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  2. Salvianolic acid B alleviates diabetic endothelial and mitochondrial dysfunction by down-regulating apoptosis and mitophagy of endothelial cells

Salvianolic acid B alleviates diabetic endothelial and mitochondrial dysfunction by down-regulating apoptosis and mitophagy of endothelial cells

  • Bioengineered. 2022 Feb;13(2):3486-3502. doi: 10.1080/21655979.2022.2026552.
Jie Xiang 1 Chunling Zhang 2 Tietao Di 3 Lu Chen 4 Wei Zhao 4 Lianggang Wei 5 Shiyong Zhou 6 Xueli Wu 7 Gengxin Wang 8 Yun Zhang 8
Affiliations

Affiliations

  • 1 Monitoring Department, Guizhou Center for Disease Control and Prevention, Institute of Chronic Disease Prevention and Treatment, Guiyang, Guizhou, China.
  • 2 Department of Nutrition, The Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, China.
  • 3 Department of Trauma Surgery, The Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, China.
  • 4 Department of Endocrinology, The Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, China.
  • 5 Department of Rheumatology, Chongqing Traditional Chinese Medicine Hospital, Chongqing, China.
  • 6 Department of General Surgery, The Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, China.
  • 7 Central Laboratory, The Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, China.
  • 8 Graduate School, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, China.
Abstract

Endothelial dysfunction is a critical mediator in the pathogenesis of vascular complications of diabetes. Herein, this study was conducted to investigate the therapeutic effects of Salvianolic acid B (Sal B) on diabetes-induced endothelial dysfunction and the underlying mechanisms. Diabetic models were established both in db/db mice and high glucose (HG)-induced human umbilical vein endothelial cells (HUVECs). Moreover, HUVECs were exposed to carbonyl cyanide m-chlorophenyl hydrazone (CCCP) to induce endothelial cell damage. Following Sal B treatment, pathological changes of thoracic aorta were investigated by hematoxylin and eosin, alcian blue (AB), elastic fiber, Masson, and reticular fiber staining. BCL2-associated X (Bax), B-cell lymphoma-2 (Bcl-2), Beclin1, Parkin and PTEN Induced Kinase 1 (Pink1) expression was detected by Western blot, immunohistochemistry, and immunofluorescence in thoracic aorta, HG- and CCCP-induced HUVECs. Cell scratch test, MitoTracker Red CMXRos staining and Flou-4 AM staining were separately presented to detect migration, mitochondrial activity and intracellular CA2+ in HUVECs. Our results showed that Sal B significantly ameliorated hyperlipidemia, hyperglycemia, hyperinsulinemia, and Insulin resistance in db/db mice. Furthermore, it significantly alleviated diabetes-induced vascular endothelial dysfunction according to histopathology analysis. In diabetic thoracic aorta, HG- and CCCP-induced HUVECs, Sal B distinctly increased Bcl-2 expression and reduced Bax, Beclin1, Parkin and Pink1 expression, thereby protecting endothelial cells from Apoptosis and Mitophagy. Moreover, Sal B markedly enhanced migration, mitochondrial activity and intracellular CA2+ levels both in HG- and CCCP-induced HUVECs. Collectively, Sal B exhibited a potential to improve diabetes-induced endothelial and mitochondrial dysfunction through down-regulating Apoptosis and Mitophagy of endothelial cells.Abbreviations: DM: diabetes mellitus; T2DM: type 2 diabetes mellitus; Sal B: Salvianolic acid B; HG: high glucose; FBG: fasting blood glucose; TC: total cholesterol; TG: triglycerides; LDL-C: low-density lipoprotein cholesterol; HDL-C: high-density lipoprotein cholesterol; FINS: fasting insulin; HOMA-IR: homeostasis model assessment Insulin resistance; QUICKI: quantitative insulin-sensitivity check index; H&E: hematoxylin and eosin; HUVECs: human umbilical vein endothelial cells; IHC: immunohistochemistry; CCCP: carbonyl cyanide m-chlorophenyl hydrazone; FCM: flow cytometry; CCK-8: cell counting kit-8.

Keywords

Salvianolic acid B; apoptosis; diabetes; endothelial dysfunction; mitophagy.

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