Recent advances in Tripterygium wilfordii Hook F against diabetic kidney disease: A review of preclinical and clinical evidences

• Diabetic kidney disease (DKD) has been recognized as a serious complication of diabetes and a leading cause of end-stage renal disease. • The development of new drug treatment strategies has always been a hot topic in the research field. • Tripterygium wilfordii (TwHF) is the first Chinese herb to be studied and used for anti-inflammatory and immune regulation. • This review presents new ideas and significant content for future research on TwHF in the treatment of DKD. Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease. Currently, the treatment of DKD primarily targets the regulation of the renin-angiotensin-aldosterone system, however, optimal therapeutic outcomes have yet to be realized. Consequently, the development of new strategies for treating DKD remains a critical area of research. Tripterygium wilfordii is the earliest discovered traditional Chinese medicine with anti-inflammatory and immunomodulatory effects, and it has shown remarkable clinical efficacy in the treatment of DKD. The objective is to present evidence that supports the need for additional research into the clinical effectiveness of TwHF in the management of DKD and to systematically clarify its possible mechanisms of action. This research employed a comprehensive approach to identify articles pertinent to the treatment of DKD. The methodology incorporated clinical trials, in vivo and in vitro studies, endpoint analyses of reviews, bioinformatics assessments, and molecular docking experiments. A systematic search and comprehensive analysis of studies regarding the treatment of DKD with TwHF were conducted utilizing various electronic databases, including Web of Science, PubMed, CNKI, Wanfang, and VIP. The search strategy incorporated a range of keywords: Tripterygium wilfordii, tripterygium glycoside, triptolide, tripterine, Celastrol, diabetic nephropathy, diabetic kidney disease, DN, DKD, clinical trial, animal experiment, and cell experiment. Ultimately, a total of 114 articles pertaining to TwHF were reviewed. TwHF improves DKD by targeting NF-κB, TGF-β/Smad, PI3K/AKT/mTOR, and JNK pathways to reduce inflammation and fibrosis, thereby inhibiting the progression of DKD. This review presents new ideas and significant content for future research on TwHF in the treatment of DKD.