Effects of tripterygium wilfordii Hook F extracts on induction of cyclooxygenase 2 activity and prostaglandin E2 production

Tao, Xiaochun; Schulze‐Koops, Hendrik; Ma, Li; Cai, Jian; Mao, Yan‐Ping; Lipsky, Peter E.

doi:10.1002/1529-0131(199801)41:1<130::aid-art16>3.3.co;2-w

Cited by 9 publications

(14 citation statements)

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“…Our results clearly demonstrate that T2 suppresses the clonogenic response of primary human HPCs at concentrations ranging from 5 to 500 ng/ml. These levels of T2 have been demonstrated previously to result in immunomodulation of both T and B lymphocytes and are likely to be achieved in patients treated with T2 (Tao et al, 1991(Tao et al, , 1996(Tao et al, , 1998. Dose-dependent suppression of CFU was observed in cells stimulated with GM-CSF, IL-3, SCF, and EPO.…”

Section: Pyatt Et Almentioning

confidence: 54%

“…Suppression occurred in the presence of hematopoietic growth factors (GM-CSF, IL-3, SCF, and EPO) and was observed in myeloid, erythroid, and mixed-lineage colonies with equal potency. The concentration of T2 resulting in complete abrogation of CFU response (500 ng/ml) is approximately one-half (or lower) of that previously demonstrated to be effective in suppressing lymphocyte functions in vitro (Tao et al, 1996(Tao et al, , 1998. Remarkably, concentrations of T2 that completely suppressed CFU activity did not result in an observable loss in cell viability.…”

Section: Resultsmentioning

confidence: 81%

“…Although many published reports have demonstrated that T2 (as well as other extracts) is efficacious in the treatment of rheumatoid arthritis (RA), its precise mechanism of action is unknown. It has long been appreciated that T2 has antiinflammatory activity, and recent reports indicate that this drug inhibits the induction of cyclooxygenase 2, thereby decreasing prostaglandin production (Tao et al, 1998). T2 is also clearly immunosuppressive, both in vitro and in vivo, as evidenced by its ability to inhibit T-and B-lymphocyte mitogen responses, Ig production, bacterial phagocytosis, and the production of several cytokines important in mediating the immune response [interleukins (IL) -1, -2, -4, -6, -8, and tumor necrosis factor-␣ (TNF-␣) (Li and Weir, 1990;Tao et al, 1996;Chang et al, 1997)].…”

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confidence: 99%

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Hematotoxicity of the Chinese Herbal MedicineTripterygium wilfordiiHook f in CD34-Positive Human Bone Marrow Cells

et al. 2000

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T2, a chloroform/methanol extract of the herb Tripterygium wilfordii Hook f, has been used in China for the treatment of autoimmune and inflammatory diseases for many years. Recent experimental evidence has confirmed that T2 has potent anti-inflammatory and immunosuppressive activity, and a United States Food and Drug Administration-approved clinical trial is currently exploring the efficacy of T2 in the treatment of rheumatoid arthritis. Despite the potential therapeutic benefits of T2, there is ample documentation that T2 is toxic, targeting, among other things, the hematopoietic system, and its use has resulted in cases of leukopenia, thrombocytopenia, and aplastic anemia. This investigation was undertaken to characterize the in vitro effects of T2 on primary human CD34-positive (CD34+) bone marrow cells. Our results demonstrate that T2 has a potent inhibitory effect on the clonogenic response of human bone marrow cells to exogenously added hematopoietic growth factors. The inhibition of colony formation by T2 is not the result of direct cytotoxicity or increased apoptosis and indicates a functional suppression of hematopoiesis. Additional experiments demonstrate that T2 also alters transcriptional regulation in bone marrow cells by inhibiting nuclear factor-kappaB. This transcription factor is found in CD34+ bone marrow cells and has been recently shown to be a requirement for colony formation. These results demonstrate that therapeutic concentrations of T2 exert a significant hematotoxic effect by inhibiting growth factor response in CD34+ bone marrow cells and suggest that inhibition of nuclear factor-kappaB may play a role in the blood dyscrasias encountered with the use of this drug.

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Section: Pyatt Et Almentioning

confidence: 54%

Section: Resultsmentioning

confidence: 81%

mentioning

confidence: 99%

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Hematotoxicity of the Chinese Herbal MedicineTripterygium wilfordiiHook f in CD34-Positive Human Bone Marrow Cells

et al. 2000

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“…This difference may be due to the differences in the metabolism or clearance rate between humans and rabbits. Additionally, EA is poorly soluble in water and is reported to accumulate in the human intestinal epithelial cells [ 47 ]. These factors could also contribute to its lower levels reported in human plasma.…”

Section: Discussionmentioning

confidence: 99%

Bioavailable constituents/metabolites of pomegranate (Punica granatum L) preferentially inhibit COX2 activity ex vivo and IL-1beta-induced PGE2 production in human chondrocytes i n vitro

et al. 2008

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Several recent studies have documented that supplementation with pomegranate fruit extract inhibits inflammatory symptoms in vivo. However, the molecular basis of the observed effects has not been fully revealed. Although previous studies have documented the inhibition of nitric oxide and cyclooxygenase (COX) activity in vitro by plant and fruit extracts added directly into the culture medium but whether concentrations of bioactive compounds sufficient enough to exert such inhibitory effects in vivo can be achieved through oral consumption has not been reported. In the present study we determined the effect of rabbit plasma obtained after ingestion of a polyphenol rich extract of pomegranate fruit (PFE) on COX enzyme activity ex vivo and the IL-1β-induced production of NO and PGE 2 in chondrocytes in vitro. Plasma samples collected before and 2 hr after supplementation with PFE were tested. Plasma samples collected after oral ingestion of PFE were found to inhibit the IL-1β-induced PGE 2 and NO production in chondrocytes. These same plasma samples also inhibited both COX-1 and COX-2 enzyme activity ex vivo but the effect was more pronounced on the enzyme activity of COX-2 enzyme. Taken together these results provide additional evidence of the bioavailability and bioactivity of compounds present in pomegranate fruit after oral ingestion. Furthermore, these studies suggest that PFE-derived bioavailable compounds may exert an anti-inflammatory effect by inhibiting the inflammatory cytokine-induced production of PGE 2 and NO in vivo.

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“…PGE 2 modulates the anabolic/catabolic process of bone, promoting bone remodeling through osteoblastic cell differentiation (53–55). It has been already reported that celastrol suppresses LPS-induced expression of PEG 2 via the downregulation of COX-1 and COX-2 activation (33, 56). Recently, Zou et al (57) have pointed out in vitro that celastrol inhibits the proliferation of PEG 2 -induced AS fibroblasts and their differentiation into an osteogenic phenotype, associated with a decrease in PI3K/Akt pathway and increase in Wnt inhibitors.…”

Section: Anti-inflammatory Properties Of Celastrolmentioning

confidence: 99%

Celastrol: A Spectrum of Treatment Opportunities in Chronic Diseases

2017

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The identification of new bioactive compounds derived from medicinal plants with significant therapeutic properties has attracted considerable interest in recent years. Such is the case of the Tripterygium wilfordii (TW), an herb used in Chinese medicine. Clinical trials performed so far using its root extracts have shown impressive therapeutic properties but also revealed substantial gastrointestinal side effects. The most promising bioactive compound obtained from TW is celastrol. During the last decade, an increasing number of studies were published highlighting the medicinal usefulness of celastrol in diverse clinical areas. Here we systematically review the mechanism of action and the therapeutic properties of celastrol in inflammatory diseases, namely, rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel diseases, osteoarthritis and allergy, as well as in cancer, neurodegenerative disorders and other diseases, such as diabetes, obesity, atherosclerosis, and hearing loss. We will also focus in the toxicological profile and limitations of celastrol formulation, namely, solubility, bioavailability, and dosage issues that still limit its further clinical application and usefulness.

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Effects of tripterygium wilfordii Hook F extracts on induction of cyclooxygenase 2 activity and prostaglandin E2 production

Cited by 9 publications

References 0 publications

Hematotoxicity of the Chinese Herbal MedicineTripterygium wilfordiiHook f in CD34-Positive Human Bone Marrow Cells

Hematotoxicity of the Chinese Herbal MedicineTripterygium wilfordiiHook f in CD34-Positive Human Bone Marrow Cells

Bioavailable constituents/metabolites of pomegranate (Punica granatum L) preferentially inhibit COX2 activity ex vivo and IL-1beta-induced PGE2 production in human chondrocytes i n vitro

Celastrol: A Spectrum of Treatment Opportunities in Chronic Diseases

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