Asiatic acid may be a potential candidate drug for preventing diabetic nephropathy fibrosis. - GreenMedInfo Summary
Asiatic acid fromregulates the autophagy-lysosome systemdirectly inhibiting TGF-βtype I receptor and ameliorates diabetic nephropathy fibrosis.
Food Funct. 2022 May 23 ;13(10):5536-5546. Epub 2022 May 23. PMID: 35531774
Xuan-Xuan Zhang
Diabetic nephropathy (DN) fibrosis is a major cause of end-stage renal disease with unsatisfactory therapy drugs and a low 5-year survival rate. There is a lack of specific and effective treatment drugs. In the present study, we report that asiatic acid (AA), a triterpenic acid found in, has good anti-fibrosis activity bothand. The STZ-induced diabetic model of rats was used to investigate the effects of AA on DN fibrosis. A 15-week AA treatment (10 mg kgor 30 mg kg) markedly decreased urine albumin and blood urea nitrogen levels, and ameliorated increased mesangial matrix and glomerular fibrosis. HG + TGF-β1-induced HK-2 cells were applied to evaluate the anti-fibrosis effect of AA. The results revealed AA selectively blocked the interaction of TGF-βtype I receptor (TGF-βRI) with Smad3 by binding to TGF-βRI, suppressed the subsequent phosphorylation and nuclear translocation of Smad3, and downregulated the major fibrotic protein expression of collagen I, fibronectin and a-smooth muscle actin (α-SMA), thereby switching the progress of epithelial-mesenchymal transition (EMT). Furthermore, the protein levels of LC3 and LAMP1 were significantly altered by AA administration, implying that the autophagy-lysosome system might be involved in DN fibrosis. However, the anti-fibrosis capacity of AA was partly counteracted by an autophagy-lysosome inhibitor (chloroquine). These findings indicate AA could decrease TGF-β1 secretion and suppress tubulointerstitial fibrosis by directly inhibiting TGF-βR1 and activating the autophagy-lysosome system. Altogether, AA may be a potential candidate drug for preventing DN fibrosis.