Article
Immunology
Shan Cao, Xinyu Meng, Yixuan Li, Li Sun, Lindi Jiang, Hanqing Xuan, Xiaoxiang Chen
Summary: This study revealed that bile acids, especially CDCA, may dampen inflammation via FXR-mediated downregulation of IL-6 in mononuclear cells, providing a protective mechanism for CP patients. The altered bile acid spectrum and signaling pathway enrichment analysis suggest a potential therapeutic target for CP in FXR agonists.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Mohamed O. Radwan, Sultan F. Kadasah, Salha M. Aljubiri, Abdulmajeed F. Alrefaei, Mahmoud H. El-Maghrabey, Mohamed A. El Hamd, Hiroshi Tateishi, Masami Otsuka, Mikako Fujita
Summary: In this review, the modulation of metabolic nuclear receptors by oleanolic acid (OA) and its semi-synthetic derivatives is highlighted. OA exhibits tissue-specific pharmacological effects on various nuclear receptors, showing potential therapeutic applications in metabolic diseases.
Article
Pharmacology & Pharmacy
Alzbeta Stefela, Miroslav Kaspar, Martin Drastik, Thales Kronenberger, Stanislav Micuda, Martin Dracinsky, Blanka Klepetarova, Eva Kudova, Petr Pavek
Summary: The study identified 7-ethylidene-lithocholic acid (7-ELCA) as a novel combined FXR antagonist/GPBAR1 agonist, which can regulate glucose, lipid, and energy homeostasis as well as stimulate the production of GLP-1 to improve postprandial glucose utilization. The dual modulation of GPBAR1 and FXR by 7-ELCA may offer a promising approach for the treatment of type II diabetes.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Takeshi Katafuchi, Makoto Makishima
Summary: Bile acids have detergent and hormone-like properties. FXR and FGF15/19 are considered as potential therapeutic targets for metabolic syndrome and cholestatic diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Zhen Xu, Zhenhua Huang, Yifan Zhang, Haitao Sun, Ulf Hinz, Ulrike Heger, Martin Loos, Frank J. Gonzalez, Thilo Hackert, Frank Bergmann, Franco Fortunato
Summary: Farnesoid X receptor (FXR) attenuates acinar cell autophagy in chronic pancreatitis, leading to reduced autophagy and promotion of pancreatic cancer. Activation of pancreatic FXR through the FXR agonist CDCA can attenuate PanIN progression and decrease cell proliferation and autophagy activity in KC mice.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2023)
Article
Pharmacology & Pharmacy
Xiaowei Sun, Zhenhui Chen, Lu Yu, Weisen Zeng, Boyuan Sun, Hongying Fan, Yang Bai
Summary: This study found that Bacteroides dorei BDX-01 improved DSS-induced acute colitis by regulating intestinal BSH activity and the FXR-NLRP3 signaling pathway. These findings suggest that BDX-01 is a promising probiotic for improving the management of ulcerative colitis.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Peiyuan Kang, Sha Li
Summary: In this study, Makisterone A (MakA) was identified as a compound that could target FXR, enhance its activity, and alleviate cholestatic liver injury in a mouse model. This suggests that MakA may have potential for the clinical treatment of cholestasis.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Pharmacology & Pharmacy
Sijing Dong, Min Zhu, Ke Wang, Xiaoye Zhao, Longlong Hu, Wanghui Jing, Haitao Lu, Sicen Wang
Summary: Recent studies have shown that DHM can alleviate IBD by modulating gut microbiota and microbial BA metabolism, leading to improvements in intestinal barrier integrity. This research provides insights into the development of novel DHM-derived drugs for the management of inflammatory bowel disease.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Chemistry, Multidisciplinary
Han Wang, Yating Sun, Hewei Li, Shengli Yang, Wen Yi
Summary: In this study, a promising FXR partial agonist was developed with low cytotoxicity and demonstrated protective effects against cholestasis. Further investigations revealed that the compound exerted its effects through multiple mechanisms, including decreasing uptake, increasing efflux, inhibiting synthesis, and promoting metabolism of bile acids.
Article
Plant Sciences
Guochao Song, Bin Zou, Jing Zhao, Fengyi Weng, Yue Li, Xiaoqing Xu, Shuang Zhang, Dongming Yan, Jingyi Jin, Xin Sun, Chenghai Liu, Furong Qiu
Summary: This study investigated the molecular mechanism of how Yinchen decoction (YCD) protects against intrahepatic cholestasis induced by a 1% cholic acid diet. The findings showed that YCD restores bile acid homeostasis by activating the liver FXR/SHP and ileal FXR/FGF15 signaling pathways, thereby protecting against cholestatic liver injury. Furthermore, chlorogenic acid and caffeic acid in YCD may be the pharmacological agents responsible for its protective effects against cholestatic liver injury.
JOURNAL OF ETHNOPHARMACOLOGY
(2023)
Article
Plant Sciences
Yuanyuan Zhai, Wenling Zhou, Xu Yan, Yuan Qiao, Lingling Guan, Zhichun Zhang, Hao Liu, Jizhi Jiang, Jiang Liu, Liang Peng
Summary: This study investigated the effect of AS-IV on NAFLD and explored the involvement of intestinal flora. AS-IV treatment alleviated diet-induced metabolic impairments, particularly hepatic steatosis. The changes in intestinal flora and BAs were found to play an essential role in the remission of hepatic steatosis by AS-IV.
Article
Toxicology
Peishi Liang, Shaoyun Zhou, Ziqiao Yuan, Luyong Zhang, Zhenzhou Jiang, Qinwei Yu
Summary: This study investigates the role of farnesoid X receptor (FXR) in abnormal bile acid metabolism and pyroptosis during TP/LPS-induced hepatotoxicity. The study found that obeticholic acid (OCA) has a protective effect and reduces serum bile acid level under this condition.
JOURNAL OF APPLIED TOXICOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Jingyi Guo, Shangyi Huang, Qincheng Yi, Naihua Liu, Tianqi Cui, Siwei Duan, Jiabing Chen, Jiayu Li, Jun Li, Lei Wang, Yong Gao, Guangning Nie
Summary: Non-alcoholic fatty liver disease (NAFLD) is a serious liver disease that is increasing globally due to high calorie and fat diets. This study analyzed the effects of calsyntenin-3 (Clstn3) on lipid metabolism in NAFLD. The results showed that overexpression of Clstn3 improved lipid metabolism disorders and reduced liver injury and inflammation in NAFLD model mice. Clstn3 was found to be closely related to lipid metabolism disorder in NAFLD and may be a potential target for treatment.
Article
Chemistry, Multidisciplinary
Jia-Xu Zhou, Cui-Na Li, Ya-Meng Liu, Su-Qin Lin, Ying Wang, Cen Xie, Fa-Jun Nan
Summary: In this study, novel 9,11-seco-cholesterol derivatives were designed and synthesized as FXR antagonists, with compound 9a exhibiting the best FXR antagonistic activity and reducing the expression of FXR target genes.
Article
Endocrinology & Metabolism
Xianjiao Liu, Jinyan Li, Mengdie Shi, Jun Fu, Yubo Wang, Weili Kang, Jinyan Liu, Fenxia Zhu, Kehe Huang, Xingxiang Chen, Yunhuan Liu
Summary: Melatonin (MT) improves hepatic injury and fibrosis in cholestatic liver disease mice by remodeling gut microbiota and activating intestinal farnesoid X receptor (FXR)/fibroblast growth factor 15 (FGF-15) axis-mediated inhibition of hepatic bile acid synthesis and promotion of bile acid excretion.
JOURNAL OF PINEAL RESEARCH
(2023)
