Ginsenoside RG1 enhances the paracrine effects of bone marrow-derived mesenchymal stem cells on radiation induced intestinal injury

Content and aims: Ginsenoside RG1 (RG1) is thought to enhance proliferation and differentiation of stem cell, however, its role on paracrine efficacy of stem cell remains unclear. Here we examined if and how RG1 enhances the paracrine effects of bone marrow-derived mesenchymal stem cells (BM-MSCs) on radiation induced intestinal injury (RIII). Method: Irradiated rats randomly received intraperitoneal injection of conditioned medium (CM) derived from non-activated BM-MSCs (MSC-CM) or BM-MSCs pre-activated by RG-1 (RG1-MSC-CM). Intestinal samples were collected, followed by the evaluation of histological and functional change, apoptosis, proliferation, inflammation, angiogenesis and stem cell regeneration. The effects of heme oxygenase-1 (HO-1) were investigated using HO-1 inhibitor or siRNA. Result: RG1 enhanced the paracrine efficacy of BM-MSCs partially through upregulation of HO-1. RG1-MSC-CM rather than MSC-CM significantly improved the survival and intestinal damage of irradiated rats via improvement of intestinal proliferation/apoptosis, inflammation, angiogenesis and stem cell regeneration in a HO-1 dependent mechanism. The mechanism for the superior paracrine efficacy of RG1-MSC-CM is related to a higher release of two pivotal cytokines VEGF and IL-6. Conclusion: Our study revealed that RG1 enhances paracrine effects of BM-MSCs on RIII, providing a novel method for maximizing the paracrine potential of MSCs.