eriophora was studied as a natural material to obtain cellulose nanofibers.Such structures can be used in various sectors of industry and medicine.Because the produced nanofibers along with their very good mechanical properties were also biocompatible and biodegradable, the possibility of using them in regenerative medicine and tissue engineering should be considered (Athinarayanan et al. 2018).

Nonmedical applications of Bassia species
In addition to medical applications, Bassia species are also valued as nonmedical products.Fresh fruits of B. scoparia are very popular in Asian cuisine as a Undef.Pakistan Khan and Qaiser (2006) undef.The plant part and the form of application were not specified food garnish called Tomburi or 'plant caviar' (Tashiro et al. 2019).Some authors also highlight the potential of Kochiae fruits in the development of functional foods (Chen et al. 2017).The shots and tender leaves of B. scoparia are eaten as a vegetable by people from Myanmar and inhabitants of the Heihe valley in China (Kang et al. 2012;Shin et al. 2018).In the inner Mongolian region, aerial parts of the plant are consumed fried or steamed with flour (Sachula et al. 2020) (Waldron et al. 2010;El Shaer 2010).Furthermore, ethnobotanical surveys revealed that B. muricata and B. indica have been used by inhabitants of Pakistan and some regions of Saudi Arabia as fuel and firewood (Badshah et al. 2012;Youssef 2013).On the other hand, there are some reports from the USA that another Bassia species, B. prostrata, may be used as a green firebreak, a management tool for wildfires (Harrison et al. 2002).Some reports indicate that aerial parts of B. scoparia have been used in different countries of Europe to produce household items, such as brooms (Nadelcheva et al. 2007;Gras et al. 2020).In turn, the people of Karak district in Pakistan produced a soaplike product from B. prostrata (Khan et al. 2011).B. scoparia, commonly called summer-cypress, is also cultivated as an ornamental plant.Currently, research is being carried out on the possibility of using various species of Bassia (B.indica, B. scoparia) in the phytoremediation of salt-and metal-contaminated soils (Shelef et al. 2012;Moubasher et al. 2015;Aihemaiti et al. 2018;Shi et al. 2022).The possibility of using B. scoparia and its associated rhizosphere microflora is also being considered in the degradation of aromatic hydrocarbons in soils contaminated with crude oil (Moubasher et al. 2015;Song et al. 2021).Furthermore, new potential applications such as the   et al. (1997a, b), Han et al. (2006)

Phytochemistry
The phytochemical studies of representatives of the genus Bassia have been conducted for many years.Notwithstanding, the chemical compositions of only few species of the genus have been investigated so far.Initially, the analyses focused mainly on B. scoparia, but in recent years there has been an increased research interest in phytochemistry of other species of the genus.Until now, more than 300 compounds have been identified in the genus, and some of them were new compounds at the time of publication (Fig. 2).Moreover, several rarely occurring phytochemicals have been detected, including some saponins, flavonoids, steroidal glycosides, or fatty acids.Examples of compounds characteristic of the genus Bassia and at the same time rarely found in the plant kingdom are shown in Fig. 3.

Triterpene saponins and triterpenes
From a pharmacological point of view, triterpenoid saponins are one of the most important groups of metabolites found in Bassia plants.However, until now, saponins have been isolated solely from three species, B. scoparia, B. indica, and B. muricata.So far, phytochemical studies of Bassia species have led to the isolation of thirty-three different saponins, while twenty-eight of them have been fully characterized by structural studies.These saponins are listed in Table 2. Interestingly, twelve saponins were novel compounds at the time of publication (see Fig. 2).Among saponins, structures with an oleanane skeleton dominated.Within this group, the highest number of saponins represented oleanolic acid glycosides, while compounds with rearranged double bond positions, such as morolic acid and 3β-hydroxyolean-13(18)-en-28-oic acid were less common (Fig. 4).Interestingly, lupane-type saponin was also detected, as well as a fairly rare type of 13,28epoxyoleanane saponins.Sapogenins found in Bassia species are presented in Fig. 4. Almost half of Bassia saponins (42.4%) are bidesmosides, the remaining 57.6% are classified as monodesmosides, usually bearing a sugar chain at C-3 of sapogenin.The sugar part is composed of β-D-glucuronic acid (GlcA), β-D-xylopyranose (Xyl), β-L-arabinofuranose (Ara) and β-D-glucopyranose (Glc).It should be noted that the vast majority (81.8%) of saponins have β-D-glucuronic acid units in the sugar chain attached to C-3 of the aglycone.Among them, 34.4% can be classified as the GOTCAB group (glucuronide oleananetype triterpenoid carboxylic acid 3, 28-O-bidesmosides).It is also worth mentioning that one new saponin (Fig. 2) and five rarely occurring secoglycosidic oleanane saponins, containing acidic constituents at C-3 of glucuronic acid, have been isolated so far exclusively from the aerial parts of B. indica (Mohamed et al. 1998;Othman et al. 2021b).
Quantitative research on the content of saponins in Bassia species is limited to Kochiae fructus.Analysis of fruit from various regions of China using the HPLC-ELSD method showed that the saponin level ranges from 3.0 to 5.8% (Xia et al. 2002a;Wang et al. 2014a).In another study, qualitative gas-liquid chromatographic analysis (GLC) of methyl esters of triterpene sapogenins (methyl oleanolate) demonstrated that the sapogenin content ranges from 0.95 to 2.09% in a single seed of B. scoparia, reflecting the content of oleanolic acid-type saponins in plant material (Kernan et al. 1973).
Although various saponin compounds have been found in plants of the genus Bassia, the quantitative determination focused on momordin Ic, which is the main saponin of Kochiae fructus (Fig. 3A).Various reports indicate that momordin Ic content in plant material ranges from 0.85 to 3.5% (Xia et al. 2002a;b;Belsevich et al. 2009).According to Hong Kong Chinese Materia Medica Standards, the content of momordin Ic in Kochiae fructus should not be less than 2.3% (HKCMMS 2012).
In addition to qualitative studies of the plant material, which reflect the quality of the product, investigations on momordin Ic content were also carried out on various extracts of Kochiae fructus.It can be seen that the amount of momordin Ic in the extract varies greatly depending on the extraction method (Choi et al. 2014;Wang et al. 2014a;Yoo et al. 2017).For example, Wang et al. (2014a), using the HPLC-ELSD method, found that the momordin content in the water extract (under infusion condition for 4 h at room temperature) was 2.88%, while in the 50% ethanol extract prepared under reflux conditions (4 h) it reached a higher value of 5.75%.

Sterols, steroidal glucosides and phytoecdysteroids
Some species of Bassia were analysed for the presence of sterols, and to date, more than 25 sterols have been identified in representatives of the genus (see Table 3).Reports indicate that the most abundant group of sterols were 4-desmethylsterols, but 4αmonomethylsterols were also detected (Narumi et al. 2001).In most of studied species, among 4-desmethylsterols, both Δ 5 -sterols and Δ 7 -sterols coexist.The exception was B. indica where exclusively Δ 5 -sterols were found (Othman et al. 2021b;Javed et al. 2018a, b).Sitosterol and stigmasterol were the main sterol components in all species studied.GC-MS-identification of sterols revealed that fruits of B. scoparia were also abundant in 24-ethyllathosterol (Narumi et al. 2001).In turn, Javed et al. (2018a) underlined that γ-sitosterol was present in considerable amounts in the stem of B. indica.In addition to free sterols, their glycosides have also been reported in some of the Bassia species, including three novel kochiosides A,B,C, belonging to the class of 14α-methylated steroidal glucosides, which are rarely encountered in nature (Fig. 3B) (Imran et al. 2007).It is interesting that some structures containing the 14α-methyl group were found in sea cucumbers (Cordeiro and Djerassi 1990).To date, kochiosides have been isolated solely from B. prostrata (Imran et al. 2007;2017).
Phytoecdysteroids are polyhydroxylated plant sterols that occur in several species from the Amaranthaceae family (Dinan et al. 1998;Das et al. 2021).In the genus Bassia, they were found exclusively in B. scoparia (Dinan et al. 1994).The species was reported to contain 20-hydroxyecdysone and polypodine B (5β,20-dihydroxyecdysone) but the level of phytoecdysteroids varied considerably between the different morphotic parts of B. scoparia.The radioimmunoassay using DBL-1 antiserum revealed that the highest content of ecdysteroids was found in the roots (143 µg ecdysone equivalents/ g dw).Lower levels were observed in leaves, flowers, stems, and seeds (44-112, 56, 26-37 and 30 µg ecdysone equivalents/g dw, respectively) (Dinan et al. 1994).

Phenolics
Phenolics, including flavonoids and phenolic acids, are one of the most widely distributed metabolites in the plant kingdom.So far, phytochemical studies of Bassia species have led to the detection of nearly 60 flavonoids.Thirty-one of them were unambiguously identified following structure elucidation of isolated compounds (Lu et al. 2012b;Shaker et al. 2013;Musa et al. 2016;Kamel et al. 2001;Xu et al. 2014;Othman et al. 2021b).The identification of the remaining flavonoids was performed directly in Bassia plant extracts using HPLC with UV detection (Rakhmankulova et al. 2015;Xiao et al. 2018;Petruk et al. 2021) and by combination of chromatographic technique coupled with tandem mass spectrometry.Said et al. (2021) have recently evaluated the flavonoid profile in aerial parts of B. eriophora using LC-ESI-MS/MS in negative-ion mode, which led to tentative detection of 28 compounds (Said et al. 2021).In turn, Xiao et al. (2016) analyzed flavonoids in B. scoparia pollen using atmospheric solid analysis probe mass spectrometry (ASAP-MS) (Xiao et al. 2016).
As shown in Table 4 various flavonoids, including flavonols, flavones, and a flavanone, were detected in the Bassia genus.It is interesting to note that free sugar isoflavones have also been found, but so far only in B. scoparia (Zhang et al. 2013).
Most of the flavonoids identified in the Bassia genus are glycosidic (75%).Flavonol glycosides, including mainly derivatives of quercetin (35%), kaempferol (15%) and isorhamnetin (15%), are definitely the most abundant.It should be noted that acylated compounds account for 30% of flavonoid glycosides.Their presence was found exclusively in the aerial parts of Bassia species.Kamel et al. (2001) 2) were isolated from the aqueous methanol extract of the aerial parts of B. indica (Othman et al. 2021b).
Although phenolic acids appear to be widely distributed in plants, data on their occurrence in the genus Bassia are limited.So far, several phenolic acids from both hydroxybenzoic and hydroxycinnamic groups have been detected only in the aerial parts of the species.Chlorogenic acid, caffeic acid, and ferulic acid were determined in shoots of B. scoparia (Lodhi 1979).Seitimova et al. (2016) detected protocatechuic, vanillic, isovanillic, and pcoumaric acids in aerial parts of B. prostrata.The latest report indicates that vanillic acid, o-hydroxybenzoic acid, p-hydroxybenzoic acid, caffeic acid, and methyl caffeate are present in B. indica (Othman et al. 2021b).Some phenolic acids may occur not as a free form, but as part of more complex structures.As mentioned above, flavonoid glycosides bearing feruloyl and caffeoyl moiety have been reported in B. muricata, B. indica and B. eriophora (Kamel et al. 2001;Said et al. 2021;Othman et al. 2021b).Recently, five lignanamides containing the feruloyl moiety were isolated from aerial parts of B. indica (Othman et al. 2021a).
Other phenolics reported in the Bassia genus include 6,7-dihydroxycoumarin and tachioside, which were detected in aerial parts of B. indica (Othman et al. 2021b).

Fatty acids
Some Bassia species were analysed for the presence of oil and fatty acids.The percentage content of oil in the seeds of B. scoparia ranges from 9.7 to 16% (Hegnauer 1964;Weber et al. 2001;Abideen et al. 2015).Due to the fact that seeds are abundant in lipids, most of the studies focused on the identification and quantification of FA in various Bassia seed oils (Kleiman et al. 1972;Escudero et al. 1999;Weber et al. 2001).Data on the analysis of other morphotic parts are scarce and limited to the aerial parts of B. prostrata, B. indica, and B. muricata (Seitimova et al. 2016;Imran et al. 2017;Bibi et al. 2021;Abu Ziada et al. 2015).The reports indicate that Bassia species are the source of saturated and unsaturated fatty acids, especially FA with chain lengths of 16 to 18 carbons.GC-MS analysis revealed that Bassia seed oil contained 54% to 89% linoleic acid (Kleiman et al. 1972;Escudero et al. 1999;Weber et al. 2001;Abideen et al. 2015).Significant amounts of palmitic acid (9%-68%) and oleic acid (4%-17%) were also observed (Kleiman et al. 1972;Weber et al. 2001;Abideen et al. 2015).Similarly, oleic acid (64.9%) and linoleic acid (22.0%) are reported to be the main FA in aerial parts of B. prostrata (Seitimova et al. 2016).It is interesting that very long-chain fatty acids (VLCFA-FA with more than 22C), have been identified in B. scoparia seeds and aerial parts of B. prostrata (Table 6) (Imran et al. 2017;Weber et al. 2001;Abideen et al. 2015).Furthermore, reports revealed that members of the Bassia genus accumulate Δ 5 unsaturated fatty acids, such as 16:1Δ 5 , 18:1Δ 5 , 18:2Δ 5,9 , 18:3Δ 5,9,12 , 20:4Δ 5,8,11,14  (Kleiman et al. 1972;Escudero et al. 1999;Olagbemiro et al. 1999;Whitney et al. 2004).(Z)-5-hexadecenoic acid (16:1Δ 5 ) (Fig. 3B) is an unusual monounsaturated FA that is considered a potentially useful substance in the control of the mosquito Culex quinquefasciatus, a vector of filariasis in humans.This is since 16:1Δ 5 can serve as an intermediate in the production of an insect oviposition pheromone (Olagbemiro et al. 1999;Whitney et al. 2004).(Z)-5-hexadecenoic acid was reported to constitute 12% of the seed oil of B. prostrata and around 5% of the oils of the seeds of B. scoparia as well as B. hyssopifolia (Kleiman et al. 1972).Fatty acids detected in Bassia species are listed in Table 5.

Nitrogen-containing compounds
Phytochemical analyzes conducted in the 1960s suggested that some Bassia species contain alkaloids.Borkowski and Drost (1965) showed the presence of four compounds in the herb of B. scoparia and B. laniflora (formerly classified as B. arenaria) (Borkowski and Drost 1965).B. indica was also reported to contain three alkaloids, which accumulate in seeds (512 mg/100 g dw), pericarp (387 mg/100 g dw), shoot (up to 294 mg/100 g dw) and roots (85 mg/ 100 g dw) (Zahran et al. 1982).The research carried out at that time was mainly based on the reaction of the isolated substances with Dragendorff's reagent and did not lead to the determination of the structure of alkaloids (Zahran and Wahid 1982).Only Drost-Karbowska (1978) on the basis of spectroscopic techniques (UV, MS, NMR) showed that compounds found in aerial parts of B. scoparia are harman and harmine, belonging to the indole alkaloids with βcarboline skeleton (Drost-Karbowska et al. 1978).It is interesting that the most recent studies revealed the presence of a novel alkaloid named bassiamide A (N- indica (Fig. 2) (Othman et al. 2021a).
Species of Bassia genus have been reported to contain proteins and multiple amino acids, and several studies have considered their potential nutritional and feeding value (Davis 1979;Riasi et al. 2008;Waldron et al. 2006Waldron et al. , 2020;;Seitimova et al. 2016;Houlihan et al. 2019;Nair et al. 2021).For example, Waldron et al. (2006) showed that the crude protein content in B. prostrata ranges from 44.6 to 116.5 g/kg of aerial parts.A similarly high protein content was found in aerial parts of B. scoparia (117 g/kg) (Riasi et al. 2008).El-Adawy et al. ( 2020) reported a crude protein concentration in aerial parts of B. indica at 12.6%.Some reports underlined that protein content depended on the maturity stage of the plant (Knipfel et al. 1989;Waldron et al. 2006;Nair et al. 2021).Differences in protein level were also observed between various parts of the plant.Seeds, leaves, and stems of B. prostrata were reported to contain 190.6 g, 123.2 g and 55.1 g of protein per kg, respectively (Waldron et al. 2006).Waldron et al. (2020) also observed that protein levels decrease with increasing salinity in the soil (Waldron et al. 2020).Seitimova et al. (2016) revealed that the main amino acids in aerial parts of B. prostrata were glutamic acid (23.46%), alanine (5.82%), proline (3.35%), arginine (3.32), leucine (3.20%) and isoleucine (3.03%) (Seitimova et al. 2016).Houlihan et al. (2019) identified 18 amino acids in water-soluble exudates from B. scoparia seeds with tyrosine and glutamic acid as predominant compounds.It should be noted that some of the Bassia (Kochia) biotypes are resistant to sulfonylurea herbicides (ALS-inhibiting herbicides) (Kumar et al. 2019).Because the acetolactate synthase enzyme (ALS) is the key step in the biosynthesis of branched chain amino acids, some differences in the valine and leucine content were observed between biotypes resistant and susceptible to herbicides.The level of free valine and leucine was elevated in seeds and aerial parts of the resistant Bassia biotype compared to susceptible plants (Dyer et al. 1993;Chodova ´and Mikulka 2000).
Furthermore, the concentration of these amino acids decreased in the susceptible Bassia population after herbicide treatment (Chodova ´and Mikulka 2000).
It is well known that plants of the Amaranthaceae family can accumulate nitrates (Salehi et al. 2019;Liubertas et al.2020;Munekata et al. 2021).Several works have been devoted to quantification of nitrates in Bassia species, especially in B. scoparia (Finley and Sherrod 1971;Steppuhn et al. 1994;Escudero et al. 1999;Lo ´pez-Aguilar et al. 2013).The studies revealed that the content of nitrates in the aerial parts of B. scoparia decreases during the growing season (Finley and Sherrod 1971;Lo ´pez-Aguilar et al. 2013).Steppuhn et al. (1994) also observed that the amount of nitrates can increase from 0.01 to 0.04 g/ kg to 0.5 g/kg after the addition of nitrogen fertilizer.Among other members of the Bassia genus, nitrates were detected also in B. hyssopifolia but only in traces (James et al. 1976).It is interesting that the accumulation of nitrates was not observed in B. prostrata, which is a perennial plant (Waldron et al. 2010;Acar et al. 2016).Other compounds Representatives of the genus Bassia can also accumulate organic acids.Among carboxylic acids, oxalic acid was the most common compound.Other compounds such as tartaric acid, malic acids, citric acid, succinic acid, lactic acid, acetic acid, formic acid, and L-ascorbic acid were also detected (Hong et al. 2006;Ma et al. 2011Ma et al. , 2016;;Lo ´pez-Aguilar et al. 2013).
A low glycolic acid content was found in the root of B. scoparia (Ma et al. 2011).Gluconic acid, citric acid, and oxalic acid were the major organic acids detected in the water-soluble exudates from the seeds of the species.Other acids identified in small amounts in seed exudates included: threonic acid, malic acid, malonic acid, glucaric acid, fumaric acid, lactic acid, ribonic acid, galacturonic acid, 2-ketogluconic acid, glucuronic acid and glucuronic acid 1,5-lactone (Houlihan et al. 2019).
It is noteworthy that the level of carboxylic acids varies between the species, its morphotic parts, and maturity stage and depends on environmental factors.B. prostrata is considered a species with a low level of oxalic acid accumulation.The content of oxalates in aerial parts of the species averaged 1.2% (Davis 1979).In turn, studies on organic acid content in aerial parts of B. scoparia provide diverse data, which may result from differences in habitat conditions of the analyzed plants.B. scoparia is an alkali resistant forage plant and is able to survive in extremely unfavourable environments with a pH greater than 10.Several studies indicate that the accumulation of organic acids in the aboveground parts is probably the way to adapt to ecological conditions (Yang et al. 2007;Ma et al. 2011Ma et al. , 2016)).The oxalate concentration in B. scoparia shoots (1.4-2.6% of dry weight) can be defined as moderate (Cohen et al. 1989;Lo ´pez-Aguilar et al. 2013).In other studies, the oxalic acid content was much higher and was estimated to be in the range of 12%-17.8% of the dry weight of aerial parts (Yang et al. 2007;Ma et al. 2011Ma et al. , 2016)).Hong et al. (2006) revealed that the roots of B. scoparia accumulate higher amounts of oxalic acid (26.76 µmol/g) than the shoots (4.305 µmol/g).A similar relationship was found for other acids, such as malic acid (6.60 µmol/g roots; 1.93 µmol/g shoots), tartaric acid (15.04 µmol/g roots; 1.29 µmol/g shoots) and succinic acid (4.70 µmol/g roots; 2.03 µmol/g shoots) (Hong et al. 2006).It is interesting that, in contrast to control conditions, the concentrations of oxalic acid, succinic acid, malic acid, and tartaric acid were higher in shoots (71.99 µmol/g, 66.73 µmol/g, 45.99 µmol/g, 44.60 µmol/g, respectively) under alkaline stress than in roots of the plant (67.39 µmol/g, 64.0 µmol/g, 26.89 µmol/g, 40.99 µmol/g, respectively) (Hong et al. 2006).Contrary to research reported by Hong et al. (2006), Ma et al. (2011) observed that under control conditions mature leaves contain the highest amount of oxalic acid (8% dry weight), followed by young leaves, old stem, and roots (1% of dry weight), while under salt and alkali stress, the concentration of oxalic acids in mature leaves reached 10% and 12% of their weight, respectively (Ma et al. 2011).
Other constituents reported in the Bassia genus include macroelements (Na, K, Mg, Ca, P) and microelements (Fe, Cu, Se).These plant species are able to accumulate ions, but the amount depends on various factors, such as soil composition or environmental contamination (Karimi et al. 2005;Yang et al. 2007;Riasi et al. 2008;Ma et al. 2011;Endo et al. 2014;Yamada et al. 2016).Environmental factors, such as salinity and cadmium stress, also affected the content of carotenoids in the Bassia genus.Seasonal variations in the level of carotenoids were also observed (Davis 1979).The published reports indicate that the carotenoids content ranged from 0.13 to1.06 mg/g of fresh aerial parts of the analysed species: B. scoparia, B. prostrata, and B. indica (Karimi et al. 2005;Abeer et al. 2015;Hashem et al. 2019;Ghaffarian et al. 2020).
In addition to the phytoconstituents mentioned above, syringaresinol, a compound of the lignan group, was recently isolated from aerial parts of B. indica (Othman et al. 2021a).

Biological activity
The biological activity studies conducted on the representatives of the genus Bassia focused on several plant species, including B. scoparia, B. eriophora, B. muricata, B. indica, and B. prostrata.It is interesting that most of the studies on B. scoparia were carried out on fruits or seeds of the plant, while the investigations of the other species were mainly focused on the other aerial parts.The various activities of extracts of Bassia species were evaluated, including anti-inflammatory, cytotoxic, hypoglycemic, antioxidant, antimicrobic and tissueprotective potential.However, it should be mentioned that published data on anti-inflammatory hypoglycemic and anti-obesity activity were limited almost completely to Kochiae fructus.
It should be noted that not only in vitro tests, but also in vivo studies were conducted.Additionally, in several investigations, an attempt was made to determine which components are responsible for the observed activity of the extract.

Anti-inflammatory activity
The dried fruit of Bassia scoparia is commonly used in traditional Chinese medicine (TCM) as an antiinflammatory agent, especially in skin disorders (Chien et al. 2013;Chen et al. 2015Chen et al. , 2016;;Weng et al. 2016).The anti-inflammatory activity of Kochiae fructus has been well documented in both in vitro studies and in various animal models (see Table 6).In most of the studies, acute inflammation models were performed, including those of edema.Due to the fact that skin inflammation often manifests itself by itching, antipruritic activity was also investigated.The water and ethanol extracts of Kochiae fructus were found to demonstrate the ability to inhibit scratching behavior in animal models (see Table 6).It should be noted that the extracts demonstrated their anti-inflammatory activity in vivo after oral administration and external application.
The effect of Kochiae fructus on various types of hypersensitivity was also investigated in animal models (see Table 6).It was found that 70% extract exhibited inhibitory activity in models of I, III and IV-type of allergy (Matsuda et al. 1997b).The activity of extracts in contact allergic dermatitis, which can be classified as type IV hypersensitivity, has been one of the most intensively studied.External application of methanol or water extracts significantly inhibited inflammation in animal contact dermatitis models (Choi et al. 2014;Jo et al. 2016).Choi et al. (2014), revealed that 1% water extract significantly reduced hyperplasia and thickening of the dermis and epidermis (by 35.6% and 39.2%, respectively) of mice in DNCB-induced dermatitis model compared to the animal group without treatment.Furthermore, histological examination by Jo et al. (2016), demonstrated that repeated topical application of methanol extract inhibited epidermal acanthosis, spongiosis and immune cell infiltration (Jo et al. 2016) in mice with DNFB-induced contact dermatitis model.The observed anti-inflammatory effect as inhibition of ear swelling was comparable to dexamethasone (Jo et al. 2016).Matsuda (1997b) observed that, in addition to antiallergic activity in type IV hypersensitivity, Kochiae fructus also influenced direct passive arthus reaction (DPAR) in rats, which is a type III allergic model.In another study, Choi et al (2002) demonstrated the potential of methanol extract in Freund's complete adjuvant-induced arthritis in Sprague-Dawley rats (Choi et al. 2002).
In addition, B. scoparia extracts also showed antiallergic potential in IgE-mediated hypersensitivity (type I).This type of allergy is associated with eczema and asthma (Matsuda et al. 1997b;Lee et al. 2011).Ethanol extracts from fruits reduced the level of interleukins (IL-4, IL-5) and the migration of inflammatory cells into the lungs in the OVA-induced asthma model in BALB/c mice.The effect may be the result of inhibition of matrix metalloproteinase-9 (MMP-9) inhibition and reduction in the expression of adhesive molecules (VCAM-1 and ICAM-1) in lung tissue (Lee et al. 2011).
The published research postulates that Kochiae fructus extracts exerted anti-inflammatory effects by influencing various factors involved in the inflammatory response.Kochiae fructus methanol extract decreased the level of INF-γ, TNFα, IL-1β and MCP-1 in the mouse model with DNCB-induced contact dermatitis (Jo et al. 2016).The methanolic extract was also observed to be a potent inhibitor of LPSinduced TNF-α, NO and PGE 2 production in LPSinduced RAW cells 264.7 in vitro.The effect was associated with LPS-induced iNOS and COX-2 gene expression by blocking nuclear factor kappa beta (NFκB) activation (Shin et al. 2004).Furthermore, Choi et al. (2014) point out that the anti-inflammatory activity of B. scoparia can be regulated via NFκB and MAP kinase pathways, such as ERK1/2, p38 and JNK (Choi et al. 2014).Furthermore, recently, Kochiae fructus was found to exert peroxisome proliferator activated receptors (PPAR) α/γ dual agonistic activity, which can alleviate the inflammation process (Jeon et al. 2016).Furthermore, the water extract showed the ability to inhibit human neutrophil elastase (HNE) (IC 50 =79.53μg/mL), the hydrolytic enzyme that can cause damage to elastase-rich tissue, and also promote inflammatory cell migration (Chen et al. 2017).
The search for active compounds revealed that various phytochemicals of Kochiae fructus could be associated with an anti-inflammatory effect.Several studies indicated that activity is related to saponins, mainly momordin Ic (Fig. 3B) (Matsuda et al. 1997a, b).This monodesmosidic saponin suppressed the production of pro-inflammatory cytokines, including TNF-α, IL-6 as well as PGE 2 in RAW 264.7 cells stimulated with LPS (Yoo et al. 2017).Furthermore, the anti-inflammatory, antiarthritic, and antiallergic potential of the compound was demonstrated in several animal models as well (see Table 6) (Kubo et al. 1997;Matsuda et al. 1997a, b).Furthermore, the antipruritic effect of Kochiae fructus was also attributed to saponins.However, it should be noted that the structure of a particular saponin affected the observed activity.Monodesmosides such as momordin Ic and oleanolic acid 3-O-glucuronide were observed to alleviate scratching behavior, while bidesmosides such as momordin IIc (Fig. 2) were almost ineffective against itching induced using compound 48/80 (Kubo et al. 1997;Matsuda et al. 1998a).However, Xiao et al. (2018) underlined that anti-inflammatory activity is related to the flavonoid fraction which was demonstrated using an animal model of DNCB-induced contact dermatitis.The flavonoid fraction, isolated from Kochiae fructus, containing rutin (24 mg/g) and quercetin (18 mg/g), after topical application, was found to reduce the level of pro-inflammatory cytokines and simultaneously increase the level of anti-inflammatory interleukin IL-10.Additionally, a significant decrease in tissue monocyte infiltration was observed.These effects could be the result of NFκB suppression via the ERK/TLR4 pathway.It should be mentioned that the flavonoid fraction exerted an effect comparable to a positive control (prednisolone acetate; 2.5 mg/kg) (Xiao et al. 2018).
In turn, Chen et al. ( 2017) with the use of bioactivity-guided fractionation revealed that the effect of the water extract of Kochiae fructus should be attributed to the polysaccharide fraction.It significantly reduced the activity of human neutrophil elastase with an IC 50 value of 3.74 μg/mL.Furthermore, the polysaccharide rich fraction was also active in the LPS-induced acute lung injury model in mice (Chen et al. 2017).
Summarizing the current state of art, the postulated main pathways involved in the antiinflammatory activity of the extracts and compounds from Kochiae fructus are presented in Fig. 5.
To our knowledge, in addition to anti-inflammatory investigations on B. scoparia, there is only one report devoted to another species of Bassia.Musa et al. 2016, demonstrated that the ethanol extract of aerial parts of B. eriophora (250, 500 and 750 mg/kg; i.p.) possessed the ability to inhibit swelling in the carrageenan-induced model of paw edema in rats (Musa et al. 2016).

Antinociceptive activity
The antinociceptive potential of some Bassia species was investigated using an acetic acid-induced writing test and a hot-plate test.The 90% ethanol extract of aerial parts from B. eriophora (250 and 500 mg/kg, p. o.) was found to cause an analgesic effect in both tests.The animals were treated with the extract after 90 min.and showed an increase in reaction time, which was comparable to indomethacin (4 mg/kg) (8.1±0.18;8.1±0.12;9.18±0.22,respectively) [control: 5.82±0.13].In the writhing method, extracts (250 and 500 mg/kg, p.o) also demonstrated significant antinociceptive activity (55.14% and 68.38%) when compared to the control vehicle group, however the effect was slightly worse than observed for indomethacin (86%) (Yusufoglu 2015a).Musa et al. (2016) also confirmed the antinociceptive activity of the ethanol extract of the aerial parts of B. eriophora using the hot plate test, but the significant effect was observed only at high doses (500 mg/kg and 750 mg/kg, p.o) (Musa et al. 2016).In turn, Matsuda et al. (1997a, b) revealed that 70% extract of Kochiae fructus (500 mg/kg) demonstrated activity only in the acetic acid-induced writhing model (Matsuda et al. 1997a).Different results were provided by Choi et al. (2002), who investigated the activity of the ethanolic extract of Kochie fructus and fractions (chloroform, ethyl acetate, butanol) derived from the extract.All extracts (100 and 200 mg/kg; p.o.) revealed an analgesic effect in both hot plate and writhing tests in male Sprague-Dawley rats (Choi et al. 2002).Furthermore, the triterpenes isolated from the extract, such as momordin Ic and oleanolic acid (5, 10 mg/kg, i.p.) were also active in both models (Choi et al. 2002).Further studies revealed that momordin Ic (20,50,100 mg/kg, p.o.) alleviated the pain response but only in the second (late) phase of the formalin test, suggesting that its antinociceptive activity is mainly associated with anti-inflammatory activity (Matsuda et al. 1997a).On the other hand, Bassia extracts also showed activity in the hot plate test, which is considered to integrate supraspinal pathways (Deuis et al. 2017).This suggests that apart from anti-inflammatory activity, other mechanisms may also be involved in antinociceptive effect, but this issue requires in-depth research.

Cytotoxic activity
Most published studies on the cytotoxic activity of the Bassia genus concern B. scoparia species, while two articles describe the activity of B. indica (Abdel-Hamid et al. 2017;Aboul-Enein et al. 2012) and one B. muricata (Al-Barri et al. 2021).Interestingly, only two of the reviewed papers defined, at least partially, the chemical content of the extracts studied (Cho et al. 2019;Wang et al. 2014a) and one paper provided a full chemical characterization of the essential oil of B. scoparia seeds which was the object of the study (Kianinodeh et al. 2017).Most of the results indicate a rather weak cytotoxic potential of Bassia extracts.
The weak cytotoxic activity of the water and ethanol extract prepared from B. indica whole plant against Ehrlich ascites carcinoma cells was observed, with a decrease of 2.88 and 1.6% decrease in cell viability (Abdoul-Enein et al. 2012).A similar weak activity of the ethanolic extract of the whole plant of B. indica was described for HepG2 cells, with IC 50 120.5 μg/mL, while for the control cytostatic 5-FU, the IC 50 value was 237.56 μg/mL.The extract was combined with 5-FU, and the most effective ratio, namely 5-FU/Bassia 1:2, decreased cell viability up to 48%, with a combination index of 0.996, suggesting a synergistic effect (Abdel-Hamid et al. 2017).In another study, a similar weak effect of Kochiae fructus aqueous and 50% ethanol extracts was investigated on the same HepG2 cells, after 4 and 24 h.Despite the difference in momordin Ic content, both extracts revealed a comparable, weak cytotoxic activity.Extracts at the dose of 1 mg/mL for 4 h or 0.1 mg/mL for 24 h decreased cell viability to approximately 60-70%, while almost total inhibition of cell viability was observed at doses as high as 5 mg/mL (Wang et al. 2014a).The methanolic extract of B. scoparia seeds revealed only weak cytotoxic activity in human lung A549 and colon Col2 cancer cells, with an IC 50 exceeding 20 µg/mL (Nam and Lee 2000).Other studies present the cytotoxic impact of ethanolic extract of B. scoparia seeds on human neuroblastoma N-2A cells, with LC 50 0.147 mg/mL.Although the authors classified the effect as strong, the value seems to indicate rather weak activity (Mazzio et al. 2009).B. scoparia seed ethanolic (80%) extract was evaluated for the possibility of its use in psoriasis.The in vitro experiment was carried out on HaCaT cells and proliferation was measured by SRB and MTT assays.The extract revealed a rather weak effect in decreasing keratinocyte proliferation, with IC 50 185.7 and 125.0 µg/mL for the SRB and MTT assay, respectively (Tse et al. 2006).
B. muricata whole plant was extracted with different solvents, namely methanol, ethanol, or the combination of methanol:chloroform:water (12:5:1), and the cytotoxicity of the extracts was examined against human lymphocytes and Chinese hamster ovary CHO cells.Not only was none of the extracts toxic to the tested cells, but an increase in cell viability was also observed during exposure at concentrations of up to 2 mg/mL (Al-Barri et al. 2021).
Several reports provide data on the mechanism of action of Bassia extracts.The cytotoxic potential of the methanolic extract of B. scoparia seeds was evaluated in a panel of prostate cancer cells, differing in metastatic potential: LNCaP, PC-3, RC-58 T, but also normal prostate epithelial cells RWPE-1, with IC 50 89.25, 123.41,141.62 and[250 µg/mL, respectively.The subtoxic dose of the extract (20 µg/mL) significantly suppressed VEGF-induced migration, invasion and formation of capillary-like structures of human umbilical vein endothelial cells (HUVECs) and micro vessels that sprout from rat aortic rings.The extract also downregulated the phosphorylation of VEGFR2 and the level of PI3K/AKT/mTOR, which resulted in decreased angiogenesis in HUVECs (Cho et al. 2019).Similar results on the antiangiogenic effect of Kochiae fructus extract were published by Na et al. (2006).The extract decreased the expression of the antiangiogenic protein HIF-1α (hypoxia-inducible factor 1-α) in HepG2 and HaCaT cells, and also reduced the level of VEGF and iNOS in HaCaT cells.The results indicate that the extract may be an antiangiogenic and anti-inflammatory agent useful in decreasing tumor progression (Na et al. 2006).
The methanolic extract of B. scoparia mature fruits was found to influence proliferation rate, cell cycle arrest, the generation of reactive oxygen species (ROS) and the stimulation of apoptosis in human breast MDA-MB-231 cancer cells.The results showed a dose-dependent decrease in cell proliferation, with IC 50 36.2μg/mL.Furthermore, the extract at 25 μg/mL significantly increased the sub-G1 DNA content in cells to 44.7%, when compared to untreated cells, and also increased pro-apoptotic proteins such as cleaved caspase 3, cleaved caspase 8, cleaved caspase 9 and cleaved Poly (ADP-ribose) polymerase (PARP), leading to cell apoptosis (Han et al 2014).In their further studies, the authors examined the effect of Bassia scoparia mature fruit methanolic extract on human (Ca9-22 and HSC-4) and murine (AT-84) oral squamous cell carcinoma, and also on human HaCaT keratinocytes.The extract arrested cancer cells in the sub-G1 phase, and also led the cells to apoptosis, by activating caspase-3 and -9 through the p38 MAPK pathway.Importantly, normal HaCaT cells were not affected (Han et al. 2016).
To our knowledge, there is only one report devoted to evaluating the cytotoxic potential and mechanism of action of essential oil from Bassia plants.The essential oil from mature fruits of B. scoparia, obtained by the Clevenger apparatus, which contained alkanes as main constituents (n-tetracosane, ntricosane, n-docosane, n-henicosane, n-eicosane), was tested in human breast cancer MCF-7 and normal HU02 fibroblast cells after 24, 48 and 72 h of incubation.The substance tested inhibited the viability of MCF-7 cells, with IC 50 125 μg/mL (72 h), while normal cells were not affected.Furthermore, incubation of MCF-7 cells with essential oil resulted in changes in cellular morphology, manifested as star-shaped cells, vacuolation, cytoplasmic and cellular shrinkage.Pyknotic nuclei were also observed, suggesting stimulation of apoptosis in cells (Kianinodeh et al. 2017).
Despite the large amount of in vitro data, so far only one animal study on Bassia extracts has been carried out.The anticancer properties of the methanolic extract of mature B. scoparia fruits were described in vivo, in C3H mice implanted with 3105AT-84 oral squamous cell carcinoma.The animals in the experimental groups received low (1 mg/kg body weight), medium (3 mg/kg body weight) or high (5 mg/kg body weight) doses of the extract, while the control animals were treated with a vehicle of 5% ethanol.The extract was introduced by intratumor injection once every two days (four times in total).The extract significantly reduced tumor volume in a dose-dependent manner, with the highest dose being the most effective.The authors also noted that the extract did not induce systemic toxicity and that no loss of body weight was also observed during treatment (Han et al. 2016).
Numerous reports indicate that momordin Ic, (Fig. 3B) a metabolite of saponin group, may be one of the active compounds of Kochiae fructus extracts as it has well-documented cytotoxic activity.Momordin Ic significantly reduced HaCaT cell viability, with IC 50 of 168.70 and 76.40 μM/L for 24 and 48 h, respectively.The compound affected cell morphology, resulting in cell shrinkage, but also stimulated cell apoptosis and arrested the cells in S-phase.Furthermore, momordin Ic treatment significantly decreased β-catenin, c-Myc, and VEGF mRNA expression, compared to untreated cells, and modified Wnt/β-catenin pathway activation by affecting β-catenin nuclear distribution.The authors suggest that such activity of momordin Ic may be of interest in antipsoriasis therapy in the future (Luo et al. 2021).In another study, the compound promoted the formation of autophagic vacuole and increased the expression of Beclin 1 and LC-3 in a dose-and time-dependent manner in HepG2 cells.The study results also revealed the crosstalk between autophagy and apoptosis stimulation by the compound, which simultaneously induced both processes by suppressing ROS-mediated PI3K/Akt and activating the ROS-related JNK and P38 pathways (Mi et al. 2016).Another study in the same HepG2 cellular model indicated that the compound induced apoptosis in cells, manifested as DNA fragmentation, caspase-3 activation, and PARP cleavage.In addition, momordin Ic stimulated reactive oxygen species (ROS) production and decreased mitochondrial membrane potential, cytochrome c release, down-regulation of Bcl-2 and up-regulation of Bax expression.Activation of p38 and JNK, inactivation of Erk1/2 and Akt, and alterations in the expression of iNOS and HO-1 were also observed after treatment with the compound.These results indicated that momordin Ic induced apoptosis through mitochondrial dysfunction regulated by oxidative stress involving the MAPK and PI3K-mediated iNOS and HO-1 pathways (Wang et al. 2013).In their further studies, the authors investigated the detailed mechanisms of momordin Ic apoptosis stimulation in HepG2 cells.The results demonstrated that momordin Ic activated PPARɣ and inhibited COX-2.PGC-1α and FoxO4 expressions were increased by the PI3K or MAPK pathways, while inhibition of PPARɣ decreased the expression of p-p38 and FoxO4, and restored COX-2 expression.ROS inhibition affected mainly PGC-1α expression, while PPARɣ, COX-2 and FoxO4 expression was almost unaffected (Wang et al. 2014b).
In mouse fibroblast NIH 3T3 cells, momordin I suppressed the activator protein-1 (AP-1), an important protein in cellular signaling, responsible for the induction of several genes in response to physiological signals.Furthermore, momordin Ic also decreased the de novo synthesis of the AP-1 protein.
The authors also suggest that the inhibitory site of momordin Ic might be in the Jun/Fos dimer and not in DNA, and the basic region of c-Jun is the most probable inhibitory action site (Park et al. 2000).Momordin Ic inhibited the proliferation of KB oral carcinoma cells with IC 50 10.4 µg/mL.Furthermore, the compound caused chromosomal DNA fragmentation and at a concentration of 20 µg/mL stimulated apoptosis in cells (approximately 20% apoptotic cells after 72 h) (Seo et al. 2007).
The small ubiquitin-like modifier (SUMO) protease, SENP1, plays an important role in cellular inflammation by regulating proteins in SUMOylation.Some studies suggest that momordin Ic might be a novel SENP1 inhibitor.In one of the studies momordin Ic reduced LPS-induced cellular inflammation in the RAW 264.7 macrophages model by depressing SENP1 expression.Furthermore, the effect of SENP1 on the LPS-induced inflammatory response was dependent on the interaction of SENP1-Sp3 and the promotion of Sp3 (transcription factor controlling the expression of genes involved in the cell cycle and inflammation response) expression by deSUMOylation of Sp3.Furthermore, momordin Icdepressed Sp3 expression altered the Sp3-nuclear factor (NF)-κB interaction, which decreased cellular inflammation (Zheng et al. 2020).SUMO-specific protease 1 (SENP1), a member of the de-SUMOylation protease family, is elevated in prostate cancer cells and is involved in cancer pathogenesis.Momordin Ιc inhibited SENP1 in vitro and altered the thermal stability of SENP1.Furthermore, the compound increased SUMOylated protein levels, namely hypoxia inducible factor-1α and nucleus accumbens associated protein 1 in PC3 prostate cancer cells, and also reduced SENP1 mRNA levels in cells.The authors suggest that momordin Ic may have therapeutic potential in prostate cancer (Wu et al. 2016).Another study focused on the effect of momordin Ic on a panel of colon cancer cells.The compound decreased the viability of colon cancer CT-116, HCT-8, SW480 and HT-29 cells, with IC 50 values ranging from 6.40 to 12.79 µM.As HCT-116 and HCT-8 cells were most vulnerable (IC 50 6.40 and 6.83 µM, respectively) they were used in subsequent experiments.Momordin Ic stimulated apoptosis in cells, and arrested cells in the G0/1 phase of the cell cycle.Furthermore, the compound enhanced the SUMOylation of c-Myc, which led to the downregulation of the c-Myc protein.The authors conclude that momordin Ic revealed its cytotoxic effect through the SENP1/c-Myc signaling pathway (Xianjun et al. 2021).
In addition to in vitro studies, the antitumor activity of momordin Ic was investigated in an animal model.Momordin Ic was administered to Balb/c nude mice implanted with PC3 prostate cancer cells, at a dose of 10 mg/kg daily for 20 days.On day 20, the xenograft tumors treated with the compound were less than those of the control group (p\0.05).The authors observed the accumulation of SUMO1and SUMO2/3-modified proteins in PC3 tumor xenografts treated with momordin Ic.However, a slight decrease in body weight was observed in the momordin Ic-treated group compared to the control group (Wu et al. 2016).
Although most of the research on cytotoxic activity has focused on momordin Ic, a single report on other compounds isolated from Bassia species has also been published recently.Three new steroidal glycosides, kochioside 1A 1 , kochioside 2A 1 and kochioside 3A 1 , isolated from Kochia prostrata, were examined in a brine shrimp lethality assay, and their potential was comparable to the standard drug etoposide, with LD 50 8.3201, 8.8205, 8.2310, and 7.4625 μg/mL, respectively (Irfan et al. 2020).

Hypoglycemic activity and anti-obesity activity
The ethanol extract of Kochiae fructus demonstrated an anti-obesity effect in diet-induced obese mice.Oral administration of extracts together with the high-fat diet (1%, 3%) prevented weight gain.After 9 weeks, a reduction in fat storage was also observed (Han et al. 2006).A similar anti-obesity effect was found for the infusion of B. scoparia seeds prepared from 1.5 g of seeds/100 mL; 3 g of seeds/100 mL; 6 g of seeds/100 mL.Consumption of a high-fat diet with infusions (ad libitum) for 12 weeks by Wistar rats with diet-induced metabolic syndrome resulted in a reduction in retroperitoneal fat weight and the corresponding fat index.Furthermore, infusions dose-dependently inhibited the elevation in cholesterol level induced by diet (Gancheva et al. 2020).The alleviation of the increase in plasma triglyceride levels by Kochiae fructus ethanol extract (250 mg/g) and its total saponins (100 mg/g), after oral administration of the lipid emulsion, was also reported by Han et al. (2006).Further investigation (in vitro) revealed that the antiobesity effect of Kochiae fructus could be associated with saponins, such as momordin Ic, 2′-O-β-D-glucopyranosyl momordin Ic and 2′-Oβ-D-glucopyranosyl momordin IIc which act as pancreatic lipase inhibitors (Han et al 2006).Furthermore, momordin can also induce an antiobesity effect via PPARδ (peroxisome-proliferator activatedreceptor) mediated mechanism (Sasa et al. 2009).
PPARs play a role in the regulation of not only lipid but also glucose homeostasis (Gawrieh et al. 2021).The methanol extract (500 mg/kg) of Kochiae fructus and its butanol fraction (200 mg/kg) exhibited a significant hypoglycemic effect in glucose-loaded rats.Oral administration of extracts decreased serum glucose level by 53-58% compared to the control group (Yoshikawa et al. 1997b).Further research based on bioassay-guided fractionation showed that triterpene saponins were responsible for the hypoglycemic activity of the extracts (Yoshikawa et al. 1997b).Dai and Liu, (2002), observed that oral administration of the total saponin fraction of Kochiae fructus also inhibits the increase in serum glucose in alloxan-induced hyperglycemic mice.Structure activity-relationship (SAR) observations on isolated Kochiae fructus saponins revealed that the free carboxyl group at C-17 (28-COOH) in oleanane-type saponins, as well as the presence of the 3-O-glucuronide moiety in the sugar part, is essential for hypoglycemic activity in vivo.Monodesmosides of oleanolic acid that have a glucoside unit in the sugar chain attached to the C-3 of the aglycone were slightly less effective (Yoshikawa et al. 1997b;Matsuda et al. 1998bMatsuda et al. , 1999a)).Furthermore, it was found that the mechanism of hypoglycemic action after oral administration of saponins is related to inhibition of gastric emptying and therefore the transfer of food to the small intestine (Matsuda et al. 1998a(Matsuda et al. , 1999a(Matsuda et al. , 1999b)).It depends on serum glucose level and is mediated, inter alia, by capsaicinsensitive sensory nerves (Matsuda et al. 1999b).In addition, an in vitro study revealed that momordin Ic and oleanolic acid 3-O-glucuronide also inhibited glucose uptake in the rat small intestine (Matsuda et al. 1998b).

Antioxidant activity in vitro
In recent years, phytochemical research has focused on the analysis of phenolic compounds in Bassia species.Phenolics are substances with a well-documented antioxidant effect, therefore, the antioxidant potential of different extracts of Bassia species were also studied.Most articles provide data on the different extracts prepared from aerial parts (leaves, shoots, fruits) of Bassia plants (Wang et al. 2014a;Yusufoglu et al. 2015a;Mohammedi et al. 2019;Gancheva et al. 2020) and fractions obtained by partitioning extracts with solvents of increasing polarity (Chemsa et al. 2016;Khalil et al. 2017;Said et al. 2021).Among the studies, the assays based on the DPPH method predominated.The results of studies on the antioxidant potential of Bassia plants are presented in Table S1 (Supplementary information).Khalil et al. (2017) evaluated the antioxidant potential of different plant parts (leaves, steams, roots) of B. eriophora.A significant DPPH radical scavenging effect (IC 50 =19.2-46µg/mL) of the ethyl acetate and butanol fraction of the 70% methanol extract was observed.A slightly lower antiradical potential was determined for the water fraction (IC 50 39.9 to 73.2 μg/mL).In turn, both the chloroform and the hexane fraction of the ethanol extract have the lowest ability to eliminate DPPH radicals (IC 50 [ 100 μg/mL).It is interesting that no significant differences in activity were found between extracts obtained from different parts of B. eriophora.In another study on B. eriophora, Said et al. (2021), revealed that 40% methanolic fraction obtained by elution of methanol (80%) extract from aerial parts of the plant on the C-18 short column has good antioxidant potential.The fraction had IC 50 values of 177.8 µg/mL in the DPPH test and showed concentration-dependent total antioxidant capacity (TAC) and reducing power (RP).The authors underline the positive correlation between TAC and RP with total flavonoid content.It should be noted that the fraction analysed was defined by LC-MS/MS, which led to tentative detection of 28 flavonoids (acetylated and non-acetylated compounds).In the same study, further theoretical calculations on the O-H bond dissociation enthalpy (BDE) allowed the antioxidant activity to be linked to the location of hydroxyl groups in the flavonoid structure.The value of BDE decreased in structures with two adjacent hydroxyl groups.Therefore, such structures should have significant antioxidant potential (Said et al. 2021).
Antiradical activity was also investigated in hexane, ethyl acetate, and methanol extracts from aerial parts of B. indica.The results showed that the most potent effect was observed in methanol and water extracts with IC 50 values of 1.30 µg/mL and 1.39 µg/ mL as well as TEAC values of 1.44 mM and 3.60 mM in the DPPH and ABTS assays, respectively.The ABTS-free radical elimination effect of the water extract was higher than observed for the reference BHT (TEAC=1.80 mM) and slightly lower than the anti-DPPH potential (IC 50 =0.91µg/mL in DPPH).Compared to those extracts, the scavenging effect of hexane extract was much lower with IC 50 values of 2.18 µg/mL in the DPPH test and 0.17 mM Trolox in the ABTS assay.It can be associated with a lower phenolic content in the hexane extract (5 mg PyE/100 g of extract) compared to the methanol and water extract (146 and 72 mg PyE/100 g of extract, respectively) (Bouaziz et al. 2009).
Several studies were also conducted to establish the antiradical activity of extracts of B. muricata.Mohammedi et al. (2019) revealed that methanol extracts from the aerial parts had stronger DPPH radical scavenging activity (EC 50 =5-5.03mg/L) than aqueous (EC 50 =5.86-5.90mg/L), ethanol (EC 50 = 6.12-6.40mg/L), acetone (EC 50 =6.70-7.14mg/L) and hexane extracts (EC 50 =7.42-8.03mg/L).However, water extracts were the most potent in the ferric reducing capacity assay (EC 50 =1.39-2.60 mg/L) and β-carotene bleaching (EC 50 =5.31-6.0mg/L).The authors noted that the high antioxidant activity of methanol and water extracts is strictly associated with a high polyphenol content (TPC=122.15-144.82mg of GAE / g of methanol extract and 98-100.12mg of GAE / g of water extract).Furthermore, in the same study it was observed that the type of extraction technique used (MAE, Soxhlet, maceration) had no significant effect on the measured values of antioxidant activity (Mohammedi et al. 2019).
Recently, the essential oil of the B. muricata shoots, extracted by hydrodistillation by Abd-ElGawad et al. ( 2020), was tested for its DPPH and ABTS radical scavenging activity.To our knowledge, this was the only study on the antioxidant potential of essential oil of any Bassia species.The study revealed that the essential oil eliminated DPPH radicals with an IC 50 value of 20.70 µL/mL and acted as anti-ABTS (IC 50 =16.32µL/mL).The authors suggested that considerable antioxidant potential may be associated with a large amount of oxygenated sesquiterpenes (53.18%), detected by the GC-MS method in the oil, including hexahydrofarnesyl acetone (47.34%) (Abd-ElGawad et al. 2020).
Unlike other Bassia species, the analysis of the antioxidant potential of B. scoparia focuses on the study of dried fruits, which are a valued medicinal agent in traditional Chinese medicine.Wang et al. (2014a) revealed that the water and ethanol (50%) extract of Kochiae fructus possess the ability to reduce the ferricyanide complex (Fe 3+ ) to the ferrous form (Fe 2+ ) in the FRAP assay.Furthermore, extracts not only demonstrated the potential to eliminate DPPH (IC 50 =0.24-0.31mg/mL) and ATBS radicals (IC 50 =0.35-0.43mg/mL) but also showed superoxide anion (IC 50 =5.42-6.64mg/mL) and hydroxyl radical scavenger properties (IC 50 =0.23 mg/mL and IC 50 =2.25 mg/mL, ethanol extract and water extract, respectively) (Wang et al. 2014a).Reactive hydroxyl radicals, superoxide anion, and their by-products may cause oxidative damage to biomolecules.Wang et al. (2014a) confirmed that water and ethanol (50%) extracts of Kochiae fructus (0.1-7 mg/mL) were able to dose-dependently inhibit the free radical-induced destruction of biomolecules.Extracts (0.1-7 mg/mL) inhibited lipid peroxidation in the range of 3-80% (compared to the control group).The ethanol extract was found to almost completely suppress lipid peroxidation (at 7 mg/mL).Furthermore, at a much lower concentration, 50% ethanol extract (0.1 mg/ mL) significantly suppressed protein oxidative damage by 73%, while water extract exerted similar activity with a dose of 10 mg/mL.It should be noted that both the ethanol and water extracts (at 0.1-7 mg/ mL) effectively protected DNA from oxidative damage by 19-70% and 4-40%, respectively.The authors indicated that the observed effect, especially observed in the ethanol extract, may be related to the presence of momordin Ic.It is interesting that this triterpene saponin was able to protect free radicalinduced protein oxidation in a dose-dependent manner (Wang et al. 2014a).Momordin Ic (at 1 µM= 0.76 µg/mL) showed significant activity in the model of AAPH-as well as Cu 2+ /H 2 O 2 -mediated oxidative damage ([80% intact proteins) (Wang et al. 2014a).
Published reports indicate that some of the extracts of Bassia plants, especially those rich in polyphenols, show significant antioxidant potential.As a result of the different methods of processing the plant material, it is very difficult to compare these results with each other.It should be noted that to date no analyses have been published that compare the antioxidant activity of several species of Bassia under the same conditions.To the best of our knowledge, only one analysis has been performed to date comparing the activity of two species: B. indica and B. muricata (Bouaziz et al. 2009).The study showed significant differences in the content of phenolic compounds and the antioxidant activity of the extracts depending on the type of extractant used (see Table S1, Supplementary information).The water extracts of aerial parts of B. indica showed the strongest antioxidant activity in the ABTS assay, even higher than the reference substance (BHT) (Bouaziz et al. 2009).
Although in vitro models may provide preliminary information on the activity of the extracts, they do not always reflect in vivo conditions.Recently, the antioxidant potential of B. scoparia and B. eriophora was investigated using animal models.The studies were related to the hepatoprotective and nephroprotective potential of the extracts (see next section).
Hepato-, nephro-, gastro-and neuroprotective activity Kim et al. (2005a), revealed that Kochiae fructus had a hepatoprotective effect against CCl 4 -induced liver damage in Wistar rats.Pre-treatment with methanol and the butanol fraction derived from the extract (200 mg/kg body weight; p.o.; once a day for 14 days) resulted in a significant reduction in serum levels of aspartate transaminase (AST), alanine transaminase (ALT), lactic dehydrogenase (LDH) and liver concentration of thiobarbituric acid reactive substances (TBARS) in the CCl 4 treated rats.Furthermore, both extracts significantly inhibited the reduction in glutathione, glutathione-S-transferase, and glutathione reductase activity produced by CCl 4 .The study demonstrated that the hepatoprotective effect of B. scoparia was closely related to the antioxidant activity of the extracts and increased the hepatic antioxidant potential (Kim 2005a).Gancheva et al. (2020) came to similar conclusions by examining the protective potential of the infusion of B. scoparia seeds in Wistar rats with diet-induced metabolic syndrome.The animals received a high-calorie diet along with infusions (ad libitum) prepared with the use of 100 mL of boiling water and 1.5 g, 3 g and 6 g of seeds, respectively.After 12 weeks of treatment, all infusions demonstrated antioxidant activity in vivo in a dose-dependent manner.In the group of animals with metabolic syndrome, which were administered infusion made from 6 g of seeds, the most potent decrease in thiobarbituric acid 1230Phytochem Rev (2023Rev ( ) 22:1197Rev ( -1246 reactive substances (TBARS) in serum, comparable to healthy rats on a regular rat chow diet was observed.Furthermore, the histopathological study demonstrated that pre-treatment with infusion prevents the appearance of liver lesions (Gancheva et al. 2020).Although no bioassay-guided fractionations were performed in the investigation, the authors assumed that oleanolic acid and momordin Ic are the hepatoprotective substances in Kochia fructus as they are known to exert the effect (30 mg/g body weight; p.o.; once a day for 14 days) in the CCl 4 -induced liver damage model in rats (Kim et al. 2005b).It is interesting that in the scientific literature there are also some reports on the gastroprotective potential of momordin Ic, oleanolic acid 3-O-glucuronide against ethanol-and indomethacin-induced gastric mucosal lesions in rats (Matsuda et al. 1998c(Matsuda et al. , 1999c)).However, to our knowledge, no reports on such activity of extracts of Bassia species have been published.Among Bassia species, B. eriophora also revealed a preventive potential in vitro, not for liver but kidney damage.To assess plant activity, the CCl 4 -induced lipid peroxidation model (Albino Wistar rats) and post-test measurement of the level of malondialdehyde in nephritic tissues, as well as histopathological investigation, were used.The study revealed that pretreatment with 90% alcoholic extract from aerial parts of the plant (250 mg/kg body weight, p.o. and 500 mg/kg body weight p.o./six days) influenced kidney functions as a reduction in serum creatinine and urea levels was observed in animals intoxicated with CCl 4 .Furthermore, the amount of total proteins, which represents the level of damage, was maintained as in normal rats.The extract of B. eriophora also significantly prevented the elevation of malondialdehyde, a marker of oxidative stress, in the kidney tissue of rats intoxicated with CCl 4 .Finally, histopathological studies confirmed that pre-treatment of animals with B. eriophora extract significantly and dose-dependently reduced injuries such as vacuolization of the cytoplasm of the epithelial lining of renal tubules induced by CCl4 intoxication.The authors emphasize that kidney protective activity results from the antioxidant and free radical scavenging potential and may be related to polyphenol compounds in the extract of B. eriophora (Yusufoglu et al. 2015a).

Antibacterial, antifungal, and antiparasitic activity
Antibacterial activity studies in representatives of the Bassia genus have been conducted mainly on extracts from aerial parts of plants, including fruits of B. scoparia, prepared with the use of different solvents.Most of the research has been carried out using agar diffusion methods, but studies on the determination of minimal inhibitory concentration (MIC) have also been performed.The list of antimicrobial studies is presented in Table S2 (Supplementary information).
In a preliminary study on the antimicrobial potential of B. eriophora, ethanol extract from aerial parts of the plant was found to inhibit Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Proteus vulgaris growth (Al-Mussawi et al. 2014).Activity toward S. aureus and E. coli was also observed for fractions obtained by partitioning 70% ethanol extract from different parts of B. eriophora plant (leaves, roots, stem) with hexane, ethyl acetate, and water.All extracts, but especially the water fraction from the roots and stems, exhibited high activity towards S. aureus, with inhibition zones between 27 and 40 mm (control: oxacillin 19 mm; erythromycin 22 mm).In turn, moderate activity towards E. coli was observed for the water extract of the roots and stems, as well as the ethyl acetate fraction of the stem (Khalil et al. 2017).In another study, the antibacterial activity of 95% ethanolic extract of aerial parts of B. eriophora against not only methicillin-sensitive S. aureus (MSSA) but also resistant (MRSA) strains were evaluated.The extract was found to inhibit the growth of both MSSA and MRSA strains, with MIC values of 25-75 μg/mL and 75 μg/mL, respectively.Interestingly, the authors also performed analyzes that evaluated the possibility of using B. eriophora extract to create an antibacterial layer on textiles against S. aureus.Furthermore, they indicate that anti-S.aureus fabrics do not lose their antibacterial properties, even after two washing cycles (prepared according to the test method 61(2A)-1996, the American Association of Textile Chemists and Colorists) (Alsaggaf et al. 2018).The potential of B. scoparia for MRSA was also investigated.The nhexane fraction of the Kochiae fructus ethanol extract exhibited significant activity (MIC=7.8-31.25 μg/ mL; ampicilin 31.25-1000μg/mL; oxacilin 500-1000 μg/mL), whereas the butanol, ethyl acetate and water fraction did not inhibit the growth of bacteria.Furthermore, synergy in antibacterial activity was observed between the hexane fraction and antibiotics (oxacillin or ampicillin) (Joung et al. 2012).El-Shamy et al. (2012), investigated the antibacterial effect of essential oil from B. scoparia shoots.Although the oil significantly inhibited the growth of E. coli, Bacillus subtilis, and S. aureus (MIC= 12.5 μg/mL, 12.5 μg/mL and 25.0 μg/mL, respectively), the effect was lower compared to cefroperazone (MIC=0.8μg/mL).The observed effect was probably related to α-thujaplicin, which is the major component of essential oil and has a well-documented antimicrobial activity (Yamaguchi et al. 1999;Morita et al. 2001;El-Shamy et al. 2012).Among Bassia species, also alcoholic extracts of B. muricata moderately suppressed the growth of B. subtilis, S. aureus, P. aeruginosa., E. coli, which was determined using the agar well diffusion method (Al-Barri et al. 2021).In another study, the ethanol extract from aerial parts of B. muricata (40 extract/ disc) showed antimicrobial activity against E. coli and P. aeruginosa, which was comparable to amoxicilin (25/disc).Additionally, a moderate effect against Vibrio cholerae, Salmonella enterica, and Enterococcus faecalis was also observed (Chemsa et al. 2016).Some reports investigating the antibacterial potential of aerial parts of B. indica can also be found in the literature (Abdel-Hameed et al. 2008;Bouaziz et al. 2009;Bibi et al. 2021;Ahmed et al. 2022).However, they provide contradictory information that can be associated with, among others, different methods of processing plant material.
In addition to antibacterial activities, the antifungal potential of various extracts of Bassia plants was also tested.Unfortunately, some of the studies are not well documented, without a corresponding positive control (antifungal drug) and seem not to be too repetitive.Significant inhibitory activity against Macrophomina phaseolina was also observed in the n-butanol fraction of the leaf methanolic extract of Kochia indica.At the concentrations tested (1.56-200 mg/ mL), the extract caused a reduction in the biomass of this fungal plant pathogen in the range of 63-92% (Javed et al. 2018b).
Unlike antimicrobial studies, data on the antiparasitic activity of Bassia species are scarce.The methanol extract of the seeds of B. scoparia (100 μg/ mL) showed moderate activity (47% inhibition) against the epimastigote stage of Trypanosoma cruzi in axenic cultures (allopurinol was used as a positive control, 67% inhibition) (Lirussi et al. 2004).In a study on the antitoxoplasmal potential of B. eriophora, a methanol extract of aerial parts of the plant (50 μg/mL) displayed very weak activity (5% of inhibition) against Toxoplasma gondii tachyzoites (Al Nasr 2020).In turn, 95% methanol extract of B. indica (100 and 200 μg/mL) was evaluated against Schistosoma mansoni, but no activity was detected (Abdel-Hameed et al. 2008).The reports published so far clearly indicate a low potential of extracts from Bassia species against analysed parasites, which cause disease in humans.
However, there are reports that show significant activity of B. scoparia extracts against animal and plant pathogens.Lu et al. (2012a) examined the antiparasitic potential of various extracts of fruits of B. scoparia against the fish pathogen Dactylogyrus intermedius using an in vivo anthelmintic efficacy model in goldfish (Carassius auratus).The methanolic extract of the fruits of the plant demonstrated potent activity with values of EC 50 and EC 90 of 31.28 mg/L and 52.52 mg/L (in bath), respectively.Furthermore, the acute toxicity assay revealed that the 48 h LC 50 values (71.04 mg/L) are higher than therapeutic concentrations.The other extracts tested (petroleum ether, chloroform, ethyl acetate, acetone) exhibited a lower potential in the anthelmintic model and caused fish mortality in the concentration range 90-130 mg/L (Lu et al. 2012a).In turn, Shi et al. (2006) screened the acaricidal activity of extracts from aerial parts of B. scoparia against the spider mites Tetranychus cinnabarinus, Tetranychus urticae, and Tetranychus viennensis, which are parasites on many different plants and crops.All extracts showed systemic and contact toxicity to mites.Chloroform extract caused a strong mite mortality rate (73.3-89.12%)and the effect was stronger than observed for methanol extract (39.78-44.78%)and petroleum ether extract (41.92-54.21%)(Shi et al. 2006).These studies have provided promising results and thus should be the subject of further in-depth analyses.

Other activities
In addition to the biological activities mentioned above, some reports also demonstrated other effects observed for some Bassia species.The aqueous extract of Kochiae fructus (200 g/1500 mL) exerted a decrease in stroke volume and pulse pressure in beating rabbit atria.However, this inotropic activity was not mediated by atrial natriuretic peptide (ANP) secretion (Lee et al. 2016).In another study, Kochiae fructus water extract (20 mg/g, p.o.) demonstrated improvement in heart function parameters in the furazolidone-induced DCM model.Furthermore, the extract showed a regulatory effect on Th1/Th2 cell activity, which suppressed myocardial injury in dilated cardiomyopathy (DCM) (Zou et al. 2021).Yusufoglu et al. (2015a) investigated the antipyretic potential of B. eriophora in the rat model of yeast-induced pyrexia.The 90% ethanol extract (250 mg/kg and 500 mg/kg) from the aerial part of the plant significantly reduced the elevated rectal temperature (39.35 °C).120 min after oral administration, the temperature decreased to 36.68 °C and 35.83 °C, while indomethacin (4 mg/kg) reduced the temperature to 35.45 °C.However, the mechanism of action has not been evaluated.The ethanol extract of aerial parts of B. eriophora (250, 500 and 750 mg/kg; i.p.) was found to cause dose-independent skeletal muscle relaxant activity using the rota-rot test in male Swiss albino mice (Musa et al. 2016) as well.Recent studies in animal models with seizures induced by pentylentetrazol and electroshock indicate that essential oil from fresh leaves of B. scoparia (75, 150 and 300 mg/kg; p.o.) had anticonvulsant activity.Unfortunately, this study is only preliminary because no phytochemical investigation was conducted on the composition of essential oil.Therefore, it is not known which phytoconstituents may be responsible for activity (Imade et al. 2020).In turn, Othman et al. (2021b) screened seventeen constituents isolated from hydroalcoholic extract of aerial parts of B. indica as acetylcholinesterase inhibitors in vitro, including a new acylated flavonol tetraglycoside and a rare triglycoside.Among them, the most potent were 6,7-dihydroxycoumarin and quercetin with IC 50 values of 3.6 μg/mL and 18 μg/mL, respectively (galantamine was used as a positive control, IC 50 = 12.5 μg/mL).Yusufoglu (2015b) investigated the wound healing potency of gel preparations containing 1% and 2% ethanol extract of the aerial part of B. indica.Both formulations showed significant and dose-dependent wound contracting ability in the excision wound model in Albino Wistar rats.The reduction in wound size caused by topical application (once a day for 20 days) of 2% gel was more potent than that observed for 1% gel or Betadine (84.21%, 78.68% and 60.25%, respectively vs. base gel 56.70%).

Safety of Bassia species
The scientific literature provides only a few data on the toxicity of Bassia plant extracts.It is worth noting, however, that some species have been clinically used in traditional medicinal systems, which also provides information on their safety in humans.One of such plants is B. scoparia.Toxicological studies in mice indicated that Kochiae fructus water extract demonstrated very low oral acute toxicity with an LD 50 value of 7.15 g/kg (Zou et al. 2021).Furthermore, in two investigations, it was confirmed that the ethanol extract from aerial parts of B. eriophora also exhibited low toxicity (Yusufoglu 2015b;Musa et al. 2016) and the LD 50 after oral administration in mice was estimated at 33.4 g/kg (Musa et al. 2016).However, it should also be noted that the data available in the literature refer to acute toxicity, while there is no information on the chronic use of various Bassia plant extracts.There are only data on the consumption of hay from certain species as feed for livestock.Some species of the genus Bassia can accumulate oxalates and nitrates, which may be associated with signs of toxicosis in animals, but only after chronic consumption of large amounts of hay (Rankins et al. 1991a, b).However, it should be noted that the level of these components in the Bassia plants depended on many factors (maturity stage, environmental factors) (Finley and Sherrod 1971;Lo ´pez-Aguilar et al. 2013;Steppuhn et al. 1994;Yang et al. 2007;Ma et al. 2011Ma et al. , 2016)).Furthermore, the observed presence of nitrates and oxalates did not exclude the medical or even food use of other plants from the Amaranthacae family, such as Beta vulgaris, Amaranthus sp., Spinacia oleracea, which also accumulate antinutritional compounds (Jaworska et al. 2005;Gadermaier et al. 2014;Liu et al. 2015;Corleto et al. 2018;Munekata et al. 2021;Avila-Nava et al. 2021).Thus, this indicates that more attention should be paid to the level of potentially toxic compounds before clinical application of Bassia plants.
Among the side effects that can appear in contact with plants of the genus Bassia, pollen allergy manifested as allergic rhinitis should also be mentioned.Most allergens found in pollen from the Amaranthaceae family belong to the profilin group (Gadermaier et al. 2014;Elvira-Rendueles et al. 2017).In a study by Zarinhadideh et al. (2015), the first pollen allergen of Bassia scoparia (named Koc s 2) was also characterized.

Conclusions
The representatives of the genus Bassia have been used by humans in different parts of the world for medical as well as nonmedical purposes.This overview gathers and summarizes available scientific data on phytochemistry, biological activity, and significance of plants belonging to the genus, reorganized by Kaderit and Freitag (2011) and denoted Bassia All.
Based on the publications covered in the review, for many years the research on Bassia plants focused solely on one species (B.scoparia), and actually only one of its parts, Kochiae fructus, which is a valuable therapeutic agent in TCM.Only in recent years has there been growing interest in the phytochemistry and biological activity of the other species of the genus.Moreover, some investigations were also conducted on other parts of the B. scoparia plant.However, it should be noted that many species of the genus Bassia still remain poorly investigated or unexplored.
Phytochemical studies conducted on Bassia species indicate that these plants synthesize metabolites that belong to very different groups of compounds.The latest studies provided information on flavonoids in B. eriophora and B. indica, as well as lignanamides in the latter species.It is interesting that some of the substances found in Bassia plants are unique and rarely found in the plant kingdom.Such structural biodiversity may have a significant impact on the overall biological activity of specific extracts, but this issue requires in-depth research.So far, only some studies on the biological activity of extracts have attempted to answer the question of which compounds are responsible for the observed effect.Most of them focused on bioassay-guided fractionation of active compounds.This approach allows for the selection of a single active compound, but ignores the possibility of a synergistic effect between the phytoconstituents, which often occurs in plant extracts.For example, for many years, the anti-inflammatory activity of Kochiae fructus extracts was attributed only to saponins.However, recent studies indicate that flavonoids and, in the case of aqueous extracts, polysaccharides may also be responsible for the effect.Therefore, determining the composition of the extract is extremely important to understand the resultant activity.Equally important are the quantitative analysis of the compounds in the extract and the selection of active markers responsible for the activity.Ensuring the standardization of extracts enables the maintenance of product quality, repeatability of test results, and potential therapy in the future.In the case of research on the activity of extracts from plants of the genus Bassia, although they undoubtedly indicate a multidirectional pharmacological effect of the extracts, including antiinflammatory, cytotoxic, antioxidant, antimicrobial, glucose-lowering and several potential nontherapeutic effects, only some studies provide information on the chemical characterization and quantification of the main components in the extracts.Interestingly, this also applies to in vivo studies.As a result, there is a lack of data that would allow determining the relationship between the phytochemistry of a given species and the activity of its extracts.This is an issue that requires extensive analysis, especially considering some studies that indicate seasonal variability in the content of individual metabolites.However, it should be noted that many of the Bassia species have been used without standardization in traditional healing systems.In such a case, it would be extremely valuable to analyze the qualitative and quantitative profile of the form of the drug used in traditional medicine or at least to identify the main markers.
In this review, we try to present the current state of knowledge and research on species of the genus Bassia.After analyzing the published reports, we schematically summarized the network of relationships between phytochemical studies and data on the biological activity of extracts and compounds from individual Bassia species (see Fig. 6).
Based on published research on biological activity, one of the most promising directions of research on extracts from plants of the genus Bassia are analyses related to the therapy of inflammatory-related diseases.This aspect is in part in line with the current use of Kochiae fructus in TMC in the treatment of skin diseases.However, it should be mentioned that inflammatory processes are the basis or cause of the progression of many other diseases that are now increasingly common in the developing society, such as cancer, diabetes, and heart disease.Many investigations revealed that extracts (e.g. of B. scoparia, B. eriophora, B. indica) and some isolated compounds (e.g.momordin Ic, flavonoids, N-trans-feruloyl-3methoxytyramine) show not only anti-inflammatory effects, but also significant cytotoxic, glucose lowering, anti-obesity, neuroprotective, and antioxidant effects in vivo.These results indicate a potential for in-depth research on activity against the metabolic syndrome and noncommunicable diseases.
The second direction related to potential further research on the biological activity of extracts from plants of the genus Bassia is the antimicrobial and antiparasitic activity.Unfortunately, some of the studies on this issue provide only preliminary information and others were conducted without comparison of results to the corresponding positive control.However, the studies that have been carried out so far indicated that extracts from plants of the genus did not have a broad and nonspecific range of antimicrobial activity, but some of them showed interesting activity against a specific pathogen, such as methicillin resistant S. aureus (MRSA), or against certain fungi or pests causing significant losses in plant crops.These studies should be significantly extended to determine which compounds present in the extracts are responsible for the effect.
In recent years, the possibilities of various nonmedical and non-food uses of Bassia species have been explored.Some of them did not produce the expected good results.An example is the use of B. prostrata for the construction of green walls near highways, reducing air pollution (Hozhabralsadat et al. 2022) and the possibility of using B. scoparia oilseeds as a source for the production of biodiesel (Abideen et al. 2015).However, it should be noted that the latter potential application is possible, but not profitable, because of the possibility of using other plants that are much more abundant in the oil.In the literature, there are some single reports on the interesting potential of different nonmedical and medical applications of Bassia plants, such as the production of cellulose nanofibrils from B. eriophora biomass or the use of B. muricata extracts as an ecological corrosion inhibitor.These studies have provided promising results, but require confirmation, and thus should be subject to further in-depth research.Another issue is the possible use of some species of Bassia (B.scoparia, B. indica) in soil phytoremediation.Research in this area is very promising from an industrial and ecological point of view.However, these studies indicate the likelihood of the accumulation of toxic substances in Bassia plants, which excludes the possibility of their use for medical purposes.Therefore, this indicates that more attention should be paid to the environmental conditions under which the plant grows or is cultivated in the case of plants of the genus Bassia used for medical purposes.
Species of the genus Bassia possess significant adaptation to unfavorable environmental conditions and the possibility of growth and cultivation even in arid areas.Therefore, one of the interesting potentials of Bassia plants may be their cultivation on wasteland and use as a source of bioactive substances.The research conducted indicates the possibility of obtaining (Z)-5-hexadecenoic acid from seeds of various species of Bassia (B.prostrata, B. scoparia, B. hyssopifolia) as an intermediate to produce insect ovioposition pheromone.It is also interesting to obtain momordin Ic, which is considered one of the main compounds of the Bassia scoparia fruit with multidirectional activity.
In summary, species of the genus Bassia are characterized by an interesting, complex phytochemical, and pharmacological profile.In addition, some of them, such as B. scoparia, exhibit several activities that justify its use in the traditional medical system.In turn, other species of Bassia, such as B. muricata or B. indica, which also have an established position in folk medicine, have not been subjected to research that justifies their traditional use.However, studies conducted in recent years have provided new data on the phytochemistry and activity of Bassia extracts that go beyond traditional applications.Additionally, considering the possibility of cultivation of some Bassia species, these plants are interesting targets for further research.However, it should be noted that, despite numerous reports, there are still many gaps in the current knowledge on species of the genus Bassia and there is a need to conduct in-depth research on the currently studied species as well as to start the analysis of plants that have not been investigated so far.

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Bassia plants are distributed from the Mediterranean region (Europe and North Africa) up to Japan (B. scoparia, B. prostrata, B. hyssopifolia).Several species are characteristic of the arid regions of the Middle East, India, and steps of Central Asia (B.odontoptera, B. indica, B. eriophora, B. stellaris).Some grow in North Africa, in the Sahara region (B.arabica, B. muricata) and South Africa (B.salsoloides, B. dinteri) (Kaderit and Freitag 2011; GBIF 2022).Plants of the Bassia genus, such as B. scoparia, B. prostrata and B. hyssopifolia, have been introduced to North America as high-yielding forage plants with nutritional value or for ornamental purposes.They spread quickly and are currently naturalized in both North and South America (Lauriault et al. 2020; Torbiak et al. 2021; Brignone et al. 2021; Ravet et al. 2021).B. scoparia and B. hyssopifolia have also been introduced to Australia.However, due to the high invasive potential of B.

Fig. 2
Fig. 2 Chemical structures of new compounds (at the time of publication) isolated from the genus Bassia

Fig. 3
Fig. 3 Chemical structures of compounds isolated from the genus Bassia: characteristic compound (A), rarely found compounds in the plant kingdom (B) of ethanol extract from fresh parts of the B. muricata as an eco-friendly and effective inhibitor of the corrosion process of the aluminium alloy are also investigated (El-Katori and Al-Mhyawi 2019).

Fig. 6
Fig. 6 Dependency network of between phytochemical studies and data on the biological activity of extracts and compounds from Bassia sp.(Abbreviations: "x"-not a promising direction of application)

Table 1
The ethnobotanical importance of Bassia plants and their use in medical systems, including TCM . Bassia plants, including B. prostrata, B. scoparia, B. muricata, B. eriophora and B. indica, are also valued as feed for livestock in various districts of Pakistan, Saudi Arabia, and Kazakhstan due to the nutritional values of aerial parts, but equally important to the possibility of their cultivation under unfavourable climatic conditions, (Khan and Khatoon 2008;Khan et al. 2013;Youssef 2013;Akhtar et al. 2018Youssef 2013;Akhtar et al. 2018).In the western United States and the Near East, B. prostrata and B. indica are gaining increasing importance as high-yielding forage plants for grazing

Table 2
Saponins isolated from plants of the genus Bassia

Table 4
Flavonoids of the genus Bassia the structure of quercetin sophorosides that contained the feruloyl and caffeoyl moiety that were isolated from B. muricata.Furthermore,Said  et al. (2021)detected several acylated flavonol glycosides in B. eriophora using the LC-ESI-MS/ MS method.Recently, a novel flavonol tetraglycoside with feruloyl moiety established

Table 6
Anti-inflammatory activity of extracts and isolated substances of Bassia Liu et al. (2012)2012)e preliminary data that alcoholic extracts from aerial parts of B. muricata, B. prostrata, and B. indica have moderate activity towards some pathogenic fungus.B. muricata, B. indica, and B. scoparia inhibited Candida albicans growth (Al-Barri et al. 2021; Ahmed et al. 2022) as well as B. prostrata was active toward Candida glabrata, Microsporum canis, Aspergillus flavus, and Trichophyton longifusus (Imran et al. 2017) (see Table S2).Most reports indicated inactivity of Bassia extracts toward Aspergillus niger or A. fumigatus (Abdel-Hameed et al. 2008; Al-Barri et al. 2021;Ahmed et al. 2022).Additionally, the essential oil obtained from the B. scoparia shoots, with α-thujaplicin as the main compound (22.91%), did not inhibit the growth of A. niger, while it showed moderate activity towards C. albicans (MIC= 12.5 μg/mL) (cefroperazone was used as a positive control, MIC=5.0 μg/mL)(El-Shamy et al. 2012).In another study,Liu et al. (2012)screened the antifungal activity of different extracts of Kochiae fructus (0.2 g fruits/mL) towards Saccharomyces cerevisiae