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| Study on the mechanism of Shuganning Injection in liver protection，enzyme reduction and jaundice regression via regulating the FXR-MRP2/BSEP pathway |
| Hits 127 Download times 45 Received:August 08, 2025 |
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| DOI
10.11656/j.issn.1673-9043.2026.01.08 |
| Key Words
Shuganning Injection;septic intrahepatic cholestasis;liver protection;enzyme reduction;jaundice regression;FXR-MRP2/BSEP pathway |
| Author Name | Affiliation | E-mail | | LIU Zhangzhen | Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, State Key Laboratory of Component-based Chinese Medicine, Tianjin Key Laboratory of Chinese Medicine Pharmacology, Tianjin 301617, China | | | WU Shihao | Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, State Key Laboratory of Component-based Chinese Medicine, Tianjin Key Laboratory of Chinese Medicine Pharmacology, Tianjin 301617, China | | | REN Mengyu | Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, State Key Laboratory of Component-based Chinese Medicine, Tianjin Key Laboratory of Chinese Medicine Pharmacology, Tianjin 301617, China | | | WANG Zehui | Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, State Key Laboratory of Component-based Chinese Medicine, Tianjin Key Laboratory of Chinese Medicine Pharmacology, Tianjin 301617, China | | | ZHU Jinqiang | Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, State Key Laboratory of Component-based Chinese Medicine, Tianjin Key Laboratory of Chinese Medicine Pharmacology, Tianjin 301617, China | zhujinqiang1860@163.com |
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| Abstract
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| [Objective] To investigate the hepatoprotective，enzyme-lowering and jaundice-relieving effects of Shuganning Injection（SGN） in rats with septic intrahepatic cholestasis（IC），and to explore its underlying mechanisms. [Methods] Thirty-six male SD rats of SPF grade were randomly assigned to the following groups：Control（blank），LPS（model），Ursodeoxycholic Acid（UDCA），SGN-L，SGN-M，and SGN-H，with six rats per group.A septic IC model was established via intraperitoneal injection of LPS（5 mg/kg）. The Control and LPS groups received tail vein injections of 10% glucose solution[6 mL/（kg·d）]，while the UDCA group received intraperitoneal injections of UDCA[25 mg/（kg·d）]. The SGN-L，SGN-M，and SGN-H groups received tail vein injections of SGN at 0.625，1.350，and 2.700 mL/（kg·d），respectively，administered continuously for 5 days.Collect rat bile and determine its flow rate. Biochemically measure total bile acids（TBA），total bilirubin（TBIL），direct bilirubin（DBIL），and reduced glutathione（GSH） in rat bile，alongside serum aspartate aminotransferase（AST），alanine aminotransferase（ALT），alkaline phosphatase（ALP） activity，and TBA，malondialdehyde（MDA），GSH，TBIL levels in serum. Enzyme-linked immunosorbent assay（ELISA） was employed to determine interleukin-6（IL-6），interleukin-1β（IL-1β），and tumour necrosis factor-α（TNF-α） concentrations in rat serum.Measurement of hepatic coefficients in rats，observation of pathological alterations via haematoxylin-eosin（HE） staining，determination of MRP2 expression levels by immunofluorescence（IF），and assessment of MRP2，BSEP，and FXR gene and protein expression levels via reverse transcription polymerase chain reaction（RT-PCR） and Western blot analysis. [Results] Compared with the LPS group，all SGN treatment groups exhibited improved hepatic tissue architecture，cellular morphology，and hepatic cord arrangement. Inflammatory cell infiltration，hepatocyte degeneration，and necrosis were reduced. Bile levels of GSH，TBA，TBIL，and DBIL increased，while serum AST，ALT，and ALP activities rose in rats. TBA，MDA，TBIL，IL-6，and IL-1β levels decreased，while GSH levels increased. MRP2 fluorescence intensity in liver tissue was enhanced（P<0.05 or P<0.01）. In the SGN-H group，the hepatic coefficient decreased and bile flow accelerated，serum TNF-α levels decreased，and MRP2，BSEP，and FXR gene and protein expression levels increased in liver tissue（P<0.05 or P<0.01）. [Conclusion] SGN ameliorates the severity of cholestasis and liver function in LPS-induced septic IC rats，alleviates inflammation，and exerts hepatoprotective，enzyme-lowering，and jaundice-reducing effects. Its mechanism may involve activating the FXR receptor in hepatocytes，thereby upregulating MRP2 and BSEP gene and protein expression to promote bile acid excretion. |
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