Synergistic neuroprotective effect of microglialconditioned media treated with geniposide and ginsenoside Rg1 on hypoxia injured neurons

Author：

Publisher： Spandidos Publications

E-ISSN： 1791-3004|12|4|5328-5334

ISSN： 1791-2997

Source： Molecular Medicine Reports, Vol.12, Iss.4, 2015-01, pp. : 5328-5334

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Abstract

The synergistic mechanism underlying the effects of multicomponent combined drug use for complex diseases remains to be fully elucidated. Microglial activation following ischemia can either affect neural survival or cause neuronal injury. The aim of the present study was to determine the synergistic effect of geniposide and ginsenoside Rg1, based on microglialneuronal communication. N2a neuronal cells were divided into the following seven groups: Control group; normal cultured microglial cells in conditioned medium (NMGCM) group; oxygenglucose deprivation (OGD) model group; OGDinjured MGCM (IMGCM) group; geniposidetreated MGCM (GMGCM) group; ginsenoside Rg1treated MGCM (RMGCM) group; and combinationtreated MGCM (CMGCM) group. A series of assays were used to detect the effects of the different MGCM on neurons in terms of: (i) cell viability, determined using a Cell Counting Kit8; (ii) lactate dehydrogenase (LDH) leakage rate; (iii) expression of NMDAR1 and activated caspase3, detected using western blotting; (iv) mitochondrial transmembrane potential, determined by JC1; and (v) mitochondrial ultrastructural features, determined using electron microscopy. The experimental results demonstrated that MGCM including the integrated use of geniposide and ginsenoside Rg1 significantly protected neuronal cell viability and inhibited LDH leakage, suppressed the expression of NmethylDaspartate receptor subunit 1 and activated caspase3, increased the mitochondrial transmembrane potential and improved the mitochondrial ultrastructure. MGCM from separately used geniposide or ginsenoside Rg1 demonstrated differential neuroprotection at different levels. These findings revealed that the synergistic drug combination of geniposide and ginsenoside Rg1 in the treatment of stroke is a feasible approach for use.