Journal of ethnopharmacology · 2024
Swertia cincta and its main active ingredients regulate the PPAR-α pathway in anti-cholestatic liver injury.
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Feng Shuaixia, Tang Jie, Wei Xia, Lu Zou, Xu Ying, Zhang Tong, Han Han
Аннотация
ETHNOPHARMACOLOGICAL RELEVANCE: Swertia cincta is a traditional remedy for cholestasis commonly utilised in Yunnan, China. Despite its widespread use, the specific active components and underlying mechanisms of action remain poorly understood.
AIM OF THIS STUDY: This study aimed to investigate the therapeutic properties, mechanisms, and active compounds of Swertia cincta in an animal model of cholestasis induced by alpha-naphthylisothiocyanate (ANIT).
MATERIALS AND METHODS: UHPLC/Q-TOF-MS and high-performance liquid chromatography (HPLC) were utilised to analyse the blood components of Swertia cincta. An ANIT-induced cholestatic liver injury animal model was established, and metabolomics was employed to explore the potential mechanisms of Swertia cincta in treating cholestatic liver injury. Hepatocellular injury induced by taurochenodeoxycholic acid was evaluated in vitro, and key bioactive components of Swertia cincta for cholestatic liver injury treatment were identified and confirmed using the ANIT-induced mouse model.
RESULTS: The established HPLC method demonstrates good specificity and reproducibility, enabling the simultaneous determination of six components in Swertia cincta. Results from serum biochemical indicators and liver pathology analysis indicated that Swertia cincta exhibits promising anti-cholestasis liver injury effects. Specifically, gentiopicroside, loganic acid, and isoorientin were identified as key active ingredients in treating cholestatic liver injury. Their mechanism of action primarily involves regulating PPAR-α, FXR, CYP3A4, NTCP, CAR, and CPT2. By modulating PPAR-α and bile acid metabolism-related proteins, reducing pro-inflammatory factors, enhancing bile acid transport, and promoting fatty acid oxidation to reduce lipid accumulation, Swertia cincta exerts protective and therapeutic effects against cholestatic liver injury. Notably, gentian bitter glycosides appear to be the most critical components for this effect.
CONCLUSION: Swertia cincta may improve cholestatic liver injury by activating the peroxisome proliferator-activated receptor alpha pathway, and the key active compounds were gentiopicroside, loganic acid, and isoorientin.
AIM OF THIS STUDY: This study aimed to investigate the therapeutic properties, mechanisms, and active compounds of Swertia cincta in an animal model of cholestasis induced by alpha-naphthylisothiocyanate (ANIT).
MATERIALS AND METHODS: UHPLC/Q-TOF-MS and high-performance liquid chromatography (HPLC) were utilised to analyse the blood components of Swertia cincta. An ANIT-induced cholestatic liver injury animal model was established, and metabolomics was employed to explore the potential mechanisms of Swertia cincta in treating cholestatic liver injury. Hepatocellular injury induced by taurochenodeoxycholic acid was evaluated in vitro, and key bioactive components of Swertia cincta for cholestatic liver injury treatment were identified and confirmed using the ANIT-induced mouse model.
RESULTS: The established HPLC method demonstrates good specificity and reproducibility, enabling the simultaneous determination of six components in Swertia cincta. Results from serum biochemical indicators and liver pathology analysis indicated that Swertia cincta exhibits promising anti-cholestasis liver injury effects. Specifically, gentiopicroside, loganic acid, and isoorientin were identified as key active ingredients in treating cholestatic liver injury. Their mechanism of action primarily involves regulating PPAR-α, FXR, CYP3A4, NTCP, CAR, and CPT2. By modulating PPAR-α and bile acid metabolism-related proteins, reducing pro-inflammatory factors, enhancing bile acid transport, and promoting fatty acid oxidation to reduce lipid accumulation, Swertia cincta exerts protective and therapeutic effects against cholestatic liver injury. Notably, gentian bitter glycosides appear to be the most critical components for this effect.
CONCLUSION: Swertia cincta may improve cholestatic liver injury by activating the peroxisome proliferator-activated receptor alpha pathway, and the key active compounds were gentiopicroside, loganic acid, and isoorientin.