The Genus Solanum: An Ethnopharmacological, Phytochemical and Biological Properties Review

Over the past 30 years, the genus Solanum has received considerable attention in chemical and biological studies. Solanum is the largest genus in the family Solanaceae, comprising of about 2000 species distributed in the subtropical and tropical regions of Africa, Australia, and parts of Asia, e.g., China, India and Japan. Many of them are economically significant species. Previous phytochemical investigations on Solanum species led to the identification of steroidal saponins, steroidal alkaloids, terpenes, flavonoids, lignans, sterols, phenolic comopunds, coumarins, amongst other compounds. Many species belonging to this genus present huge range of pharmacological activities such as cytotoxicity to different tumors as breast cancer (4T1 and EMT), colorectal cancer (HCT116, HT29, and SW480), and prostate cancer (DU145) cell lines. The biological activities have been attributed to a number of steroidal saponins, steroidal alkaloids and phenols. This review features 65 phytochemically studied species of Solanum between 1990 and 2018, fetched from SciFinder, Pubmed, ScienceDirect, Wikipedia and Baidu, using “Solanum” and the species’ names as search terms (“all fields”).


Distribution and Ethnopharmacological Uses
Sixty-six species commonly used as important folk medicine, ornamental plants, or wild food sources were selected in this review, and their local names, distribution and ethnopharmacologi-cal uses were summarized in Table 1. Local names are given in different languages with which the inhabitants of a particular region use to identify a specific species. Each species' natural habitat and/or places of cultivation are mentioned. Traditional as well as modern day applications are presented.

Steroidal Alkaloids
Sixty-three steroidal alkaloids , as other principal components in Solanum were reported from this genus (Fig. 2). Compounds 139-156 are derivatives of solasodine (145), one of the main glycoalkaloid constituents in Solanum spp., even as indicated by several numbers of species from which it has been isolated. Solamargine (139) is the major steroidal alkaloid constituent of Solanum plants and literature data showed that it has been revealed in 18 species.
Compounds such as 139, solasonine (142), β1-solasonine (143) and solanigroside P (156) with three sugar units and α-l-rhamnose at C-2 or a hydroxyl group on the steroidal backbone may be potential candidates for the treatment of gastric cancer [228].
Antioxidant activity of 145 and tomatidine (167) from the berries of S. aculeastrum was investigated using DPPH, ABTS and reducing power assays, and the highest inhibition was observed when the two compounds were combined, followed by 145 and 167 [13]. Furthermore, 145 exhibited significant anti-inflammatory activity at doses of 30 mg/kg, with a maximum inhibition of 77.75% in carrageenan-induced rat paw edema, comparing to indomethacin (81.69%). It also showed stronger (46.79effect in xylene induced ear edema in mice [303]. Intraperitoneal injection of 145 (25 mgkg) significantly delayed latency of hind limb tonic extensor phase in the picrotoxin-induced convulsions, and it also potentiated thiopental-provoked sleep in a dose-dependent manner [294]. Moreover, 145 exhibited not only the antibacterial activity against Klebsiella and Staphylococcus spp. at concentration of 1 mg, together with 139 and 141 [403], but also a potent stemness and invasion inhibitory effect on human colorectal cancer HCT116 cells [155]. Colony Spheroid formation assay showed that solasodine dosedependently prohibited HCT116 cell stemness. CD133, CD44, Nanog, Oct-4 and Sox-2 were inhibited by 145 to reverse stemness and similar mechanism was stimulated in vivo. Transwell and scratch wound assays revealed that 145 impeded HCT116 cell invasion and migration potential strengthened by TGF-β1. Moreover, solasodine attenuated TGF-β1-induced EMT and decreased MMPs while in vivo study showed the same trend. The results of this study implied that 145 may be a novel therapeutic drug for CRC treatment [155].
Burger et al. documented that the crude extract and aqueous fraction containing 139 displayed potent nonselective cytotoxicity (IC 50 15.62 μgmL) and noteworthy 9.1-fold P-glycoprotein inhibition at 100 μgmL [15]. Zhang et al. assessed the molecular mechanism underlying the anti-cancer effect of 139 in human cholangiocarcinoma QBC939 cells. The results revealed that 139 inhibited the viability of QBC939 cells in a dose-dependent manner. Furthermore, it significantly induced the apoptosis of QBC939 cells and altered the mitochondrial membrane potential of cells. Quantitative polymerase chain reaction analysis revealed that 139 decreased the mRNA level of B cell lymphoma-2 (Bcl-2) Bcl-extra-large and X-linked inhibitor of apoptosis protein but increased the mRNA level of Bcl-2-associated X protein (Bax) In addition, western blot analysis demonstrated that 139 inhibited the protein expression of Bcl-2 and poly ADP ribose polymerase (PARP) and promoted the protein expression of Bax, cleaved PARP, caspase 3, cleaved caspase 3 and caspase [97].   [407]. Moreover, 139 and solasonine (142) displayed not only leishmanicidal activity against promastigote forms of Leishmania amazonensis [185], but also antidiabetic activity by inhibiting the serum glucose increase in oral sucrose-loaded rats and suppressing gastric emptying in mice [182]. A synergistic effect was observed for a mixture of the compounds [183]. Compound 139 also expressed stronger trypanocidal activity (IC 50 = 15.3 μg/mL), when compared to benznidazol (IC 50 = 9.0 μg/mL), the only drug used to treat Chagas' disease [186].
Solanum triterpenes have indicated to possess anticancer properties. For instance, 213 presented significant activity against KB-Oral cavity cancer (IC 50 = 26.73 μgmL) [297], while 213 exhibited selective activity against lung tumor cell line (NCIH460). The anti-nociceptive activity observed for 213 and 214 was found to be related to the inhibition of different mediators involved in inflammation and nociceptive process. Both compounds decreased cyclooxygenase 2 (COX-2) protein expression, although only 214 reached a significant response (P < 0.05 vs control) [107].

Lignans
Lignans, widely distributed in the plant kingdom, are a family of secondary metabolites produced by oxidative dimerization of two phenylpropanoid units. Although their molecular scaffold consists only of two phenylpropane (C6-C3) units, lignans exhibit an enormous structural diversity originating from various linkage patterns of these phenylpropane units. As the C-8-C-3′/C-7-O-C-4′ linked lignans containing two chiral centers (C-7 and C-8) comprise the core of 2, 3-dihydrobenzo[b]furan [480].

Coumarinolignoids
Four coumarinolignoids known as indicumines A-D (614-617) were obtained from the seeds of S. indicum [535] (Fig. 14). Coumarinolignoids, including cleomiscosins, aquillochins and malloapelins, are unique and rare in nature. Coumarinolignoids of the cleomiscosins type bearing cleomiscosins A-D, 8-epi-cleomiscosin A, and malloapeli A functionalities have been identified in a few genera, including Cleome viscosa, Mallotus apelta, and Rhododendron collettianum. The compounds with such functionalities, especially cleomiscosins A-C and 8-epicleomiscosin A, which contributed to biological activities, have been reported with hepatoprotective and tyrosinase inhibition activities [535].
The genus Solanum seems to possess great potential, yet majority of the species remain unknown or scantily studied for the chemical constituents. It would be very necessary for the phytochemistry researchers to explore and investigate more of its species. The vast pharmacological activities envinced by many compounds from Solanum genus should attract the attention of the pharmacological community to determine their exact target sites, structure-activity relationships and other medicinal applications.

Compliance with Ethical Standards
Conflict of interest The authors declare no conflict of interest.
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