SIRT3 suppresses vascular endothelial senescence via DHRS2 and contributes to the anti-vascular aging effect of Bazi Bushen capsule

IF 6.7 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine Pub Date : 2025-02-25 DOI:10.1016/j.phymed.2025.156571

Yuan Zhao , Chunmei Zhang , Chen Zhang , Xuehui Zheng , Yan Qi , Binghui Kong , Yunlong Hou , Yun Ti , Peili Bu

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引用次数: 0

Abstract

Aims

Vascular and endothelial aging are significant causes of chronic diseases among the elderly. This study investigated the specific mechanism by which sirtuin 3 (SIRT3) regulates vascular endothelial senescence and the beneficial role of Bazi Bushen capsule (BZBS) in preventing vascular aging.

Methods

Human umbilical vein endothelial cells and mouse aortic endothelial cells were cultured with D-galactose (D-gal) to induce aging and evaluate the beneficial effects of the SIRT3-dehydrogenase/reductase member 2 (DHRS2) axis on the inhibition of vascular endothelial aging. d-Gal was injected intraperitoneally into wild-type and Sirt3 knockout mice, while BZBS was administered orally. Histochemical staining, immunohistochemistry, and western blotting assays were used to explore the beneficial effects of BZBS against aging-associated vascular remodelling. Endothelial cell function assays were used to evaluate the role of BZBS in suppressing endothelial aging in vitro.

Results

SIRT3 deacetylated DHRS2 and modulated the translation of DHRS2. The SIRT3-DHRS2 axis played an important role in preserving mitochondrial homeostasis and reducing reactive oxygen species generation through suppressing endothelial nitric oxide synthase (eNOS) translocating to mitochondria and eNOS-Thr495 phosphorylation mediated by protein kinase C δ (PKCδ). BZBS mitigated vascular remodelling and relieved endothelial oxidative stress via the SIRT3-DHRS2 axis.

Conclusion

SIRT3 activates DHRS2-PKCδ to stop aging in endothelial cells by inhibiting uncoupled eNOS translocating to mitochondria. BZBS rescued vascular aging and endothelial dysfunction via the SIRT3-DHRS2 axis. Revealing a protective mechanism by which SIRT3 inhibits endothelial senescence, this study provides evidence for BZBS in delaying vascular aging.

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来源期刊

Phytomedicine 医学-药学

CiteScore

10.30

自引率

5.10%

发文量

670

审稿时长

91 days

期刊介绍： Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.