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.