Immunoregulatory effects of Tripterygium wilfordii Hook F and its extracts in clinical practice

Luo, Di; Zuo, Zhuang; Zhao, Hongyan; Tan, Yong; Xiao, Cheng

doi:10.1007/s11684-018-0649-5

Cited by 60 publications

(31 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…), harbors the greatest proportion (99.18%) of Tw HF‐producing sites (Figure 1). Tw HF has been used for the treatment of a wide spectrum of autoimmune disorders and inflammatory diseases, particularly RA, for a long period in China due to its prominent anti‐inflammatory and immunosuppressive effects 9,10 . Based on the theory of traditional Chinese medicine (TCM), Tw HF is an arthralgia‐dispelling herb with the benefits of activating blood circulation and collaterals, resisting rheumatism, and relieving pain and swelling.…”

Section: Introductionmentioning

confidence: 99%

Tripterygium wilfordii: An inspiring resource for rheumatoid arthritis treatment

Zhang

Mao

et al. 2020

Medicinal Research Reviews

126

View full text Add to dashboard Cite

Tripterygium wilfordii Hook F (TwHF)‐based therapy is among the most efficient and crucial therapeutics for the treatment of rheumatoid arthritis (RA), which indicates that TwHF is a potential source of novel anti‐RA drugs. However, accumulating studies have observed that TwHF‐based therapy induces multi‐organ toxicity, which prevents the wide use of this herb in clinical practice, although several recent studies have attempted to reduce the toxicity of TwHF. Notably, our research group developed a “Clinical Practice Guideline for Tripterygium Glycosides/Tripterygium wilfordii Tablets in the Treatment of Rheumatoid Arthritis” (No. T/CACM 1337‐2020) approved by the China Association of Chinese Medicine to standardize the clinical application of TwHF‐based therapy and thus avoid adverse effects. Although great strides have been made toward the characterization of TwHF‐based therapy and revealing its underlying pharmacological and toxicological mechanisms, several crucial gaps in knowledge remain as potential barriers to enhance its therapeutic effects on the premise of safety assurance. This review offers a global view of TwHF, ranging from its chemical constituents, quality control, clinical observations, and underlying pharmacological mechanisms to toxic manifestations and mechanisms. We focus on the important and emerging aspects of this field and highlight the major challenges and strategies for using novel techniques and approaches to gain new insights into unresolved questions. We hope that this review will improve the understanding of TwHF application and draw increasing interdisciplinary attention from clinicians that practice both Chinese and Western medicine, basic researchers, and computer scientists.

show abstract

Section: Introductionmentioning

confidence: 99%

Tripterygium wilfordii: An inspiring resource for rheumatoid arthritis treatment

Zhang

Mao

et al. 2020

Medicinal Research Reviews

126

View full text Add to dashboard Cite

show abstract

“…F. and is approved by National Medical Products Administration (NMPA) to be prescribed to patients with rheumatoid arthritis, nephrotic syndrome, ankylosing spondylitis, psoriasis, and systemic erythematosus lupus. [7][8][9][10] The mechanisms of TWP suppressing immune responses are limited explored and remain elucidated. 11,12 Tripterygium glycoside was proved to ameliorate experimental allergic encephalomyelitis (EAE) inflammation by inhibiting NF-κB p65 activation, simultaneously inducing CD4 + T cell apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Tripterygium wilfordii Polyglycoside Ameliorated TNBS-Induced Colitis in Rats via Regulating Th17/Treg Balance in Intestinal Mucosa

Zhang¹,

Ju²,

Wu³

et al. 2021

JIR

View full text Add to dashboard Cite

Purpose: To investigate the therapeutic effect of Tripterygium wilfordii polyglycoside (TWP), a derivative from a Chinese traditional herb, on 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis, in a model for inflammatory bowel disease (IBD) in rats. Methods: TWP was administrated to Wistar rats during TNBS-induced colitis to determine its therapeutic effect on active inflammation using the Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR), flow cytometry, and Western blotting. Peripheral blood CD4 + T-cells were isolated from patients with ulcerative colitis (UC) and incubated with TWP to verify its immune regulation mechanism by qRT-PCR and flow cytometry. Results: Intragastric administration of TWP attenuated the severity of intestinal inflammation in TNBS-induced rat colitis, characterized by decreased DAI, histopathological scores, and expression of IL-6, TNFα, IFNγ, and IL-17A in intestinal mucosa. Furthermore, TWP reduced IL-17A + CD4 + T-cells, while enhanced Foxp3 + CD25 + CD4 + T-cells in peripheral blood, mesenteric lymph nodes (MLN), and spleen in rat colitis. Downstream signaling including ROR-γt, STAT3, and HIF1α expression in intestinal mucosa were suppressed by TWP. In addition, incubation with TWP suppressed IL-17A + CD4 + T-cell differentiation, while it promoted Foxp3 + CD25 + CD4 + T-cell differentiation in CD4 + T-cells isolated from UC patients. Conclusion: TWP successfully ameliorated experimental rat colitis via regulating innate immune responses as well as Th17/Treg balance in intestinal mucosa, peripheral blood, MLN, and spleen. Moreover, the differentiation of peripheral blood CD4 + T-cell isolated from patients with UC was modulated by TWP. TWP may act as an optional complementary and alternative medicine for IBD.

show abstract

“…Tripterygium wilfordii Hook F is a promising antitumor Chinese herb with the ability to regulate disease by promoting blood circulation, improving blood stasis and detoxifying harmful metabolites (6). Triptolide (TP), a lactone compound with a unique diterpene and triperoxide structural form, is the major biologically active component extracted from the root, stem, rhizome and leaf of Tripterygium wilfordii Hook F (7).…”

Section: Introductionmentioning

confidence: 99%

“…TP increases the binding of RPL23 with MDM2 and activates p53 and p53-regulated proteins. (A) Cell lysates of TP-treated cells (5x106 ) were immunoprecipitated with anti-MDM2 antibodies, followed by immunoblotting with anti-MDM2, p53 and RPL23 antibodies. For each lysate, 20% of the quantity used for IP was loaded as an input control.…”

mentioning

confidence: 99%

Triptolide interrupts rRNA synthesis and induces the RPL23‑MDM2‑p53 pathway to repress lung cancer cells

Wang

Zhang

et al. 2020

Oncol Rep

View full text Add to dashboard Cite

Lung cancer has one of the highest mortalities of any cancer worldwide. Triptolide (TP) is a promising tumor suppressor extracted from the Chinese herb Tripterygium wilfordii. Our previous proteomics analysis revealed that TP significantly interfered with the ribosome biogenesis pathway; however, the underlying molecular mechanism remains poorly understood. The aim of the present study was to determine the molecular mechanism of TP's anticancer effect by investigating the association between ribosomal stress and p53 activation. It was found that TP induces nucleolar disintegration together with RNA polymerase I (Pol I) and upstream binding factor (UBF) translocation. TP interrupted ribosomal (r)RNA synthesis through inhibition of RNA Pol I and UBF transcriptional activation. TP treatment increased the binding of ribosomal protein L23 (RPL23) to mouse double minute 2 protein (MDM2), resulting in p53 being released from MDM2 and stabilized. Activation of p53 induced apoptosis and cell cycle arrest by enhancing the activation of p53 upregulated modulator of apoptosis, caspase 9 and caspase 3, and suppressing BCL2. In vivo experiments showed that TP significantly reduced xenograft tumor size and increased mouse body weight. Immunohistochemical assays confirmed that TP significantly increased the p53 level and induced nucleolus disintegration, during which nucleolin distribution moved from the nucleolus to the nucleoplasm, and RPL23 clustered at the edge of the cell membrane. Therefore, it was proposed that TP induces ribosomal stress, which leads to nucleolus disintegration, and inhibition of rRNA transcription and synthesis, resulting in increased binding of RPL23 with MDM2. Consequently, p53 is activated, which induces apoptosis and cell cycle arrest.

show abstract

Immunoregulatory effects of Tripterygium wilfordii Hook F and its extracts in clinical practice

Cited by 60 publications

References 29 publications

Tripterygium wilfordii: An inspiring resource for rheumatoid arthritis treatment

Tripterygium wilfordii: An inspiring resource for rheumatoid arthritis treatment

Tripterygium wilfordii Polyglycoside Ameliorated TNBS-Induced Colitis in Rats via Regulating Th17/Treg Balance in Intestinal Mucosa

Triptolide interrupts rRNA synthesis and induces the RPL23‑MDM2‑p53 pathway to repress lung cancer cells

Contact Info

Product

Resources

About