In conclusion, we identify a safe dosage and optimal combination ratio of AANG for preventive treatment of T2D and T2DN by effectively rebalancing Smad3/Smad7 signaling, thereby inhibiting TGF-β/Smad3-mediated renal fibrosis and NF-κB-driven renal inflammation. The gene discussed is TGFB1; the disease is renal fibrosis.