Buyang Huanwu Decoction ameliorates atherosclerosis by regulating TGF-β/Smad2 pathway to promote the differentiation of regulatory T cells. (6th April 2021)

• Record Type: Journal Article
• Authors: Chen, Shujing; Wang, Yuan; Liang, Chunxiao; Li, Jin; Li, Yuhong; Wu, Qi; Liu, Zhijian; Pang, Xiaoli; Chang, Yan-xu
• Is Part Of: Journal of ethnopharmacology. Volume 269(2021)
• Publication Date: 2021-04-06
• Subjects: Buyang Huanwu decoction -- Atherosclerosis -- Regulatory T cells -- TGF-β/Smad2 pathway; BYHWD Buyang Huanwu Decoction -- ApoE-/- Apolipoprotein E gene knockout -- Tregs regulatory T cells -- AS Atherosclerosis -- TCM Traditional Chinese medicine -- UHPLC ultra-high performance liquid chromatograph -- LC-MS/MS liquid chromatography-tandem mass spectrometry -- ELISA Enzyme linked immunosorbent assay -- PBS phosphate buffered saline -- RT-PCR real time polymerase chain reaction -- IFN-γ interferon-γ -- IL-6 interleukin-6 -- TGF-β Transforming growth factor beta -- ox-LDL oxidized low density lipoprotein; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2020.113724
• Languages: English
• ISSNs: 0378-8741

Abstract

Abstract: Ethnopharmacological relevance: As a classic prescription of Traditional Chinese Medicine in Correction on the Errors of Medical Works, Buyang Huanwu Decoction (BYHWD) has a good curative effect on prevention of atherosclerosis (AS). Aim of the study: This study aims to elucidate the anti-atherosclerosis mechanism of BYHWD, which may promote the differentiation of regulatory T cells by regulating the TGF-β/Smad2 pathway. Materials and methods: ApoE-/- mice were fed a high-fat diet for 12 weeks, then drugs group were given BYHWD with intragastric administration once a day for 4 weeks. The effect of BYHWD on lipid content in peripheral blood and plaque was evaluated by blood lipid test and oil red O staining. The number of Tregs in peripheral blood was tested by flow cytometry, and that in the spleen was evaluated by immunohistochemistry methods. Gene and protein expression relating with Tregs differentiation pathway in mice were checked by RT-PCR and Western blot experiments. CD4 + T cells were isolated and interfered by BYHWD drug-loaded serum. The proportion of Tregs was evaluated by flow cytometry. The chemical compositions of BYHWD and rat drug-loaded serum were analyzed by ultra-high performance liquid chromatograph and liquid chromatography-tandem mass spectrometry. Results: BYHWD significantly reduced plaque area and cholesterol accumulation, increased the number of Tregs in spleen and peripheral blood of ApoE-/- AS mice, raised the proportion of Tregs in CD4 + T cells, and regulated the levels of inflammatory factors. It also increased the TGF-β and Smad2 mRNA and protein levels relating with Tregs differentiation pathway in vivo . The mRNA levels of Foxp3/TGF-β/Smad2 were enhanced via BYHWD in vitro . Conclusions: BYHWD regulates TGF-β/Smad2 signaling pathway to promotes the peripheral differentiation of Tregs, increases the number of Tregs, restores the immune balance between CD4 + T cells, regulates lipid metabolism, inhibits inflammatory reaction and possesses the potential of enhancing plaque stability. Graphical abstract: Image 1 Highlights: BYHWD possesses the potential of enhancing plaque stability in ApoE-/- AS mice. BYHWD regulates TGF-β/Smad2 to promote the differentiation of Tregs in AS mice. BYHWD regulates lipid metabolism and inhibits inflammatory reaction.