Metabolomics Reveals Mechanism of Abelmoschi Corolla Total Flavonoids in Regulating Endoplasmic Reticulum Stress in IgA Nephropathy
10.13422/j.cnki.syfjx.20260106
- VernacularTitle:基于代谢组学探讨黄葵总黄酮调控IgA肾病内质网应激的机制
- Author:
Shuying SONG
1
;
Changqing WEN
2
;
Luwan XING
2
;
Yan ZHANG
1
;
Haitao GE
1
;
Fujiang WANG
2
Author Information
1. Nanjing University of Chinese Medicine，Nanjing 210023，China
2. Jiangsu Suzhong Pharmaceutical Research Institute Co. Ltd.，Nanjing 210023，China
- Publication Type:Journal Article
- Keywords:
Abelmoschi Corolla total flavonoids;
immunoglobulin A （IgA） nephropathy;
arachidonic acid metabolism pathway;
metabolomics;
endoplasmic reticulum stress
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2026;32(11):153-161
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo elucidate the mechanism by which total flavonoids of Abelmoschi Corolla （TFA） treat immunoglobulin A （IgA） nephropathy （IgAN） through serum metabolomics analysis. MethodsSPF-grade male SD rats were randomly assigned into six groups （n=10）： blank， model， low-dose TFA （TFA-L， 27 mg·kg-1）， medium-dose TFA （TFA-M， 54 mg·kg-1）， high-dose TFA （TFA-H， 108 mg·kg-1）， and losartan potassium （LST， 4.5 mg·kg-1） groups. The remaining five groups， excluding the blank group， were modeled with bovine serum albumin （BSA）， lipopolysaccharide （LPS）， and carbon tetrachloride （CCl4）. Specifically， from weeks 1 to 10， BSA was administered via gavage every other day， and a mixture of castor oil and CCl4 was injected subcutaneously once a week， with LPS injected into the tail vein at weeks 6 and 8. After successful modeling， each intervention group was administrated with the medication prepared with distilled water once daily by gavage for a continuous period of 4 weeks. The levels of 24-hour urinary total protein （24 h UP） and serum creatinine （SCr） were quantified by kits， and the serum IgA level was determined by enzyme-linked immunosorbent assay （ELISA）. Renal pathological changes were observed by hematoxylin-eosin （HE） staining and periodic acid-Schiff （PAS） staining. Renal IgA deposition was assessed by immunofluorescence （IF）. Endoplasmic reticulum （ER） stress was observed by transmission electron microscopy. Western blot and immunohistochemistry （IHC） were employed to detect the expression of ER stress-related factors. Non-targeted metabolomics was used to screen differential metabolites for analysis， and key metabolites arachidonic acid （AA）， prostaglandin E2 （PGE2）， and cyclooxygenase-2 （COX-2） were validated. ResultsCompared with the blank group， the model group showed increased 24-hour urine protein （24 h UP） and serum creatinine （SCr） levels （P<0.01）， obvious renal pathological damage， elevated serum IgA level （P<0.01）， increased renal AA and PGE2 levels （P<0.01）， and up-regulated protein levels of COX-2， glucose-regulated protein 78 （GRP78）， phosphorylated eukaryotic initiation factor 2α （P-EIF2α）， activating transcription factor 4 （ATF4）， inositol-requiring enzyme 1α （IRE1α）， and spliced X-box binding protein 1 （XBP1s） in the renal tissue （P<0.05， P<0.01）. Compared with the model group， the intervention groups showed reductions in 24 h UP and SCr levels （P<0.05， P<0.01）， alleviated renal pathological injury， decreased serum IgA level （P<0.05， P<0.01）， and reduced renal AA and PGE2 levels （P<0.01）. Western blot and IHC results showed that TFA reduced the levels of COX-2， GRP78， P-EIF2α， ATF4， IRE1α， and XBP1s in the renal tissue （P<0.05， P<0.01）. Metabolomics results indicated that 51 commonly differential metabolites were found among the normal， model， and TFA-M groups. TFA ameliorated IgAN by affecting metabolic pathways related to the biosynthesis of arachidonic acid and arginine through L-aspartic acid， prostaglandin 2α， leukotriene B4， leukotriene D4， among others. ConclusionTFA can regulate the arachidonic acid metabolism pathway， thereby modulating ER stress， reducing renal damage， and ameliorating IgA nephropathy.
