Wumei pills attenuates 5-fluorouracil-induced intestinal mucositis through Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB pathway and microbiota regulation

Abstract

BACKGROUND Radiotherapy and chemotherapy can kill tumor cells and improve the survival rate of cancer patients. However, they can also damage normal cells and cause serious intestinal toxicity, leading to gastrointestinal mucositis[ 1 ]. Traditional Chinese medicine is effective in improving the side effects of chemotherapy. Wumei pills (WMP) was originally documented in the Treatise on Exogenous Febrile Diseases. It has a significant effect on chronic diarrhea and other gastrointestinal diseases, but it is not clear whether it affects chemotherapy-induced intestinal mucositis (CIM). AIM To explore the potential mechanism of WMP in the treatment of CIM through experimental research. METHODS We used an intraperitoneal injection of 5-fluorouracil (5-Fu) to establish a CIM mouse model and an oral gavage of WMP decoction (11325 and 22650 mg/kg) to evaluate the efficacy of WMP in CIM. We evaluated the effect of WMP on CIM by observing the general conditions of the mice (body weight, food intake, spleen weight, diarrhea score, and hematoxylin and eosin stained tissues). The expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β, and myeloperoxidase (MPO), as well as the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB (TLR4/MyD88/NF-κB) signaling pathway proteins and tight junction proteins (zonula occludens-1, claudin-1, E-cadherin, and mucin-2) was determined. Furthermore, intestinal permeability, intestinal flora, and the levels of short-chain fatty acids (SCFA) were also assessed. RESULTS WMP effectively improved the body weight, spleen weight, food intake, diarrhea score, and inflammatory status of the mice with intestinal mucositis, which preliminarily confirmed the efficacy of WMP in CIM. Further experiments showed that in addition to reducing the levels of TNF-α, IL-1β, IL-6, and MPO and inhibiting the expression of the TLR4/MyD88/NF-κB pathway proteins, WMP also repaired the integrity of the mucosal barrier of mice, regulated the intestinal flora, and increased the levels of SCFA (such as butyric acid). CONCLUSION WMP can play a therapeutic role in CIM by alleviating inflammation, restoring the mucosal barrier, and regulating gut microbiota.

Common mechanisms of Wumei pills in treating ulcerative colitis and type 2 diabetes: Exploring an integrative approach through network pharmacology

“…WMP is widely used in clinical practice, and numerous researchers have explored its mechanisms. [14,[20][21][22][23] However, there is currently a gap in research concerning the common mechanisms of action of WMP in treating both UC and T2DM.…”

“…Studies have demonstrated that WMP alleviates UC symptoms by impacting inflammatory factors and the gut microbiota. [14] Furthermore, combined treatment with WMP and metformin for T2DM has resulted in significantly better outcomes compared to treatment with metformin alone. [15] These studies substantiate the concept of “treating different diseases with the same treatment.” However, there is limited research on the common mechanisms of WMP in treating both UC and T2DM.…”

Uncovering the molecular mechanism of Mume Fructus in treatment of Sjögren’s syndrome

“…[ 25 ] Quercetin has been shown to reduce the production of inflammatory factors through the NF-κB and MAPK pathways. [ 26 , 27 ] In addition, quercetin has a significant immunoregulatory effect, and it can inhibit the abnormal proliferation and activation of T lymphocytes and improve the chronic inflammation caused by the infiltration of T lymphocytes in the early stage of SS. [ 28 , 29 ] Kaempferol can regulate the Th1/Th2 cell subpopulation to achieve the goal of immune regulation.…”

Quantitative proteomic analysis of circulating exosomes reveals the mechanism by which Triptolide protects against collagen‐induced arthritis

“…For instance, Naringenin, a natural product known for its antioxidative stress properties, inhibits macrophage M1 polarization by reducing the release of exosomal miR‐21‐3p derived from BEAS‐2B cells. 9 Schisandrol A, a bioactive constituent from Schisandrae Chinensis Fructus, has been reported to alleviate drug‐induced liver injury through autophagy activation via exosomes. 10 Shikonin, a naphthoquinone isolated from Lithospermum, inhibits human breast cancer cell proliferation by reducing tumor‐derived exosomes.…”