Journal of ethnopharmacology · 2025
Sea buckthorn regulates PXR/CAR/NF-κB signaling and restores CYP2C metabolic function in BCG-induced hepatitis.
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Hao Peipei, Ding Ruifeng, Bai Xuefeng, Zhang Aimin, Jin Ziqi, Zhang Jiayi, Xue Yongzhi
Аннотация
ETHNOPHARMACOLOGICAL RELEVANCE: Sea buckthorn (Hippophae rhamnoides L.) exhibits anti-oxidation, anti-atherosclerosis, anti-inflammation, anti-cancer, and liver protective effects; it may also inhibit ECM collagen deposition and alleviate liver fibrosis. Therefore, we hypothesized that sea buckthorn granule (SG) polysaccharides may possess anti-hepatitis activity.
AIM OF THE STUDY: To investigate the role of sea buckthorn in regulating hepatic pregnane X receptor (PXR)/constitutive androstane receptor (CAR)/NF-κB signal transduction and CYP2C following BCG-induced liver injury.
MATERIALS AND METHODS: A mouse liver injury model was established through single tail vein injection of Bacillus Calmette-Guérin (BCG) vaccine. SGs were administrated intragastrically for 7 days. Pregnenolone 16alpha-carbonitrile (PCN, PXR agonists) and 1,4-bis-(2-[3,5-dichloropyridyloxy]) benzene (TCPOBOP, CAR agonists) were administered as positive controls. To evaluate modeling success, serum alanine aminotransferase (ALT) and aspartate transferase (AST) levels and hepatic IL-1β, TNF-α, 11,12-epoxyeicosatrienoic acid (EET), and 14,15-EET expressions were measured.
RESULTS: Overall, 5281 reliable proteins were identified, including 43 cytochrome P450 (CYP) subtypes, with the CYP2C subfamily accounting for approximately 27 %. BCG-induced hepatitis downregulated 23 CYPs. The BCG group exhibited increased inflammatory infiltration and ALT/AST levels. PXR, CAR, CYP2C, 11,12-EET, and 14,15-EET were downregulated, whereas NF-κB, IL-1β, and TNF-α were upregulated. Following SG administration, hepatic inflammation and ALT/AST levels decreased; PXR, CAR, CYP2C, 11,12-EET, and 14,15-EET increased, and NF-κB, IL-1β, and TNF-α decreased. The SG high-dose group effects were comparable to the PCN and TCPOBOP group effects.
CONCLUSIONS: SGs may regulate the PXR/CAR/NF-κB signaling pathway and CYP reprogramming, mitigating BCG-induced liver injury and inflammation.
AIM OF THE STUDY: To investigate the role of sea buckthorn in regulating hepatic pregnane X receptor (PXR)/constitutive androstane receptor (CAR)/NF-κB signal transduction and CYP2C following BCG-induced liver injury.
MATERIALS AND METHODS: A mouse liver injury model was established through single tail vein injection of Bacillus Calmette-Guérin (BCG) vaccine. SGs were administrated intragastrically for 7 days. Pregnenolone 16alpha-carbonitrile (PCN, PXR agonists) and 1,4-bis-(2-[3,5-dichloropyridyloxy]) benzene (TCPOBOP, CAR agonists) were administered as positive controls. To evaluate modeling success, serum alanine aminotransferase (ALT) and aspartate transferase (AST) levels and hepatic IL-1β, TNF-α, 11,12-epoxyeicosatrienoic acid (EET), and 14,15-EET expressions were measured.
RESULTS: Overall, 5281 reliable proteins were identified, including 43 cytochrome P450 (CYP) subtypes, with the CYP2C subfamily accounting for approximately 27 %. BCG-induced hepatitis downregulated 23 CYPs. The BCG group exhibited increased inflammatory infiltration and ALT/AST levels. PXR, CAR, CYP2C, 11,12-EET, and 14,15-EET were downregulated, whereas NF-κB, IL-1β, and TNF-α were upregulated. Following SG administration, hepatic inflammation and ALT/AST levels decreased; PXR, CAR, CYP2C, 11,12-EET, and 14,15-EET increased, and NF-κB, IL-1β, and TNF-α decreased. The SG high-dose group effects were comparable to the PCN and TCPOBOP group effects.
CONCLUSIONS: SGs may regulate the PXR/CAR/NF-κB signaling pathway and CYP reprogramming, mitigating BCG-induced liver injury and inflammation.