DNA methylation is mediated by DNA methyltransferase, which inhibits gene expression by recruiting transcription repressors to the promoter region of genes and interfering with transcription

Diabetic nephropathy (DN) is a serious complication of diabetes. According to estimates by the World Health Organization, there are approximately 422 million diabetic patients in the world, of which more than 90% have type 2 diabetes (T2DM) (Cho et al., 2018; World Health Organization, 2015). As we all know, DN is the main cause of chronic kidney disease and endstage renal disease, and it is closely related to T2DM (Ritz et al., 1999; Wang et al., 2021). In China, there are approximately 114 million people with diabetes, which greatly harms public health(Zhen et al., 2020). The epigenetic modification of genes plays an important role in the development of DN, among which DNA methylation is the most common (Keating et al., 2017). Related research reported that DNA methylation could participate in the regulation of genes related to the functions of glomeruli and proximal tubular epithelial cells, including filtration, glucose and solute processing (Wanner & Bechtel-Walz, 2017). DNA methylation is mediated by DNA methyltransferase, which inhibits gene expression by recruiting transcription repressors to the promoter region of genes and interfering with transcription factor binding (Jones, 2012). According to reports, in the state of diabetes, the expression of DNA methyltransferase 1 (DNMT1) in podocytes in vivo and in vitro is significantly increased. In the in vitro diabetes model induced by high glucose (HG), 5-azacytidine treatment can significantly reduce the expression of DNMT1, and improve the reduction of podocyte slit diaphragm protein caused by hypermethylation (Zhang et al., 2017). At present, the treatment of type 2 diabetes with traditional Chinese medicine has become more and more common (Ahmad et al., 2020). Parthenolide (PN) was originally extracted from the shoots of plant Feverfew, and has strong anti-tumor, anti-inflammatory and antibacterial biological activities (Freund et al., 2020). A study claimed that PN as an inhibitor of nuclear factor kappa B (NF-κB), after treating diabetic mice, it could reduce inflammation, alleviate glomerular hypertrophy, remodel the damaged insulin signal transduction pathway, and promote the expression of renal tubular cubicin protein and uptake of albumin (Hao et al., 2020). Moreover, it is reported that PN could regulate the expression and methylation level of tumor-related genes by inhibiting the Parthenolide regulates DNMT1-mediated methylation of VDR promoter to relieve podocyte damage in mice with diabetic nephropathy