Celastrol, a Triterpene Extracted From Tripterygium wilfordii Hook F, Inhibits Platelet Activation

Hu, Houyuan; Straub, Andreas; Tian, Zhuo; Bassler, Nicole; Cheng, Jun; Peter, Karlheinz

doi:10.1097/fjc.0b013e3181b21472

Cited by 22 publications

(16 citation statements)

References 20 publications

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“…Celastrol-A stock solution of celastrol (20 mg in 0.6 ml of dimethyl sulfoxide (DMSO; Sigma) was prepared and frozen at Ϫ20°C in small aliquots until needed, following the method described previously (31,32). The dose of celastrol (1 mg/kg) used in vivo in our study matched that used previously in different (non-arthritic) model systems (31,32).…”

Section: Treatment Of Arthritic Lewis Rats With Celastrus Extract/celmentioning

confidence: 81%

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Celastrus-derived Celastrol Suppresses Autoimmune Arthritis by Modulating Antigen-induced Cellular and Humoral Effector Responses

Venkatesha¹,

Yu²,

Rajesh³

et al. 2011

Journal of Biological Chemistry

140

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Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial inflammation and articular damage. Proinflammatory cytokines, antibodies, and matrix-degrading enzymes orchestrate the pathogenic events in autoimmune arthritis. Accordingly, these mediators of inflammation are the targets of several anti-arthritic drugs. However, the prolonged use of such drugs is associated with severe adverse reactions. This limitation has necessitated the search for less toxic natural plant products that possess anti-arthritic activity. Furthermore, it is imperative that the mechanism of action of such products be explored before they can be recommended for further preclinical testing. Using the rat adjuvant-induced arthritis model of human RA, we demonstrate that celastrol derived from Celastrus has potent anti-arthritic activity. This suppression of arthritis is mediated via modulation of the key proinflammatory cytokines (IL-17, IL-6, and IFN-␥) in response to the diseaserelated antigens, of the IL-6/IL-17-related transcription factor STAT3, of antibodies directed against cyclic citrullinated peptides and Bhsp65, and of the activity of matrix metalloproteinase-9 and phospho-ERK. Most of the clinical and mechanistic attributes of celastrol are similar to those of Celastrus extract. Several studies have addressed the antitumor activity of celastrol. Our study highlights the anti-arthritic activity of Celastrusderived celastrol and the underlying mechanisms. These results provide a strong rationale for further testing and validation of the use of celastrol and the natural plant extract from Celastrus as an adjunct (with conventional drugs) or alternative modality for the treatment of RA. Rheumatoid arthritis (RA)2 is a chronic debilitating autoimmune disease affecting millions of people all over the world (1-3). Both cell-mediated and humoral immune reactions participate in the pathogenesis of RA (1, 4). Several proinflammatory cytokines secreted by immune cells, including TNF-␣, IL-1␤, IL-15, IL-18, and IFN-␥, have been shown to play a role in the initiation and progression of RA (4, 5). Over the past decade, a new subset of T helper cells producing IL-17 (Th17) has become the focus of RA pathogenesis (6, 7). Induction of a Th17 response involves IL-6 and TGF-␤, as well as the transcription factors STAT3 and retinoid related orphan receptor-␥t (ROR-␥t) (8, 9). In regard to the humoral response, serum levels of anti-cyclic citrullinated protein/peptide (aCCP) antibodies correlate well with the disease severity in RA patients and serve as the specific autoantibody marker for the diagnosis of RA (10, 11). In view of the above, modulation of the proinflammatory cytokines and aCCP antibody levels is a desired goal for the management of RA.A variety of drugs are available for the treatment of RA. These include corticosteroids, nonsteroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs, and biologics (1, 12). However, besides their high cost, the use of these drugs is associated with severe adverse reacti...

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Section: Treatment Of Arthritic Lewis Rats With Celastrus Extract/celmentioning

confidence: 81%

“…The dose of celastrol (1 mg/kg) used in vivo in our study matched that used previously in different (non-arthritic) model systems (31,32). The stock solution of celastrol was diluted in PBS (6-l stock in 500 l of PBS/rat) and injected intraperitoneally.…”

Section: Treatment Of Arthritic Lewis Rats With Celastrus Extract/celmentioning

confidence: 99%

Celastrus-derived Celastrol Suppresses Autoimmune Arthritis by Modulating Antigen-induced Cellular and Humoral Effector Responses

Venkatesha¹,

Yu²,

Rajesh³

et al. 2011

Journal of Biological Chemistry

140

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“…Meanwhile, many studies have been dedicated to elucidating the potential molecular mechanisms underlying the anti-inflammatory and immunosuppressive effects of TEs [18], including the inhibition of platelet activation [20], the induction of nitric oxide [21], and prostaglandin E 2 [22] production. Based on studies both in vitro and in vivo , it is easy to speculate that TEs are likely to be types of herbal DMARDs, which differ from synthetic DMARDs.…”

Section: Introductionmentioning

confidence: 99%

Extracts ofTripterygium wilfordiiHook F in the Treatment of Rheumatoid Arthritis: A Systemic Review and Meta-Analysis of Randomised Controlled Trials

Liu

Gao

et al. 2013

Evidence-Based Complementary and Alternative Medicine

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Clinical trials have reported the effects of Tripterygium wilfordii Hook F (TwHF) extracts (TEs) in the treatment of rheumatoid arthritis (RA); however, the results have been inconsistent. This meta-analysis is aimed to assess the safety of TEs and their effects on the treatment of RA. Randomised controlled trials (RCTs) comparing the effects of TEs and placebo (PBO) or disease-modifying antirheumatic drugs (DMARDs) in patients with RA were included. Weighted mean differences (MDs) were calculated for net changes by employing fixed-effect or random-effects models. After filtering, ten RCTs (involving 733 participants) were included in this study. The methodological quality of these studies was generally low. Compared with DMARDs, TEs alone produced a mild increase in grip strength (GS) (P = 0.02; standard mean difference (SMD) = 0.81; 95% confidence interval (CI): 0.14 to 1.48). The most common adverse effects (AEs) of TEs were gastrointestinal discomfort, menstruation disorders, and amenorrhea. In conclusion, TEs, as a sort of “herbal DMARD,” could be as effective as synthetic DMARDs in the treatment of RA. However, the efficacy of TEs in treating RA should be further estimated with better designed, fully powered, confirmatory RCTs that apply the American College of Rheumatology (ACR) improvement criteria to evaluate their outcomes.

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“…Intraperitoneal injection of celastrol (1 to 3 mg/kg/day for 31 days), has anti-proliferative effects against prostate cancer in nude mice (Yang et al, 2006). Our recent study has demonstrated that celastrol inhibits platelet activation, adhesion to fibrinogen and aggregation in vitro, as well as fibrinogen binding of platelets in celastrol-treated mice, which may contribute to explain celastrol's anti-inflammatory and immunosuppressive effects (Hu et al, 2009). Furthermore, our previous data indicate that celastrol may also have anti-thrombotic properties.…”

Section: Introductionmentioning

confidence: 99%

Celastrol attenuates atherosclerosis in Apolipoprotein E (apoE) knockout mice fed an atherogenic diet

Cheng¹

2011

Afr. J. Pharm. Pharmacol.

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The study is aimed to investigate the effects of celastrol on the atherogenesis in apolipoprotein E knockout (apoE -/-) mice fed an atherogenic diet. All mice were fed a high-fat and high-cholesterol diet for 8 weeks. In the last 4 weeks, apoE -/-mice were randomly grouped to receive treatment with either celastrol (2 mg/kg/day in DMSO, i.p.) or vehicle DMSO (n=6 per group). Plasma lipids were determined enzymatically. The area of atherosclerotic lesions was measured by hematoxylin and eosin staining. The expression of macrophage migration inhibitory factor (MIF), matrix metalloproteinase-9 (MMP-9), CD40 ligand (CD40L) and C-reactive protein (CRP) were assayed by immunohistochemistry. Celastrol inhibited the development of atherosclerotic lesions in apoE -/-mice. The expressions of MIF, MMP-9, CD40L and CRP in the artery wall were significantly reduced by celastrol. Meanwhile, the lipid profile in the mice was not improved. In conclusion, our study demonstrates that celastrol inhibits atherogenesis in celastrol-treated apoE -/-mice fed an atherogenic diet by inhibiting inflammation in the arterial wall without improving the lipid profile.

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Celastrol, a Triterpene Extracted From Tripterygium wilfordii Hook F, Inhibits Platelet Activation

Cited by 22 publications

References 20 publications

Celastrus-derived Celastrol Suppresses Autoimmune Arthritis by Modulating Antigen-induced Cellular and Humoral Effector Responses

Celastrus-derived Celastrol Suppresses Autoimmune Arthritis by Modulating Antigen-induced Cellular and Humoral Effector Responses

Extracts ofTripterygium wilfordiiHook F in the Treatment of Rheumatoid Arthritis: A Systemic Review and Meta-Analysis of Randomised Controlled Trials

Celastrol attenuates atherosclerosis in Apolipoprotein E (apoE) knockout mice fed an atherogenic diet

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