Gypenoside XVII is a novel phytoestrogen primarily isolated from the plants Gynostemma pentaphyllum and Panax notoginseng and dose-dependently decreases glutamate release of with a IC50 value of 16µM[1]. Gypenoside XVII has neuroprotective and cardiovascular benefits, which make it a potential candidate for the development of treatments for conditions such as atherosclerosis and Alzheimer's disease[2][3][5][7]. Furthermore, the estrogenic properties of Gypenoside XVII could be explored for hormone replacement therapy[4][6].
In vitro, Gypenoside XVII has protective effects against atherosclerosis. Gypenoside XVII(3.125-100μg/mL) incubation for 24h dose-dependently mitigated the toxic effect of oxidized low-density lipoprotein (Ox-LDL）on human umbilical vein endothelial cell (HUVEC) viability. Incubation of HUVECs with Gypenoside XVII (50μg/mL) for 12h before exposure to Ox-LDL markedly reduced the ROS generation and increased Antioxidant Defense via the ERα/PI3K/Akt Pathway[2]. Gypenoside XVII (100μg/mL) treated Ox-LDL-induced THP-1 macrophage-derived foam cells for 24h, exhibiting protective effects by enhancing cholesterol efflux and mitigating inflammation via upregulating ABCA1, ABCG1, and miR-182–5p expression while downregulating HDAC9, and facilitating the M2 macrophage phenotype and curbing the inflammatory response[3]. Pretreated with rat pheochromocytoma PC-12 cells with Gypenoside XVII (10μM) for 12h conferred protection against Aβ25–35-induced neurotoxicity through estrogen receptor-dependent activation of PI3K/Akt pathways, inactivation of GSK-3β and activation of Nrf2/ARE/HO-1 pathways[4].
In vivo, Gypenoside XVII (50mg/kg) administered into ApoE−/− mice via intragastric gavage (i.g.) once a day for 10 weeks reduced the serum lipid levels, increase expression of antioxidant enzymes and decrease atherosclerotic lesion formation in ApoE−/− mice[5]. Gypenoside XVII (1, 2.5, 5 and 10mg/kg) orally administrated once produced the antidepressant-like effects in mice, which was mediated by the inhibition of complement C3/C3aR/STAT3/cytokine signaling in the prefrontal cortex[6]. Gypenoside XVII (40mg/kg) administered by gavage for 60 days significantly improved the spatial learning and memory abilities of double-transgenic APPswe/PS1dE9 (APP/PS1) mice, reduced Aβ deposition and AβPP expression, and enhanced autophagy and lysosomal biosynthesis by activating TFEB. These results suggest that Gypenoside XVII may be a promising candidate drug for the prevention and treatment of Alzheimer's disease[7].
References:
[1] Lu C W, Lin T Y, Chiu K M, et al. Gypenoside XVII Reduces Synaptic Glutamate Release and Protects against Excitotoxic Injury in Rats. Biomolecules. 2024 May 16;14(5):589.
[2] Yang K, Zhang H J, Luo Y, et al. Gypenoside XVII Prevents Atherosclerosis by Attenuating Endothelial Apoptosis and Oxidative Stress: Insight into the ERα-Mediated PI3K/Akt Pathway. Int J Mol Sci. 2017 Feb 9;18(2):77.
[3] Deng W Y, Zhou C L, Zeng M Y. Gypenoside XVII inhibits ox-LDL-induced macrophage inflammatory responses and promotes cholesterol efflux through activating the miR-182-5p/HDAC9 signaling pathway. J Ethnopharmacol. 2024 Jan 30;319(Pt 1):117070.
[4] Meng X B, Wang M, Sun G B, et al. Attenuation of Aβ25-35-induced parallel autophagic and apoptotic cell death by gypenoside XVII through the estrogen receptor-dependent activation of Nrf2/ARE pathways. Toxicol Appl Pharmacol. 2014 Aug 15;279(1):63-75.
[5] Wang J R, Yu Y L, Zhang H R, et al. Gypenoside XVII attenuates renal ischemia-reperfusion injury by inhibiting endoplasmic reticulum stress and NLRP3 inflammasome-triggered pyroptosis. Eur J Pharmacol. 2024 Jan 5:962:176187.
[6] Zhang M M, G H, Cheng J, et al. Gypenoside XVII, an Active Ingredient from Gynostemma Pentaphyllum, Inhibits C3aR-Associated Synaptic Pruning in Stressed Mice. Nutrients. 2022 Jun 10;14(12):2418.
[7] Meng X B, Luo Y, Liang T, et al. Gypenoside XVII Enhances Lysosome Biogenesis and Autophagy Flux and Accelerates Autophagic Clearance of Amyloid-β through TFEB Activation. J Alzheimers Dis. 2016 Apr 5;52(3):1135-50.
Gypenoside XVII是一种新型植物雌激素，主要从植物绞股蓝和三七中分离得到，可剂量依赖性地降低谷氨酸释放，IC50值为16µM[1]。Gypenoside XVII具有神经保护和心血管益处，使其有望成为治疗动脉粥样硬化和阿尔茨海默病等疾病的潜在候选药物[2][3][5][7]。此外，Gypenoside XVII的雌激素特性可用于激素替代疗法的研究[4][6]。
体外研究显示，Gypenoside XVII对动脉粥样硬化具有保护作用。Gypenoside XVII（3.125-100µg/mL）与人脐静脉内皮细胞（HUVEC）共孵育24h，可剂量依赖性地减轻氧化低密度脂蛋白（Ox-LDL）对HUVEC细胞活性的毒性影响。在暴露于Ox-LDL前12h用Gypenoside XVII（50µg/mL）孵育HUVECs，可显著降低活性氧（ROS）生成，并通过雌激素受体α/PI3K/Akt通路增强抗氧化防御[2]。Gypenoside XVII（100µg/mL）处理Ox-LDL诱导的THP-1巨噬细胞来源的泡沫细胞24h，通过上调ABCA1、ABCG1和miR-182-5p表达，下调HDAC9，促进M2型巨噬细胞表型，抑制炎症反应，从而发挥保护作用[3]。用Gypenoside XVII（10µM）预处理大鼠嗜铬细胞瘤PC12细胞12h，可通过雌激素受体依赖的PI3K/Akt通路激活、GSK-3β失活以及Nrf2/ARE/HO-1通路激活，对Aβ25-35诱导的神经毒性提供保护[4]。
体内研究方面，Gypenoside XVII（50mg/kg）通过灌胃给ApoE⁻/⁻小鼠每天一次，连续10周，可降低血清脂质水平，增加抗氧化酶表达，并减少ApoE⁻/⁻小鼠的动脉粥样硬化病变形成[5]。Gypenoside XVII（1、2.5、5和10mg/kg）单次口服给药抑郁症小鼠模型，可产生抗抑郁样效应，其机制是通过抑制前额叶皮质中补体C3/C3aR/STAT3/细胞因子信号通路[6]。Gypenoside XVII（40mg/kg）灌胃给药60天，显著改善了双转基因APPswe/PS1dE9（APP/PS1）小鼠的空间学习和记忆能力，减少Aβ沉积和AβPP表达，并通过激活TFEB增强自噬和溶酶体生物合成。这些结果表明，Gypenoside XVII可能是预防和治疗阿尔茨海默病的有前景的候选药物[7]。