Hesperetin alleviates renal interstitial fibrosis by inhibiting tubular epithelial-mesenchymal transition in vivo and in vitro

Abstract

Hesperetin (HES) is a flavonoid that has been reported to exert protective effects against cardiac remodeling, lung fibrosis and hepatic fibrosis. However, reports on the effects and potential mechanisms of HES in renal fibrosis are limited. In the present study, a unilateral ureteric obstruction (UUO) mouse model and a transforming growth factor (TGF)-β1-activated normal rat kidney (NRK)-52E cell model were established. HES was subsequently administered to these models to evaluate its anti-fibrotic effects and potential underlying mechanisms of action. The results demonstrated that HES reduced obstruction-induced renal injury and deposition of the extracellular matrix components collagen-I and fibronectin in UUO mouse kidneys (P<0.05). Furthermore, HES treatment significantly suppressed EMT, as evidenced by decreased expression of α-smooth muscle actin and E-cadherin, (P<0.05). Additionally, HES inhibited the hedgehog signaling pathway in UUO mice and TGF-β1-treated NRK-52E cells. The present findings indicate that HES treatment may inhibit EMT and renal fibrosis in vivo and in vitro by antagonizing the hedgehog signaling pathway.

The upshot of Polyphenolic compounds on immunity amid COVID-19 pandemic and other emerging communicable diseases: An appraisal

“…In addition, the anti-fibrotic effects of hespertein have been indicated in the liver and kidney [ 155 , 156 ]. Hespertin exerted inhibitory effect on the intracellular replication of transmitted Chikungunya virus (CHIKV) and exhibits drug-like properties which maybe a potential as a therapeutic option for CHIKV infection [ 157 ]. Moreover, hesperetin has shown an antiviral activity against the human Respiratory Syncytial Virus (hRSV) trough binding to M2-1 virus protein, which is an important transcriptional anti-termination factor and a potential target for viral replication inhibitor development [ 158 ].…”

Molecular landscape of pelvic organ prolapse provides insights into disease etiology and clues towards putative novel treatments

“…Another 'drug' that inhibits TGFB1 signaling and could be tested for POP is hesperitin, a natural compound from citrus fruits that has been studied for a possible beneficial effect in multiple diseases due to its anti-oxidant and anti-inflammatory properties 44 . Like halofuginone, hesperitin decreases TGFB1 signaling through inhibiting SMAD3 phosphorylation and activation 45 and also directly inhibits EMT in rodent kidneys 46 . Further, simvastatin, a commonly used oral drug to reduce cholesterol levels, inhibits TGFB1-dependent EMT and ROS production of kidney cells 47 while it also specifically inhibits TGFB1-induced collagen type I production by and SMAD3 phosphorylation in fibroblasts 48 .…”

Chemotherapeutic potential of hesperetin for cancer treatment, with mechanistic insights: A comprehensive review

“…Wang and his co-workers performed a study both in vivo and in vitro on (NRK)-52E cell line and UUO-mouse model to evaluate the efficacy of HSP at 50-100 μM and 60 mg/kg/day concentration, respectively. Their study proved that HSP decreased the expression of fibronectin (FN), Collagen I, α-SMA, EMT, Shh, Gli-1, deceased E-cadherin expression, reducing renal fibrosis normalize the renal function [92].…”