Suppression of carrageenan-induced inflammation in vivo by an extract of the Chinese herbal remedy Tripterygium wilfordii Hook F

Tao, Xiaochun; Ma, Li; Mao, Yan‐Ping; Lipsky, Peter E.

doi:10.1007/s000110050437

Cited by 40 publications

(38 citation statements)

References 16 publications

(27 reference statements)

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“…A detailed analysis of the pharmacokinetics of triptolide that is currently in progress should provide necessary information to confirm this. The results of the in vitro experiments are consistent with the in vivo findings that treatment with the EA extract inhibited production of NO in models of nonimmune inflammation (8), and suggest that the EA extract may be a potential therapeutic inhibitor of NO synthesis in various pathologic conditions.…”

Section: Discussionsupporting

confidence: 83%

“…One possibility, therefore, to explain the therapeutic effect of the EA extract on RA could relate to its ability to inhibit NO production. Consistent with this possibility, treatment of rats with the EA extract at doses equivalent to one-fifth to one-eighth of its LD 50 was previously shown to suppress NO production by lining cells in the carrageenan-stimulated air pouch model of inflammation (8) and to inhibit the levels of urinary nitrite in rats with inflammatory arthritis (21). In these experiments, a decrease in NO generation was corre- Figure 6.…”

Section: Discussionsupporting

confidence: 58%

“…Total RNA was extracted from mitogen-stimulated cells, as previously described (7,8). Briefly, after the culture supernatants were removed, total RNA was extracted from the remaining cells with guanidinium thiocyanate-phenol-chloroform (Ultraspec; Biotecx, Houston, TX).…”

Section: Methodsmentioning

confidence: 99%

“…Previous studies showed that the antiinflammatory and immunosuppressive effects of the EA extract could be accounted for by the content of specific diterpenoids, including triptolide and tripdiolide (5,6). Recently, it has been reported that the EA extract of TWHF inhibited prostaglandin E 2 production by in vitro lipopolysaccharide (LPS)-stimulated human monocytes and synovial fibroblasts derived from RA patients and by carrageenan-induced air pouch lining cells in rats (7,8).…”

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confidence: 99%

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Triptolide, an active component of the Chinese herbal remedy Tripterygium wilfordii Hook F, inhibits production of nitric oxide by decreasing inducible nitric oxide synthase gene transcription

Wang¹,

Ma²,

Tao³

et al. 2004

Arthritis & Rheumatism

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Objective. The ethyl acetate (EA) extract of Tripterygium wilfordii Hook F (TWHF) and its major active component, triptolide, have been reported to be effective in the treatment of rheumatoid arthritis and other autoimmune inflammatory diseases. Nitric oxide (NO) has been recognized as an important mediator of inflammation. This study was therefore undertaken to examine the effects of the EA extract and triptolide on the production of NO and inducible NO synthase (iNOS) gene expression and transcription in vivo and in vitro.Methods. Peritoneal macrophages from C57BL/6J mice treated orally with the EA extract of TWHF were assayed for NO production and iNOS messenger RNA (mRNA) expression by reverse transcriptase-polymerase chain reaction. The murine fibroblast cell line NIH3T3 was also assessed for NO production and iNOS mRNA expression, as well as for iNOS promoter activation, Oct-1 nuclear binding capacity, and Oct-1 protein content by transient transfection, electrophoretic mobility shift assay, and immunoblotting, respectively.Results. NO production and iNOS mRNA expression by macrophages from C57BL/6J mice immunized with trinitrophenyl-bovine serum albumin in Freund's complete adjuvant were significantly inhibited by oral administration of the EA extract (52.3% and 59.8% of control, respectively, at one-eighth of the dose that is lethal for 50% of the animals [LD 50 ] and 21.0% and 38.1% of control, respectively, at one-fourth the LD 50 ). Moreover, the EA extract and triptolide significantly inhibited NO production in vitro in activated peritoneal macrophages, which reflected a decreased level of iNOS mRNA. Finally, triptolide inhibited promoter activity of the iNOS gene and induction of the activity of the regulator of iNOS transcription, Oct-1.Conclusion. The EA extract of TWHF and triptolide inhibit transcription of the iNOS gene. This may contribute to the antiinflammatory effects of this traditional herbal remedy.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionsupporting

confidence: 58%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Triptolide, an active component of the Chinese herbal remedy Tripterygium wilfordii Hook F, inhibits production of nitric oxide by decreasing inducible nitric oxide synthase gene transcription

Wang¹,

Ma²,

Tao³

et al. 2004

Arthritis & Rheumatism

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“…These extracts showed strong activity in several standard in vivo assays for antiinflammatory activity, including the adjuvant-induced and carrageenan-induced paw edema assays, the carrageenan-induced air pouch model, and the cotton-induced granuloma assay (Chou, 1997;Su et al, 1999;Tao et al, 1999;Zhang et al, 2000a). Inhibition of antibody production in rats and mice was also observed Hu et al, 2003).…”

Section: Antiinflammatory and Autoimmune Conditionsmentioning

confidence: 99%

Medicinal chemistry and pharmacology of genus Tripterygium (Celastraceae)

et al. 2007

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Plants in the genus Tripterygium, such as Tripterygium wilfordii Hook. f., have a long history of use in traditional Chinese medicine. In recent years there has been considerable interest in the use of Tripterygium extracts and of the main bioactive constituent, the diterpene triepoxide triptolide (1), to treat a variety of autoimmune and inflammation-related conditions. The main mode of action of the Tripterygium extracts and triptolide (1) is the inhibition of expression of proinflammatory genes such as those for interleukin-2 (IL-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2) and interferon-gamma (IFN-γ). The efficacy and safety of certain types of Tripterygium extracts were confirmed in human clinical trials in the US and abroad. Over 300 compounds have been identified in the genus Tripterygium, and many of these have been evaluated for biological activity. The overall activity of the extract is based on the interaction between its components. Therefore, the safety and efficacy of the extract cannot be fully mimicked by any individual constituent. This review discusses the biochemical composition and biological and pharmacological activities of Tripterygium extracts, and their main bioactive components.

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Triptolide, a novel diterpenoid triepoxide fromTripterygium wilfordii Hook. f., suppresses the production and gene expression of pro-matrix metalloproteinases 1 and 3 and augments those of tissue inhibitors of metalloproteinases 1 and 2 in human synovial fibroblasts

Lin¹,

Sato²,

Ito³

2001

Arthritis & Rheumatism

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Objective Various extracts of the Chinese herbal remedy Tripterygium wilfordii Hook. f. (TWHF) have been reported to be therapeutically efficacious in rheumatoid arthritis (RA) in China, but their mechanism of action remains unclear. We investigated the effect of triptolide, a diterpenoid triepoxide from TWHF, on the production of pro–matrix metalloproteinase 1 (proMMP‐1; or procollagenase 1 or pro–interstitial collagenase 1), proMMP‐3 (or prostromelysin 1), tissue inhibitors of metalloproteinases (TIMPs), and proinflammatory cytokines in human synovial fibroblasts and J774A.1 mouse macrophages. Methods Human synovial fibroblasts and mouse macrophages were cultured with interleukin‐1α (IL‐1α) or lipopolysaccharide (LPS) in the presence or absence of triptolide. The production of proMMPs 1 and 3, TIMPs 1 and 2, cyclooxygenase 1 (COX‐1) and COX‐2, prostaglandin E2 (PGE2), IL‐1β, and IL‐6 was assayed by Western blot analysis and enzyme‐linked immunosorbent assay. Gene expression of proMMPs 1 and 3, TIMPs 1 and 2, COX‐1 and COX‐2, IL‐1α, IL‐1β, tumor necrosis factor α (TNFα), and IL‐6 was also monitored by Northern blot analysis and reverse transcriptase–polymerase chain reaction. Results Triptolide suppressed the IL‐1α–induced production of proMMPs 1 and 3 and decreased their messenger RNA levels in human synovial fibroblasts. In contrast, the IL‐1α–induced gene expression and production of TIMPs 1 and 2 were further augmented by triptolide in the synovial cells. Triptolide also inhibited the IL‐1α–induced production of PGE2 by selectively suppressing the gene expression and production of COX‐2, but not those of COX‐1. In addition, triptolide suppressed the LPS‐induced production of PGE2 in mouse macrophages. Furthermore, the gene expression of IL‐1α, IL‐1β, TNFα, and IL‐6, as well as the production of IL‐1β and IL‐6, were inhibited by triptolide in the LPS‐treated mouse macrophages. Conclusion We have demonstrated for the first time that the therapeutic effects of TWHF in RA are due in part to the novel chondroprotective effect of triptolide via the direct suppression of the production of proMMPs 1 and 3 and the simultaneous up‐regulation of TIMPs in IL‐1–treated synovial fibroblasts. Triptolide's interference with gene expression of proinflammatory cytokines and its known inhibitory effects on PGE2 production are also probably very effective.

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Suppression of carrageenan-induced inflammation in vivo by an extract of the Chinese herbal remedy Tripterygium wilfordii Hook F

Abstract: These results indicate that TWHF exerts a significant anti-inflammatory activity in vivo.

Cited by 40 publications

References 16 publications

Triptolide, an active component of the Chinese herbal remedy Tripterygium wilfordii Hook F, inhibits production of nitric oxide by decreasing inducible nitric oxide synthase gene transcription

Triptolide, an active component of the Chinese herbal remedy Tripterygium wilfordii Hook F, inhibits production of nitric oxide by decreasing inducible nitric oxide synthase gene transcription

Medicinal chemistry and pharmacology of genus Tripterygium (Celastraceae)

Triptolide, a novel diterpenoid triepoxide fromTripterygium wilfordii Hook. f., suppresses the production and gene expression of pro-matrix metalloproteinases 1 and 3 and augments those of tissue inhibitors of metalloproteinases 1 and 2 in human synovial fibroblasts

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