Article

Magnesium lithospermate B ameliorates microcirculation perfusion in rats by promoting vascular NO production via activating the PI3K/AKT pathway

Authors: Ying-luo Liu1,2, Xiao-yu Zhou1, Li-jiang Xuan3
1 State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, 555 Zuchongzhi Road, Shanghai 201203, China
2 School of Pharmacy, University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China
3 State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, 501 Haike Road, Shanghai 201203, China
Correspondence to: Li-jiang Xuan: ljxuan@simm.ac.cn,
DOI: 10.1038/s41401-018-0203-7
Received: 3 July 2018
Accepted: 4 December 2018
Advance online: 13 February 2019

Abstract

Microcirculation morphologically refers to the blood flow in vessels of less than 150 μm in diameter, including arterioles, capillaries and venules, which provides nutrients and removes metabolic byproducts within tissues. Microcirculation dysfunction is involved in the pathological progress of many diseases, such as obesity, hypertension, and insulin resistance. In this study we investigated the effects of magnesium lithospermate B (MLB), an active compound of the traditional Chinese medicine Slavia miltiorrhiza, on the microcirculation dysfunction in rats and the underlying molecular mechanisms. The effects of MLB on microcirculation were assessed in vivo by measuring the hindlimb blood perfusion in dextran-induced microcirculation dysfunction rats and mesentery blood flow in anesthetized rats. We demonstrated that administration of MLB restored the impaired rat hindlimb blood flow and promoted the mesenteric micoperfusion in vivo. We further revealed in these two animal models that MLB treatment significantly increased the production of total nitrite in vascular tissues (mesentery, aorta, and heart), which was confirmed in human microvascular endothelial cells (HMEC-1) treated with MLB in vitro. Moreover, we showed that MLB treatment significantly increased the phosphorylation of endothelium nitric oxide synthase (eNOS) via inducing AKT phosphorylation in vivo and in vitro. Co-administration of the eNOS inhibitor L-NAME (20 mg/kg) abolished the protective effects of MLB against dextran-induced microcirculation dysfunction in rats, whereas pretreatment with PI3K inhibitor LY294002 (10 μM) prevented eNOS activation in MLB-treated HMEC-1 cells. Our results suggest that MLB can restore the microcirculation dysfunction via activating eNOS, and in turn enhancing the vascular nitric oxide production, which is medicated by MLB-caused activation of the PI3K/AKT pathway.
Keywords: traditional Chinese medicine; Salvia miltiorrhiza; magnesium lithospermate B; microcirculation dysfunction; NO; endothelium nitric oxide synthase; PI3K/AKT pathway

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