[Review Article] A Comprehensive Overview on Pharmacological and Therapeutic Insights of Solanum nigrum

Solanum nigrum is a traditional Chinese bush renowned for its dynamic therapeutic activities in the Indian and Chinese systems of medicine. It is a typical, palatable herbal remedy that belongs to the family Solanaceae. This overview assembles the prospective pharmacological and medicinal significance of the last three decades' accomplishments of scholarly reports from internet sources and publications. According to several literature reviews, Solanum nigrum encompasses a variety of phytochemical compounds that could be isolated and identified using various extraction techniques. The major chemical components of this herb are alkaloids, glycoproteins, polysaccharides, and phenolic compounds with a broad spectrum of pharmacological outcomes such as anticancer, immunostimulant, antibacterial, antidiabetic, antiviral, antiinflammatory, antioxidant, antipyretic, antidiarrheal, cardioprotective, anti-hyperlipidemic, anti-ulcerogenic, hepatoprotective, anti-seizure, anti-larvicidal, anti-allergic, anti-asthmatic, and neuropharmacological efficacy. Recently, scientists and researchers have been searching for potentially biologically active plants due to the increasing toxicity and adverse effects of modern synthetic drugs. As every part of Solanum nigrum contains a variety of therapeutically active phytochemicals, it could be a significant source for scientists to conduct further research and discover the proper mechanism for preventing diseases. In conclusion, Solanum nigrum emerges as a valuable


Introduction
The use of plants as a source of therapeutic agents has been a cornerstone of traditional medicine for millennia.Solanum nigrum, a widely distributed edible medicinal herb, has long held a significant place in traditional medicine, particularly in Southeast Asia [1][2] .This flowering plant species, a member of the Solanaceae family, encompasses over 2,000 distinct species that are widely distributed across tropical and subtropical regions globally [3] .The species was first mentioned by renowned herbalists and naturalists Pliny the Elder and Pedanius Dioscorides in the first century AD.It grows wild and widely in the open area [4] [5] .It may grow in moist areas in a variety of soil types, including deep, dry, rocky, and shallow S. Meonah et al., (2012) studied the aq.and hydroalcoholic extracts for antidiabetic efficacy in rats (200 and 400mg/kg b.w.) to assess oral glucose tolerance with conventional Metformin.Results show the stem has no hypoglycemic activity [21] .

J. Sugunabai et al., (2014)
conducted a study on a group of male patients, aged 35-60, for 90 days to check the efficacy of aq.extract for their hypoglycemic and hyperlipidemic activities.Results showed the level of glucose, LDL, triglyceride, and glycosylated hemoglobin was reduced by 19%, 8%, 17%, and 10%, respectively, and HDL was increased by 2%.
Alkaloids possibly increase insulin secretion, and glycoprotein increases the activity of antioxidant enzymes [22] .

M. Umamageswari et al., (2017
) conducted a study to estimate the hypoglycemic effects of S. nigrum berries in alloxaninduced diabetic mice.The animals were treated with AESNB 200 and 400 mg/kg and standard, i.e., 0.1 mg/kg of glimepiride.The results provide clear evidence that the dosage of 400 mg/kg per day formed a substantial drop (P<0.001)than 200 mg/kg/day (P<0.01) [23].

S. Sultana et al. (1995)
investigated the ethanolic leaf extracts for their hepatoprotective activity on mice using a DNAsugar damage assay.At 25 g/ml, the highest significant inhibition was 29%.According to the study, the herb is hepatoprotective [24] .

K. Raju et al., (2003)
investigated the ethanolic fruit extract to evaluate its ability to protect against hepatotoxicity caused by CCl 4 in albino male rodents (130-160g).The animals were treated with 250 mg/kg for seven days.The findings showed remarkable hepatoprotective efficacy [25] .
The research findings suggested that SNE has hepatoprotective effects on rats [17] .R. Elhag et al., (2011) evaluated the protective effects of aqueous and methanol extracts on albino rats (80-130g) using a CCl 4 -induced hepatotoxicity model.Both extracts were administered dose-dependently to the rats (250 and 500 mg/kg).
The findings showed that S. nigrum has a hepatoprotective effect. [26].

A. Elshater et al., (2013
) used a rat model of CCl4-induced hepatotoxicity at 250 and 500 mg/kg to test the hepatoprotective effects of fruit and plant aq.extracts.There are claims that an extract of the S. nigrum fruit is more effective at treating liver damage than the plant itself [27] .

R. Ali et al., (2014)
tested the efficacy of fruit aq.extracts in protecting albino rat livers from CdCl2-induced damage.
According to the findings, its hepatoprotective characteristics help prevent liver damage caused by CdCl2 [28] .oxidative stress in the brain and protecting it from damage caused by stress.Findings suggest that S. nigrum might be employed as a safe therapeutic approach for any neurological condition, including physical or psychological stress [29] .

Anti-larvicidal activities
Rawani et al. (2010) investigated the effectiveness of several extracts of S. nigrum leaf in preventing larvicidal activity in Culex quinquefasciatus.The mortality rate was significantly higher (p less than 0.05) at 50 ppm of ethyl acetate extract.
According to the findings, S. nigrum exhibited potential as an anti-larvicidal agent [30] .

Rawani et al. (2013)
evaluated the larvicidal activity of silver nanoparticles (AgNPs) from leaf and fruit extracts of S.
nigrum against larvae using a larvicidal mosquito bioassay.The results show that the AgNPs of S. nigrum can be used to control mosquito larvae in a way that is good for the environment [32] .

A. Rawani et al., (2014)
exploring the biocontrol potential of an active component (Glucosinolate) produced from S.
nigrum leaf extracts by conducting this study on Culex quinquefasciatus larvae was the goal of this particular investigation.
Out of all the quantities that were examined, the one that had 25 mg/L of the active chemical had the highest fatality rate.
The findings suggested that the larvicidal efficacy tested could be effective [33] .

A. Rawani et al. (2017)
The bioactive components of phytosterol in S. nigrum leaf extract (chloroform: methanol, 1: were tested against larvae of the Cx.vishnui group and An.subpictus at a variety of doses.In a bioassay that lasted for 72 hours, the mortality rate was noticeably greater when the concentration was 60 mg/L.It is possible that the isolated phytochemical will prove to be an effective mosquitocidal agent [34] .

S. Jisha et al. (2011)
experimented on S. nigrum fruits methanolic extract for its estrogenic potential.The result of a competitive binding assay using 3H-E2 demonstrates a rise with increasing dosage in MCF cells at a lower concentration (40μg/ml) and progressive cell growth inhibition at a higher concentration (80-320μg/ml) mediated by the estrogen receptor.The finding reveals that methanol extracts demonstrated a characteristic uterotrophic response in mice [35] .able to reduce the amount of HCV NS3 protease expression as well as its function.The findings suggest that the seeds extract may have antiviral properties that can aid in the battle against HCV, and that using the extracts in conjunction with interferon is a more effective strategy to treat chronic HCV [36] .effectively stopped seizures in chicks, mice, and rats.The animals were given various proconvulsants in increasing doses after the treatment period of 30 minutes.According to the findings, aqueous leaf extracts significantly prevented electrically induced seizures in rats and chicks and seizures induced by pentylenetetrazole and picrotoxin in mice [37] .

K. Ruby et al. (2012)
evaluated the CNS-depressing action of S. nigrum by injecting it intraperitoneally.Isotonic contraction of the rectus abdominis muscle is observed in the solitary toad.The toad heart has a detrimental influence on the chronotropic and inotropic systems.The rat jejunum exhibits isotonic contraction.The cat's BP is reduced [38] .

H. Le Son et al. (2014)
studied the anticonvulsant effect of S. nigrum ethanolic extracts on PTZ-induced convulsions in mice.At 300 mg/kg, the extract substantially delayed convulsion latency.According to the findings, the ethanolic extract of Solanum possesses anticonvulsant activity [39] .percent after being treated with SNL extract at a concentration of 50 mg/mL for 12 hours.About seventy percent of the MCF-7 cells exhibited a positive staining response to trypan blue after being treated with the extract at a dose of fifty milligrammes per millilitre.In addition to this, the cytotoxicity that was brought on by the SNL extract manifested itself in a more significant manner as time went on [40] .

H. Lin et al. (2007)
investigated the cytotoxicity of Solanum aqueous extracts on HepG2 cells at 2 and 5 mg/ml; SNEinduced apoptosis.Low doses of SNE (50-1000 g/mL) caused morphological and ultrastructural changes that indicated autophagocytic death.In addition, SNE caused apoptosis and autophagocytosis in hepatoma cells, suggesting it might be used to treat liver cancer [41] .

H. Huang et al. (2010)
tested Solanum extracts on cancer and regular cell lines.The extract was more effective against AU565 breast cancer cells.Higher amounts of SN leaf extract (>100 g/mL) blocked p-Akt and caused autophagy and apoptosis.SN leaf extract enhanced breast cell death through apoptosis and autophagy via two anti-neoplastic actions [42] .
3.11.Anti-cancer activities K. Hu et al. (1999) investigated the Solanum nigrum glycoside (Solamargine) for in-vitro cytotoxic effects on various human tumour cell lines (colon and breast).The results of the cytotoxic assay performed on S. nigrum demonstrated that solamargine is the primary anti-neoplastic agent [45] .

An. Lei et al. (2006)
evaluated the ethanolic extract of unripe fruits for cytotoxicity on breast and liver cell lines rather than the ethanolic extract of leaves.Fruits had an IC50 value of 12.7 and 16.6 micrograms per millilitre when tested for their ability to kill breast and liver cancer cell lines, respectively.This activity can be attributed to the high levels of steroidal glycoalkaloid concentration in unripe fruit [46] .

H. Lin et al. (2007)
investigated S. nigrum extract (SNE) for cytotoxic activity on HepG2 cells.HepG2 cells were made to undergo apoptosis when exposed to SNE at doses of 2 and 5 mg/mL, respectively.According to these findings, SNE was able to cause apoptosis and autophagocytosis in hepatoma cells.These are two distinct anti-cancer activities, and they point to the possibility that it could be effective in the treatment of liver cancer [41] .

S. Patel et al. (2009)
evaluated the anti-cancer effects of Solanum nigrum fruit extract on the HeLa cell line.Both the SRB and the MTT tests were performed on HeLa cells in order to evaluate the cytotoxicity of the Solanum nigrum extract.In both the SRB and the MTT tests, the presence of 10-0.0196g/ml of methanolic extract had a substantial effect on the viability of HeLa cell lines.The results showed the potency of Solanum nigrum to inhibit cancerous growth [47] .

H. Wang et al. (2010)
reported that the S. nigrum water extract (SNWE) was effective in preventing the progression of melanoma.Following treatment with SNWE, an analysis was performed to determine whether B16-F1 cells retained their capacity to migrate and invade.According to the findings, a dose-dependent relationship existed between SNWE's ability to block B16-F1 cell migration and invasion and its ability to treat melanoma [48] .

M. Shokrzedah et al. (2010)
investigated S. nigrum extract on cancer cell lines HepG2 and CT26, as well as rat fibroblast and Chinese hamster ovary cells.After conducting a clonogenic experiment, researchers examined the cytotoxic effects of the extracts on several cell lines and determined their IC 50 values.As a consequence of this, cytotoxicity against cancer cells has been demonstrated in the S. nigrum extract [49] .cells at a concentration of 1 g/ml.The in-vitro and in-vivo effects on the growth inhibition of HepG2 cells were investigated.
According to the findings of this study, the extract is an effective therapeutic therapy for head and neck cancer because it inhibits cell proliferation by inducing G(2)/M arrest and cell death [50] .

X. Ding et al. (2012)
measured the growth inhibition of human hepatoma SMMC-7721 tumour cell lines using the MTT test, as solamargine (SM) is a significant steroidal alkaloid glycoside isolated from SNL.The study's findings demonstrated that solamargine dramatically reduced the proliferation of SMMC-7721 and HepG2 cells, promoted cell death, and exhibited some degree of potential anti-cancer efficacy [51] .

N. Akbar et al. (2012)
conducted a study to evaluate the effects of the SN extract on growth inhibition.Solanum nigrum extract has been shown to induce cell cycle arrest and apoptosis in different human prostate cancer cells while having no impact on normal prostate epithelial cells.In prostate cancer cells, the SN extract has the potential to inhibit the proliferation of cells.It could be developed into a potential treatment for prostate cancer as well as a prophylactic agent [52] .

Y. Lai et al. (2016)
demonstrated that the aqueous extract of Solanum nigrum (AESN) has considerable anti-cancer and curative properties.Researchers employed the Mitotracker Deep-Red FM stain as a means of determining whether AESN was effective in preventing EMT in MCF-7 breast cancer cells.These findings suggest that AESN may be able to prevent EMT in breast cancer cells via reducing the function of the mitochondria [53] .
3.12.Anti-ulcer/ gastritis activities M. Akhtar et al. (1989) investigated three plants to study their antiulcer activity against an aspirin-induced gastric ulcer in rats (male albino rat, 170-200 gm).The methanol extract of S. nigrum significantly decreased pepsin levels and gastric pepsin content.The results showed that the acid content was reduced in rats treated with SN methanolic and aqueous extracts.The results suggest that due to its anti-ulcerogenic effect, acid and pepsin outputs decrease, enhancing gastric mucosal strength [54] .

M. Jainu et al. (2006)
has been demonstrated to significantly reduce the severity of stomach lesions in rats caused by cold-resistant stress (76.6 percent), indomethacin (73.8 percent), pyloric ligation (80 percent), ethanol-induced gastric ulcer models (70.6 percent), and acetic acid-induced ulcer models (70%).(85 percent ).SNE reduced the volume of gastric secretion, the acidity of the stomach, and the amount of pepsin that was secreted in rats that had gastric ulcers.It does this by inhibiting the activities of H+, K+, and ATPase in ulcers caused by ethanol and by lowering the discharge of the stomach.According to the findings, the fruit of the S. nigrum tree has both antiulcerogenic and ulcer-healing properties [55] .

M. Rajeswari et al. (2013)
evaluated the experiments conducted on pylorus-ligated female albino rats with ethanolinduced gastritis and aspirin-induced stomach ulcers to determine the efficacy of extracts from the Solanum nigrum leaf and fruit.Stomach ulcers were induced by administering aspirin to the rats (Sprague-Dawley strain, 180-200 gm).The Ulcer Index was drastically reduced after 250 mg/kg of leaf and berry aqueous extracts and 50 mg/kg of fruit extract were orally administered.The results showed that the berry aqueous extract was more effective than the leaf extracts in treating gastritis [56] .

F. Razali et al. (2016)
have confirmed that the ground, dried stem of Solanum nigrum contains a non-toxic polysaccharide fraction (SN-PPF3) that inhibits malignancies by boosting the host immune response.Mice with breast tumours were given SN-PPF3 orally at 250 and 500 mg/kg for 10 days, and the tumour volume and body weight were measured.
According to the data, there was a discernible decline of 65 percent in the volume of the tumour and a drop of 40 percent in the weight of the tumour.In mice that were given treatment, the tumour tissue was infiltrated by a greater number of T cells, NK cells, and macrophages.In mice that were given treatment, there was an increase in the levels of TNF-alpha, IFN-gamma, and IL-4, but there was a reduction in the levels of IL-6 [57] .

Anti-oxygenic activities
Padmashree et al., (2014) have used a sunflower oil model system to investigate the anti-oxygenic action of Solanum nigrum leaves.Refined sunflower oil showed considerable anti-oxygenic activity from both the leaf powder and its methanol/water (80:20) soluble fraction, but the ethyl acetate fraction showed only minimal anti-oxygenic activity.This research confirmed previous results that leaves contain compounds that stifle oxygen synthesis.Particularly promising as a natural antioxidant that could lessen lipid peroxidation in food was the 80:20 methanol to water extract they created [58] . in the ethanol-induced rats compared to the control group, and the antioxidant defence system was decreased (GSH, Vit-C, and E).According to these findings, SNF-E is a potent antioxidant and anti-hyperlipidemic agent [59] .

Anti-hyperlipidemic activities
Imran Ali et al. (2016) carried out research to determine whether or not an ethanolic extract of Solanum nigrum (300 mg/kg) was effective in decreasing the cholesterol level in rabbits that had been caused to be hyperlipidemic with lipofundin (20 percent).The elevated levels of total serum cholesterol, triglycerides, high-density lipoprotein, and lowdensity lipoprotein in the test group dropped towards usual values after being treated with an ethanolic extract of S.
nigrum.According to the findings, S. nigrum exhibited strong anti-hyperlipidemic efficacy in rabbits whose hyperlipidemia was caused by lipofuscin [60] .CAT, GPx).Overall lipid peroxidation levels dropped as a result (LPO).These results give conclusive evidence that S.

A. Patel et al. (2014)
carried out an experiment to investigate the prophylactic effect of an aqueous extract of Solanum nigrum leaves (AESN) in two rat models of oral mucositis: one caused by busulfan combined with infrared radiation (chemoradiotherapy), and the other caused by methotrexate (chemotherapy) at doses of 100 and 200 mg/kg.Although AESN was protective in both of the oral mucositis models, the higher dose seemed to have a greater impact on treating chemotherapy-induced oral mucositis.The findings of the study indicate that administration of AESN can protect rats from developing oral mucositis as a consequence of receiving either chemoradiotherapy or chemotherapy [62] .
3.16.Anti-spermatogenic and anti-androgenic activities According to the research author, the weights of testes, testosterone levels, FSH, and LH levels all decreased significantly in Solanum nigrum extract-treated rats.The results suggest that 50% ethanolic extract of the S. nigrum fruit has a considerable detrimental impact on sex hormone levels and spermatogenesis [63] .
3.17 heat-killed Aphanomyces invadans was tested in six groups of experimental fish (E.suratensis).The death rate was reduced in the ethanol and methanol extract-treated groups compared to the chloroform, toluene, and water extracttreated groups.The findings suggest that plant extracts can be utilised to treat bacterial infectious illnesses and have great promise as immunostimulants against germs [64] .an increase in the number of apoptotic tumour cells, an increase in Bax expression, and a drastic reduction in the expression of Bcl-2 and mutant p53 in cervical cancer sections [65] .

Y.B. Ji et al. (2008)
have shown that solanine, extracted from the Solanum nigrum, inhibits the growth of tumour cells in three different cell lines derived from the digestive tract using an MTT experiment to determine the IC50.Flow cytometry was used to evaluate cell proliferation, apoptosis, and cell cycle phase (FCM).Western blot analysis confirmed the level of Bcl-2 protein expression.HepG2 cells were induced to undergo programmed cell death by solanine at a rate of 6.0%,This suggests that solanine induces apoptosis in HepG2 cells by blocking their ability to produce Bcl-2 protein [66] .
Jian Li et al. (2008) tested mice that had been genetically engineered to carry tumours with a Solanum nigrum aqueous extract (SNL-AE), and a FACScan flow cytometer was utilised to assess whether or not the extract decreased the growth of the tumours.Both the number of CD4+ T lymphocyte subsets and the CD4+/CD8+ T lymphocyte ratio rose as a result of treatment with SNL-AE, which prevented the proliferation of U-14 cervical cancer cells.Based on these findings, it appears as though SNL-AE might be able to reduce the risk of developing cervical cancer by modifying the immune responses of tumor-bearing mice, causing tumour cell cycle arrest in the G0/G1 phase, and causing apoptosis with only very mildly detrimental effects on the animals [4] .

Jain Li et al. (2009)
examined the effects of crude polysaccharides derived from Solanum nigrum Linn.(SNL-P) on U-14 cervical cancer cells.At dosages of 1 mg/ml, SNL-P did not exhibit any antiproliferative effects when tested in vitro.In-vivo therapy of U14 cervical cancer-bearing mice with SNL-P (90, 180, or 360 mg/kg bw, orally) resulted in a reduction in the amount of tumour cells found in the ascites and an increase in the mice's lifespan.The SNL-P therapy made use of the ELISA method, which led to a remarkable decrease in the amount of II-4 while simultaneously producing a notable rise in the amount of IFN-g.In mice with U-14 cervical carcinoma, the research demonstrated that SNL-P has a significant anticancer effect and may exhibit anti-tumor action by stimulating a variety of host immune responses rather than directly eliminating cancer cells [67] .labelling were used to assess SNL-P fraction 1a's (SNL-P1a) ability to protect thymus tissue against tumours in tumorbearing animals.The growth of U14 cervical carcinoma is considerably slowed by SNL-P1a, as has been demonstrated [68] .

R. Gabrani et al. (2012)
conducted research on leukemic, Jurkat, and HL60 cell lines to investigate the antiproliferative efficacy of organic solvent and aqueous extracts produced from Solanum nigrum berries.The MTT test was used to determine cell viability after treatment with Solanum nigrum extract.According to the observations, higher extract concentrations increased cytotoxicity [69] .

H. Chen et al. (2013)
examined the antitumor activity of polysaccharides derived from Solanum nigrum Linn.(SNL-P) in Kunming mice that had been surgically implanted with tumours.The MTT test was utilised in order to investigate how various dosages of SNL-P affected the rate of lymphocyte proliferation in animals that had tumours.The growth of mouse H22 solid was substantially inhibited by additional doses of SNL-P, which also promoted lymphocyte proliferation, elevated IL-2 levels, increased the concentration of calcium ions in lymphocytes, and improved the survival time of mice that carried tumours [70] .Hedgehog/Gli1 pathway [71] .

Y. Huang et al. (2018)
conducted experiments in mice with H22 hepatocarcinoma cells to determine whether polysaccharides (SNPs) from the Solanum nigrum Linn.plant have an effect on the formation of tumour cells.After administering SNP to experimental animals at dosages of 30, 60, and 120 mg/kg, the tumour inhibition rate as well as the spleen and thymus indexes were computed.The dose of SNP that was administered resulted in a dose-dependent reduction in the average tumour weight, with respective tumour inhibition rates of 37.73, 38.24, and 42.60 percent.The findings demonstrated that mice carrying H22 had less tumour growth and better immune function when SNP was administered [72] .

J. Li et al. (2021)
identified a treatment for HGG; the anti-tumor effects of SN extract were investigated utilising both invitro and in-vivo rat C6 glioma models.C6 cells had a dose-dependent drop in their viability, as well as a reduction in their capacity to clone and migrate when treated with extract from S. nigrum, which also caused a decrease in their ability to proliferate.The presence of the active ingredient in S. nigrum caused a reduction in the rate of both the growth of C6 HGG (high-grade glioma) and its invasion into surrounding tissue [73] .

Razali et al. (2021)
performed a preclinical study that assessed the acute toxicity of a crude polysaccharide extracted from Solanum nigrum stem.The key findings indicate that when orally administered at a concentration of 2,000 mg/kg/bw, the polysaccharide exhibited a very mild acute toxicity effect, with an estimated LD50 ranging from 2,500 to 5,000 mg/kg/bw.This suggests that the polysaccharide has a relatively low toxicity profile, making it a promising candidate for further investigation as a potential immunomodulatory and anti-tumor agent [74] 3.19.Anti-asthmatic activities

S. Nirmal et al. (2012) demonstrated using guinea pig ileum to test the anti-asthmatic potential of extracts of Solanum
nigrum berries prepared using petroleum ether, ethanol, and aqueous medium at doses of 50, 100, and 200 mg/kg, administered intraperitoneally.According to the findings, the catalepsy brought on by clonidine was greatly alleviated by the petroleum ether extract, but none of the extracts was able to stop the catalepsy brought on by haloperidol.When compared to other extracts, the histamine-induced relaxation in the guinea pig ileum was shown to be greater in the ileum produced by the petroleum extract.According to the findings of HPTLC, the petroleum extract has a B-sitosterol component, which is the active ingredient in the anti-asthmatic activity [75] .Powerful cytotoxic and dose-dependent apoptosis-inducing capabilities were demonstrated by the SNL glycoprotein.
HCT-116 cells triggered with TPA (61.68 g/ml) showed inhibition of NF-jB DNA binding activity, NF-jB protein activity, and NO production at doses as low as 10 g/ml.These results suggest that the SNL glycoprotein can induce apoptosis by regulating signal mediators [76] .

X. Zhang et al. (2018)
investigated the impact that solamargine has on human cholangiocarcinoma QBC939 cells.
Solamargine lowered the viability of QBC939 cells in a dose-dependent way.According to the findings of this study, solamargine possesses the ability to trigger apoptosis in human cholangiocarcinoma QBC939 cells by way of the mitochondrial pathway and to change the levels of proteins linked with apoptosis [77] .

Y. Son et al. (2003)
investigated the impact on human breast cancer cell proliferation of an ethanol extract of Solanum nigrum ripe fruits.Also, unlike superoxide anions, the hydroxyl and DPPH radicals were neutralised by the SNL extract, making it a potential scavenger.The results of the trials suggest that the fruit extract has potential as an anti-cancer antioxidant and chemopreventive agent [40] .

X. Ding et al. (2012)
discovered that solamargine (SM), a major steroidal alkaloid glycoside generated from SNL, inhibits the growth of the human hepatoma SMMC-7721 cell line.The IC 50 for tumour cell lines was determined using the MTT assay, which led to this discovery.Both SMMC-7721 and HepG2 cell growth was significantly suppressed, and both cell types were induced to undergo apoptosis in the presence of SM.The results of this study show that SM is able to induce apoptosis and suppress the growth of hepatoma cells in vitro by targeting malignant SMMC-7721 cells through activation of caspase-3 and regulation of the cell cycle [51] .

Cardioprotective activities
Bhatia Nitish et al. (2011) evaluated the preventive properties of a methanol extract of Solanum nigrum berries against a worldwide in-vitro ischemia-reperfusion injury model in rats.Individuals were given either 2.5 or 5.0 mg/kg over the course of thirty days, with therapy occurring six days per week during the whole period.The extract had a cardioprotective effect against global ischemia-reperfusion damage that was statistically significant (p ≤0.001) [78] .

P. Varshney et al. (2016)
tested S. nigrum aqueous extract for its potential to protect against doxorubicin-induced cardiotoxicity in mature Wistar albino rats (150-200 gm).Experiments were conducted with 100 mg/kg daily for 20, 30, and 40 days.Cardioprotection was shown by a significant (p0.001) reduction in the time-dependent increase of these parameters in the Solanum nigrum pretreatment group.Rats given SN extract showed a dose-dependent increase in cardioprotective effects [79] .

S. Shaik et al. (2016) performed an investigation on the hydroalcoholic (ethanolic) extract of Solanum nigrum (SNL) for its
cardioprotective activity in isoproterenol-induced myocardial infarction in male Wistar albino rats (200-250g).The study was carried out using 75, 150, and 300 mg/kg SNL for 21 days.SNL extract-treated rats showed an increase in SOD, CAT, and GSH levels.The treatment group significantly reduced the effects of isoproterenol-induced myocardial infarction.The rats treated with the ethanolic extract showed dose-dependent cardioprotective action [80] .

K. Heo et al. (2004
) conducted a study on the glycoprotein isolated from Solanum nigrum L. for antioxidative properties against oxygen free radicals using a DPPH assay.In cell cultures (NIH/3T3), SNL glycoprotein was more efficient against hydroxyl radicals.It has a catalase activity of 0.1μg/ml, which can scavenge hydroxyl radicals.The results indicate that SNL glycoprotein possesses antioxidative properties [5] .

M. Devi et al. (2004)
research was carried out on the biochemical antioxidant profile of the tissue, and the antioxidant potential of a methanolic fruit extract of Solanum nigrum was evaluated.According to the findings of the cardiac tissue biochemical antioxidant profile, the extract possessed a considerable (p 0.001) level of antioxidant capacity.Based on the findings, one can draw the conclusion that an extract of Solanum nigrum berries made with methanol had antioxidant activity [81] .

U. Karmakar et al. (2010)
looked into the potential of an ethanolic extract of the dried fruit of Solanum nigrum Linn for a variety of medical uses, including pain relief, preventing diarrhoea, killing bacteria, and killing cancer cells.An investigation into the qualitative antioxidant properties of an extract utilising a DPPH test revealed that the extract possessed free radical scavenging capabilities.Based on the findings, one can draw the conclusion that the antioxidant potential of Solanum nigrum extract can be utilized [14] .

J. Jeong et al. (2010)
explored whether the antioxidant lunasin, which was isolated from Solanum nigrum L., might prevent oxidative damage to DNA.It has been demonstrated that lunasin can protect DNA from the oxidative damage that is generated by the hydroxyl radical and the Fe2+ ion.It was shown that consumption of lunasin protects DNA from oxidation via chelation of Fe2+, which suggests that lunasin may play a significant role in the chemoprevention of oxidative carcinogenesis [82] .
Bhatia Nitish et al., (2011) investigated the fact that an experiment was carried out in order to assess the level of antioxidant activity that the methanolic extract of Solanum nigrum berries contained in comparison to the tissue biochemical antioxidant profile.Berries from the Solanum genus were used in the experiment.During the course of the study, doses of 2.5 and 5.0 mg/kg were given to the participants on six days out of every week for a total of thirty days.
The data showed that the methanolic extract had a significant amount of antioxidant potential (p ≤0.001), which was able to be deduced from the heart tissue biochemical antioxidant profile [78] .

U. Akula et al. (2013)
explored the anti-inflammatory effects, total phenolic content, and free radical scavenging activity of aqueous and methanolic extracts of 18 South African leafy vegetables.These extracts were examined (Solanum nigrum is one of these).In tests of radical scavenging, methanolic extracts from six different plants were able to minimise DPPH absorption.It is possible that the high quantities of phenolic compounds found in the plants that were analysed contribute to their antioxidant and anti-inflammatory benefits [83] .
A. Campisi et al. (2019) compared the antioxidant activities of methanolic:water (80:20) and water extracts of Solanum nigrum plant leaves.These extracts significantly reduced the cell-damaging effects of glutamate by blocking both glutamate uptake and glutamate excitotoxicity [82] .

D. Kaushik et al. (2009)
explored whether an extract of Solanum nigrum fruit that had been processed with ethanol had any effect on reducing pain.Using Eddy's hot plate and acetic acid-induced writhing, the analgesic efficacy was assessed for both central and peripheral pharmacological activity.At a dose of 500 mg/kg, the extract demonstrated substantial analgesic effectiveness [84] .

U. Karmakar et al. (2010)
explored whether an ethanolic extract of the dried fruit of Solanum nigrum could have a possible analgesic effect.The writhing reflex in mice was induced by the administration of acetic acid; the ethanolic extract, at doses of 250 and 500 mg/kg, was found to inhibit the writhing reflex by 51.39 and 66.67 percent, respectively.
According to research, ethanolic extracts possess characteristics that make them analgesic [14] .

Anti-diarrheal activities
Karmakar et al. (2010) investigated the efficacy of a treatment for diarrhoea that was derived from an ethanolic extract of the dried fruit of the Solanum nigrum Linn plant.At dosages of 250 mg/kg and 500 mg/kg, the extract demonstrated strong anti-diarrheal efficacy against castor oil-induced diarrhoea in mice [14] .

Gbadamosi et al. (2015)
investigated the efficacy of ethanol extracts of the Solanum nigrum plant in combating the pathogenic organisms that are the root cause of diarrheal diseases.The agar well diffusion method was used as the screening technique while testing antibacterial agents for indicator organisms.This method was utilised in the testing process.During the course of this investigation, it was found out that the extracts of S. nigrum have the potential to be used in the treatment of diarrhoea [85] .antimicrobial action [84] .suggest that Solanum nigrum extract's anti-microbial characteristics can be put to good use [14] .

G. Ravishankar et al. (2011) investigated 10 medicinal plants for anti-bacterial activity using aqueous and methanol
extracts against various bacterial strains using the agar-well diffusion method.Based on the findings, it is possible to deduce that methanol extract could contain anti-microbial substances.The current investigation found that plant extracts had antibacterial properties [86] .

D. A. John de Britto et al. (2011)
checked the disc diffusion method to investigate the antibacterial properties of leaf extracts from a selection of plants in the Solanaceae family against two gram-negative bacteria.It was found that all of the plant samples' methanol extracts significantly inhibited the growth of the two bacteria used in the study [87] .
T. Sridhar et al., (2011) evaluated the antifungal efficacy of Solanum nigrum leaf, seed, and root extracts using three distinct solvent extraction methods.When compared to leaf and root extracts, seed extract showed the most antifungal activity, while ethanol seed extracts had the lowest MIC value (2.0-6.0 g/ml) [88] .

T. Sridhar et al. (2011) performed an investigation on
Solanum nigrum extracts in-vitro for antibacterial potential against microorganisms.Compared to leaves and roots, the seeds showed excellent antibacterial effects against various pathogenic organisms [89] .

S. Ramya et al.
(2012) conducted a study using the disc diffusion assay in antibacterial research on leaf extracts of chosen bacterial strains.The aqueous leaf extract of S. nigrum leaves may elucidate the weak antibacterial and selective antifungal activities [90] .

K. Abbas et al.
(2014) used the hot plate diffusion method to determine the zone of inhibition for Solanum nigrum methanolic extract at concentrations of 5, 10, and 15 mg/ml, all of which were found to pointedly inhibit the growth of bacteria and fungus.The results of this research reveal that Solanum nigrum fruit extracts have antimicrobial and antifungal properties [91] .

I. Hameed et al. (2017)
evaluated the antibacterial activity of the ethanolic extract of Solanum nigrum dried fruit against four different bacterial strains using the disc diffusion method.Resistance to the ethanolic extract was shown to have developed in a bacterial strain [92] .

Z. Zakaria et al. (2006) investigated
Solanum nigrum leaf extract to assess the anti-inflammatory effects using the carrageenan-induced paw edema assay.The results showed that SNE has potential anti-inflammatory properties [93] .

D. Kaushik et al. (2009)
discovered the anti-inflammatory potential of an ethanolic extract of Solanum nigrum fruits by employing a carrageenan-induced rat paw edema model at oral doses of 100, 250, and 500 mg/kg.At a dose of 500 mg/kg, the extract demonstrated a significant anti-inflammatory effect [84] .

G. Arunachalam et al. (2009)
evaluated the anti-inflammatory activity of S. nigrum extract on a carrageenan-induced paw edema model at dosages of 100 and 200 mg/kg, orally administered.The findings demonstrated a strong antiinflammatory response that was dose-dependent.As a result of the observations, it was determined that Solanum nigrum could be used to treat conditions associated with inflammation [94] .

Y. Wang et al.
(2017) conducted a study to investigate the solanigrosides, novel steroidal saponins isolated from S. nigrum berries.These findings imply that S. nigrum berries have potent anti-inflammatory properties [96] .suggested that Solanum extracts have antipyretic effects [97] .

Clinical trials
There have been several clinical trials conducted on the pharmacological and therapeutic effects of Solanum nigrum Linn.
Here are some examples:

4.1.
In individuals with type 2 diabetes, a Solanum nigrum extract was found to have a considerable hypoglycemic impact, according to the results of a trial that was randomised and controlled.According to the findings of the study, the extract might be an effective complementary treatment for the control of diabetes [98] .

4.2.
In yet another randomised controlled experiment, researchers looked into the effects that S. nigrum had on the lipid profiles of patients who suffered from hyperlipidemia.According to the findings of the study, the extract dramatically lowered levels of total cholesterol as well as triglycerides and LDL cholesterol, while simultaneously raising levels of HDL cholesterol [99] .

4.3.
In a preliminary investigation, the medicinal benefits of S. nigrum for the treatment of basal cell carcinoma were explored.According to the findings of the study, applying a topical ointment that contained the plant extract was beneficial in reducing the size of the tumours as well as the severity of the condition [100] .

4.4.
A decoction made from the fruit of S. nigrum has been found to be helpful against numerous cancers.These include liver, lung, cervical, esophageal, breast, nasopharyngeal cancer, and others [101] .boost liver cancer patients' survival rates [102] .

4.6.
Another clinical trial showed that administering a S. nigrum mixture to advanced primary liver cancer patients improved their clinical symptoms, liver function, and immunological function, improving their quality of life [103] .
Overall, while more research is needed, these clinical trials suggest that Solanum nigrum has promising pharmacological and therapeutic effects and could be a valuable addition to the range of treatments available for a variety of medical conditions.

Marketed Formulations
There are several marketed formulations of Solanum nigrum Linn.available in different countries that are used for various therapeutic purposes.Some of the popular formulations are:

Iphigenia indica, Wikstroemia indica
Orally Decoction Scrofula with phlegm, breast bulk, wheezing, and vomiting [110]   It is important to note that the efficacy and safety of these marketed formulations of Solanum nigrum vary and may not be supported by sufficient scientific evidence.Therefore, it is advisable to consult a healthcare professional before using any formulation for therapeutic purposes.

Patents
S. nigrum extract is one component of a number of traditional Chinese medications that have found widespread usage in clinical practice.As demonstrated in Table 4, S. nigrum's pharmacological effects are most well-studied when used in combination with other herbs for the treatment of skin and tumour diseases.

Results and Discussions
The present trend of increased knowledge in ethnomedicine, plant-derived medications has sparked attention as natural substitutes for synthetic pharmaceuticals.Scientists and researchers are attempting to extract these undiscovered plants' medicinal and nutritional properties.The pharmaceutical industry anticipates that traditional medicinal plants will be a substantial source of new chemicals and natural resources.
The extensive literature review and empirical investigation in the present research led us to conclude that Solanum nigrum includes significant bioactive elements responsible for its beneficial effects on several substantial pharmacological activities, such as immunostimulant and immunomodulator, which can boost and improve our immune system.The hepatotoxicity and hepatoprotective activity of this plant helps to enhance kidney and liver function.This herb also promotes brain and CNS health.This strategy has several therapeutical potentials, but it is currently being investigated for anti-cancer, anti-tumor, anti-diabetic, and antioxidant activities.This plant might provide unique chemical components for drug development.To assess the efficacy of a wide range of medicinal properties and develop the optimal new drugs, well-designed pre-clinical research and human trials are necessary.

Future Prospective
The study of Solanum nigrum Linn.has already shown promise in the development of new treatments for various medical conditions.However, there is still much to learn about this plant and its potential therapeutic applications.One of the most exciting prospects for future research is the identification of novel bioactive compounds.Scientists may be able to isolate and characterize new molecules from Solanum nigrum Linn.that could have significant pharmacological effects, leading to the development of new drugs for a variety of diseases.Additionally, continued investigation into the mechanisms of action of this plant could reveal new insights into disease processes, potentially leading to the discovery of more effective treatments.Finally, the study of Solanum nigrum in the context of traditional medicine could help to validate its use in traditional healing practices and provide a basis for the development of evidence-based treatments.Overall, the future of research on Solanum nigrum Linn.looks promising, with the potential to make significant contributions to the field of pharmacology and therapeutic development.

Y.
Son et al. (2003) tested the Solanum nigrum fruit extract for its ability to suppress DNA synthesis in MCF-7 cells by utilising the MTT and trypan blue exclusion tests.MCF-7 cells displayed a cytotoxic response that ranged from 11 to 16

Arulmozhi
et al. (2010) examined the Solanum nigrum fruit aqueous extract's (SNF-AE) antioxidant and antihyperlipidemic efficacy against ethanol-induced toxicity in adult albino Wistar rats (150-17-gm).Each rat received 250 mg/kg of body weight in 20 percent ethanol once day for 30 days.Thiobarbituric acid reactive compounds were increased . Immunostimulant activities M. Haniffa et al. (2011) undertook research to identify plant species with immunostimulant potential for use in combating fish diseases.Immunization with 0.2 mL (4 ppm) of five different Solanum nigrum extracts and subsequent challenge with

Jian
Li et al. (2007) analysed the effect on tumour development of SNL-P, a crude polysaccharide extracted from the plant Solanum nigrum Linn.The growth of cervical cancer (U14) in tumor-bearing mice was also dramatically delayed by SNL-P.After 12 days of oral administration of SNL-P, further examination into the tumour inhibition mechanism indicated Li et al. (2010) have investigated the polysaccharide component from Solanum nigrum Linn that has anti-tumor properties (SNL-P).This chemical has been utilised to investigate the protective effects of the active component on the thymus, and it has been shown to have anti-cervical cancer and modifying characteristics.Injections of ascites U14 cells into animal models allowed researchers to assess SNL-P's ability to prevent cervical cancer.Histological and TUNEL

Z.
Zhao et al. (2018) explored the anti-cancer properties of the compound known as degalactotigonin (DGT), which was isolated from the Solanum nigrum plant.DGT can prevent osteosarcoma from developing and spreading throughout the body.Using the MTT, colony formation, and apoptosis assays, researchers looked at the effects that DGT had on the viability of osteosarcoma cells in vitro.In this study, animal models were used to investigate the role of DGT in osteosarcoma tumour growth and metastasis.DGT inhibited osteosarcoma cell growth, induced apoptosis, and lowered both migration and invasion of osteosarcoma cells.According to the findings of the study, DGT is able to inhibit human osteosarcoma development and metastasis through modifying the GSK3b inactivation-mediated control of the

3. 20 .
Anti-apoptotic activities S. Lee et al. (2004) used HCT-116 cells that had been subjected to chemically generated tumour promotion to test the anti-cancer effects of a glycoprotein derived from Solanum nigrum L. (SNL glycoprotein) with a 150-kDa molecular weight.

D.
Kaushik et al. (2009) conducted an investigation of the antibacterial properties of an ethanolic extract of Solanum nigrum fruit in this work.At each of the tested concentrations (100, 75, 50, and 25 mg/ml), the extract from the plant was able to significantly inhibit the growth of S. aureus and B. subtilis.According to the findings, ethanolic extracts exhibited

U.
Karmakar et al. (2010) tested the antibacterial properties of an ethanolic extract of Solanum nigrum fruits.Both grampositive and gram-negative bacteria were resistant to the ethanolic extract's lack of antibacterial activity.The results

Zakaria
et al. (2012) investigated carrageenan-induced paw edema in rats to test the antipyretic properties of Solanum nigrum chloroform extract.The extract demonstrated significant antipyretic effects dose-dependently.Research findings

Prashant Kumar et al. (2001) examined
the cytoprotective properties of Solanum against gentamicin-induced toxicity in Vero cells.Research findings displayed remarkable hydroxyl radical scavenging activity, indicating a potential strategy of

. Perez et al. (1998) studied
the neuroprotective effects of Solanum ethanolic fruit extracts in Wistar rats.The results demonstrate that S. nigrum fruit may have CNS-depressant properties

Wang et al. (2011) investigated
the extract of Solanum nigrum and its effect on the development of hepatocarcinoma Meerwal et al. (2012)have done on the ethanolic extract of S. nigrum at doses of 100, 250, and 500 mg/kg for 60 days orally.The impact on testis weight, blood testosterone, FSH, LH levels, and testis histoarchitecture was studied.