Tripterygium wilfordii polyglycosidium ameliorates pouchitis induced by dextran sulfate sodium in rats.

BACKGROUND: The aim of this study was to investigate the therapeutic effects of Tripterygium wilfordii polyglycosidium (TWP) to rats with dextran sulfate sodium (DSS)-induced pouchitis and its possible mechanism. METHODS: Sprague-Dawley rats underwent surgery of ileal pouch anal anastomosis (IPAA) and pouchitis was induced by DSS. Rats were randomly divided into no intervention (NI), normal saline (NS) and TWP groups. Rats were lavaged with normal saline (3ml/day in NS group) or TWP (12mg/kg/day in TWP group) for 7days. General conditions of animals and histopathological examinations were evaluated. Interleukin (IL)-1ß, IL-6, IL-10, and tumor necrosis factor (TNF)-α mRNA expression was measured. Levels of occludin and Zo-1 proteins were measured by immunohistochemistry. In addition, ALT and AST were assessed. RESULTS: TWP significantly attenuated the symptoms of pouchitis characterized by body weight loss, diarrhea, and bloody stool. Furthermore, TWP diminished histological damage compared with other groups. There was a significant reduction in levels of IL-1ß, IL-6, and TNF-α, as well as an increase in IL-10 in the TWP group. The expression of tight junction proteins occludin and Zo-1 were increased in the TWP group. There were no statistical differences in serum ALT and AST among the three groups. CONCLUSIONS: TWP significantly ameliorated pouchitis and inhibited the production of IL-1ß, IL-6, and TNF-α as well as increased the levels of IL-10, occludin, and Zo-1 protein in rats. These findings suggest TWP might be a potential therapeutic agent for patients with pouchitis.

Celastrol attenuates bone erosion in collagen-Induced arthritis mice and inhibits osteoclast differentiation and function in RANKL-induced RAW264.7.

Recently, the traditional Chinese medicine Tripterygium wilfordii Hook f (TwHF) of the Celastraceae family has attracted increasing attention for its potential therapeutic application in patients with rheumatoid arthritis (RA). It is well accepted that TwHF exerts the antirheumatic activity and mainly depends on its potent anti-inflammatory property. To further explore the therapeutic potential of the well-defined TwHF-derived single compound - celastrol in RA, we study the therapeutic efficacy of celastrol on bone erosion in collagen-induced arthritis (CIA) mice and delineate its effects on osteoclast differentiation and functions in RANKL-induced osteoclast precursors RAW264.7 cell line. In CIA mice, daily injection of celastrol (beginning on day 28 after arthritis induction) markedly suppressed arthritis, and reduced bone damage in the joints as demonstrated by histology and bone micro-computed tomography (CT). The effects were accompanied by reductions of osteoclast cells in joints, serum tartrate-resistant acid phosphatase (TRAP) 5b, and expression of osteoclastic genes (Trap, Ctsk, Ctr, Mmp-9) and transcriptional factors (c-Fos, c-Jun and NFATc1). When RAW264.7 cells were treated with RANKL, celastrol inhibited the formation of TRAP+ multinucleated cells and the bone-resorbing activity in dose-dependent manners. Furthermore, celastrol reduced the RANKL-induced expression of osteoclastic genes and transcriptional factors, as well as phosphorylation of NF-kB and mitogen-activated protein kinases (MAPK). These findings show that celastrol could directly inhibit osteoclast formation and function, suggesting a novel therapeutic strategy of celastrol for managing RA, especially in preventing bone destruction.

Contrasting dose-effects of multi-glycoside of Tripterygium wilfordii HOOK. f. on glomerular inflammation and hepatic damage in two types of anti-Thy1.1 glomerulonephritis.

Multi-glycoside, one of the extracted compounds from Tripterygium wilfordii HOOK. f. (GTW), has been shown to be clinically effective in suppressing glomerular inflammation in chronic kidney disease. However, its clinical application is often limited by its cytotoxic actions on the liver. This study was performed to contrast the dose-effects of GTW on glomerular inflammation and hepatic damage in two types of anti-Thy1.1 glomerulonephritis (GN). Rats with acute or chronic anti-Thy1.1 GN were either left untreated (the Vehicle group) or treated with a high or low dose of GTW and sacrificed on day 7 or day 45. GTW was administrated 3 days before or at the same time as the antibody injection and lasted until sacrifice. GTW at high dose ameliorated glomerular macrophage accumulation, mesangial proliferation, proteinuria, and interleukin-2 expression in the acute anti-Thy1.1 GN model, but caused structural and functional lesions in the liver. In contrast, GTW at low dose improved activated macrophage and T lymphocyte infiltration, mesangial injury, proteinuria, and interleukin-2 and interferon-γ expressions without hepatic toxicity in the chronic model of GN induced by anti-Thy1.1 antibody. In conclusion, GTW at low dose not only effectively inhibits glomerular inflammation but also avoids severe injuries to the liver.

Triptolide protects mice from ischemia/reperfusion injury by inhibition of IL-17 production.

Ischemia and reperfusion have been identified as a complex cascade of inflammatory mediators that are involved in the pathogenesis of hepatic injury. Triptolide (diterpenoid triepoxide), was extracted from a purified component of a traditional Chinese Medicine, Tripterygium wilfondii Hook F. Currently, triptolide has been shown to have anti-inflammatory, immunosuppressive, and antineoplastic activity. Accumulated data have shown that Th17 cells might contribute to the pathogenesis of liver diseases. Triptolide has been shown to reduce interleukin (IL)-17 expression in inflammatory bowel disease and arthritis. However, the role of triptolide in liver ischemia/reperfusion (I/R) and whether it can attenuate injury and the potential mechanism have not been investigated. Mice were treated with triptolide (0.1mg/kg) for 1 week or IL-17 antibody (50 µg/mouse) 2 days before ischemic insult. Partial warm ischemia was produced in the hepatic lobes of C57BL/6 mice for 90 min, followed by various periods of reperfusion. We demonstrated that IL-17 was involved in the inflammatory response to hepatic I/R injury, and that triptolide inhibited IL-17 generation and suppressed neutrophil migration after liver I/R injury through downregulation of signal transducer and activator of transcription 3 (STAT3) transcription. Also, triptolide pretreatment protected the liver from warm I/R injury, at least in part, mediated by the upregulation of Foxp3 expression. These results could pave the way for the use of triptolide as a novel agent to attenuate I/R injury.