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San-Huang-Yi-Shen capsule ameliorates diabetic nephropathy in mice through inhibiting ferroptosis.

Abstract
Diabetic nephropathy (DN) is one of the main complications of diabetes. However, effective therapy to block or slow down the progression of DN is still lacking. San-Huang-Yi-Shen capsule (SHYS) has been shown to significantly improve renal function and delay the progression of DN. However, the mechanism of SHYS on DN is still unclear. In this study, we established a mouse model of DN. Then, we investigated the anti-ferroptotic effects of SHYS including the reduction of iron overload and the activation of cystine/GSH/GPX4 axis. Finally, we used a GPX4 inhibitor (RSL3) and ferroptosis inhibitor (ferrostatin-1) to determine whether SHYS ameliorates DN through inhibiting ferroptosis. The results showed that SHYS treatment was effective for mice with DN in terms of improving renal function, and reducing inflammation and oxidative stress. Besides, SHYS treatment reduced iron overload and upregulated the expression of cystine/GSH/GPX4 axis-related factors in kidney. Moreover, SHYS exhibited similar therapeutic effect on DN as ferrostatin-1, RSL3 could abolish the therapeutic and anti- ferroptotic effects of SHYS on DN. In conclusion, SHYS can be used to treat mice with DN. Furthermore, SHYS could inhibit ferroptosis in DN through reducing iron overload and upregulating the expression of cystine/GSH/GPX4 axis.
AuthorsShuquan Lv, Huajun Li, Tianyu Zhang, Xiuhai Su, Wenjuan Sun, Qinghai Wang, Lixin Wang, Nana Feng, Shufang Zhang, Yuansong Wang, Huantian Cui
JournalBiomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 165 Pg. 115086 (Sep 2023) ISSN: 1950-6007 [Electronic] France
PMID37418978 (Publication Type: Journal Article)
CopyrightCopyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.
Chemical References
  • ferrostatin-1
  • San-Huang
  • Cystine
Topics
  • Animals
  • Mice
  • Diabetic Nephropathies (drug therapy)
  • Cystine
  • Ferroptosis
  • Iron Overload
  • Diabetes Mellitus

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