Novel cytokine release inhibitors. Part III: Truncated analogs of tripterine

He, Wei; Huang, Fu‐Chih; Gavai, Ashvin; Chan, Wan; Amato, George; Yu, Kin‐Tak; Zilberstein, Asher

doi:10.1016/s0960-894x(98)00671-4

Cited by 26 publications

(22 citation statements)

References 8 publications

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“…Furthermore, celastrol has been shown to inhibit lipid peroxidation induced by ADP and Fe 2+ in rat liver mitochondria with an IC50 of 7 mM. 5,13,[15][16][17] Yang et al 6 have demonstrated that celastrol inhibits the chymotrypsin-like activity of a purified 20S proteasome and human prostate cancer cellular 26S proteasome in a concentration range of 1-5 mM. Our experiments indicate that celastrol suppresses ADP-induced platelet activation in vitro in similar concentrations.…”

Section: Discussionsupporting

confidence: 66%

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

Hu¹,

Straub²,

Tian³

et al. 2009

Journal of Cardiovascular Pharmacology

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Celastrol is an active ingredient of the traditional Chinese medicinal plant, Tripterygium wilfordii Hook F, which is known especially for its anti-inflammatory effects. However, on the cellular and molecular levels, celastrol's mechanism of action is only poorly understood. Because platelets contribute to inflammatory events, this study investigates the effects of celastrol on platelet function using flow cytometry, aggregometry, and adhesion assays. In in vitro experiments with human platelets, celastrol inhibits adenosine-5-diphosphate (ADP)-induced expression of the platelet activation marker P-selectin and glycoprotein IIb/IIIa activation with 50% inhibition values of 1.62 and 1.86 microM, respectively. Celastrol also inhibits thrombin-stimulated and phorbol 12-myristate 13-acetate-stimulated P-selectin expression on platelets. Furthermore, ADP-stimulated platelet adhesion on fibrinogen is partially prevented by 5 microM celastrol. In platelet aggregometry, celastrol (0.05-0.5 mM) inhibits ADP-induced aggregation of platelet-rich plasma. Moreover, 12 male C57BL/6J mice were randomly grouped to receive intraperitoneal treatment with either celastrol (2 mg x kg x day) or vehicle. After 4 weeks of the respective treatment, celastrol inhibited 2 and 20 microM ADP-stimulated platelet fibrinogen binding by 34.5% (P < 0.01) and 28.9% (P < 0.05), respectively, compared with controls. In conclusion, these results indicate that celastrol exerts inhibitory effects on platelets. This new finding contributes to the understanding of antithrombotic and also anti-inflammatory effects of celastrol.

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Section: Discussionsupporting

confidence: 66%

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

Hu¹,

Straub²,

Tian³

et al. 2009

Journal of Cardiovascular Pharmacology

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“…It is a potent inhibitor of lipid peroxidation. It inhibits TNF-␣ and interleukin-1 ␤ (IL-1 ␤ ) production by human monocytes, and it suppresses NO production by macrophages and endothelial cells, as well as microglial activation in vitro [20][21][22][23] . Both microglial activation and TNF-␣ and IL-1 ␤ production have been implicated in the pathogenesis of ALS in transgenic mice expressing mutations in human Cu/Zn superoxide dismutase (SOD1).…”

Section: Discussionmentioning

confidence: 99%

Celastrol Blocks Neuronal Cell Death and Extends Life in Transgenic Mouse Model of Amyotrophic Lateral Sclerosis

et al. 2005

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There is substantial evidence that both inflammation and oxidative damage contribute to the pathogenesis of motor neuron degeneration in the G93A SOD1 transgenic mouse model of amyotrophic lateral sclerosis (ALS). Celastrol is a natural product from Southern China, which exerts potent anti-inflammatory and antioxidative effects. It also acts potently to increase expression of heat shock proteins including HSP70. We administered it in the diet to G93A SOD1 mice starting at 30 days of age. Celastrol treatment significantly improved weight loss, motor performance and delayed the onset of ALS. Survival of celastrol-treated G93A mice increased by 9.4% and 13% for 2 mg/kg/day and 8 mg/kg/day doses, respectively. Cell counts of lumbar spinal cord neurons confirmed a protective effect, i.e. 30% increase in neuronal number in the lumbar spinal cords of celastrol-treated animals. Celastrol treatment reduced TNF-α, iNOS, CD40, and GFAP immunoreactivity in the lumbar spinal cord sections of celastrol-treated G93A mice compared to untreated G93A mice. TNF-α immunoreactivity co-localized with SMI-32 (neuronal marker) and GFAP (astrocyte marker). HSP70 immunoreactivity was increased in lumbar spinal cord neurons of celastrol-treated G93A mice. Celastrol has been widely used in treating inflammatory diseases in man, and is well tolerated; therefore, it may be a promising therapeutic candidate for the treatment of human ALS.

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“…interleukin-1 production from murine peritoneal macrophages and human monocyte, concanavalin A-activated interleukin-2 production from murine splenocytes, and prostaglandin E 2 released from synovial cells (Xu et al, 1991;Huang et al, 1998). Tripterine has shown interesting disease-modifying activity in the streptococcus cell wall induced model of arthritis, collagen induced arthritis in rats and systemic lupus erythematosus-like syndrome in mice (Li et al, 1997(Li et al, , 2005He et al, 1998). Tripterine was reported to inhibit NF-B activation, nitric oxide production, interleukin-6, interleukin-8, and prostaglandin E2 formation and lipid peroxidation (Jin et al, 2002;Pinna et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Therapeutic effect of tripterine on adjuvant arthritis in rats

Zhang

Tan

et al. 2008

Journal of Ethnopharmacology

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a b s t r a c tAims of the study: Tripterygium wilfordii Hoog f., a perennial vine, is used in traditional Chinese medicine for treatment of rheumatoid arthritis. This study was to determine whether tripterine, isolated from Tripterygium wilfordii Hoog f., had therapeutic effects on adjuvant arthritis. Materials and methods: Adjuvant arthritis (AA) was induced in rats on day 0. Tripterine 5, 10 and 20 mg kg −1 day −1 , or prednisone 10 mg kg −1 day −1 was given to rats intragastrically from day 19 to day 24. Results: Tripterine significantly inhibited paw swelling and bone destruction in AA rats. Serum level of IgG anti-Mycobacterium tuberculosis antibodies and delayed-type hypersensitivity (DTH) induced by Mycobacterium tuberculosis were also decreased by tripterine. The effects of tripterine were associated with decreased interleukin-1␤ (IL-1␤) mRNA expression in ankle joint synovial membrane and tumor necrosis factor-␣ (TNF-␣) mRNA expression in homogenized paws from adjuvant-induced arthritic rats. Conclusions: These findings suggested that tripterine had a therapeutic effect on adjuvant arthritis.

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Novel cytokine release inhibitors. Part III: Truncated analogs of tripterine

Cited by 26 publications

References 8 publications

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

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

Celastrol Blocks Neuronal Cell Death and Extends Life in Transgenic Mouse Model of Amyotrophic Lateral Sclerosis

Therapeutic effect of tripterine on adjuvant arthritis in rats

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