TABLE 4.
Pharmacological effects of different compounds isolated from Tripterygium hypoglaucum in vitro studies.
| Pharmacological activity | Compound | Experimental design | Molecular targets/mode of action | References |
|---|---|---|---|---|
| Anti-inflammatory | THH alkaloids | 10 µg of total RNA isolated from THH-treated (40 µg/ml, 8 h) and untreated HL-60 cells | ↑genes related to the NF-κB signalling pathway and cell apoptosis (such as NFKBIB, PRG1 and B2M),↓c-myc binding protein and apoptosis-related cysteine proteases caspase-3 and caspase-8 | Zhuang et al. (2004) |
| — | Triptolide | Corneal fibroblasts absence or presence of IL-1 (10 ng/ml), with or without triptolide (30 nM) or dexamethasone (100 nM) | ↓IL-1, IL-8 and MCP-1 | Lu et al. (2005) |
| — | Triptolide | Raw 264.7 cells stimulated with LPS (50 ng/ml) in the presence or absence of triptolide (30 µM) for 24 h | ↓DNA binding activity of NF-κB, ↓NO production, ↓phosphorylation of c-Jun NH(2)-terminal kinase (JNK) | Kim et al. (2004) |
| — | Triptolide | Microglia were pre-treated with PBS, triptolide (10, 30, or 50 µM), with or without Bay11-7,082 for 30 min before LPS treatment (10 ng/ml, 24 h) | ↓p38-NF-kappaB-COX-2-PGE(2) and JNK-PGE(2) | Gong et al. (2008) |
| — | Triptolide | TP-mmc (15 μM) with or without TP (1.2, 12, 15, 30 µM) was added to RAW 264.7 cells (middle panel: bar, 50 μM) for 2 h | ↓TAK1-TAB1 complex kinase activity | Lu et al. (2014) |
| — | Celastrol | fibroblast-like synoviocytes (FLSs) were treated with celastrol (0.05, 0.1, 0.2, 0.4 and 0.8 mM) for 24 h | ↓MMP-9 promoter activity, ↓TLR4/MyD88/NF-κB pathway, ↓ FLS migration and invasion | Li et al. (2013a) |
| — | Celastrol | HaCaT cells were incubated with celastrol (0, 0.1, 0.5, 1 µg/ml) for 1h, and stimulated with IFN-c (100 U/ml) for 4 h (for RNA) or 12 h (for protein) | ↓IFN-γ-induced ICAM-1 mRNA and protein expression | Seo et al. (2010) |
| — | Celastrol | HaCaT cells were pretreated with DPI (10 μM), NAC (20 mM) or EUK 134 (50 μM) for 1 h, and then incubated with celastrol (1 μg/ml) for 6 h (for RNA) or 12 h (for protein) | ↑ROS-ERK/p38-Nrf2-ARE, ↑HO-1 | Seo et al. (2011) |
| — | Celastrol | RAW264.7 cells were treated with 0–1 μM of celastrol for 24 h | ↓ nitric oxide synthase and cyclooxygenase-2, ↓ MPO activity, ↓IL-6 and TNF-α | Kim et al. (2009) |
| — | Celastrol | BV-2 cells were pre-treated with various concentrations of celastrol (1, 10 and 100 nM) for 30 min prior to stimulation with LPS (10 ng/ml) for 6 h (for TNF-α) and 24 h (for IL-1β) | ↓expression of mRNAs of iNOS and cytokines; ↓NO, IL-1β and TNF-α; ↓ERK1/2 phosphorylation and NF-κB activation | Jung et al. (2007) |
| — | Celastrol | Jurkat T cells were preincubated for 30 min with celastrol (0, 0.3, 1 µg/ml) and followed by the stimulation with of TNF-a (20 ng/ml) or PMA (50 ng/ml) for 90 min | ↓IKK activity and IKKβ activity, ↓Bfl-1/A1 expression | Lee et al. (2006) |
| — | Celastrol | Neutrophils were pre-incubated with different doses of celastrol (0.5–20 μM) or vehicle only at RT for 45 min | ↓neutrophil oxidative burst and NET formation, ↓SYK-MEK-ERK-NF-κB signalling cascade | Yu et al. (2015) |
| Immuno-suppression | Triptolide | Monocytes were cultured for 5 days in the presence of various concentrations (1–20 ng/ml) of triptolide and Dex (10−8–10–6 M) | ↓CD1a, CD40, CD80, CD86 and HLA-DR expression; ↑CD14 expression | Zhu et al. (2005) |
| — | Triptolide | LPS (100 ng/ml)-stimulated U937 cells were treated with or without triptolide (12.5 nM) | ↓TREM-1 and DNAX-associated protein (DAP)12, ↓activation of JAK2 and STAT3, ↓TNF-α, IL-1β and IL-6 | Fan et al. (2016) |
| — | Celastrol | Bone marrow-derived macrophages were pre-treated with celastrol (0.1, 0.5 and 1 μM) for 1 h and treated with Alexa Fluor 594 conjugated with LPS (1.5 μg/sample) for 30 min | ↓TNF-α, IL-6, IL-12, and IL-1β, ↓LPS binding to the TLR4/MD2 complex | Lee et al. (2015) |
| — | Celastrol | Purified CD4+CD25− T cells were treated in the presence or absence (control) of Celastrol (200 nM) | ↓mTOR, HIF-1α, c-Myc and Akt expression in Th17 cells, ↑FAO of lipids by upregulating CPT1A and AMPKα expression in iTreg cells | Zhang et al. (2018) |
| — | Triptolide | Confluent synovial cells were treated with recombinant human interleukin-1α (IL-1α; 1 ng/ml), dexamethasone (Dex), and/or triptolide (2.8–140 nM) at the indicated concentrations | ↓IL-1α-induced production of proMMP- 1 and -3, ↑IL-1alpha-induced gene expression and production of TIMP-1 and -2 | Lin et al. (2001) |
| — | Triptolide | Human monocytes were cultured for 7 days with G4 medium in the presence of TPT (D2-7, 0.5–10 nM) or medium alone | ↓production of IL-12 p70 | Chen et al. (2005) |
| — | Triptolide | C57BL/6 mouse bone marrow cells were cultured with mGM-CSF and mIL-4, and triptolide (0, 1, 5, 10, 20, 50, and 100 ng/ml) added on day 3 of culture (Trip-DC) | ↑activation of p38, ↓activation of caspase 3 | Liu et al. (2004) |
| Triptolide | THP-1 cells were differentiated into macrophage-like cells upon exposure to Me2SO, and then cultured with IFN-gamma (500 kU/L) and lipopolysaccharide (LPS) (1 mg/L) with or without triptolide (2.5–0.625 µg/L) | ↓CD80 and CD86 expression on IFN-gamma- (500 kU/L) and LPS- (1 mg/L) activated THP-1 cells, ↓IL-12p40 and IL-12p70 | Liu et al. (2008) | |
| Antitumour effect | Total alkaloids | JB6 Cl41 cells were suspended containing 10% FBS, 10 μM TPA with or without THHta (1.25–10 μg/ml) | ↑activation of caspase-3 and PARP, ↓Bcl-2, Bcl-xL and XIAP | Jiang et al. (2014) |
| — | Triptonide | treatment of the pancreatic cancer cell lines Patu8988 and Panc1 with triptonide at the doses of 0–20 nM | ↓VE-cadherin and CXCL2 genes | Han et al. (2018) |
| — | Triptolide | PC-3 and DU145 cells were incubated with triptolide (0, 25, 50 nM) for 24 h | ↓RNA polymerase activity, ↓CDC25A, and MYC and Src oncogenes | Yuan et al. (2020) |
| — | Triptolide | Malignant (BxPc-3, MIA-PaCa2 and AsPC-1) and nonmalignant (pancreatic ductal cells and MSC) cells grown under normoxia or hypoxia in the presence or absence of triptolide (20 nM) | ↓epithelial-mesenchymal transition (EMT) and CSC features | Liu et al. (2014a) |
| — | Triptolide | Urothelial cancer cells were treated with CDDP at the concentration corresponding to IC25 (30 mM) with or without 1 h pretreatment of 30 nM triptolide for 12 h | ↓CDDP-induced p53 transcriptional activity | Matsui et al. (2008) |
| — | Triptolide | The JNK1 knockdown cells were treated with triptolide (14–56 nM) for 15 h | ↓phosphatidylinositol 3-kinase (PI3K) activity, ↑c-Jun NH(2)-terminal kinase 1 (JNK1) | Miyata et al. (2005) |
| — | Celastrol | SO-Rb 50 cells were treated with celastrol nanoparticles (0–54.4 µg/ml) and the same dosage of PEG-b-PCL micelles without celastrol for 48 h | ↓elevated levels of ALT, AST, ALP and AFP; ↓anti-apoptotic Bcl-2 and Bcl-xl; induced the expression of pro-apoptotic Bax, cytochrome C, PARP and caspases | Li et al. (2012b) |
| — | Celastrol | A549 cells were treated with celastrol (0–8 µM) at the indicated concentration for 24, 48, and 72 h | ↑expression of pro-apoptotic Bax, ↓anti-apoptotic Bcl-2 and Akt phosphorylation | Mou et al. (2011) |
| — | Celastrol | H1650 cells were collected for apoptosis analysis at 24 h after the treatment of celastrol (0.5, 1, 2, 4 μM) | ↓EGFR and AKT | Fan et al. (2014) |
| — | Celastrol | H1299 cells were treated with or without 4 μM celastrol in the absence or presence of 50 μM Z-VAD for 24 h | ↑cleavage of PARP, caspase 9 and caspase 3 | Chen et al. (2011) |
| — | Celastrol | Human myeloma cell line U266 cells were treated with celastrol (0.25 and 0.5 µM) for the indicated times (0–48 h) | ↑caspase-3 and NF-κB pathways | Tozawa et al. (2011) |
| Anti-obesity and insulin resistance | Celastrol | Fully differentiated 3T3-L1 adipocytes were incubated with different doses of oligomycin (5, 10, 20 and 30 µg/ml) and celastrol (5, 10, 20 and 30 μM) in DMSO for 48 h | ↓oxidative DNA damage, protein carbonylation and lipid peroxidation | Bakar et al. (2014) |
| — | Celastrol | C3A human hepatocytes were exposed to various concentration (10–50 nM) of celastrol in the serum-free media for 48 h | ↓PA-induced GLUT4 and IRS1 | Abu Bakar et al. (2017) |
| — | Celastrol | Myoblasts were treated with different concentrations (10, 20, 30, 40, 50 and 60 nM) of celastrol were prepared and mixed with 0.1% (v/v) DMSO. The vehicle consisted of an equal amount of DMSO was used as a control | ↑NF-κB p65, c-Jun NH(2)-terminal kinase (JNK) signalling pathways,↑IL-8, IL-6, TNF-α and CRP | Abu Bakar and Tan (2017) |
| Antiviral effect | Triptolide | HONE1/Akata, HK1/Akata, C666–1, and CNE1 cells were placed in 35 mm culture dishes (500 cells/dish) and cultured in standard medium with DMSO control (0.01%) or triptolide (1, 2, or 5 nM) for 2 weeks | ↓ratio of Bax/Bcl-2, ↑activated caspase-3 and Nrf2 | Zhou et al. (2018) |
| — | Triptolide | Human umbilical vascular endothelial cells (HUVEC) were trested with or without brusatol (40 nmol/L)/celastrol (50 nmol/L)/AngII(400 nmol/L) for 24 h | ↑caspase-9-dependent apoptosis | Li et al. (2017a) |
| — | Celastrol | The transfected ava5 cells were treated with celastrol (0, 0.2,0.3,0.4,0.5 μM) for 3 days | ↓iNOS, TNF-α, and NF-κB phospho-p65 expression, ↑nuclear levels of Nrf2 and HSF-1 | Tseng et al. (2017) |
| Other effects | Triptolide | The model microglial group was treated with Aβ1–40 (20 μg/ml). The low-dose triptolide microglial group was treated with Aβ1–40 (20 μg/ml) and triptolide (5 μg/ml). The high-dose triptolide microglial group was treated with Aβ1–40 (20 μg/ml) and triptolide (25 μg/ml) | ↑IL-10, ↓IL-4 | Nie et al. (2012) |
| — | Triptolide | RASF, HM, HFF, or U937 cells were incubated overnight with or without LPS (2 μg/ml) in the presence or absence of the indicated concentrations of T2 (1,2,4 μg/ml), triptolide (1,2,4 ng/ml), DEX (0.1,1,10 μM), or Indo (0.01,0.1 μg/ml) | ↓protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) | Tao et al. (1998) |