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In Vitro Evaluation of the Neuroprotective Effect of Panax notoginseng Saponins by Activating the EGFR/PI3K/AKT Pathway.

ABSTRACT: Objective:This study investigated whether Panax notoginseng saponins (PNS) extracted from Panax notoginseng (Bruk.) F. H. Chen played a neuroprotective role by affecting the EGFR/PI3K/AKT pathway in oxygen-glucose deprived (OGD) SH-SY5Y cells. Materials and Methods:Different groups of OGD SH-SY5Y cells were treated with varying doses of PNS, PNS?+?AG1478 (a specific inhibitor of EGFR), or AG1478 for 16 hours. CCK8, Annexin V-FITC/PI apoptosis analysis, and LDH release analysis were used to determine cell viability, apoptosis rate, and amounts of LDH. Quantitative real-time PCR (q-RT-PCR) and western blotting were used to measure mRNA and proteins levels of p-EGFR/EGFR, p-PI3K/PI3K, and p-AKT/AKT in SH-SY5Y cells subjected to OGD. Results:PNS significantly enhanced cell viability, reduced apoptosis, and weakened cytotoxicity by inhibiting the release of LDH. The mRNA expression profiles of EGFR, PI3K, and AKT showed no difference between model and other groups. Additionally, ratios of p-EGFR, p-PI3K, and p-AKT to EGFR, PI3K, and AKT proteins expression, respectively, all increased significantly. Conclusions:These findings indicate that PNS enhanced neuroprotective effects by activating the EGFR/PI3K/AKT pathway and elevating phosphorylation levels in OGD SH-SY5Y cells.

SUBMITTER: Wu S

PROVIDER: S-EPMC7415117 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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In Vitro Evaluation of the Neuroprotective Effect of <i>Panax notoginseng</i> Saponins by Activating the EGFR/PI3K/AKT Pathway.

Wu Shuang S Yang Tiantian T Cen Kai K Zou Yihuai Y Shi Xiaowei X Zhou Dongrui D Gao Yonghong Y Chai Limin L Zhao Yizhou Y Sun Yikun Y Zhu Lingqun L

Evidence-based complementary and alternative medicine : eCAM 20200731

<h4>Objective</h4>This study investigated whether <i>Panax notoginseng</i> saponins (PNS) extracted from <i>Panax notoginseng</i> (Bruk.) F. H. Chen played a neuroprotective role by affecting the EGFR/PI3K/AKT pathway in oxygen-glucose deprived (OGD) SH-SY5Y cells.<h4>Materials and methods</h4>Different groups of OGD SH-SY5Y cells were treated with varying doses of PNS, PNS + AG1478 (a specific inhibitor of EGFR), or AG1478 for 16 hours. CCK8, Annexin V-FITC/PI apoptosis analysis, and LDH releas ...[more]

PMID: 32802113

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Project description:Panax notoginseng saponins (PNS) are a commonly used traditional medicine to treat diabetes in China. Recent studies have confirmed their anti-diabetic effects, but the underlying mechanisms have remained unclear. The present study was designed to explore whether PNS decrease hyperglycemia by improving insulin sensitivity in skeletal muscle and to elucidate the molecular mechanisms. The anti-diabetic effects of PNS were analyzed in a skeletal myoblast cell line, C2C12, and in high fat diet-induced diabetic KKAy mice. C2C12 cells were treated with PNS (50, 100, and 200 μg·L-1 ) and examined for glucose uptake, cell viability and expression of components of the phosphoinositide 3-kinase (PI3K)-protein kinase B (AKT) signaling pathway. KKAy mice were intraperitoneally injected with PNS (200 mg·kg-1 ) for 6 weeks. Body weight, blood glucose, serum insulin, serum lipid, glucose and insulin tolerance were measured to evaluate the anti-diabetic effects of PNS. Pathological changes, apoptosis and the PI3K-AKT signaling pathway were analyzed in KKAy skeletal muscle. PNS significantly increased insulin-induced glucose uptake, but did not affect the cell viability of C2C12 cells. In addition, PNS reduced blood glucose and serum insulin levels and improved glucose tolerance and insulin tolerance of KKAy mice. Pathological changes and apoptosis of skeletal muscle were relieved by PNS treatment. Moreover, PNS treatment enhanced expression of mRNA encoding IRS1 and GLUT4, as well as the protein expression of phosphorylated (p) -insulin receptor substrate 1 (IRS1), p-PI3K, p-AKT and glucose transporter type 4 (GLUT4) in C2C12 and KKAy mouse muscle. Collectively, these data indicate that PNS reduces hyperglycemia and insulin resistance through up-regulating GLUT4 expression and the IRS1-PI3K-AKT signaling pathway. Furthermore, PNS alleviated diabetes skeletal muscle pathological damage. Thus, our data suggest that PNS may be promising anti-diabetic compounds.

Dataset Information

In Vitro Evaluation of the Neuroprotective Effect of Panax notoginseng Saponins by Activating the EGFR/PI3K/AKT Pathway.

Publications

In Vitro Evaluation of the Neuroprotective Effect of <i>Panax notoginseng</i> Saponins by Activating the EGFR/PI3K/AKT Pathway.

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