Introduction

Hesperidin (Hesp; C28H34O15; 3′,5,7-trihydroxy-4′-methoxy-flavanone-7-O-rutinoside) is a flavanone glycoside with poor solubility in water and most organic solvents. This flavanone is typically found in the Citrus genus, especially in the albedo, at different concentrations (Escobedo-Avellaneda et al. 2014). Some examples include sweet and red oranges (28.6 and 43.6 mg/100 mL of juice, respectively), tangerine (24.3 mg/100 mL of juice), clementine (39.9 mg/100 mL of juice), and lemon (20.5 mg/100 mL of juice) (Bellavite and Donzelli 2020). Apart from these fruits, this flavonoid was also identified in other plant species, such as Mentha piperita L. (504.2 mg/L) and Stevia rebaudiana (493.4 mg/L) (Gu et al. 2016). Hesp has been extracted from these sources by conventional methods, such as maceration (Victor et al. 2021) and Soxhlet extraction (Cypriano et al. 2018), and non-conventional techniques, like ultrasound-assisted extraction (Ma et al. 2008; Xu et al. 2019), microwave-assisted extraction (Inoue et al. 2010; Gu et al. 2016), supercritical fluid extraction (Lachos-Perez et al. 2018; Hwang et al. 2021), pressurized liquid extraction (Alasalvar et al. 2023; Sanches et al. 2024), and pulsed electric field (El Kantar et al. 2018). Several solvents have been proposed as extractants, namely, alkaline water (Zhou et al. 2022), organic solvents (Ma et al. 2008), ionic liquids (Gu et al. 2016), and deep eutectic solvents (Xu et al. 2019). More recently, consecutive extraction schemes of Hesp and other bioactive compounds from the Citrus species have been reported to increase purity (Zhou et al. 2022; Figueira et al. 2023).

Figure 1 illustrates the proposed biosynthetic pathway of Hesp in citrus plants. Flavonoid synthesis begins with the condensation of three malonyl-CoA molecules derived from the acetate-malonate pathway, with one molecule of p-coumaroyl-CoA produced via the phenylpropanoid pathway. This reaction produces the first important intermediate in this pathway, naringenin chalcone, through the intervention of chalcone synthetase (CHS). Subsequently, chalcone isomerase (CHI) isomerizes this metabolite to form the flavanone naringenin. Through the intervention of different enzymes, this key molecule generates other flavanones, flavones, and dihydroflavonol. These groups give rise to flavonols, leucoanthocyanidins, anthocyanidins, and polymethoxylated flavones. In this specific case, flavanone eriodyctiol can be obtained from naringenin through flavanone 3′hydroxylase (F3′H), which adds a hydroxyl group at position C3′ of ring B. The enzyme 4′ methoxytransferase (OMT) transforms this compound into hesperetin by converting the hydroxyl group at position C4′ of ring B into a methoxyl group. Hesperetin undergoes glycosylation at position C7 by flavanone-7-O-glucosyltransferase (7GlcT), leading to the formation of hesperetin-7-O-glucoside. Hesperidin is obtained from this last flavanone through 1–2 rhamnosyltransferase (1,2RhaT) which adds the l-rhamnose to glucose in position C2″ (Liu et al. 2021; Karim et al. 2022). In contrast with flavones, it should be noted that Hesp and respective precursors present a chiral carbon in position C2 of ring C and, therefore, S or R isomers of this flavanone can be isolated from natural sources (Donia et al. 2023).

Fig. 1
figure 1

Hesperidin biosynthesis in plants

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This flavanone is well-known for its antioxidant activity, which may be related to the aglycone structure, particularly, to the presence of a hydroxyl group in position C3′ and a methoxyl group in position C4′ in ring B. The mechanism underlying this activity may rely on its capacity to scavenge free radicals or reactive oxygen ions, such as superoxide and hydrogen peroxide, which usually results in a lower activity of detoxifying enzymes (Wilmsen et al. 2005; Chen et al. 2010; Elavarasan et al. 2012). This capacity makes it an interesting molecule for use as a therapeutic agent for several diseases in the biomedical field, which are briefly summarized in Fig. 2. This flavanone has proven antioxidant and anti-inflammatory activities (Lahmer et al. 2015; Xiao et al. 2018), which potentiated Hesp investigation as an anticancer (Aggarwal et al. 2020; Pandey and Khan 2021; Yao et al. 2022), antiviral (Saha et al. 2009; Parvez et al. 2019; Bellavite and Donzelli 2020), anti-obesity (Xiong et al. 2019), anti-aging (Stanisic et al. 2020), cardio- (Mas-Capdevila et al. 2020) and neuroprotective agent (Roohbakhsh et al. 2014; Hajialyani et al. 2019). Moreover, this citrus flavonoid presents a good safety profile, as it shows a median lethal dose higher than 2000 mg/kg in Sprague–Dawley rats (Li et al. 2019; Moriwaki et al. 2023).

Fig. 2
figure 2

Hesperidin biological and pharmacological properties

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Besides this direct applications, this antioxidant has been recently studied against disease transmitting vectors. The essential oil of Poncirus trifoliate containing Hesp showed the highest mortality against Culex quinquefasciatus, an insect vector of lymphatic filariasis (Selvan et al. 2021). In another study, through molecular docking, Hesp targeted the enzyme sterol C-24 reductase, one of the major enzymes from the ergosterol biosynthetic pathway of Leishmania donovani, the protozoa vector of Leishmaniasis (Tabrez et al. 2021). Even though the possible mechanism of action was not described, the authors verified that Hesp established six intermolecular hydrogen bonds with three residues from the active site (Cys304, Thr307, and Arg464), one π-anion bond with Asp468 to stabilize the interaction, and a carbon hydrogen bond and π–π interaction with Phe416 residue via the aromatic ring. This interactions may have prevented substrate binding and consequent enzyme inhibition.

Most review articles focus mainly on the pharmaceutical applications of Hesp, leaving behind possible applications in food, animal feed, and environment research fields. Owing to this lack of research, the present literature review provides an overview of the current applications and potential of Hesp across these fields, highlighting how their antioxidant property could be involved in each application.

Hesperidin derivatives, pharmacokinetics, and bioavailability

Hesp (Fig. 3) presents the typic flavonoid backbone structure of C6-C3-C6, consisting of two phenyl rings connected through a heterocyclic pyran ring. This glycosylated flavanone is more abundant in nature than the respective aglycone, hesperetin, which is mainly responsible for its bioactivity. Hesperetin (Fig. 3) can be obtained from hesperidin via one step acid hydrolysis with a hydrolysis system composed of acetic acid, sulfuric acid, and methanol (1:1:9) (Evseeva et al. 2014). This can also be accomplished via two-step enzymatic hydrolysis with encapsulated hesperidinase, yielding the intermediate hesperetin-7-O-glucoside (Fig. 3) (Furtado et al. 2012). However, Hesp and its aglycone exhibit poor water solubility, contributing to the estimation that only 20% of the consumed Hesp is bioavailable (Wdowiak et al. 2022). Typically, absorption occurs in the epithelial cells of the small intestine through the intervention of specific enzymes that promote hydrolysis to the corresponding aglycone (Pla-Pagà et al. 2019). Hesperetin is released into the bloodstream and transformed into glucuronide (approximately 87%) and sulfatate (13%) conjugates, both detected in the plasma after 3h of oral ingestion (Pereira-Caro et al. 2017; Mas-Capdevila et al. 2020; Pyrzynska 2022). A portion of the metabolized hesperetin (approximately 70%) is transformed by the microbiota present in the colon (Pla-Pagà et al. 2019). Bearing this in mind, Hesp molecular structure has been studied and modified in order to increase biological activity and/or to overcome its poor solubility issues in water and other generally recognized as safe solvents (Stanisic et al. 2020). α-glycosyl hesperidin (Fig. 3) is a water-soluble derivative formed in a reaction mixture containing Hesp, α-glucosyl saccharide, and saccharide-transferring enzyme, followed by recovery with a synthetic microporous resin (EU Patent No. 0402049A2) (Hijiya and Miyake 1995). The glycosylated flavone diosmin (Fig. 3) can be originated from hesperidin via one-step reaction with the addition of iodine to a hesperidin solution in dry pyridine for 15 h at 95 °C (Victor et al. 2021). Neohesperidin can be obtained from hesperetin or hesperetin-7-O-glucoside via biotransformation with the recombinants 7GlcT + 1,2RhaT or 1,2RhaT, respectively (Frydman et al. 2005).

Fig. 3
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Chemical structures of hesperidin and its main derivatives

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The poor bioavailability of Hesp and some of its derivatives can be also improved through encapsulation, which allows controlled release over time and, in most cases, improves the solubility of molecules in water. Although the encapsulation method chosen depends highly on the final application, some of the used techniques are emulsification (Wei and Huang 2019; Wei et al. 2019; Liao et al. 2020; Tsirigotis-Maniecka et al. 2021; Dangre et al. 2022), extrusion (Tsirigotis-Maniecka et al. 2021), self-assembly (Zhou et al. 2024), freeze-drying (Meng et al. 2024), and spray-drying (Sansone et al. 2009). Polysaccharides are the most common carrier materials (Tsirigotis-Maniecka et al. 2021; Dangre et al. 2022; Zhou et al. 2024), followed by lipids (Dammak and do Amaral Sobral 2018; Jangde et al. 2022; Meng et al. 2024), oligosaccharides (Elmoghayer et al. 2024), glycoproteins (Wei et al. 2019), and proteins (Khan et al. 2024; Mariano et al. 2024).

Food applications

Nutraceuticals

In 1930, Hesp was initially designated as Vitamin P, nowadays known to be the flavonol rutin, because of its innumerous health benefits. For instance, it is recognized as gastroprotective (Actis‐Goretta et al. 2015; da Silva et al. 2019), hepatoprotective agent (Tabeshpour et al. 2020; Moriwaki et al. 2023), and has no effect on insulin levels (Escudero-López et al. 2018). These health benefits have potentiated the search for Hesp sources, and, nowadays, this flavanone is mainly consumed through pressed orange juice, with an estimated average consumption of 200–500 mg in the western world (Donia et al. 2023). Although it is more abundant in other plants, such as M. piperita, its intake from this source remains negligible owing to its poor water solubility (Brown et al. 2019). Moreover, Hesp is found in greater quantities in orange albedo than in pulp, making its consumption and incorporation into the diet more difficult. For these reasons, Hesp supplements are widely commercialized, normally in combination with other citrus flavonoids, derivatives, and/or vitamins, such as Vitamin C.

Hesp supplementation is usually associated with health benefits, particularly in the prevention and treatment of diseases. For instance, Daflon® is a micronized flavonoid mixture of 90% diosmin and 10% Hesp recommended in the treatment of chronic venous insufficiency and hemorrhoidal crisis (Geroulakos and Nicolaides 1994; Sheikh et al. 2020). Furthermore, Hesp supplementation in amateur cyclists improved aerobic performance, post-rectangular test antioxidant (↑SOD and ↓AUC-GSSG), and inflammatory status during the acute phase of post-exercise recovery (↓MCP1) (Martínez-Noguera et al. 2020, 2021). In nonalcoholic fatty liver disease, Hesp supplementation decreased alanine aminotransferase, γ‐glutamyltransferase, total cholesterol and triglyceride content, hepatic steatosis, high‐sensitivity C‐reactive protein, tumor necrosis factor‐α, and nuclear factor‐κB (Cheraghpour et al. 2019). Patients with metabolic syndrome showed a significant reduction of systolic blood pressure and serum concentrations of triglyceride when supplemented with Hesp, and this reduction intensified when Hesp and flaxseed supplementation were combined (Yari et al. 2021). A clinical trial revealed that Hesp supplementation decreased the serum concentration of triglycerides in patients subjected to coronary artery bypass graft (CABG) surgery compared to the placebo group, and therefore, could be effective in preventing the progression of atherosclerosis after surgery (Booyani et al. 2023). In another study, Hesp decreased depression symptoms after 12 weeks in patients subjected to CABG surgery and with mild depression (Khorasanian et al. 2023). Among other applications, Hesp has been suggested as a promising prebiotic, a category of functional food ingredients which promotes the good function and activity of Lactobacillus and Bifidobacterium genera in healthy rats (Estruel-Amades et al. 2019). These effects in human microbiota can also be attributed to the enzymatic hydrolysis of the sugar moiety of Hesp by the enzyme α-rhamnosidase secreted by Bifidobacterium pseudocatenultum in the colon, releasing hesperetin, which can be absorbed by colonocytes and enter the bloodstream (Mas-Capdevila et al. 2020; Wdowiak et al. 2022; Donia et al. 2023).

Food additives

Food additives are commonly used in food processing for several reasons, including enhancing flavor, preventing food discoloration, and avoiding food spoilage by inhibiting microbial growth. Interest in natural food additives has risen because of consumer preference for natural and minimally processed foods. Flavonoids, such as Hesp, have been widely studied in the food industry as food additives, particularly as antioxidants and emulsion stabilizers. Yang et al. (2015) studied the effects of flavonoids, including Hesp and its aglycone, on the emulsion properties and oxidative stability of soybean water-in-oil emulsions (Yang et al. 2015). The authors verified that Hesp and hesperetin were able to increase the physical stability of these food emulsions over time and to reduce the amount of lipid hydroperoxides and thiobarbituric acid-reactive substances, in the absence of ferric chloride. Active gelatin films incorporated with pickering emulsions stabilized with chitosan nanoparticles and encapsulating Hesp revealed that Hesp addition improved the physical stability and emulsifying properties of chitosan nanoparticles (Dammak et al. 2019). In another study, Hesp complexation with whey protein increased the overall antioxidant capacity and improved the emulsification characteristics of whey by producing emulsions with smaller mean droplet diameters, higher stability against changes in pH and salt concentration, and oxidative stability compared to the respective controls (Wang et al. 2023). Hesp can also complement the currently used food additives to reduce their applied concentration, enhance nutritional value, and decrease the eventual hazardous effects from their overconsumption on human health. For instance, sodium nitrate (E251 – E252) is a food preservative that increases lipid peroxidation via the production of nitrosamines or free radicals in the stomach. The combination of this additive with Hesp isolated from mandarin extract was reported to have a synergistic effect against Bacillus cereus and Pseudomonas aeruginosa and an additive effect against Staphylococcus aureus and Escherichia coli (Attia et al. 2021).

Nowadays, Hesp derivatives are well-known food additives in the European Union (EU). The European Commission (EC) has approved the use of neohesperidin dihydrochalcone (E959) as an artificial sweetener in a wide variety of food products, ranging from breakfast cereals to processed fish (Annex II to Regulation EC No. 1333/2008). Hesperetin is used as a food flavouring in all categories of flavoured foods (Annex I to Regulation EC No. 1334/2008). α-glycosyl Hesp has been advocated as a possible yellow coloring agent, stabilizer, and preservative in food and beverages (EU Patent No. 0402049A2) (Hijiya and Miyake 1995). In contrast, Hesp and derivatives are not considered as food additives by the United States Food and Drug Administration.

Food packaging

Food packaging innovation has become necessary to decrease the dependence on plastic packages and films that persist in the environment over time and whose biodegradation products can enter the food chain and consequently pose risks to health. Researchers are dedicated to designing sustainable and edible packaging from biodegradable polymers in combination with polyphenols to increase their antioxidant and antimicrobial properties, and consequently, the longevity of food products. Besides Hesp being a well-recognized antioxidant, this flavanone consumption is associated with health benefits, and some of its water-soluble derivatives are considered food additives, which may have also potentiated its research as an active additive or ingredient in edible food packaging.

Nonetheless, Hesp incorporation in food packaging for diverse types of food, from meat products to cheeses, has revealed an increase on the antimicrobial properties of films and packages, enhancing the product shelf-life. In a preliminary study, Feng and Arai (2022) investigated the effect of Hesp on the quality of sausages stuffed with three different types of casings over 171 days of cold storage (Feng and Arai 2022). The authors concluded that casings treated with Hesp significantly decreased the number of bacterial colonies compared to casings without this flavanone. In another study, Hesp released from polylactic acid electrospun fibers inhibited the production of Pseudomonas fluorescens water-soluble extracellular polysaccharides and Ca2+-ATPase activity in Scophthalmus maximus fillets while also improving their sensory quality under cold storage (Ding et al. 2022). Cellulose-based coating films incorporating Hesp on white cheese samples showed reduced Escherichia coli and Staphylococcus aureus contamination by 57 and 54%, respectively, after 15 days of storage at 4ºC (Yildirim and Ates 2022). Increasing concentrations of methyl Hesp in an edible ternary blend film led to higher antibacterial activity against Escherichia coli and Staphylococcus aureus (Zhang et al. 2023). Yet, Hesp application in food packaging may not be only resumed to their good antioxidant and antimicrobial properties, since polyphenols can also inhibit key enzymes involved in food browning, which usually leads to food spoilage and waste. For instance, the aglycone hesperetin has been suggested to be a competitive and reversible inhibitor of polyphenol oxidase (Si et al. 2012; Hong et al. 2023).

Animal feed applications

Phytogenic feed additives, including polyphenols, have been widely researched in animal diets because of consumer demand for safe animal food and the prohibition of using antibiotics in managing animal diseases and health (Mahfuz et al. 2021). These additives are cost-effective and can act as growth promoters and improve animal health and meat or product quality, given their antioxidant properties (Abdelli et al. 2021). Neohesperidine dihydrochalcone, a chemical analogue of Hesp, has been approved as a flavoring compound for fattening piglets, sheep, fish, and dogs (Regulation EU No. 2015/264).

Over the years, Hesp has been proposed and researched as a potential feed additive, given that its supplementation in animal diets has been associated with an increase in product shelf-life and stability due to its antioxidant properties. For example, fresh and stored hen eggs had improved oxidative stability when the hen diet was supplemented with Hesp, which could translate into an improved shelf life without affecting the egg quality parameters (Goliomytis et al. 2014). The eggs of quails fed with this flavonoid showed an increase in egg weight, white width, and yolk diameter (Özbilgin et al. 2021). Interestingly, the content of linoleic acid (n-6) in the yolk increased significantly with Hesp concentration, while the saturated fatty acid values decreased when compared to the control values. In the breast meat and fat pad of broiler chickens, the Hesp diet reduced saturated fatty acids content and increased polysaturated lipids and n-6 content (Hager-Theodorides et al. 2021). It was hypothesized that these effects on the fatty acid profile resulted from an increase in β-oxidation, consequent of a higher expression of related genes (PPAR and ACOX1) in the liver. In another study, lipid oxidation of lamb longissimus thoracis muscle was delayed in refrigerated (at 4 °C) and long-term frozen (at −20 °C) conditions when lamb diets were supplemented with Hesp (Simitzis et al. 2013, 2019). Red swamp crayfish fed 50–150 mg kg−1 of Hesp showed increased final body weight, specific growth rate, and weight gain (Liu et al. 2020). Among other results, it decreased protein carbonyl content and ROS and malondialdehyde levels in the hepatopancreas and hemocytes, while the antioxidant capacity, glutathione peroxidase activity, and superoxide dismutase activity increased when compared to the control group.

Environmental applications

Plants can face several biotic (such as pathogen infection) and abiotic (such as nutrient and water scarcity) stress conditions, which can affect their growth and development. Bearing this in mind, researchers have focused on understanding plant adaptation mechanisms to adopt strategies that can mitigate the effects of stress and safeguard crop viability and food security. Polyphenols, such as Hesp, are secondary metabolites naturally produced by plants in their responses and adaptation mechanisms, helping to attenuate these stress effects in plants owing to their antioxidant and metal chelation capacities, and their ability to enhance stress tolerance (Pereira et al. 2024).

Abiotic stress

Heatwaves have become more frequent and intense as a result of climate change, and prolonged periods of high temperatures contribute to depletion of water resources and drought conditions, affecting agricultural productivity. Along with soil erosion, these conditions can lead also to salt accumulation, which can affect several biochemical processes such as mRNA processing, transcription, and protein synthesis (Hameed et al. 2021). In Arabidopsis thaliana plants grown under heat stress, Hesp, either alone or in combination with rosmarinic acid, increased the level of total saturated fatty acids, decreased radical accumulation, and regulated photosynthetic efficiency by assisting in carbon assimilation, transpiration rate, and internal carbon dioxide concentrations (Arikan et al. 2022a). In another study, infusions of Mentha piperita grown under drought conditions (24% soil moisture) showed a twofold higher concentration than those grown in normal conditions, which may have contributed to a higher antioxidant activity (Figueroa-Pérez et al. 2014). In another study, Lactuca sativa L. plants treated with Hesp, either alone or in combination with chlorogenic acid, coped better under salinity stress conditions than the non-treated ones by improving their photosynthetic performance (Zhang et al. 2021).

Heavy metal accumulation in soils is a result of urbanization and industrialization, intensification of agricultural practices (for instance, the use of organic fertilizers), mining, and fossil fuel combustion, leading to several physicochemical and biochemical alterations in plants (Hussain et al. 2024). In Zea mays plants under arsenate stress, those treated with Hesp alone or in combination with chlorogenic acid improved and induced the activity of detoxifying enzymes, such as superoxide dismutase, preventing radical accumulation (Arikan et al. 2022b). Hesp may also have helped to maintain non-stomatal photosynthesis, to retain cellular membrane integrity, and to prevent arsenic accumulation by regulating the expression of genes belonging to the PHT family. This results were later supported by Elbasan et al. (2024), which verified that the application of Hesp, either alone or in combination with chlorogenic acid, led to ROS scavenging and decrease of thiobarbituric acid accumulation, and stimulated chloroplast antioxidant activities in Zea mays plants under arsenate stress (Elbasan et al. 2024). Moreover, the gene expression analysis demonstrated that these polyphenols regulated the photosystems related-gene expressions, more specifically, the downregulation of PSI and PSII genes. In both studies, it maintained the cellular redox status by enhancing the ascorbic acid-glutathione pathway (Arikan et al. 2022b; Elbasan et al. 2024). In Celosia argentea L., Hesp mitigated ROS generation, lipoxygenase activity, methylglyoxal production, and relative membrane permeability in plants under metal stress induced by the uptake and hyperaccumulation of cadmium, copper, chromium and zinc. Besides improving the redox balance, Hesp provoked the production and accumulation of nitric oxide, hydrogen sulphate, non-protein thiol, phytochelatins, osmolytes, and antioxidant compounds, and improved plant growth (Hussain et al. 2024).

Biotic stress

Besides climatic conditions, plants can be subjected to stress induced by a pathogenic infection of several organisms, including insects, fungi, bacteria, viruses, and nematodes. Pesticides are currently known for their adverse effects in the environment, from water pollution to non-target organisms toxicity, and for human health, from neurodegenerative diseases to hormonal dysregulation. Researchers have focused on finding eco-friendlier and safer complements to these agrochemicals, the usually called biopesticides, which can be found in plant essential oils and extracts. Hesp itself has drawn attention of researchers given natural accumulation in these stress conditions and its antioxidant mechanisms. For instance, citrus with symptoms of the disease citrus variegated chlorosis, induced by the infection of Xylella fastidiosa, presented a higher concentration of Hesp in petioles and leaves (approximately, an increase of 56 and 52%, respectively) than in the control, indicating that this flavanone has an underlying role in plant-pathogen interaction by inducing defense mechanisms (Soares et al. 2015). In another study, hairy roots cultures from leaf and stem of Fagopyrum esculentum induced by Agrobacterium rhizogenes accumulated three flavonoids, including Hesp, absent in control roots and which could have contributed to a higher antioxidant capacity (Gabr et al. 2019).

Table 1 summarizes some studies about Hesp biopesticide activity against phytopathogenic organisms. No reports were found regarding its potential as an herbicide, nematicide, and anti-viral. As an insecticide, this flavanone has been applied in its natural form, showing low to no toxicity to target insects, but also in coordination complexes with metals, such as copper and magnesium. Interestingly, the magnesium complex [Mg(Hesp)2(phen)]OAc has been advocated as an alternative to sulfluramid, typically used against leaf-cutting ants (Guida et al. 2023). Studies have shown that this complex has low ecological impact on non-target organisms, including plants and zebrafish (de Souza et al. 2017; Bonomo et al. 2020, 2021). Moreover, this magnesium complex is more hydrosoluble and exhibits a higher antioxidant activity than free hesperidin (Oliveira et al. 2013). This translates into a more active insecticide and safer formulation because it avoids the use of organic solvents. Nonetheless, little is known about the pesticide activity of flavanone and its mechanisms of action against a target pest. No reports were found regarding its potential as an herbicide, nematicide, and anti-viral.

Table 1 Broad description of hesperidin research as a biopesticide for specific target organisms and the main results
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Conclusion and future directions

This review highlights the diverse and current applications of Hesp across various research domains outside the pharmaceutical field, while underlining how Hesp antioxidant activity is involved in each application. Although the potential of this flavanone is evident across these sectors, its poor solubility in water poses a significant barrier to increasing its number of applications. Use of food grade polyethylene glycol (PEG 400), techniques of encapsulation, complexation, or even the design of new molecules based on its chemical structure could be interesting ways to enhance its solubility and/or bioavailability. If this issue is addressed, this can potentiate the discovery of new applications of this flavonoid, leading as well to possible advances in the food, animal feed, and environmental fields.