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. 2018 Oct 28;29(1):111–124. doi: 10.1016/j.bjp.2018.07.009

Box 2.

The pharmacological activities of Toona sinensis.

Pharmacological effects Detail Tested substance Doses/concentrations References
Antitumor effect Leukemia (K562 cell line) ACTSL IC50 was 102.53 μg/ml Chen et al. (2011a)
Leukemia (WEHI-3 cell line) TSL 50 mg/kg on WEHI-3 cell bearing mice Yang et al. (2017)
Leukemia (HL-60 cell line) TSL 10–75 μg/ml Huang et al. (2012)
Gallic acid 5, 10 μg/ml Huang et al. (2012)
Kakumu et al. (2014)
Leukemia (HL-60 and K562 cell lines) Cedralins A IC50 were 26.2 and 22.4 μg/ml Lee et al. (2010)
Leukemia (HL-60 cell line) Loropetalin D 50 μM Kakumu et al. (2014)
Quercetin
Quercitrin
Afzelin
Astragalin 2′′-O-gallate
(+)-Catechin
Lung cancer (H441, H520, H661 cell lines) TSL 0.125–1.0 mg/ml for 24 or 48 h,
IC50 were 1.2, 0.73 and 0.29 mg/ml for H441, H520 and H661 cells
Wang et al. (2010);
Yang et al., 2010a, Yang et al., 2010b
Oral carcinoma TSL 1.0 g/kg Wang et al. (2016)
Gallic acid 250, 500 μg/ml Chia et al. (2010)
Gastric cancer (MGC-803 cell line) Betulonic acid IC50 was 17.7 μM Yang et al. (2013)
3-Oxo-12-en-28-oic acid IC50 was 13.6 μM
Gastric cancer (SGC-7901 cell line) ACTSL IC50 was 168.47 μg/ml Chen et al. (2011a)
Prostatic cancer (DU145 cell line) Gallic acid 25–100 μg/ml Chen et al., 2009a, Chen et al., 2009b
Prostatic cancer (PC3 cell line) Betulonic acid IC50 was 26.5 μM Yang et al. (2013)
3-Oxo-12-en-28-oic acid IC50 was 21.9 μM
Ovarian cancer (SKOV3 cell line) TSL 0–1000 μg/ml Chang et al. (2006)
Cervical carcinoma (Hela cell line) TSL 25, 50 μg/ml Zhen et al. (2014)
Renal carcinoma (ccRCC cell line) TSL Chen et al. (2016)
Rsteosarcoma (Saos-2 cell line) TSL IC50 was 42.8–52.3 μg/ml in vitro
1 g/kg and 5 g/kg on Saos-2 cell bearing mice
Chen et al. (2017b)
Colon cancer Caco-2 cell TSL IC50 was 4.0 μg/ml Liu et al. (2012)
Liver cancer HepG2 cell TSL IC50 was 153.16 μg/ml
Breast cancer MCF-7 cell TSL IC50 was 193.46 μg/ml



Hypoglycemic effects Glucose uptake-enhancing effect ETSL 0.001, 0.01, 0.1 mg/ml, for 60 min Yang et al. (2003)
Inhibiting LDL glycation induced by glucose and glyoxal TSL 0.5 mg/ml Hsieh et al. (2005)
Alleviating hyperglycemia via altering adipose glucose transporter 4 TSL 0.5, 1, 2 g/kg/14 days Wang et al. (2008a)
Hypoglcemic effects on diabetic mice FTSL 0.6, 0.12 mg/kg Zhang et al., 2008, Zhang et al., 2011
Protective effects on hepatic injury at early stage in diabetic rats TPST 60, 80, 100 mg/kg, for 14 days Xing and Chen (2011)
Hypoglycemic effect in diabetic rats STSL 15 mg/kg, for 15 days Du et al. (2011)
kidney protecting effects in diabetic rats STSL 50 mg/kg, for 10 weeks Li et al. (2016)
Preventing the progression of diabetes NPTSL 12.5–100 μg/ml in vitro;
150 mg/kg for 8 weeks in vivo
Hsieh et al. (2012)
Stimulating glucose uptake and ameliorating insulin resistance ETSL 0, 10, 50, 70, and 95% Liu et al. (2015)
α-Glucosidase inhibitory activities Gallic acid IC50 was 24.3 μM
(+)-Catechin IC50 was 190.7 μM Zhao et al. (2009)
(−)-Epicatechin IC50 was 189.0 μM
Procyanidin B3 IC50 was 111.0 μM
Procyanidin B4 IC50 was 89.0 μM
Reducing the risk of diabetes and its secondary complications via reducing oxidative stress in the liver Quercetin 200 mg/kg Zhang et al. (2016)



Antioxidant effects Against hydrogen peroxide-induced oxidative stress and DNA damage in MDCK cells Methyl gallate 100 μM Hsieh et al. (2004)
In vitro antioxidant experiments TSL 0.1–1.6 mg/ml Zhang et al. (2007)
TSL 25–100 μg/ml Hseu et al. (2008)
Gallic acid 50 μg/ml
TPST _ Wang et al., 2008a, Wang et al., 2008b
Antioxidant properties that protect endothelial cells from oxidative stress TSL 50–100 μg/ml Yang et al. (2011)
Up-regulating antioxidant enzymes in SD rats FETSL 0.5 and 1.0 mg/kg Chen et al. (2013)



Anti-inflammatory effects Inhibiting carrageenin-induced paw edema in rats TSL 0.5 and 1.0 mg/kg (p.o.) Ruan et al. (2010)
Treating adjuvant-induced arthritis in rats TPST 35 and 70 mg/kg (p.o.) Yang and Chen (2012)
Inhibiting LPS-induced inflammation in mice via suppressing NF-κB pathway TSL 100 mg/kg (p.o.) Hsiang et al. (2013)
Gallic acid 5 mg/kg (p.o.)
Inhibiting LPS-induced inflammation in vascular smooth muscle cells (A7r5 cell line) via suppressing NF-κB pathway TSL 25–100 μg/ml Yang et al. (2014)
Gallic acid 5 μg/ml
Inhibiting inflammatory responses in RAW264.7 cells via activating Keap1/Nrf2/HO-1 pathway 7-deacetylgedunin 1–25 μM Chen et al. (2017a)



Protecting effects on ischemia–reperfusion Protective effect on myocardial ischemia/reperfusion injury in rats TPST 50, 100, 200 mg/kg/d (p.o., for 7 days) Li and Chen, 2011a, Li and Chen, 2011b, Li and Chen, 2012
protective effects on MODS caused by brain ischemia–reperfusion in rats BUST 20,30 mg/kg/d (p.o., for 7 days) Yuan et al. (2013)



Hepatoprotective effect Alleviating thioacetamide induced liver fibrosis TSL 1 g/kg/d (p.o., for 7 days) Fan et al. (2007)
Ameliorating antioxidant enzymes activity in H2O2 induced oxidative rats liver TSL 0.013– 1.88 g/kg/d (p.o., for 8 weeks) Yu et al. (2012a)
Protective effects on hepatic injury at early stage in diabetic rats TPST 60, 80, 100 mg/kg (p.o., for 14 days) Xing and Chen (2011)
Attenuating acetaminophen induced acute liver toxicity in HepG2 cells and mice via inducing antioxidant machinery and inhibiting inflammation Quercitrin 25, 50 μg/ml;
10, 50 mg/kg/d (p.o., for 7 days)
Truong et al. (2016)



Antiviral and antibacterial effects Antiviral activity against SARS-CoV TSL IC50 = 30 μg/ml Chen et al. (2008)
Antiviral activity against H1N1 TSL 10–100 μg/ml You et al. (2013)
Antibacterial activity against E. coli C83902 TSL MIC = 0.25 g/ml Chen et al. (2011b)
Antibacterial activity against E. coli K88 TSL MIC = 0.125 g/ml
Antibacterial activity against Salmonella C500 TSL MIC = 0.25 g/ml
Antibacterial activity against Staphylococcus CAU0183 TSL MIC = 0.25 g/ml



Anti-gout activity Inhibiting XO TSL IC50 = 151.6 μg/ml Liang et al. (2011)
Inhibiting COX- 2 TSL IC50 = 2.26 μg/ml
Hypouricemic effects on hyperuricemic mice FTSL 50, 100, 200 mg/kg/d (p.o., for 7 days) Wang et al. (2011)



Male reproductive system protection Suppressing steroidogenesis, cAMP-PKA pathway and steroidogenic enzymes activities in normal mouse leydig cells TSL 0.005, 0.05, 0.5 mg/ml Poon et al. (2005)
TSL could improves the functions of sperm and testes TSL 13 mg/kg/d (p.o., for 8 weeks) Yu et al. (2012a)



Anticoagulation effect Anticoagulation effect of on adrenaline induced hypercoagulable rats via prolonging RT, APTT, TT and PT, and increasing AT-III activity BUST 10, 20 mg/kg/d (p.o., for 7 days) Jin and Chen (2011)
Enhancing fibrinolysis of topical FeCl3 induced carotid artery thrombosis rats via increasing t-PA, PL G and DD. BUST 40 mg/kg/d (p.o., for 7 days) Jin and Chen (2011)



Other pharmacological effects Lipolytic effect in differentiated 3T3-L1 adipocytes via protein kinase C pathway TSL 0.001, 0.01, 0.1 mg/ml Hsu et al. (2003)
Suppressing BV-2 microglia mediated neuroinflammation TSL 5, 10, 50 mg/ml Wang et al. (2014a)
Antinociceptive effect on acetic acid induced writhing in mice TSL 0.003–1 g/kg (p.o.) Su et al. (2015)
Anticomplementary activity on complement-injured SH-SY5Y cells 1-O-methyl-2,3,4,6-tetra-O-
galloyl-β-d-glucopyanose
100, 200 mg/ml Zhao et al. (2011)
Improving capacities of stress resistance and delaying senescence for Caenorhabditis elegans FTSL 100 μg/ml Yang et al. (2010)

ACTSL, ethyl acetate extracts of T. sinensis leaf; APTT, activated partial thromboplastin time; AT-III, increasing the activity of antithrombin III; BUST, n-butanol extract of the seeds of T. sinensis; CLP, cecal ligation and puncture; COX-2, cyclooxygenase-2; DD, D-dimer; FETSL, anaerobic fermented leaves extract of T. sinensis; ETSL, ethanol extracts of T. sinensis leaf; FTSL, total flavonoids of T. sinensis leaf; IC50, half maximal inhibitory concentration; PLG, plasminogen; MODS, multiple organ dysfunction syndrome; ROS, reactive oxygen species; RT, cation time; STSL, water extracts of the seeds of T. sinensis; TSL, water extracts of T. sinensis leaf; t-PA, tissue plasminogen activator; TPST, total polyphenols from the seeds of T. sinensis; TT, thrombin time; PT, prothrombin time; XO, xanthine oxidase.