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IL-6/STAT3通路
JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY · 2025 · IF 3.1

Naringenin Inhibits Colorectal Cancer associated with a High-Fat Diet through Modulation of Gut Microbiota and IL-6/STAT3 Pathway

Jiahui Sun,Luyao Shi,Fan Xu,Hanyan Sun,Yitong Liu,Jiangyun Sun,Qingxin Zhou

Colorectal cancer (CRC) is a worldwide health issue. It causes illness and death in millions of people each year. A positive correlation has been observed between the intake of dietary fat and the development of CRC. The composition of gut microbiota exhibits a significant correlation with pathophysiologic processes in intestine. Clinical treatment remains inadequate due to the complex pathogenic mechanisms of CRC triggered by a high-fat diet (HFD). Naringenin, a flavonoid from grapefruit, has anti-cancer activity. Our findings suggest that naringenin enhances gut microbiota diversity by increasing the abundance of beneficial bacterial species while reducing opportunistic pathogenic bacteria. The fecal microbiota transplantation assay (FMT) demonstrated that the anti-HFD-CRC activity of naringenin depended on the gut microbiota. Furthermore, naringenin antagonized the IL-6/STAT3 pathway. These results suggest that naringenin may be a potential treatment for HFD-CRC.

CAS / MDL: 25843-45-2 67604-48-2
研究领域: 肿瘤学 · 营养学 · 微生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF ETHNOPHARMACOLOGY · 2025 · IF 5.4

Mechanism of Yinxu Weitong Capsule in the treatment of precancerous lesions of gastric cancer based on network pharmacology and experimental validation

Yichong Wang,Danyan Li,Luqing Zhao,Jixiang Liu,Dan Dou,Nian Liu,Yudi Zhuo,Shengsheng Zhang

Ethnopharmacological relevance Yinxu Weitong Capsule (YXWTC) is a Chinese patent medicine used to treat chronic gastritis. However, its efficacy and mechanisms of action in treating precancerous lesions of gastric cancer (PLGC) remain unclear. Aim of the study To evaluate the effects of YXWTC on PLGC and explore the underlying mechanisms. Materials and methods YXWTC components were identified using ultra-high-performance liquid chromatography coupled with electrospray ionization quadrupole-exactive orbitrap mass spectrometry. A PLGC animal model was established and the protective effects of YXWTC on the gastric mucosa in PLGC rats were evaluated using hematoxylin and eosin (H&E), Alcian blue-periodic acid-Schiff and Alcian blue-high iron diamine staining, and transmission electron microscopy (TEM). The vital organs of the rats were examined using H&E staining to evaluate biosafety. Network pharmacology identified potential targets and pathways of YXWTC in PLGC treatment, followed by molecular docking validation. Various techniques, including enzyme-linked immunosorbent assay, real-time quantitative reverse transcription PCR, Western blotting, immunohistochemistry, apoptosis detection, and reactive oxygen species fluorescence staining were employed to elucidate the underlying mechanisms. Results In total, 340 YXWTC components were identified. YXWTC effectively improves gastric mucosal pathology in rats with PLGC. Network pharmacology identified 403 targets common to PLGC and YXWTC. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses identified 2,323 biological processes and 206 signaling pathways, respectively. Molecular docking revealed that the primary target proteins and major drug molecules exhibited strong binding affinities. Animal studies demonstrated that YXWTC inhibited the IL-6/STAT3 pathway, promoted mitochondrial apoptosis, and induced ROS release. Conclusions We verified the pharmacodynamic effects of YXWTC in PLGC. In summary, the effects are mediated by inhibition of the IL-6/STAT3 pathway, promotion of mitochondrial apoptosis, and induction of ROS release.

CAS / MDL: 66357-59-3
研究领域: 药理学 · 肿瘤学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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FEBS Open Bio · 2023 · IF 2.6

Inhibition of PRMT1 alleviates sepsis-induced acute kidney injury in mice by blocking the TGF-β1 and IL-6 trans-signaling pathways

Yu Zhu,Longmei Wang,Rui Liu,Xiurong Ding,Song Yin,Yuankun Chen,Chuanlong Zhu,Zheng Wang,Wenting Li

Sepsis-induced acute kidney injury (SI-AKI) causes renal dysfunction and has a high mortality rate. Protein arginine methyltransferase-1 (PRMT1) is a key regulator of renal insufficiency. In this study, we explored the potential involvement of PRMT1 in SI-AKI. A murine model of SI-AKI was induced by cecal ligation and perforation (CLP). The expression and localization of PRMT1 and molecules involved in the TGF-β1/Smad3 and IL-6/STAT3 signaling pathways were detected in mouse kidney tissues by western blot, immunofluorescence, and immunohistochemistry. The association of PRMT1 with downstream molecules of the TGF-β1/Smad3 and IL-6/STAT3 signaling pathways were further verified in vitro in mouse renal tubular epithelial cells (mRTECs). CLP caused epithelial-mesenchymal transition (EMT), apoptosis, and inflammation in renal tissues, and this was alleviated by inhibition of PRMT1. Inhibition of PRMT1 in SI-AKI mice decreased the expression of TGF-β1 and phosphorylation of Smad3 in the renal cortex, and downregulated the expression of sIL-6R and phosphorylation of STAT3 in the medulla. Knockdown of PRMT1 in mRTECs restricted the expression of Cox-2, E-cad, Pro-caspase3 and p-Smad3 (involved in the TGF-β1-mediated signaling pathway), and blocked IL-6/sIL-6R, inducing the expression of Cox-2 and p-STAT3. In conclusion, our findings suggest inhibition of PRMT1 mitigates SI-AKI by inactivating the TGF-β1/Smad3 pathway in the cortex and IL-6/STAT3 pathway in the medulla. Our findings may aid in the identification of potential therapeutic target molecules for SI-AKI.

CAS / MDL: 9048-46-8 28718-90-3
研究领域: 肾病学 · 免疫学 · 分子生物学 · 病理生理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2024 · IF 5.4

Dual-ligand-functionalized nanostructured lipid carriers as a novel dehydrocavidine delivery system for liver fibrosis therapy

Xiaodan Su,Huashuai Zhong,Yongzhu Zeng,Yuyan Zhang,Bo Zhang,Wei Guo,Qiujie Huang,Yong Ye

Background Liver fibrosis is a common stage of various chronic liver diseases, often developing into liver cirrhosis, and even liver cancer. Activated hepatic stellate cells (aHSCs) have been shown to promote the development of liver fibrosis. Therefore, dual-targeted combination therapy for liver may be an effective strategy for the treatment of liver fibrosis. Purpose In this study, the novel nanostructured lipid carriers (GA&GalNH 2 -DC-NLCs) were prepared for Dehydrocavidine (DC), glycyrrhetinic acid (GA) and galactose-PEG 2000 -NH 2 (GalNH 2 ) were selected as targeted ligand-modified nanostructured lipid carriers (NLCs), which enables dual-targeting to the liver for the treatment of liver fibrosis. Study design To study the targeting effect of GA&GalNH 2 -DC-NLCs on liver and its therapeutic effect on liver fibrosis, we established aHSC-T6 cell model and rat model of liver fibrosis for study. Results GA&GalNH 2 -DC-NLCs promoted drug liver targeting efficiency and apoptosis rate by upregulating the expression of Bax. It showed that compared with no and/or GA-modified NLCs and GalNH 2 -modified NLCs, GA&GalNH 2 -DC-NLCs exhibited less extracellular matrix (ECM) deposition, induced apoptosis of aHSCs, and stronger anti-fibrosis effects in vivo. This may be due the fact that GA or GalNH 2 -modifified NLCs simultaneously block HSCs activation and inhibit the IL-6/STAT3 pathway. Conclusion GA&GalNH 2 -DC-NLCs is thus a potential strategy for liver fibrosis treatment.

研究领域: 药学 · 生物技术 · 药理学 · 细胞生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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