Article
Chemistry, Medicinal
Hao Ma, Yunyang Bao, Shuaishuai Niu, Shaorong Wang, Yiming Li, Hongwei He, Na Zhang, Weishuo Fang
Summary: The farnesoid X receptor (FXR) is important for regulating the metabolism of bile acids, lipids, and sugars and is implicated in the treatment of various diseases. This study focuses on the design and synthesis of oleanolic acid (OA) derivatives to identify potent compounds that selectively antagonize FXR and modulate downstream genes. Compound 10b shows promising results in inhibiting lipid accumulation and preventing liver fibrosis, making it a potential treatment for nonalcoholic steatohepatitis (NASH).
Article
Pharmacology & Pharmacy
Songjie Liao, Xiaolong Fu, Jianxiang Huang, Yi Wang, Yuanfu Lu, Shaoyu Zhou
Summary: Oleanolic acid (OA) causes hepatotoxicity by suppressing the expression of FXR signaling pathway, leading to bile acid imbalance. Activation of SIRT1/FXR pathway can alleviate the hepatotoxicity.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2023)
Review
Endocrinology & Metabolism
Yuanyuan Liu, Haomeng Hao, Tingting Lan, Rui Jia, Mingya Cao, Liang Zhou, Zhiming Zhao, Wensen Pan
Summary: The local Renin-Angiotensin System (RAS) plays a role in the female reproductive system, regulating follicle development and physiological functions of the placenta and uterus. Ang II and Ang-(1-7) have similar functions in this system and can influence the occurrence and development of diseases.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Nutrition & Dietetics
Ruixia Bao, Wei Wang, Beibei Chen, Jujie Pan, Qian Chen, Mengyang Liu, Dan Wang, Yuzheng Wu, Haiyang Yu, Lifeng Han, Yi Zhang, Tao Wang
Summary: This study investigates the association between uric acid and cholesterol metabolism and the effect of dioscin in preventing hyperuricemia-induced atherosclerosis. The results show that dioscin can ameliorate atherosclerosis in a hyperuricemic state and regulate the farnesoid X receptor (FXR) -small heterodimer partner (SHP) -7 alpha-hydroxylase (CYP7A1) signaling pathway in the liver. Tigogenin, a metabolite of dioscin, increases the conversion rate of cholesterols into bile acids. Clinical study also demonstrates that treatment with a dioscin-enriched preparation decreases serum cholesterol levels in individuals with hyperuricemia.
Article
Toxicology
Jianxiang Huang, Songjie Liao, Xiaolong Fu, Yi Wang, Shaoyu Zhou, Yuanfu Lu
Summary: The study found that natural pentacyclic triterpenoid oleanolic acid (OA) activates AMPK and reduces the expression of FXR and bile acid efflux transport proteins, leading to cholestatic liver injury.
JOURNAL OF APPLIED TOXICOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Shaorong Wang, Yi Huan, Shuaishuai Niu, Hui Cao, Mingyan Yang, Xinyue Zhou, Xuefeng Gao, Xing Wang, Zhufang Shen, Wei-Shuo Fang
Summary: This study identified a new series of selective FXR modulators, with compound 7b significantly improving hyperglycemia in KKay fat mice fed with high fat diet. These findings provide evidence for the potential of FXR antagonism in improving hyperglycemia in diabetic mice.
BIOORGANIC CHEMISTRY
(2022)
Article
Orthopedics
Ying Li, Jiao Song, Yangyang Jiang, Xue Yang, Li Cao, Chun Xiao, Suli Li, Birong Dong, Xiaoli Huang
Summary: The ACE2/Ang-(1-7) axis plays a protective role in skeletal muscle function and administering exogenous Ang-(1-7) can delay age-related decline in skeletal muscle function. Aged mice showed reduced skeletal muscle function and Ang-(1-7) expression levels compared to younger mice. ACE2KO mice had significantly lower skeletal muscle function and MEF2A protein expression than age-matched wild-type mice. After one month of Ang-(1-7) treatment, skeletal muscle function in aged ACE2KO mice improved, with similar MEF2A protein expression to the untreated group. Ang-(1-7) was shown to promote Glut4 expression in C2C12 cells.
BMC MUSCULOSKELETAL DISORDERS
(2021)
Article
Toxicology
Hong Feng, Yan Hu, Shaoyu Zhou, Yuanfu Lu
Summary: Knockout of FXR can alleviate OA-induced cholestatic liver injury in mice by reducing bile acid accumulation in the liver and serum, increasing bile acid export via bile, and upregulating bile acid detoxification enzymes.
JOURNAL OF APPLIED TOXICOLOGY
(2022)
Review
Food Science & Technology
Wang Liao, Jianping Wu
Summary: Food protein-derived bioactive peptides, especially antihypertensive peptides, play an important role in regulating blood pressure through the ACE2/Ang (1-7)/MasR axis, demonstrating a new mechanism for reducing hypertension.
CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION
(2021)
Article
Medicine, Research & Experimental
Rocco Bernasconi, Kerstin Thriene, Elena Romero-Fernandez, Christine Gretzmeier, Tobias Kuehl, Mareike Maler, Pauline Nauroy, Svenja Kleiser, Anne-Catherine Ruehl-Muth, Michael Stumpe, Dimitra Kiritsi, Stefan F. Martin, Boris Hinz, Leena Bruckner-Tuderman, Joern Dengjel, Alexander Nystroem
Summary: This study reveals that the progression of fibrosis in patients with recessive dystrophic epidermolysis bullosa (RDEB) is associated with increased pro-inflammatory immunity, which can be mitigated by targeting the interaction between inflammatory cells and fibroblasts. The use of Ang-(1-7) can attenuate the progression of multi-organ fibrosis and improve survival rates in RDEB mice, highlighting the potential of down-modulating pro-inflammatory immunity in treating injury-induced fibrosis.
EMBO MOLECULAR MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Zuhair M. Mohammedsaleh, Emad H. M. Hassanein, Fares E. M. Ali, Hanan S. Althagafy, Nouf S. Al-Abbas, Ahmed M. Atwa
Summary: The study shows that Perindopril can mitigate the kidney damage caused by cadmium exposure. It achieves this by modulating inflammation, Ang II/Ang 1-7 axis, and apoptosis signals.
BIOLOGICAL TRACE ELEMENT RESEARCH
(2023)
Article
Plant Sciences
Yu Fu, Han Feng, Xue Ding, Qing-Hai Meng, Shu-Rui Zhang, Jun Li, Ying Chao, Ting-Ting Ji, Yun-Hui Bi, Wei-Wei Zhang, Qi Chen, Yu-Han Zhang, You-Long Feng, Hui-Min Bian
Summary: AB23A may prevent postmenopausal atherosclerosis by regulating hepatic farnesoid X receptor, increasing bile acid and cholesterol excretion, and reducing plasma cholesterol levels, providing a potential therapeutic approach.
Article
Gastroenterology & Hepatology
Kyounghwa Jung, Minwook Kim, Juhoon So, Seung-Hoon Lee, Sungjin Ko, Donghun Shin
Summary: This study identifies that activation of farnesoid X receptor (FXR) impairs biliary epithelial cell (BEC)-driven liver regeneration by enhancing PTEN activity. FXR activation reduces hepatic progenitor cell proliferation and increases cell death by inhibiting the PI3K-AKT-mTOR signaling pathway.
Article
Cardiac & Cardiovascular Systems
M. Amin Sharifi, Michael Wierer, Tan An Dang, Jelena Milic, Aldo Moggio, Nadja Sachs, Moritz von Scheidt, Julia Hinterdobler, Philipp Mueller, Julia Werner, Barbara Stiller, Zouhair Aherrahrou, Jeanette Erdmann, Andrea Zaliani, Mira Graettinger, Jeanette Reinshagen, Sheraz Gul, Philip Gribbon, Lars Maegdefessel, Juergen Bernhagen, Hendrik B. Sager, Matthias Mann, Heribert Schunkert, Thorsten Kessler
Summary: ADAMTS-7 plays a role in the development of atherosclerotic plaques by reducing the stability of TIMP-1, which in turn promotes the activity of MMP-9 and the degradation of collagen. Disrupting the interaction between ADAMTS-7 and TIMP-1 may be a strategy to increase plaque stability and reduce the risk of atherosclerosis-related events.
CIRCULATION RESEARCH
(2023)
Article
Plant Sciences
Yan Wu, Xin Yang, Yuanyuan Ju, Fei Zhao
Summary: This study found that fraxinol has significant therapeutic effects in the treatment of acute lung injury (ALI). It works by balancing the ACE-Ang II-AT1R and ACE2-Ang (1-7)-Mas axis and inhibiting the activation of NLRP3 inflammasome.
PHARMACEUTICAL BIOLOGY
(2022)
Review
Medicine, Research & Experimental
Weizhuo Lu, Zhiwu Chen, Jiyue Wen
Summary: Ischemic stroke is a common and serious disease, and neuroinflammation plays a crucial role in its progression. Microglia, astrocytes, and infiltrating immune cells are involved in the complicated neuroinflammation cascade, releasing different molecules that affect inflammation. Flavonoids, plant-specific compounds, have shown protective effects against cerebral ischemia injury by modulating the inflammatory responses.
BIOMEDICINE & PHARMACOTHERAPY
(2024)