Therapeutic Potential of Triptolide as an Anti-Inflammatory Agent in Dextran Sulfate Sodium-Induced Murine Experimental Colitis

Tang, Bufu; Zhu, Jinyu; Zhang, Baohui; Wu, Fazong; Wang, Yajie; Weng, Qiaoyou; Fang, Shiji; Yang, Yang; Qiu, Rongfang; Chen, Minjiang; Xu, Min; Zhao, Zhongwei; Ji, Jiansong

doi:10.3389/fimmu.2020.592084

Cited by 47 publications

(26 citation statements)

References 70 publications

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“…[22][23][24] TWP was proved to be effective in relieving DSS-induced colitis by suppressing pro-inflammatory mediator production and modulating luminal microbiota. [25][26][27] In our study, we found that TWP successfully reduced elevated amounts of proinflammatory cytokines, eg, IL-6, TNFα, IFNγ, and IL-17A, prevented colon shortening, and relieved histologic inflammation in intestinal mucosa. Furthermore, Th17 cell differentiation was weakened, whereas Treg differentiation was enhanced in peripheral blood, MLN, and spleen from rats treated with TWP.…”

Section: Discussionsupporting

confidence: 51%

“…F. and its derivates can alleviate colitis via shaping macrophage polarization, reducing pro-inflammatory mediators, inducing T-cell apoptosis, and modulating gut microbiota composition. 16,[25][26][27] Our study provided evidence that TWP could also modulate Th17 as well as Treg differentiation via regulating innate immune responses as well as transcriptional factors that controlled the balance between Th17 and Treg. Particularly, our study found that TWP could directly polarize CD4 + T-cells derived from patients with IBD, and the mechanism research revealed an important roles of transcription factors in the differentiation process, which was consistent with the results from rats.…”

mentioning

confidence: 72%

“…We did not explore the IL-6 producers for previous reports have found triptolide has inhibited polarization of IL-6-producing M1 macrophages in intestinal mucosa during DSS-induced colitis. 25 We presumed that TWP might modify macrophage polarization in TNBS-induced colitis as well. Further investigation needs to be performed to confirm this hypothesis.…”

Section: Discussionmentioning

confidence: 97%

“…However, no difference of the Th1 cells was observed between the TNBS group and TWP group in draining MLN. Considering that macrophages can secrete IFNγ during inflammation and triptolide can modify macrophage polarization, 25 , 40 we speculated that TWP might modulate macrophages rather than Th1 cell function in intestinal mucosa during colitis. Natural killer cells and innate lymphoid cells can generate IFNγ, 40 hence we cannot rule out that TWP functions on those innate immune cells during colitis.…”

Section: Discussionmentioning

confidence: 99%

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

Zhang¹,

Ju²,

Wu³

et al. 2021

JIR

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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.

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Section: Discussionsupporting

confidence: 51%

mentioning

confidence: 72%

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

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

Zhang¹,

Ju²,

Wu³

et al. 2021

JIR

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“…13,15 Some studies also found that terpenoids and anti-oxidants can relieve the intestinal inflammation of IBDs. [41][42][43] In the present work, three drugs, commonly prescribed for the management of IBDs which included 5-ASA, Dex, and IFX, were used as positive controls to assess the efficacy of STV-Na. In the present study, we found that the efficiency of STV-Na was equal to or even greater than that of 5-ASA and Dex.…”

Section: Discussionmentioning

confidence: 99%

Isosteviol Sodium Exerts Anti-Colitic Effects on BALB/c Mice with Dextran Sodium Sulfate-Induced Colitis Through Metabolic Reprogramming and Immune Response Modulation

Wang¹,

Huang²,

Liu³

et al. 2021

JIR

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Purpose: Inflammatory bowel diseases (IBDs) are global health problems that are associated with immune regulation, but clinical IBDs treatment is currently inadequate. Effective preventive or therapeutic methods for immune disorders rely on controlling the function of immune cells. Isosteviol sodium (STV-Na) has antioxidant activity, but the therapeutic effect of STV-Na against IBD remain undocumented. Herein, we investigated the therapeutic effect of STV-Na in mice models with IBDs. Methods: Mice received 3.5% DSS for 7 days to establish IBD models. Intraperitoneal STV-Na was given 2 days before DSS and lasted for 9 days. Commercially available drugs used in treating IBDs (5-aminosalicylic acid, dexamethasone, and infliximab) were used as positive controls. Samples were collected 7 days after colitis induction. Histopathological score, biochemical parameters, molecular biology methods, and metabolomics were used for evaluating the therapeutic effect of STV-Na. Results: Our data revealed that STV-Na could significantly alleviate colon inflammation in mice with colitis. Specifically, STV-Na treatment improved body weight loss, increased colon length, decreased histology scores, and restored the hematological parameters of mice with colitis. The untargeted metabolomics analysis revealed that metabolic profiles were restored by STV-Na treatment. Furthermore, STV-Na therapy suppressed the number of CD68 macrophages and F4/ 80 cell infiltration. And STV-Na suppressed M1 and M2 macrophage numbers along with the mRNA expressions of proinflammatory cytokines. Moreover, STV-Na administration increased the number of regulatory T (Treg) cells while decreasing Th1/Th2/Th17 cell counts in the spleen. Additionally, STV-Na treatment restored intestinal barrier disruption in DSS-triggered colitis tissues by ameliorating the TJ proteins, increasing goblet cell proportions, and mucin protein production, and decreasing the permeability to FITC-dextran, which was accompanied by decreased plasma LPS and DAO contents. Conclusion:These results indicate that STV-Na can ameliorate colitis by modulating immune responses along with metabolic reprogramming, and could therefore be a promising therapeutic strategy for IBDs.

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Therapeutic Potential of Terpenoids in Cancer Treatment: Targeting Mitochondrial Pathways

Guo,

Huang,

Hou

et al. 2024

Cancer Reports

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BackgroundIn recent decades, natural compounds have been considered a significant source of new antitumor medicines due to their unique advantages. Several in vitro and in vivo studies have focused on the effect of terpenoids on apoptosis mediated by mitochondria in malignant cells.Recent findingsIn this review article, we focused on six extensively studied terpenoids, including sesquiterpenes (dihydroartemisinin and parthenolide), diterpenes (oridonin and triptolide), and triterpenes (betulinic acid and oleanolic acid), and their efficacy in targeting mitochondria to induce cell death. Terpenoid‐induced mitochondria‐related cell death includes apoptosis, pyroptosis, necroptosis, ferroptosis, autophagy, and necrosis caused by mitochondrial permeability transition. Apoptosis and autophagy interact in meaningful ways. In addition, in view of several disadvantages of terpenoids, such as low stability and bioavailability, advances in research on combination chemotherapy and chemical modification were surveyed.ConclusionThis article deepens our understanding of the association between terpenoids and mitochondrial cell death, presenting a hypothetical basis for the use of terpenoids in anticancer management.

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Therapeutic Potential of Triptolide as an Anti-Inflammatory Agent in Dextran Sulfate Sodium-Induced Murine Experimental Colitis

Cited by 47 publications

References 70 publications

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

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

Isosteviol Sodium Exerts Anti-Colitic Effects on BALB/c Mice with Dextran Sodium Sulfate-Induced Colitis Through Metabolic Reprogramming and Immune Response Modulation

Therapeutic Potential of Terpenoids in Cancer Treatment: Targeting Mitochondrial Pathways

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