Department of Pharmacology of Chinese Materia Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, No. 639 Longmian Road, Nanjing 211198, China.
State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, No. 24 Tongjiaxiang, Nanjing 210009, China.
Phytomedicine. 2019 May;58:152745. doi: 10.1016/j.phymed.2018.11.006. Epub 2018 Nov 5.
Rare ginsenosides are found in ginseng and notoginseng, two medicinal plants widely used in China for treatment of cardiovascular diseases and type 2 diabetes. However, their pharmacological studies regarding myocardial fuel metabolism and insulin signaling are not clear.
To explore the effect of a rare ginsenoside-standardized extract (RGSE), derived from steamed notoginseng, on cardiac fuel metabolism and insulin signaling.
We used palmitic acid (PA) to treat H9c2 cells in vitro and high fat diet (HFD) to mice to induce insulin resistance in vivo.
In vitro, differentiated H9c2 cells were pretreated with RGSE, metformin, mildronate or dichloroacetate (DCA) and stimulated with PA. In vivo, mice were fed with HFD and received RGSE, metformin or DCA for 6 weeks. Protein expression was determined by Western blotting. Mitochondrial membrane potential (Δψm), glucose uptake and reactive oxygen species (ROS) production were measured by fluorescence labeling. Other assessments including oxygen consumption rate (OCR) were also performed.
RGSE prevented PA-induced decrease in pyruvate dehydrogenase (PDH) activity and increase in carnitine palmitoyltransferase 1 (CPT1) expression, and ameliorated insulin-mediated glucose uptake and utilization in H9c2 cells. Metformin and mildronate exhibited similar effects. In vivo, RGSE counteracted HFD-induced increase in myocardial expression of p-PDH and CPT1 and ameliorated cardiac insulin signaling. Metformin and DCA also showed beneficial effects. Further study showed that RGSE decreased OCR and mitochondrial complex I activity in PA-treated H9c2 cells, reduced ROS production and relieved mitochondrial oxidative stress, thus decreased serine phosphorylation in IRS-1.
RGSE ameliorated myocardial insulin sensitivity under conditions of lipid overload, which was tightly associated with the decrease in mitochondrial oxidative stress via modulating glucose and fatty acid oxidation.
人参和三七是两种药用植物，都含有罕见的人参皂苷，在中国广泛用于治疗心血管疾病和 2 型糖尿病。然而，它们在心肌燃料代谢和胰岛素信号方面的药理学研究尚不清楚。
探讨源于蒸制三七的罕见人参皂苷标准化提取物（RGSE）对心脏燃料代谢和胰岛素信号的影响。
我们在体外使用棕榈酸（PA）处理 H9c2 细胞，在体内使用高脂肪饮食（HFD）诱导胰岛素抵抗。
在体外，用 RGSE、二甲双胍、米力农或二氯乙酸（DCA）预处理分化的 H9c2 细胞，然后用 PA 刺激。在体内，用 HFD 喂养小鼠，并给予 RGSE、二甲双胍或 DCA 治疗 6 周。通过 Western blot 测定蛋白质表达。通过荧光标记测定线粒体膜电位（Δψm）、葡萄糖摄取和活性氧（ROS）产生。还进行了其他评估，包括耗氧量（OCR）。
RGSE 可预防 PA 诱导的丙酮酸脱氢酶（PDH）活性降低和肉碱棕榈酰转移酶 1（CPT1）表达增加，并改善 H9c2 细胞中胰岛素介导的葡萄糖摄取和利用。二甲双胍和米力农也表现出相似的作用。在体内，RGSE 可拮抗 HFD 诱导的心肌 PDH 和 CPT1 表达增加，并改善心脏胰岛素信号。二甲双胍和 DCA 也有有益的作用。进一步的研究表明，RGSE 降低了 PA 处理的 H9c2 细胞中的 OCR 和线粒体复合物 I 活性，减少了 ROS 产生并缓解了线粒体氧化应激，从而减少了 IRS-1 的丝氨酸磷酸化。
RGSE 可改善脂质超负荷条件下的心肌胰岛素敏感性，这与通过调节葡萄糖和脂肪酸氧化来降低线粒体氧化应激密切相关。
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