The Immunomodulatory And Liver Protect Effects Of Two Antagonistic Compounds Of Sesquiterpene And Flavonoid Purified From Chrysanthemum Indicum L.

BACKGROUND:Clearly, the hepatitis B virus (HBV) is a crucial aetiology of the second legal contagious disease, with the charateritics of strong infectivity through complex routes to be widespreaded and high morbility. Screening its antagonists from natural Chinese drugs has been exploring to date.OBJECTIVE:To purify some compounds as antagonists of HBV from Flos Chrysanthemi Indic(FCI) on the base of its component pharmacodynamics and then determine the anti-HBV mechanisms by which the compounds extrated from wild FCI induce an immune inhibitition and protect liver effect.METHODS:The wild chrysanthemi arising from Xinyang, Henan Province was subjected to the consuccive extraction and separation. Subsequent chemical identification demonstrates that FCI-A is rich in terpenes, FCI-B rich in terpenes and flavonoids, and FCI-C rich in flavonoids. These three main active components were thereafter employed in the mouse toxicology and carbon clearance experiments, along with chicken red blood cell phagocytosis experiments.The proliferation of lymphocytes in the toxical response was examined by cell counting kit (CCK-8, WST-8). Further experimental animal disease models were established on the base of the immunological injury of liver induced by concanavalin A (Con A) and then used to determine the protect liver effectors stimulated by the active components of FCI.RESULTS:I) The acute toxicity experiments indicate that wild FCI has some toxic side effects with varying extents; the intensity of the toxicity of its components is FCI-A>FCI-B>FCI-C.II) Intriguingly, the wild FCI active components exerted the opposing immunomodulatory effects on the host:their lower doses enhanced immunity, but conservely their higher doses caused immunosuppression, the strength of which is FCI-B>FCI-C,FCI-A’s role is not obvious.III) The in vivo animal experiments suggest that the FCI main active components could significantly inhibit the elevation of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) produced from the liver with the immunological injury. Furthermore, FCI-C can reduce production of interferon (IFN)-gamma, whilst both FCI-A and FCI-B reduces the abundance of tumor necrosis factor (TNF)-alpha (TNF-alpha).IV) Examination of the liver malondialdehyde (MDA) suggests that FCI-B was strongest than the FCI-A and FCI-C.CONLUSION:Both terpenoids and flavonoids rich in wild chrysanthemum have synergistic pharmacological effects for antagonistic hepatitis B virus. In stimulating the host non-specific immune response, the terpenoids are stronger than others, and upon combining with flavonoids, they can synergistically suppress the immunological liver injury. The two types of compounds inhibit the relevant cytokine secretion, and also synergistic inhibit lipid peroxidation. Collectively, terpenes and flavonoids can confer upon the host cytoprotection against HBV.This study will help understanding the immune response mechanism by which the two types of compounds synergistically induce the liver protective effect against the injury.