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

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 MLBtreated 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.

Magnesium lithospermate B supplementation improved prenatal Bisphenol A exposure‐induced metabolic abnormalities in male offspring

“…Its estrogenic activity may partly explain gender differences in disease susceptibility 33 . Studies have indicated the antiobesity effects of MLB involving the activation of Akt signaling and amelioration of endoplasmic reticulum stress, insulin resistance, and inflammation 16,34,35 . Despite the limited evidence, the current findings demonstrated an altered glucocorticoid receptor and PPARγ axis in BPA‐exposed rats and their reversal by MLB.…”

β-Hydroxybutyrate inhibits histone deacetylase 3 to promote claudin-5 generation and attenuate cardiac microvascular hyperpermeability in diabetes

“…Cardiovascular disease is the principal cause of death and morbidity among people with diabetes, who have a two-to fourfold increased cardiovascular risk compared with adults without diabetes [1]. The cardiac microvasculature refers to vessels <150 μm in diameter, which provide nutrients and remove metabolic byproducts within the heart tissue [2]. Endothelial dysfunction is the initial factor and early pathological manifestation leading to diabetic microvascular diseases, which are believed to play important pathophysiological roles in the development of heart failure [3,4].…”

Magnesium Lithospermate B Downregulates the Levels of Blood Pressure, Inflammation, and Oxidative Stress in Pregnant Rats with Hypertension

“…VEGF is involved in both vasculogenesis and angiogenesis, which are critical for the development of the placenta. Previous study suggested that MLB can restore the microcirculation dysfunction via activating eNOS, and in turn, enhancing the vascular NO production [ 10 ]. In the present study, MLB also rescued the expressions of VEGF and NO, indicating the protective effect of MLB on the placental development.…”

“…Magnesium lithospermate B (MLB), an active component of the water-soluble fraction of Salvia miltiorrhiza , is noted for scavenging oxygen free radicals, protecting cell mitochondria, improving energy metabolism, and regulating gene expression. The protective effects of MLB on cerebral/hepatic/myocardial ischemia/reperfusion injury and renal injury together with vascular endothelial dysfunction via regulating inflammation and oxidative stress have been extensively demonstrated [ 10 – 14 ]. In another report, MLB was shown to prevent phenotypic transformation of pulmonary arteries with pulmonary hypertension and alleviate sodium-induced hypertension and renal failure in rats [ 15 , 16 ].…”