Ginger Ethanolic Extract Mitigates Oxidative Stress and Apoptotic Signaling Following Serum Deprivation and Hydrogen Peroxide Exposure in Bone Marrow Mesenchymal Stem Cells

Document Type : Research Article

Authors

1 Herbal and Traditional Medicines Research Center, Institute of Pharmaceutical Sciences, Kerman University of Medical Sciences, Kerman, Iran

2 Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran

3 Applied Cellular and Molecular Research Center, Kerman University of Medical Sciences, Kerman, Iran

4 Pharmaceutical Sciences and Cosmetic Products Research Center, Institute of Pharmaceutical Sciences, Kerman University of Medical Sciences, Kerman, Iran

5 Pharmaceutics Research Center, Institute of Pharmaceutical Sciences, Kerman University of Medical Sciences, Kerman, Iran

6 Student Research Committee, Kerman University of Medical Science, Kerman, Iran

7 Nervous System Stem Cells Research Center, Neuroscience Research Institute, Semnan University of Medical Sciences, Semnan, Iran

8 Immunogenetics Research Center, Mazandaran University of Medical Sciences, Sari, Iran

9 Institute of Animal Pathology, Vetsuisse Faculty, University of Bern, Bern, Switzerland

Abstract

Engraftment of bone marrow mesenchymal stem cells (BM-MSCs) exhibited promise for treating various disorders; however, oxidative stress-related lesions impair their survival and therapeutic potential during transplantation. Promoting their antioxidant capacity is therefore important. Here, we investigated whether ginger, as a medicinal plant, could attenuate oxidative stress-induced apoptosis in rat BM-MSCs in vitro and elucidated the underlying molecular pathways. rBM-MSCs were pretreated with serum-free media containing different concentrations of ginger ethanolic extract (3, 6, 12, 25 and 50 μg/mL), followed by hydrogen peroxide (H2O2) exposure (300 µM) for 3.5 h. Cell viability was assessed by a water-soluble tetrazolium salt assay. The antioxidant activity of the ethanolic extract of ginger (EEG) was also evaluated by total antioxidant capacity (TAC) and thiobarbituric acid reactive substances (TBARS) assays. The expression of proapoptotic and antiapoptotic proteins was examined by western blotting. All experiments were performed in triplicate using independent biological replicates. The results indicated that the ethanolic extract of dried ginger rhizome meaningfully elevated the viability of rBM-MSCs and protected them against H2O2-induced oxidative stress. Treatment with EEG (50 µg/mL) resulted in statistically significant reductions in lipid peroxidation, the Bax/Bcl-2 ratio, and cleaved caspase-3 levels (all P < 0.001), along with a statistically significant increase in TAC (P < 0.01). Our data support that EEG pretreatment may also protect rBM-MSCs from oxidative stress and boost their therapeutic efficacy by downregulating the proapoptotic/antiapoptotic protein ratio following transplantation.

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