Flavonoids of Coreopsis tinctoria Nutt alleviate the oxidative stress and inflammation of glomerular mesangial cells in diabetic nephropathy via RhoA/ROCK signaling

Abstract

• FC improved glucolipid metabolic disorder, abnormal renal function, and renal pathological injury in db/db DN mice. • FC could exert a protective effect on DN by regulating oxidative stress mediated by RhoA/ROCK signaling both in vivo and in vitro. • FC down-regulated inflammatory responses by NF-κB/TGF-β1/Smad signaling both in vivo and in vitro. Diabetic nephropathy (DN) is one of the serious diabetic microvascular complications, and oxidative stress and inflammation may play a vital role in its initiation and development. Previous studies indicated that Coreopsis tinctoria Nutt had anti-inflammatory and antioxidant activities. This study aimed to examine the protective effects of flavonoids from Coreopsis tinctoria Nutt (FC) on DN. In vivo, db/db mice were treated with FC (150, 300 mg/kg), FC150 + Metformin. DN model in vivo of high glucose and palmitic acid-induced glomerular mesangial cell (HBZY-1) was established and treated with FC . The results showed that treatment of FC, especially in the dose of 150 mg/kg and FC150 mg/kg plus metformin significantly improved glucolipid metabolic disorder, abnormal renal function, and pathological renal injury in db/db mice. Both in vivo and in vitro , FC intervention reduced the levels of renal oxidative stress-related factors, inflammatory cytokines, and fibrotic factors. Additionally, FC down-regulated the expressions of proteins related to Ras homolog gene family member (RhoA)/Rho-associated protein kinase (ROCK), nuclear factor kappa-B (NF-κB), and transforming growth factor (TGF-β)/Smad signaling pathways. In conclusion, FC might protect against diabetic renal injury by inhibiting renal oxidation, inflammation, and fibrosis via RhoA/ROCK and NF-κB/TGF-β/Smad signalings.