Ginkgetin alleviates high glucose‐evoked mesangial cell oxidative stress injury, inflammation, and extracellular matrix (ECM) deposition in an AMPK/mTOR‐mediated autophagy axis.

Diabetic nephropathy constitutes the leading cause for end‐stage kidney disease. Ginkgetin is a common natural non‐toxic biflavone and fulfills pleiotropic pharmacological characterizations, such as anti‐inflammation and kidney injury. Nevertheless, its efficacy in diabetic nephropathy remains elusive. Here, ginkgetin exhibited little cytotoxicity in glomerular mesangial cells. Of note, ginkgetin restrained high glucose (HG)‐induced mesangial cell proliferation and oxidative stress by inhibiting ROS and malonaldehyde levels, but enhancing antioxidant SOD activity. Additionally, ginkgetin suppressed HG‐evoked transcript and release of inflammatory cytokine TNF‐α, IL‐1β, and IL‐6. Concomitantly, the increased extracellular matrix (ECM) deposition in HG‐treated glomerular mesangial cells was attenuated by ginkgetin via decreasing expression of collagen IV, fibronectin, and laminin. Intriguingly, ginkgetin‐restored HG‐impaired autophagy; whereas blocking autophagy by its inhibitor 3‐MA overturned ginkgetin function against HG‐evoked mesangial cell dysfunction. Mechanistically, ginkgetin‐mediated AMPK/mTOR axis accounted for HG‐impaired autophagy. Importantly, blockage of AMPK signaling reversed ginkgetin‐restored autophagy and its protective efficacy against HG‐induced dysfunction in mesangial cells. Thus, these findings highlight that ginkgetin may attenuate HG‐evoked mesangial cell hyperplasia, oxidative stress, inflammation, and ECM accumulation by activating AMPk/mTOR‐mediated autophagy pathway. Therefore, ginkgetin may alleviate the progression of diabetic nephropathy by regulating glomerular mesangial cell dysfunction, supporting a promising therapeutic agent against diabetic nephropathy. [ABSTRACT FROM AUTHOR]