Protective effect and mechanism of water extract of Poria cocos on alcoholic hepatic injury
OBJECTIVE To explore the therapeutic efficacy and mechanism of water extract of Poria cocos(PC)on alco-holic hepatic injury.METHODS Mice were divided into normal group(control),model group(model),bifendate group(bifen-date),water extract of PC high-dose group(PCD-H)and water extract of PC low-dose group(PCD-L).Alcoholic hepatic injury model was established by a gavage of"Hongxing Erguotou".Except for normal group,the corresponding drugs were dosed through a simultaneous gavage of alcohol.At Week 8,blood samples were collected from orbital region.The serum levels of aspartate aminotransferase(AST),alanine aminotransferase(ALT),triglyceride(TG),total cholesterol(TC),low-density lipoproteins(LDL-C),tumor necrosis factor-alpha(TNF-α)and interleukin(IL)-1β were examined.Hepatic pathological changes were observed after hematoxylin-eosin(HE)stain.And quantitative polymerase chain reaction(qRT-PCR)was utilized for detecting the mRNA expressions of inflammatory genes TNF-α and IL-1β.Western blot was utilized for detecting the intracel-lular expressions of phosphatidylinositol kinase/serine protein kinase B(PI3K/AKT)pathway,NOD-like receptor thermoprotein structural domain-related protein 3(NLRP3),farnesoid X receptor(FXR),nuclear factor kappa-B(NF-κB),TNF-α and IL-1β.RESULTS As compared with normal group,model group showed marked elevations of AST,ALT,TG,TC and LDL-C(P＜0.01 or P＜0.05)and higher levels of TNF-α and IL-1β mRNA(P＜0.01 or P＜0.05).Phosphorylated intracellular phos-phatidylinositol kinase(p-P13K)/PI3K,phosphorylated serine protein kinase B(p-AKT)/AKT ratio and FXR protein expres-sion declined sharply(P＜0.01 or P＜0.05)while protein expression of NF-κB,NLRP3 and IL-1β were markedly up-regulated(P＜0.01 or P＜0.05).As compared with model group,water extracts of PC could lower the levels of AST,ALT,TG,TC,LDL-C,TNF-α and IL-1β(P＜0.01 or P＜0.05),down-regulate the mRNA expressions of TNF-α and IL-1β(P＜0.01 or P＜0.05)and protein expressions of NF-κB,NLRP3,TNF-α and IL-1β(P＜0.01 or P＜0.05)and boost the protein expression of p-P13K/PI3K,p-AKT/AKT ratio and FXR(P＜0.01 or P＜0.05).CONCLUSION Water extract of PC may play a thera-peutic role for alcoholic hepatic injury through modulating the PI3K-AKT,NF-κB,NLRP3 signaling pathway,FXR protein and the level of inflammation in vivo,providing scientific rationales for clinical expanded indications.
Poria cocos water extractalcoholic hepatic injuryPI3K/AKTNF-κBNLRP3
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