JOURNAL OF ETHNOPHARMACOLOGY
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2025
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IF 5.4
Zhengwen Zhang,Zhaojun Wang,Yushun Cui,Min Yao,Jiajian Lu,Mingzhen He,Yulin Feng,JunMao Li
Ethnopharmacological relevance Ainsliaea fragrans Champ. (AFC) , a traditional Chinese medicinal herb with a well-documented history in the management of gynecological disorders, serves as the principal component of several Chinese patent medicines that have demonstrated significant clinical efficacy against cervicitis, endometritis, and pelvic inflammatory disease. However, its specific mechanism of action against cervicitis has not been fully elucidated. Purpose This study aims to determine the therapeutic efficacy and underlying mechanisms of AFC in treating cervicitis, and identifying its key active components. Materials and methods First, an in vivo model of cervicitis was established using a phenolic mucilage solution, while an in vitro LPS induced RAW264.7 cell inflammation model was employed. The therapeutic effects of AFC were evaluated through HE staining, uterine index measurements, RT-qPCR and ELISA. The chemical constituents of AFC were identified using ultra-performance liquid chromatography coupled with UPLC-Q-TOF/MS. Subsequently, cellular metabolomics and network pharmacology were utilized to predict the potential targets, mechanisms, and active components of AFC in treating cervicitis. Finally, the underlying mechanisms and active ingredients were validated using methods such as RT-qPCR, Western blot, and molecular docking. Results Both in vivo and in vitro experiments demonstrated that AFC ameliorated phenol mucilage-induced cervicitis in rats and significantly suppressed the expression of inflammatory factors including IL-6, TNF-α, and IL-1β. UPLC-Q-TOF-MS/MS analysis identified 93 chemical constituents in AFC. Cellular metabolomics revealed 79 differential metabolites, including PGE2 and COX-2, among others. Integrated network pharmacology analysis identified potential targets including IDO1 and COX-2, and enriched signaling pathways such as TLR4 and PI3K/AKT-mTOR. Among the nine candidate compounds screened, luteolin, apigenin, and isorhamnetin ranked as the top three by degree value were hypothesized to be the primary active constituents of AFC against cervicitis. Subsequent experimental validation through RT-qPCR, Western blot, and molecular docking demonstrated that AFC treats cervicitis by modulating the PGE2/COX-2/IDO1-FLG in coordination with the TLR4 and PI3K/AKT-mTOR pathways, with luteolin, apigenin, and isorhamnetin confirmed as the key active compounds. Conclusion AFC exerts its therapeutic effects against cervicitis through coordinated regulation of the PGE2/COX-2/IDO1-FLG in conjunction with the TLR4 and PI3K/AKT-mTOR signaling pathways.
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PubMed
高影响因子
Journal of Immunology Research
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2020
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IF 3.327
Yanan Shi,Jingming Xu,Bin Ding,Guiping Chen,Lu Jin,Liang Ke,Xiao Xu,JingXia Wang,Qiuhua Sun,Xiaohong Xu
Constipation, a gastrointestinal function disorder, is one of the side effects of paclitaxel (PTX) chemotherapy. Shenhuang plaster (SHP) application on the Shenque acupoint promotes gut motility in clinical settings. In this study, we elucidated the ingredients in SHP and evaluated its effects on PTX-induced constipation using a tumour-bearing mouse model. SHP was prepared using the traditional Chinese plaster preparation method. The ingredients were analysed using UPLC-MS/MS and identified via screening in a standard drug database. The gastrointestinal transit was evaluated by the movement of a fluorescein-labelled dextran in the gastrointestinal tract. A histological study of the mucosa was carried out after haematoxylin and eosin staining. mRNA expression was assessed using real-time RT-PCR, and the foetal microbiota composition was elucidated through 16 s rDNA sequencing and BLAST analysis. Our results indicate that the application of SHP attenuated weight gain inhibition by PTX; however, no inhibitory effect was observed on tumour growth. PTX-induced sluggish intestine, villus, and mucosal base layer damage were significantly improved following the application of SHP. Further, SHP enhanced the stimulation efficiency of PTX on TLR4 and its downstream cytokines, as well as on IL-1β in intestinal cells. SHP combined with PTX reshaped the microbiota, which showed beneficial effects on health. Hence, these results provide evidence that SHP alleviates PTX-induced constipation and intestinal morphological damage but augments the effects of PTX on the expression of cytokines in the TLR4 pathway and IL-1β. Therefore, we propose that SHP stimulates the host immune response to eradicate cancer cells.
研究领域:
药理学
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肿瘤学
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中医
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胃肠病学
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免疫学
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微生物学
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Huiling Tang,Qiuping Li,Zhengqi Zha,Yuzhi Jiao,Baowei Yang,Zhaoyan Cheng,Ting Wang,Hongping Yin
Ulcerative colitis (UC) is a chronic inflammatory disease resulting from abnormal immune response to gut microflora translocating through damaged intestinal barrier. Xylan acetate ester (XylA) can increase colon short-chain fatty acids (SCFAs) levels and alleviate kidney disease by inhibiting inflammation through the G protein-coupled receptor pathway. Here, we synthesized and purified XylA, and then the effects and mechanisms of XylA on dextran sodium sulfate-induced UC in mice were investigated. The results showed that in mice, similar to the positive drug 5-aminosalicylic acid, oral administration of XylA significantly alleviated all UC symptoms, including weight loss, diarrhea, and hematochezia. Further mechanism studies revealed that XylA could repair the damaged colon structure and intestinal barrier function by increasing the expression of tight junction protein zonula occludens 1 and occludin, thus reducing LPS penetration. Moreover, XylA could also restrain intestinal inflammation via inhibiting LPS-TLR4 pathway, downregulating M1 macrophage polarization, and reducing proinflammatory cytokines expression, and in vitro cell experiments showed that these effects may be mediated by XylA derived SCFAs, particularly acetates, propionates and butyrates. All these results suggested that XylA may be a potential improving agent for UC treatment, and natural polysaccharides may represent a novel avenue for drug development of UC.
研究领域:
药理学
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免疫学
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胃肠病学
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炎症性肠病
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高影响因子
CARBOHYDRATE POLYMERS
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2024
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IF 10.7
Yu Zhang,Wenting Ji,Hailong Qin,Zehong Chen,Yinxing Zhou,Zhihong Zhou,Jinglin Wang,Kaiping Wang
Natural polysaccharides from Astragalus membranaceus have been shown to relieve ulcerative colitis (UC). However, the mechanism and causal relationship between the gut microbiota and Astragalus polysaccharides (APS) treatment of UC are unclear. The results of the present study showed that APS ameliorated colonic injury and the disruption of the gut microbiota and restored intestinal immune homeostasis in mice with DSS-induced colitis. Meanwhile, we found that APS treatment was ineffective in antibiotic-treated colitis mice but was effective when FMT (Fecal microbiota transplantation) was performed on UC mice using APS-treated mice as donors. APS increased the proportion of relevant microbiota that produce SCFAs and both direct administration of APS and administration of APS-adjusted gut microbiota significantly promoted the production of SCFAs in colitis mice. We demonstrated that APS dually inhibited NF-κB activation via the TLR4 and HDAC3 pathways and improved the balance in Th17/Treg cells in UC mice. In conclusion, our study revealed that APS is a promising prebiotic agent for the maintenance of intestinal health and demonstrated that APS may ameliorate colitis in a gut microbiota-dependent manner.
研究领域:
胃肠病学
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免疫学
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微生物学
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药理学
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DOI
PubMed
高影响因子
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