Ginkgolide B Combined With Umbilical Cord Mesenchymal Stem Cell‐Derived Exosomes Alleviate Diabetic Nephropathy by Modulating the Nuclear Factor Erythroid‐2‐Related Factor 2/Heme Oxygenase 1 Pathway

Diabetic nephropathy (DN) is the main reason for the emergence of end-stage renal disease. Both ginkgolide B (GB) and umbilical cord mesenchymal stem cell-derived exosomes can improve DN, but their combination efficacy is unknown. High glucose (HG)-induced SV40-MES13 cells and streptozotocin-injected high-fat diet mice were treated with MSC-Exos alone or in combination with GB. The activities of reactive oxygen species, malondialdehyde (MDA), glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) were analyzed by commercial kits. Pro-inflammatory factors tumor necrosis factor alpha, interleukin-1beta, and interleukin-6 were detected by ELISA. Protein levels of collagen I, fibronectin, alpha smooth muscle actin, nuclear factor erythroid-2-related factor 2 (NRF2), heme oxygenase 1 (HO1), and NAD(P)H:quinine oxidoreductase (NQO1) were assessed by western blot. Pathological changes in mouse kidneys were determined by HE, Masson's, and PAS staining. Both MSC-Exos alone and in combination with GB alleviated HG-induced SV40-MES13 cell OxS, inflammation, and fibrosis. Moreover, MSC-Exos alone and in combination with GB attenuated pathological changes and repressed inflammation and fibrosis in DN mice. Importantly, MSC-Exos was less effective than MSC-Exos in combination with GB. Furthermore, GB plus MSC-Exos activated the NRF2/HO1/NQO1 pathway in HG-induced SV40-MES13 cells and DN mouse models. GB plus umbilical cord MSC-Exos attenuates pathological changes in DN via repressing inflammation, oxidative stress, and fibrosis by activating the NRF2/HO1/NQO1 pathway.