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. 2022 Aug 16;13:918071. doi: 10.3389/fphar.2022.918071

TABLE 4.

Biological activity of bioactive compounds and extracts of S. nigrum.

Biological activities Extracts/compounds Types Testing subjects Doses/duration Mechanisms/effects References
Antitumor activity
SNPE In vitro HepG2 cells 0.5, 1.0 and 2.0 mg/ml for 24 h IC50 value was 0.75 mg/ml, arrested the cell cycle at the G2/M phase and CDK1, Bcl-2 and Bid protein expression levels ↓ Wang et al. (2010)
SNPE In vivo HepG2 tumor-bearing mice 1 or 2 µg/ml for 35 days Tumor weight and tumor volume ↓ Wang et al. (2011)
SNWE In vitro HepG2 cells 0.05–2 mg/ml for 24 h The IC50 of SNWE and SNPE was 2.18 and 0.86 mg/ml, respectively, inhibited TPA-induced HepG2 migration, TPA-induced PKCα and p38 protein expression levels ↓ Yang et al. (2010)
SNPE
SNWE In vitro HUVEC and HepG2 cells 0.1–2 mg/ml for 24, 48, 72, and 96 h Suppression of the VEGF-induced activation of AKT and mTOR Yang et al. (2016)
SNPE
SNWE In vivo HepG2 tumor-bearing mice 0–2% for 35 days Reduced the volume and weight of the tumors, and CD31 protein expression levels ↓ Yang et al. (2016)
SNPE
SNEE In vitro A549 cells 100 µg/ml for 16 h Exhibited specifically stat3-suppressing activity in A549 cells through the decrease of Bcl-xL expression Park et al. (2014)
SNTA In vitro RPMI-8226 cells 12.5, 25, and 50 mg/kg for 14 days Inhibited I κB-α Phosphorylation and NF-κB/IRF4 signaling pathway to induce apoptosis Liu et al. (2021)
SNFME In vitro C6 cells 0.025–0.4 mg/ml IC50 value was 0.23 mg/ml, attenuated cell cloning, migration and invasion Li et al. (2021)
SNWE In vitro TG-elicited peritoneal macrophages 10–500 mg/ml for 12 h Decreased NO production and increased the expression of iNOS protein An et al. (2005)
SNLP-1 In vivo Lung Cancer Bearing Mice 200 mg/kg/day Played an antitumor role by enhancing the function of the immune system in the body Pu (2020)
SNCE In vitro 786-O cells 40 mg/ml Inhibited proliferation and promoted apoptosis by inhibiting the activation of PI3K/Akt signaling pathway Liao et al. (2020)
2 In vitro Human hepatoma cancer cell line (HepG2 cell) 3.125, 6.25, 12.5, 25, 50, and 100 µM IC50 value against HepG2 cell was 0.245 μg/ml Wang (2007)
2 In vitro Human tumor cells lines (NCI-H460, SF-268, MCF-7, HepG2 Cell) 3.125, 6.25, 12.5, 25, 50, and 100 µM for 48 h IC50 values against four tumor cells were 4.4, 3.1, 1.5, and 0.2 μM, respectively Zhou (2006)
26 In vitro Human tumor cells lines (NCI-H460, SF-268, MCF-7, HepG2 Cell) 3.125, 6.25, 12.5, 25, 50, and 100 µM for 48 h IC50 values against four tumor cells were 31.8, 34.7, 29.1, and 19.6 μM, respectively Zhou (2006)
28 In vitro Human tumor cells lines (NCI-H460, SF-268, MCF-7, HepG2 Cell) 3.125, 6.25, 12.5, 25, 50, and 100 µM for 48 h IC50 values against four tumor cells were 52.3, 260.4, 64.7, and 48.6 μM, respectively Zhou (2006)
78 In vitro Human tumor cells lines (NCI-H460, SF-268, MCF-7, HepG2 Cell) 3.125, 6.25, 12.5, 25, 50, and 100 µM for 48 h IC50 values against four tumor cells were 22.9, 34.2, 42.2, and 19.2 μM, respectively Zhou (2006)
79 In vitro Human tumor cells lines (K562, KB, K562/A02, and KB/VCR) NW IC50 values against four tumor cells were 8.0, 7.8, 5.4, and 7.1 μM, respectively Zhao (2010)
79 In vitro HepG2 3.125, 6.25, 12.5, 25, 50, and 100 µM IC50 value against HepG2 cell was 19.2 μg/ml Wang (2007)
79 In vitro Human tumor cells lines (HL-60, U-937, Jurkat, K562, and HepG2) NW Exhibited the most potent cytotoxicity to all the cell lines with IC50 values of 3.53, 9.31, 2.72, 8.75, 5.36 μM, respectively Xiang et al. (2019)
79 In vitro Human tumor cells lines (MDA-MB-231, A549, Hep3B, PC3) 30 and 100 µM IC50 values against 4 tumor cells were 1.86, 2.24, 0.78, 5.13 μM, respectively Tai et al. (2018)
79 In vitro Human tumor cells lines (NCI-H460, SF-268, MCF-7, HepG2) 3.125, 6.25, 12.5, 25, 50, and 100 µM for 48 h IC50 values against 4 tumor cells were 21.4, 25.1, 15.2, and 7.6 μM, respectively Zhou (2006)
79 In vitro K562 cells 5, 7.5 and 10 μM for 0, 2, 4, 6, 8, and 24 h Induced tumor apoptosis by initiating an early lysosomal destabilization pathway Sun et al. (2010)
79 In vitro SMMC-7721 cells 0, 5, 10, 15 μg/ml for 72 h The IC50 values were 9.21 μg/ml Ding et al. (2012a)
79 In vitro QBC939 cells 0–10 μΜ The IC50 value was 9.81 μΜ, Inhibited the metastasis and invasion by inhibiting the expression of PI3K/Akt signal pathway Zhang (2018)
84 In vitro Lung cancer A549 cells 1–20 μmol/L for 24 h IC50 values against A549 cells were 2.36 μM, respectively Shi et al. (2019)
99 In vitro PANC-1 cells 0, 2, 4, 6 μg/ml N-cadherin, vimentin, MMP2 expression level ↓; E-cadherin expression level ↑ Kong et al. (2020)
99 In vitro RKO and HCT-116 cells 13–32 µM in RKO cells, 11–28 µM in HCT-116 cells IC50 were 20.84 and 20.32 µM respectively. The expression levels of cyclin D1 and cyclin-dependent kinase 2 in RKO cells↓; production of ROS in RKO cells ↑; inhibited the migration and invasion of HCT-116 cells Yan et al. (2020)
99 In vitro HCT-116 cells 4–32 μmol/L for 48 h Inhibited proliferation and clone, induced apoptosis by activating Caspase-3 Hu et al. (2019)
99 In vitro SK-OV3 cells 5–15 μmol/L for 24, 48, 72 h Inhibited proliferation and induced apoptosis by regulating the expression of p-Akt, cleaved Caspase-3 and p53 protein Zhu et al. (2019)
99 In vitro RKO cells NW Induced apoptosis by activation of Caspase-3, the increase of intracellular ROS level and the inhibition of FAK phosphorylation Yan and Hu (2019)
99 In vitro U87 cells 2.5–30 μg/μl Inhibited proliferation and induced apoptosisby by down-regulating the expression of Ki-67, PCNA and Bcl-2 protein and up-regulating the expression of Bax protein Zhao et al. (2019)
99 In vitro SGC-7901 cells 25, 50, 100 μg/ml for 48, 72 h Inhibited proliferation and promoted apoptosis by up-regulating the expression of mir-140 and down-regulating the expression of MACC1 Huang et al. (2020)
99 In vitro EC9706, KYSE30 cells 4 μmol/L Enhanced the drug sensitivity of esophageal cancer cell lines EC9706 and kyse30 to 5-fluorouracil and cisplatin via Wu (2019)
99 In vivo ACHN-induced tumor-bearing mice 20 mg/kg for 28 days Inhibited tumor growth through HIF-1α pathway to affect the expression and activity of key enzymes of glycolysis Wang et al. (2019)
100 In vitro THP-1, MV4-11, NB-4, HL-60, HEL cells NW IC50 were 11.19, 12.50, 15.45, 15.87, 17 mM, promoted apoptosis and caused less cell cycle arrest in the G2/M phase through the activation of the AMPK/FOXO3A Axis Zhang et al. (2021)
100 In vitro HepG2 and QGY-7703 cells 0–50 µM for 24, 48, 72 h The proliferation of hepatoma cells was inhibited by activating mir-375-3p, ccat1, Sp1 and IRF5 protein expression levels ↓ Zhang et al. (2021)
100 In vitro A549 cells 0, 15, 20, 25 μmol/L for 24, 48, and 72 h Induced apoptosis by inhibiting the expression of p65 and Bcl-2 protein, enhancing the expression of bik and Bak protein, and activating Caspase-3 pathway Li et al. (2020)
100 In vitro Human tumor cells lines (NCI-H460, SF-268, MCF-7, HepG2) 3.125, 6.25, 12.5, 25, 50, and 100 µM for 48 h IC50 values against four tumor cells were 97.5, 113.5, 75.7, and 48.9 μM, respectively Zhou (2006)
100 In vitro Human tumor cells lines (HL-60, U-937, Jurkat, K562, and HepG2) NW IC50 values against five tumor cells were 33.32, 39.16, 12.85, 26.83, and 17.33 μM, respectively Xiang et al. (2019)
180 In vitro HepG2 3.125, 6.25, 12.5, 25, 50, and 100 µM IC50 value was 62.3 μg/ml Wang (2007)
181 In vitro HepG2 3.125, 6.25, 12.5, 25, 50, and 100 µM IC50 value was 57.5 μg/ml Wang (2007)
Anti-inflammatory activity
SNCFE In vitro Peritoneal macrophages 0–200 μg/ml for 4 and 24 h NO, TNF-α and IL-6 levels ↓; p38, JNK and ERK1/2 expression levels ↓ Kang et al. (2011)
SNFEE In vivo Acute ear edema mouse model 0.125, 0.250, 0.500, and 1.000 mg/ml The cell viability below 0.5 mg/ml was about 90%, alleviating edema and decreased thickness of ear tissue Yeom et al. (2019)
SNEE In vivo Acute and sub-acute rat model 100 and 200 mg/kg The pathological changes of granuloma, kidney, liver and stomach were lighter than those in the model group Aryaa and Viswanathswamy (2017)
SNWE In vitro Patients with thoracic malignant tumor after radiotherapy NW PDGF, TGF-β1, IL-6,TNF-α expression level ↑ Che (2018)
SNFPEFE In vitro Hyaluronidase, lipoxygenase 100–1,000 µg/ml The IC50 values of hyaluronidase and lipoxygenase were 810.67 and 781.28 µg/ml Guo et al. (2020)
43 In vitro LPS-induced RAW 264.7 cells 2.5, 5, 10, 20, 40, and 50 μM NO inhibition (IC50 = 40.11 μM) Xiang et al. (2018)
44 In vitro LPS-induced RAW 264.7 cells 2.5, 5, 10, 20, 40, and 50 μM NO inhibition (IC50 = 72.39 μM) Xiang et al. (2018)
45 In vitro LPS-induced RAW 264.7 cells 2.5, 5, 10, 20, 40, and 50 μM NO inhibition (IC50 = 33.00 μM) Xiang et al. (2018)
46 In vitro LPS-induced RAW 264.7 cells 2.5, 5, 10, 20, 40, and 50 μM NO inhibition (IC50 = 48.75 μM) Xiang et al. (2018)
47 In vitro LPS-induced RAW 264.7 cells 2.5, 5, 10, 20, 40, and 50 μM NO inhibition (IC50 = 50.77 μM) Xiang et al. (2018)
48 In vitro LPS-induced RAW 264.7 cells 2.5, 5, 10, 20, 40, and 50 μM NO inhibition (IC50 = 63.66 μM) Xiang et al. (2018)
49 In vitro LPS-induced RAW 264.7 cells 2.5, 5, 10, 20, 40, and 50 μM NO inhibition (IC50 = 11.33 μM) Xiang et al. (2018)
52 In vitro LPS-induced RAW 264.7 cells 12.5 and 25.0 μM for 24 h NO inhibition (IC50 = 9.7 μM) Wang et al. (2017)
53 In vitro LPS-induced RAW 264.7 cells 12.5 and 25.0 μM for 24 h NO inhibition (IC50 = 17.8 μM) Wang et al. (2017)
54 In vitro LPS-induced RAW 264.7 cells 12.5 and 25.0 μM for 24 h NO inhibition (IC50 = 14.0 μM) Wang et al. (2017)
56 In vitro LPS-induced RAW 264.7 cells 12.5 and 25.0 μM for 24 h NO inhibition (IC50 = 38.3 μM) Wang et al. (2017)
57 In vitro LPS-induced RAW 264.7 cells 12.5 and 25.0 μM for 24 h NO inhibition (IC50 = 41.0 μM) Wang et al. (2017)
59 In vitro LPS-induced RAW 264.7 cells 12.5 and 25.0 μM for 24 h NO inhibition (IC50 = 48.5 μM) Wang et al. (2017)
60 In vitro LPS-induced RAW 264.7 cells 12.5 and 25.0 μM for 24 h NO inhibition (IC50 = 44.0 μM) Wang et al. (2017)
63 In vitro LPS-induced RAW 264.7 cells 12.5 and 25.0 μM for 24 h NO inhibition (IC50 = 22.1 μM) Wang et al. (2017)
85 In vitro LPS-induced RAW 264.7 cells NW NO inhibition (IC50 = 23.42 μM) Xiang et al. (2019)
164 In vitro BChE assay NW moderate BChE inhibitory activity (IC50 = 195.2 µg/ml) Sabudak et al. (2017)
165 In vitro BChE assay NW Moderate BChE inhibitory activity (IC50 = 299.1 µg/ml) Sabudak et al. (2017)
Antioxidant activity
SNFME In vitro DPPH and hydrogen peroxide radicals 25, 50,100, 150, and 200 μg/ml The IC50 value of 70.73 μg/ml for DPPH radical scavenging and IC50 59.72 μg/ml for hydrogen peroxide scavenging activity Veerapagu et al. (2018)
SNFEE In vitro DPPH and hydroxyl radical 0–2.4 mg/ml The scavenging rate on DPPH, hydroxyl radical scavenging assay were 68.45% and 49.12%, respectively Teng et al. (2014)
SNFP In vitro DPPH and hydroxyl radicals 0–1.2 mg/ml The IC50 values were 65.43 μg/ml and 0.33 mg/ml for DPPH, hydroxyl radical scavenging assay Chen et al. (2020)
SNFEAE In vitro FRAP and DPPH· scavenging assays 100–2,500 μg/ml for FRAP 50–1,000 µg/ml for DPPH The IC50 values were 119.43 µg/ml and 2.674 µg/ml, FeSO4/L for DPPH and FRAP scavenging activity Guo et al. (2020)
SNFEE In vitro DPPH and ABTS radical 0–120 μg/ml Showed moderate free radical scavenging activity against DPPH and ABTS+ free radical with the IC50 were 81.02 and 35.56 μg/ml, respectively Sivaraj et al. (2020)
Immunoregulatory activity
SNLWP-1 SNLAP-1 SNLAP-2 In vivo H22-bearing mice 50, 100, and 200 mg/kg for 10 days IL-2, IFN-c levels ↑; IL-10 levels↓ Ding et al. (2012b)
SNCP In vivo Male BALB/C mice 200, 400, 800 mg/kg for 28 days B.T, NK cell activity ↑ Tian et al. (2019)
SNLP-1 In vivo Lung Cancer Bearing Mice 200 mg/kg/day CD4+/CD8+of T lymphocytes levels ↑; Th1 cytokines levels ↑ Pu (2020)
Hepatoprotective activity
SNWE in vivo CCl4-induced chronic hepatotoxicity in rats 0.2, 0.5, and 1.0 g/kg for 6 weeks GOT, GPT, ALP, total bilirubin, superoxide , hydroxyl radical levels↓; GSH, SOD, GST Al, GST Mu levels ↑ Lin et al. (2008)
SNFBFE in vivo D-GalN-induced hepatic fibrosis rats  16 and 25 mg/kg for 10 days ALT, AST, ALP enzymes, GSH, SOD, and CAT levels↓ Chester et al. (2019)
SNWSP in vivo CCl4-induced acute injury in rats 100, 200, 400 mg/kg for 7 days ALT, AST, ALP, MDA levels↓; SOD, GSH-Px, CAT levels ↑ Yang et al. (2014)
SNWE in vivo Ethanol-induced liver injury in rats 100, 150, 200 mg/kg for 7 days ALT, AST, GSTA1, MDA levels↓; SOD, GSH, GSH-Px ↑ Han (2014)
Antibacterial activity
SNFEE in vitro Aspergillus’s Niger, Fusarium oxysprum 250–1,000 µg/ml for 24 h Highest antifungal zone was 32.42 and 28.16 mm against Aspergillus’s Niger and Fusarium oxysprum Mazher et al. (2017)
SNFEE in vitro Escherichia coli 250–625 µg/ml The maximum zone of inhibition was 25 mm for Escherichia coli at 625 µg/ml concentration Sivaraj et al. (2020)
SNEE in vitro Staphylococcus aureus 12.5–200 mg/ml The maximum zones of inhibition were 16.88, 11.33, and 19.25 mm for Staphylococcus aureus, Escherichia coli, Aeromona sobria at 200 mg/ml concentration Ge (2019)
Escherichia coli
Aeromona sobria
SNEE in vitro Alternaria solani NW The EC50 values of Rhizoctonia solani and Fusarium oxysporun were 1,629 and 1,262 ppm Cai (2003)
Cladosporium cucumerinum
Fusarium oxysporun
Rhizoctonia solani
93 in vitro Candida albicans 0, 8, 16, 32, and 64 mg/L for 12, 24, 36, 48 h Inhibited the activity of Candida albicans via regulating Ras-cAMP-PKA signaling pathway and reducing the intracellular cAMP content Li et al. (2015)
93 in vitro Candida albicans 32, 64 µg/ml Alkalizing the intracellular vacuole of Candida albicans and causing hyper-permeability of the vacuole membrane Chang et al. (2017)
Insecticidal activity
SNLME in vitro 2nd instar larvae of CPB 5, 10,15, 20, 25, 30, 35, 40, and 45 mg/ml Caused 50% mortality for 2nd instar CPB larvae at concentration of 5 ppm and foliar consumption was decreased by 74% Ben-Abdallah et al. (2019)
SNLCME in vitro Cx. vishnui group and An. subpictus 25, 45, 60 mg/L for 24, 48, and 72 h Showed 100 percent larval mortality against early 3rd instar of An. subpictus at 60 mg/L Rawani et al. (2017)
SNFMWE in vitro Galba truncatula NW The hydro-methanol LC50 = 3.96 mg/L, LC90 = 7.49 mg/L Hammami et al. (2011)
SNLEAE in vitro Culex quinquefasciatus 10–50 ppm for 24–72 h LC50 values of ethyl acetate extracts were 17.04 ppm Rawani et al. (2010)
SNLEE in vitro Green Peach Aphid Myzus persicae Sulzer 4.24 mg/ml for 24, 48, and 72 h Caused 28.54%, 56.8%, and 57.42% mortality rates after 24, 48, and 72 h exposure Madanat et al. (2016)
SNLME in vitro Culex quinquefasciatus 6.25–1,000 ppm Methanol leaves extract causing 90% mortality rate Rahuman et al. (2009)
Neuroprotective activity
SNL in vivo SCOP-induced cognitive impairment rats 5% and 10% leaf inclusions ChEs levels↑; restored the impaired memory function Ogunsuyi et al. (2018)
SNL in vivo AlCl3-induced neurodegeneration in Drosophila melanogaster 0.1% and 1.0% pulverized vegetable for 7 days GST, MAO, ChE, ROS, TBARS levels ↓; Athletic, memory ability ↑ Ogunsuyi et al. (2020)
SNL in vivo AlCl3-induced neurodegeneration in Drosophila melanogaster 0.1% and 1.0% pulverized vegetable for 7 days ROS, GST, Hsp70, Jafrac1, reaper and NF-kҝB/Relish ↓; cnc/Nrf2 and FOXO ↑ Ogunsuyi et al. (2021)
112 In vitro MPP+-induced SH-SY5Y cells 12.5, 25, and 50 μM for 1 h Induced protective autophagy to protect SH-SY5Y cells from MPP+-induced apoptosis, the cell viability of which improved by 12% at 25 μM Li et al. (2019)
Gastroprotective activity
SNEE in vivo Ethanol-induced gastric ulcer mice 5–500 mg/kg At dose of 500 mg/kg, the extract was as effective as lansoprazole in reducing all parameters of peptic ulcer in both models El-Meligy et al. (2015)
SNFME in vivo Gastric ulcer rats 200 and 400 mg/kg Gastric secretory volume, acidity, pepsin secretion ↓ Jainu and Devi (2006)
Hypoglycemic activity
SNFWE in vivo Streptozotocin-induced Diabetic rats 1 g/L for 8 weeks Ca/Mg ratio, plasma glucose, HDL, LDL, VLDL, cholesterol, triglyceride ↓ Sohrabipour et al. (2013)
Antimalarial activity
79 in vivo Plasmodium yoelii-infected mice 7.5 mg/kg for 4 days At a dose of 7.50 mg/kg, the parasitemia suppressions of solamargine were 64.89%, respectively Chen et al. (2010)
100 in vivo Plasmodium yoelii-infected mice 7.5 mg/kg for 4 days At a dose of 7.50 mg/kg, the parasitemia suppressions of solasonine were 57.47%, respectively Chen et al. (2010)
CNS-depressant activity
SNFEE in vivo Wistar rats and CD1 mice 51, 127.5, and 255 mg/kg Exploratory and aggressive behavior↓; locomotor activity↓; pentobarbital-induced sleeping time ↑ Perez et al. (1998)
Hypolipidemic activity
SNWE in vitro 3T3L1 cells model 0.3, 0.4, 0.5 mg/ml PPARα, CPT-1 ↑; FaS, HMG-CoR↓; amount and lipid content of adipocytes ↓; inhibiting lipogenesis Peng et al. (2020)
SNSEE in vivo Triton-induced hyperlipidemic rats 200 and 400 mg/kg Total cholesterol, triglycerides, LDL cholesterol ↓; HDL cholesterol ↑ Sohrabipour et al. (2013)

Note: NM, not mentioned; SNWE, water extracts of S. nigrum; SNPE, polyphenol extracts of S. nigrum; SNEE, ethanol extracts of S. nigrum; SNTA, total alkaloids of S. nigrum; SNFME, Methanol extracts of S. nigrum fruits; SNCE, chloroform Extracts of S. nigrum; SNFEE, ethanol extracts of S. nigrum fruits; SNFP, Polysaccharide from S. nigrum fruit; SNFEAE, Ethyl acetate extracts of S. nigrum fruit; SNCFE, chloroform Fraction extracts of S. nigrum; SNFPEFE, Petroleum ether fraction extracts of S. nigrum fruit; SNCP, Crude Polysaccharides from S. nigrum; SNFBFE, n-butanol fraction extracts of S. nigrum fruit; SNWSP, water-soluble polysaccharides from S. nigrum; SNLME, methanol extracts of S. nigrum leaves; SNLCME, chloroform: methanol (1:1 v/v) extracts of S. nigrum leaves; SNFMWE, methanol-water (8:2 v/v) extracts of S. nigrum fruit; SNLEAE,Ethyl acetate extracts of S. nigrum leaves; SNLEE, ethanol extracts of S. nigrum leaves; SNFWE, water extracts of S. nigrum fruits; SNL, S. nigrum leaves; SNSEE, ethanol extracts of S. nigrum seeds.