Ting-Ting Chang1, Yi-An Chen1, Szu-Yuan Li2, Jaw-Wen Chen3. 1. Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan. 2. Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan; Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan. 3. Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Healthcare and Services Center, Taipei Veterans General Hospital, Taiwan; Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan; Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan. Electronic address: jwchen@vghtpe.gov.tw.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Ginkgo biloba extract (GbE) is derived from a medicinal plant and suggested as a treatment for diabetic nephropathy (DN), but the mechanism was not clarified. AIM OF STUDY: The present study investigated whether GbE prevented DN via activation of heme oxygenase (HO)-1. MATERIALS AND METHODS: Streptozotocin-induced diabetic mice were fed a high-fat diet to generate DN. Human and murine podocytes were used for the in vitro study. RESULTS: GbE improved renal function via decreasing glomerular hypertrophy, the kidney/body weight ratio, and albuminuria in DN mice. GbE reversed the reduction of synaptopodin and nephrin and enhanced HO-1 expression in the kidneys of DN mice. GbE decreased the enhancement of TNF-α, IL-6, fibronectin, and lipid accumulation in the glomeruli of DN mice. GbE attenuated the uptake of oxidized low-density lipoprotein and reduced the production of ROS in high glucose-stimulated podocytes, and HO-1 inhibitor treatment abrogated the protective effects of GbE. Nuclear factor erythroid 2-related factor 2 (Nrf-2) siRNA significantly abolished the beneficial effects of GbE via decreased HO-1 expression and enhanced TNF-α and IL-6 levels. CONCLUSIONS: GbE protected podocytes against hyperglycemia and prevented the development of DN via Nrf-2/HO-1 activation. Our findings provide further mechanistic insight into the potential use of GbE in clinical DN.
ETHNOPHARMACOLOGICAL RELEVANCE: Ginkgo biloba extract (GbE) is derived from a medicinal plant and suggested as a treatment for diabetic nephropathy (DN), but the mechanism was not clarified. AIM OF STUDY: The present study investigated whether GbE prevented DN via activation of heme oxygenase (HO)-1. MATERIALS AND METHODS:Streptozotocin-induced diabeticmice were fed a high-fat diet to generate DN. Human and murine podocytes were used for the in vitro study. RESULTS: GbE improved renal function via decreasing glomerular hypertrophy, the kidney/body weight ratio, and albuminuria in DN mice. GbE reversed the reduction of synaptopodin and nephrin and enhanced HO-1 expression in the kidneys of DN mice. GbE decreased the enhancement of TNF-α, IL-6, fibronectin, and lipid accumulation in the glomeruli of DN mice. GbE attenuated the uptake of oxidized low-density lipoprotein and reduced the production of ROS in high glucose-stimulated podocytes, and HO-1 inhibitor treatment abrogated the protective effects of GbE. Nuclear factor erythroid 2-related factor 2 (Nrf-2) siRNA significantly abolished the beneficial effects of GbE via decreased HO-1 expression and enhanced TNF-α and IL-6 levels. CONCLUSIONS: GbE protected podocytes against hyperglycemia and prevented the development of DN via Nrf-2/HO-1 activation. Our findings provide further mechanistic insight into the potential use of GbE in clinical DN.