Extract of Corallodiscus Flabellata Attenuates Renal Fibrosis in Aging Mice via the Wnt/β-catenin/RAS Signaling Pathway

Background: Renal fibrosis is a common pathological feature of chronic kidney disease (CKD). Aging accelerates renal fibrosis and further aggravates the process of CKD. Corallodiscus flabellata B. L. Burtt ( C. flabellata ) is a commonly used botanical drug in the Chinese population. However, few studies have reported its physiological effects. This study aimed to explore the effect of C. flabellata extract on renal fibrosis in aging mice and identify potentially active compounds. Methods: : Using Senescence-accelerated mouse-prone 8 (SAMP8) mice and β-galactosidase (β-gal)-induced normal rat kidney epithelial cells (NRK-52E cells) as a model, to explore the mechanism of C. flabellata extract on senescence-related renal fibrosis, and initially clarified the material basis of C. flabellata . Results: : The C. flabellata extract reduced the senescence and fibrosis of the kidneys in SAMP8 mice by activating nuclear factor erythroid 2–related factor 2 (Nrf2) to balance oxidative stress and inflammation, and interrupting the fibrinogen signaling in the Wnt/β-catenin/renin–angiotensin system. Moreover, 3,4-dihydroxyphenylethanol (SDC-0-14, 16) and (3,4-dihydroxyphenylethanol-8-O-[4-O-trans-caffeoyl-β-D-apiofuranosyl-(1→3)-β-D-glucopyranosyl (1→6)]-β-D-glucopyranoside (SDC-1-8) were isolated compounds from C. flabellata , which reduced the senescence of NRK-52E cells, and maybe the material basis for the function of C. flabellata . Conclusion: Our experiments illuminated that the extract of C. flabellata may improve the aging-related renal fibrosis through the Wnt/β-catenin/RAS pathway, and the material basis of its function may be SDC-0-14, 16 and SDC-1- 8.