TABLE 5.

Pharmacological effects of different compounds isolated from Tripterygium hypoglaucum in vivo studies.

Pharmacological activity	Compound	Experimental design	Molecular targets/mode of action	Duration of treatment	Route of administration	References
Anti-inflammation	Triptolide	Triptolide (8, 16 and 32 mg/(kg day); n = 16, respectively), dexamethasone (1 mg/(kg every 2 days); n = 16) or vehicle (n = 20)	↓metalloproteinases-13 and -3,↓COX-2 and PGE(2),↓IL-1β, TNF-α and IL-6,↑metalloproteinases-1 and -2	Daily for a period of 21 days	Oral administration	Lin et al. (2007)
—	Triptolide	Triptolide (0.1 mg/kg/d) dissolved in 5% dimethyl sulfoxide was intraperitoneally injected into the SCI rats	↑miR-96, ↓Iba-1 and IKKβ/NF-κB-related proteins, ↓IL-1β and TNF-α	Continued for successive 10 days	Intraperitoneal injection	Huang et al. (2019)
—	Tripterine	tripterine (5, 10 and 20 mg kg−1 day−1), or prednisone (10 mg kg−1 day−1); 0.5% CMC solution as vehicle-treated group	↓ IgG and delayed-type hypersensitivity (DTH), ↓IL-1β and TNF-α	5 days	Intragastrical administration	Li et al. (2008)
—	Celastrol	1 μg/g Celastrol or 2 μg/g digoxin were administrated at adjuvant-induced arthritis (AIA) rats	↓IL-1β and TNF	After 4 days (early treatment group) and after 11 days (late treatment group) of disease induction	Intraperitoneal injection	Cascão et al. (2012)
—	Celastrol	Saline (20 μL) containing 4 μg of sPLA2IIA with celastrol (1, 10, 30 μM and 100 µM)/vehicle was injected into the intra-plantar surface of the right hind footpad of mice	↓sPLA2IIA, 5-LOX and COX-2 enzymes	After 45 min, mice were anaesthetized with pentobarbitone (30 mg/kg, i.p.) and euthanized	Injected into the intra-plantar surface of the right hind footpad of mice	Joshi et al. (2016)
—	Celastrol	Hepa1-6 single-cell suspension cells (2 × 107/ml) were injected subcutaneously at a volume of 0.1 ml in the right flank of each mouse	↓AKT pathway and VEGF autocrine system	21 days of administration	Intraperitoneal injection	Zhang et al. (2019a)
Immuno-suppression	THH	C57BL/6 mice were used to model CIA mice received THH 420 mg/kg/day or the same amount of normal saline (NS)	↓TNF-α, IFN-γ, and IL-17A mRNA and protein levels; ↓NF-κB-STAT3-IL-17 pathway	20 days	Intragastrical administration	Zhou et al. (2020)
—	Celastrol	CIA mice were treated intraperitoneally (IP) with celastrol in phosphate buffered saline (PBS; 3 mg/kg) or PBS alone	↓osteoclastic genes (Trap, Ctsk, Ctr, Mmp-9) and transcription factors (c-Fos, c-Jun and NFATc1), ↓NF-κB and MAPK phosphorylation	15 days	Intraperitoneal injection	Gan et al. (2015)
—	Triptolide	CIA rats were treated with triptolide (11–45 µg/kg/day) starting on the day 1 after first immunization	↓Matrigel-induced cell adhesion of HFLS-RA and HUVEC, ↓TNF-α, IL-17, VEGF, VEGFR, Ang-1, Ang-2 and Tie2, ↓IL1-β-induced ERK phosphorylation and p38 and JNK protein levels	Daily for a period of 28 days from day 1 to day 28 of first immunization	Oral administration intragastrically using syringe feeding	Kong et al. (2013)
—	Celastrol	Female Sprague Dawley rats were treated by celastrol (1 mg/kg/day, i.p.)	↑IL-10, ↓TNF-α, ↓immunohistochemical expression of TLR2 and CD3+ T-lymphocytic count	32 days	Intraperitoneal injection	Abdin and Hasby, (2014)
Antitumour effect	Celastrol	C57BL/6N mice were treated with 1 mg/kg of celastrol, 3 mg/kg of celastrol, or a vehicle control. Celastrol was dissolved in vehicle (10% DMSO, 70% Cremophor/ethanol (3:1), and 20% PBS)	↑ROS-mediated caspase-dependent apoptosis; ↓PI3K/AKT/mTOR signalling	20 days	Oral gavage every 2 days	Lee et al. (2012)
Anti-obesity and insulin resistance	Celastrol	C57BL/6 mice were allowed to recover for 2 weeks postsurgery before receiving intraperitoneal vehicle or celastrol (100 μg/kg) at 6 pm each day	↓TC, TG, LDL-c and Apo B in plasma,↓NADPH oxidase activity	10 consecutive days	Intraperitoneal injection	Kyriakou et al. (2018)
—	Celastrol	Sprague–Dawley rats were treated with celastrol (1.0 ml/100 g) or simvastatin (1.0 ml/100 g)	↑protein phosphorylation of insulin signalling cascades with amplified expression of AMPK protein, ↓attenuated NF-κB and PKC θ activation	6 weeks	Intragastrical administration	Wang et al. (2014)
Antiviral effect	Triptolide	Male BALB/C mice were intravenously (i.v.) treated with a single dose of TP (1.2 mg/kg)	↓TNF-α, IL-1β, IL-6 malondialdehyde (MDA) and antioxidative superoxide dismutase (SOD), ↑glutathione (GSH) and glutathione peroxidase (GPx)	24 h	Intravenous injection	Zhou et al. (2014)
Other effects	Celastrol	Celastrol (0.5 and 1.0 mg/kg, i.v.) was administered to anaesthetized rats 2 h before and 30 min after LPS challenge (10 mg/kg, i.v.)	↑Nrf2 activation, ↓Nox2/AT1 receptor expression, ↑phosphorylation of ERK1/2	8 h	Intravenous injection	Wang et al. (2015)