Panax Notoginseng Protects against Diabetes-Associated Endothelial Dysfunction: Comparison between Ethanolic Extract and Total Saponin.

Xutao Zhang,Yitao Wang,Yan Zhou,Yi Tan,Yu Huang,Hua Yu,Meng Sam Cheong,Wai San Cheang,Lingchao Miao,Chunxiu Zhou,Yanwei Xing

doi:10.1155/2021/4722797

Xutao Zhang, Yitao Wang + Show 9 more

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https://doi.org/10.1155/2021/4722797

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Abstract

Previous studies revealed a cardioprotective potential of Panax notoginseng to relieve acute myocardial infarction and focal cerebral ischemia-reperfusion. However, whether P. notoginseng protects endothelial function in diabetes and the underlying mechanisms remain to be explored. P. notoginseng contains several chemical components including saponins, which are commonly believed as the major bioactive ingredients. The present study was aimed to examine and compare the vaso-protective effects of the ethanolic extract of P. notoginseng (PNE) and total saponin (PNS). Both aortas and carotid arteries were isolated from male C57BL/6J mice for ex vivo treatment with risk factors (high glucose or tunicamycin) with and without the presence of PNS and PNE. Diabetic model was established by feeding the mice with a high-fat diet (45% kcal% fat) for 12 weeks, while PNS and PNE were administrated by oral gavage at 20 mg/kg/day for another 4 weeks. Ex vivo exposure to high glucose impaired acetylcholine-induced endothelium-dependent relaxations in mouse aortas, decreased phosphorylation of AMPK and eNOS, and induced endoplasmic reticulum (ER) stress and oxidative stress. These effects were reversed by cotreatment of PNS and PNE with PNS being more potent. Furthermore, the vaso-protective effects were abolished by Compound C (AMPK inhibitor). Chronic treatment with PNS and PNE improved endothelium-dependent relaxations and alleviated ER stress and oxidative stress in aortas from high-fat diet-induced obese mice. PNE was more effective to improve glucose sensitivity and normalize blood pressure in diabetic mice. The present results showed that PNS and PNE reduced ER stress and oxidative stress and, subsequently, improved endothelial function in diabetes through AMPK activation. This study provides new inspiration on the therapeutic potential of P. notoginseng extract against vascular diseases associated with metabolic disorders.

Highlights

For the insulin tolerance test (ITT), mice after 2-h fasting were injected with insulin (0.5 U/kg body weight) intraperitoneal, and the blood glucose levels were detected at the same time intervals as oral glucose tolerance test (OGTT)
Our observations are in line with these previous studies, reporting that ex vivo high glucose exposure impaired Endothelium-dependent relaxations (EDRs) and stimulated reactive oxygen species (ROS) production, which were reversed by cotreatment of P. notoginseng saponins (PNS) and P. notoginseng (PNE)
The present results show that both PNS and PNE effectively improved high glucose-induced endothelial dysfunction with alleviation of endoplasmic reticulum (ER) stress and oxidative stress through the AMPK/endothelial nitric oxide synthase (eNOS) pathway

Summary

Introduction

Notoginsenoside R1 was reported to prevent cardiomyocyte apoptosis and ischemic/reperfusion injuries via inhibition of signaling pathways related to oxidative stress and endoplasmic reticulum (ER) stress [11]. Another recent study showed that PNS protect against thapsigargin-induced mitochondrial injury, reducing ROS accumulation and Ca2+-dependent ER stress [12]. Our previous findings support that ER stress induces ROS production and endothelial dysfunction; and that alleviation of ER stress and oxidative stress protects against diabetic vasculopathy [21, 22]. We examined and compared the vaso-protective effects of total ethanolic extract of P. notoginseng (PNE) and PNS in alleviating ER stress and endothelial dysfunction associated with diabetes in vitro and in vivo

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