Protective effect of total glucosides of paeony on glucocorticoid-induced liver inj ury and preliminary mechanisms
10.19405/j.cnki.issn1000-1492.2025.08.014
- VernacularTitle:白芍总苷对糖皮质激素致肝损伤的保护作用及初步机制
- Author:
Qinxiang Deng
1
;
Fei Ma
1
;
Rui Shi
1
;
Chun Wang
2
;
Bingfa Xu
1
Author Information
1. School of Pharmaceutical Sciences , Anhui Medical University, Hefei 230032;Dept of Pharmacy, The Third Afiliated Hospital of Anhui Medical University, Hefei 230032
2. School of Pharmaceutical Sciences , Anhui Medical University, Hefei 230032
- Publication Type:Journal Article
- Keywords:
total glycosides of paeony;
glucocorticoid;
dexamethasone;
liver injury;
oxidative stress;
endoplasmic reticulum stress
- From:
Acta Universitatis Medicinalis Anhui
2025;60(8):1463-1469,1477
- CountryChina
- Language:Chinese
-
Abstract:
Objective :To investigate the protective effect of total glucosides of paeony ( TGP) on dexamethasone(DEX) ⁃induced liver injury in rats.
Methods:Thirty SD rats were randomly divided into normal ( N) , DEX ,DEX + TGP (50 mg/kg) , DEX + TGP ( 100 mg/kg) , and DEX + TGP (200 mg/kg) groups , with 6 rats in each group. A rat model of liver injury was established by intraperitoneal injection of DEX ( 17. 5 mg/kg) . Serum levels of alanine aminotransferase ( ALT) , aspartate aminotransferase ( AST) , and alkaline phosphatase ( ALP) were measured , and the liver⁃to⁃body weight ratio was calculated. HE staining was performed to observe histopathological changes in the liver. The contents of malondialdehyde ( MDA) , superoxide dismutase ( SOD) , and glutathione (GSH) in liver tissues were determined. Western blot analysis was conducted to detect the expression levels of NADPH oxidase 4 ( NOX4 ) and endoplasmic reticulum stress⁃related proteins : glucose regulatory protein 94 homologous protein (CHOP) expression level in liver tissues.
Results:Compared with the normal group , the DEX group exhibited significantly elevated serum levels of ALT , AST , ALP and liver⁃to⁃body weight ratio ( t = 14. 96 ,ing, degeneration , and necrosis ( t = 15. 49 , P < 0. 01) . Compared with the DEX group , there was no significant change in liver function biochemical indexes and liver histopathology in the TGP (50 mg/kg) treatment group. TGP treatment at 100 mg/kg and 200 mg/kg significantly attenuated these effects : both doses reduced ALT , AST , ALP and liver⁃to⁃body weight ratio( t = 3. 30 , 4. 13 , 7. 45 , 2. 97 , P < 0. 05 ; t = 8. 92 , 6. 45 , 8. 65 , 7. 47 , P < 0. 01) ,vealed that DEX administration significantly increased hepatic MDA levels ( t = 7. 06 , P < 0. 01) and NOX4 ex⁃pression ( t = 4. 23 , P < 0. 01) , whereas SOD activity ( t = 7. 78 , P < 0. 01) and GSH content ( t = 7. 92 , P <0. 01) were markedly suppressed. There was no significant change in the TGP (50 mg/kg) treatment group , TGP intervention at 100 mg/kg and 200 mg/kg effectively reversed these changes , lowering MDA and NOX4 levels( t = 3. 35 , 4. 30 , P < 0. 05 ; t = 5. 44 , 7. 44 , P < 0. 01) , while restoring SOD ( t200 mg/kg = 4. 04 , P < 0. 05) and GSH ( t = 4. 70 , P < 0. 05 ; t = 5. 50 , P < 0. 01) . Endoplasmic reticulum stress markers , including GRP94、GRP78、p- elF2α、CHOP ( t = 3. 31 , 6. 53 , 5. 18 , 3. 09 ; P < 0. 05 , 0. 01 , 0. 01 , 0. 05 ) , were significantly upregulated in the DEX group compared to the normal group. However, TGP treatment at 100 mg/kg and 200 mg/kg dose-dependent- ly suppressed the expression of GRP94、GRP78、p-elF2α、CHOP ( t = 3. 14 ,4. 95 , 3. 13 ,4. 25 , P < 0. 05 ; t = 4. 03 , 7. 48 ,4. 68 ,5. 10 ,P < 0. 01) expression levels were significantly reduced compared to the DEX group , and there was no significant change in the TGP (50 mg/kg) treatment group.
Conclusion :TGP exerts protective effects a- gainst DEX-induced liver injury , and its mechanism is likely mediated by suppressing hepatic oxidative stress and endoplasmic reticulum stress triggered by DEX in rats.
- Full text:202604050035276301白芍总苷对糖皮质激素致肝损伤的保护作用及初步机制_邓琴香.pdf