Hypericin Ameliorates Renal Tubulointerstitial Fibrosis via Inhibiting YAP
10.3870/j.issn.1672-0741.24.11.033
- VernacularTitle:金丝桃苷通过抑制YAP改善肾小管间质纤维化
- Author:
Junqing WANG
1
;
Huifan YU
;
Linsheng HUANG
Author Information
1. 湖北医药学院药学院,十堰 442000
- Publication Type:Journal Article
- Keywords:
hypericin;
renal interstitial fibrosis;
kidney protection;
unilateral ureteral obstruction;
Yes-associat-ed protein
- From:
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong
2025;54(2):190-197
- CountryChina
- Language:Chinese
-
Abstract:
Objective To clarify the anti-fibrotic effect of hypericin on preventing renal fibrosis.To explore if hypericin can improve renal tubulointerstitial fibrosis by inhibiting the Yes-associated protein(YAP).Methods Thirty-six male mice were randomly allocated into 6 groups(n=6 per group):sham group,sham+hypericin(120 mg/kg)group,UUO model group,hyperi-cin(30,60,120 mg/kg)treatment groups.Except for the sham group,renal interstitial fibrosis was induced in all other groups via unilateral ureteral obstruction(UUO).Mice in the hypericin treatment group received corresponding doses of hypericin sus-pension via oral gavage,while sham group and UUO model group were administered equivalent volumes of normal saline through the same route for 14 consecutive days.Additionally,an in vitro model was established using NRK-52E cells treated with TGF-β1(10 ng/mL).To evaluate the anti-fibrotic effects of hypericin,protein expression levels of α-SMA,fibronectin,col-lagen Ⅰ and collagen Ⅲ were assessed in both the UUO mouse kidney tissues and TGF-β1-stimulated NRK-52E cells using Western blotting.Blood urea nitrogen(BUN)and creatinine(Cr)levels in mice were measured to assess the renal protective effects of hypericin.Histological changes and collagen deposition in the kidneys were observed using hematoxylin-eosin and Masson staining.The expression levels of YAP and its downstream target gene CTGF were also determined using Western blot-ting.The specific mechanism of hypericin in improving renal interstitial fibrosis was further explored using the YAP inhibitor verteporfin.Results The protein expression levels of α-SMA,FN,collagen Ⅰ,and collagen Ⅲ in renal tissues of UUO mice and TGF-β1-induced NRK-52E cells were markedly reversed by hypericin(all P＜0.01).The levels of Cr and BUN in UUO mice se-rum were effectively reduced(both P＜0.01),and renal histopathological alterations and interstitial collagen deposition were markedly ameliorated.Potent inhibitory effects on YAP and CTGF protein expression were observed both in vivo and in vitro(both P＜0.01),exhibiting similar effects to verteporfin.Both treatments dramatically reduced TGF-β1-induced fibrosis in NRK-52E cells.Conclusion Hypericin can inhibit renal tubulointerstitial fibrosis by inhibiting YAP.
