Pharmacological Exploration Of Corilagin On Chelostatic Hepatitis Via Anti-inflammation Pathway

Aim: Corilagin is a novel member of the tannin family which has been discovered from many medicinal plants and has been confirmed many pharmacological activities. However, the purified Corilagin that was used in experiment is rare, and the anti-inflammatory mechanism of Corilagin has not been investigated clearly. This study is to explore the inner anti-inflammatory mechanism of Corilagin.Methods: Inflammatory cellular model was established by lipopolysaccharide (LPS) interfering on RAW264.7 cell line. Levels of TNF-α, IL-1β, IL-6, NO and IL-10 in supernatant, mRNA expression of TNF-α, COX-2, iNOS and HO-1, protein expression of COX-2 and HO-1, translocation of NF-κB were assayed by ELISA or Griess method, real-time quantitative PCR, western-blot and immunocytochemistry method, respectively.Results: Corilagin could significantly reduce production of pro-inflammatory cytokines and mediators TNF-α, IL-1β, IL-6, NO (iNOS) and COX-2 on both protein and gene level by blocking NF-κB nuclear translocation. Meanwhile Corilagin could notably promote release of anti-inflammatory factor HO-1 on both protein and gene level, but suppress the release of IL-10.Conclusion: the anti-inflammatory effects of Corilagin are attributed to the suppression of pro-inflammatory cytokines and mediators by blocking NF-κB activation. Corilagin also can promote HO-1 production to induce regression of inflammation but can inhibit IL-10 production like Dexamethasone. Corilagin possesses a potential anti-inflammatory effect by not only abating inflammatory impairment but also promoting regression of inflammation and has a good prospect to be used in many inflammation- related diseases.Part 2: Exploration of Corilagin on the effect of anti-hepatitis B virusAim: To explore the antiviral effect of Corilagin on hepatitis B.Methods: The max non-cytotoxic concentration of Corilagin was determined by MTT assay. The HepG 2.2.15 cell line was interfered by Corilagin. The amount of HBV-DNA in supernatant was measured by real-time PCR assay. The HBsAg and HBeAg in supernatant were detected by EIA.Results: The max non-cytotoxic concentration of Corilagin was 80mg/L after 9d persistent intervention. There were no differences between Corilagin group and control group on HBV-DNA, HBsAg and HBeAg in supernantant.Conclusion: Corilain has no effect on inhibiting hepatitis B virus.Part 3: Exploration of Corilagin to treat alpha-naphthylisothiocyanate- induced chelostatic hepatitis via anti-inflammation pathwayAim: This study is to disclose the mechanism of Corilagin to treat chelostatic hepatitis via anti-inflammation pathway. Methods: Rats were divided into Corilagin, ursodeoxycholic acid, Dexamethasone, model and blank control groups with treatment of respective agent after administration of alpha-naphthylisothiocyanate. At 24h, 48h and 72h time points after administration those rats were examined liver function, pathological changes of hepatic tissue, tumor necrosis factor (TNF)-α, interleukin (IL)-6, myeloperoxidase (MPO), malondialdehyde (MDA), superoxide dismutase (SOD), cytokine-induced neutrophil chemoattractant (CINC)-1, monocyte inflammatory protein (MIP)-2, intercellular adhesion molecule (ICAM)-1, nuclear factor (NF)-κB and early growth response (Egr)-1, nitric oxide (NO) and inducible nitric oxide synthase (iNOS).Result: Compared to the controls, Corilagin had a notable effect on rat's living condition, pathological manifestation of hepatic tissue, total bilirubin, direct bilirubin, (P<0.05), and little effect on ALP, GGT and total bile acid. With Corilagin intervention, levels of TNF-α, IL-6, MPO, MDA, CINC-1, MIP-2, ICAM-1, Egr-1 and translocation of NF-κB was decreased to different extent, and levels of SOD, NO and iNOS was markedly increased.Conclusion: Corilagin has a protective effect on liver function and a restoring activity on chelostatic hepatitis by anti-inflammation. The effects are mainly due to antagonizing pro-inflammatory cytokines and mediators, inhibiting oxidative damage, improving hepatic microcirculation, reducing impairment signals, and controlling nutrophil infiltration.