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Ginsenoside Rb1 reduces H2O2?induced HUVEC dysfunction by stimulating the sirtuin?1/AMP?activated protein kinase pathway.

ABSTRACT: Endothelial dysfunction and senescence are closely associated with cardiovascular diseases including atherosclerosis and hypertension. Ginsenoside Rb1 (Rb1), the major active constituent of ginseng, has been investigated intensively because of its anti?obesity and anti?inflammatory effects. In a previous study, hydrogen peroxide (H2O2) was applied to induce human umbilical vein endothelial cell (HUVEC) aging. It was demonstrated that Sirtuin?1 (SIRT1) was activated by Rb1 to protect HUVECs from H2O2?induced senescence. However, the mechanisms are not fully understood. The present study examined the role of AMP?activated protein kinase (AMPK), an energy sensor of cellular metabolism, in the signaling pathway of SIRT1 during H2O2?stimulated HUVEC aging. It was identified that Rb1 restored the H2O2?induced reduction of SIRT1 expression, which was consistent with our previous study, together with the activation of AMPK phosphorylation. Using compound C, an AMPK inhibitor, the role of AMPK in the protective effect of Rb1 against H2O2?induced HUVEC senescence was examined. It was identified that the induction of phosphorylated AMPK by Rb1 markedly increased endothelial nitric oxide synthase expression and nitric oxide production, and suppressed PAI?1 expression, which were abrogated in HUVECs pretreated with compound C. Further experiments demonstrated that nicotinamide, a SIRT1 inhibitor, downregulated the phosphorylation of AMPK and reduced the protective effects of Rb1 against H2O2?induced endothelial aging. Taken together, these results provide new insights into the possible molecular mechanisms by which Rb1 protects against H2O2?induced HUVEC senescence via the SIRT1/AMPK pathway.

SUBMITTER: Zheng Z

PROVIDER: S-EPMC7248484 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Ginsenoside Rb1 reduces H2O2‑induced HUVEC dysfunction by stimulating the sirtuin‑1/AMP‑activated protein kinase pathway.

Zheng Zhenda Z Wang Min M Cheng Cailian C Liu Dinghui D Wu Lin L Zhu Jieming J Qian Xiaoxian X

Molecular medicine reports 20200428 1

Endothelial dysfunction and senescence are closely associated with cardiovascular diseases including atherosclerosis and hypertension. Ginsenoside Rb1 (Rb1), the major active constituent of ginseng, has been investigated intensively because of its anti‑obesity and anti‑inflammatory effects. In a previous study, hydrogen peroxide (H2O2) was applied to induce human umbilical vein endothelial cell (HUVEC) aging. It was demonstrated that Sirtuin‑1 (SIRT1) was activated by Rb1 to protect HUVECs from ...[more]

PMID: 32377712

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Project description:Osteoporosis (OP) is a systemic skeletal disorder, manifesting with a reduction in bone mass and deterioration of the microarchitecture. Mesenchymal stem cells (MSCs) have an innate ability to differentiate into several cell types, including osteoblasts (OB). Ginsenoside Rb1 (GRb1) is an ethanol extract from ginseng and contains a highly concentrated form of ginsenoside. GRb1 shows extensive beneficial health effects such as anti-oxidative and anti-inflammatory functions, modulating the immune system and inhibiting osteoclastogenesis. We hypothesized that GRb1 can promote MSC differentiation into OBs and inhibit bone loss. In the present study, we aimed to address two questions: (1) Will GRb1 have a positive effect on osteogenic differentiation of MSCs? and (2) Will GRb1 halt bone loss in ovariectomized (OVX) rats? We investigated the effects of GRb1 on viability and osteogenic differentiation of rat mesenchymal stem cells (rMSCs). Our results showed that GRb1 at concentrations of 10-8 M and 10-6 M can increase alkaline phosphatase activity, mineralization and the expression of osteogenic related proteins, such as osteopontin and osteoprotegerin, while incubating rMSCs with osteogenic induction medium and GRb1. Adding GRb1 into the medium can prevent rMSCs from Oxidative damage at the concentration of 25?M H2O2. Furthermore, 40 4-month-old rats were assigned to 5 groups(8 rats per group): the basal group, the sham group, the OVX group, the high dose of GRb1 group (6 mg/kg/day) and the low dose of GRb1 group (3 mg/kg/day). Rats recrived treatment 3days after surgery and last for 14 weeks. Examinations included serum analysis, mechanical testing, Masson-Goldner trichrome staining and bone histomorphometry analysis. The results showed that OVX can lead to dyslipidemia and excessive oxidative stress, whereas GRb1 cannot significantly halt dyslipidemia and excessive oxidative stress in OVX rats. In addition, the bone density of the lumbar vertebra and femur were decreased significantly in the OVX rats, and GRb1 could not inhibit bone loss. Bone histomorphometry analysis showed that the number and width of bone trabecula of the tibia were reduced in OVX rats, and GRb1 could not prevent their occurrence. A bone biomechanics assay showed that GRb1 cannot improve the ability of bone structure to resist fracture of the femur in OVX rats. The current study demonstrated that GRb1 has an obvious effect on osteogenic differentiation in rMSCs but no obvious effect on bone loss in OVX rats. These findings indicate GRb1 has a positive effect on rMSCs but does not have an effect on bone loss in OVX rats at the concentration we used.

Dataset Information

Ginsenoside Rb1 reduces H2O2?induced HUVEC dysfunction by stimulating the sirtuin?1/AMP?activated protein kinase pathway.

Publications

Ginsenoside Rb1 reduces H2O2‑induced HUVEC dysfunction by stimulating the sirtuin‑1/AMP‑activated protein kinase pathway.

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