抗發炎中草藥之開發應用與機轉

Abstract

無中文摘要

Traditional Chinese herbal medicine has been widely used for thousands of years for health promotion, disease prevention and treatment. the clinical effect of Traditional Chinese herbal medicine is remarkable, but the mechanism of those herbal medicine are incompletely clear. In our study, we chose two famous and widely used herbal medicine to explore the mechanism by determine the anti-inflammatory and anti-oxidant effect. We chose Antrodia cinnamomea and Monascus Adlay as the study subject. Antrodia cinnamomea (A. cinnamomea), a popular medicinal mushroom in Taiwan, is widely used for prevention or treatment of liver diseases. Systematic studies on the anti-inflammatory effect of A. cinnamomea and its molecular mechanisms have not yet been fully investigated. HPLC fingerprint analysis identified seven ergostane-type triterpenoids from A. cinnamomea water extract (ACW) including highest content of Antcin K (AC), Antcin C, Antcin H, Dehydrosulphurenic acid, Antcin B, Antcin A and Dehydroeburicoic acid. Here, we explored the effects and mechanisms of ACW and the highest content AC on N-nitrosodiethylamine (DEN) induced liver inflammation, fibrosis and carcinogenesis in rats. In in vitro study, we found ACW and AC dose-dependently scavenged O2-., H2O2 and HOCl amount by a chemiluminescence analyzer. In in vivo experiment, oral intake ACW and AC significantly inhibited DEN-enhanced hepatocellular inflammation, fibrosis and carcinoma by pathologic observation, the elevated bile and liver reactive oxygen species (ROS) amounts, plasma γ-glutamyl transpeptidase, and oxidative stress including 3-nitrotyrosine, 4-hydroxynonenal and Kuppfer cell infiltration (ED-1 stains) in the inflammatory livers. DEN enhanced nuclear factor-B (NF-B) translocation, whereas ACW and AC suppressed DEN-enhanced NF-B translocation through the inhibition of its upstream signaling of p85/phosphoinositide-3-kinase, mitogen activated protein kinase and CYP2E1 expression. In conclusion, DEN can induce hepatocellular inflammation, fibrosis and carcinoma through the increase in NF-B translocation to nucleus and oxidative injury. ACW and its active component, Antcin K, counteract DEN-induced hepatic injury and inflammation by the protective and therapeutic mechanisms of a direct scavenging ROS activity and an upregulation of antioxidant defense mechanisms. Monascus Adlay (MA) prepared from fungal fermentation of Monascus purpureus inoculating with cooked adlay contains high content of monakolin K (MK) and phenolic compounds. We explored whether MA and MK improve FeCl3-induced arterial thrombosis in rats. The rats were divided into control, FeCl3-treated rat carotid artery occlusion (TTO), TTO determined with one-week MA, and TTO determined with one-week MK. We compared MA or MK effects on oxidative stress by chemiluminescence amplification and immunohistochemistry, TTO by a transonic system, NFB, ICAM-1, endoplasmic reticulum stress CHOP and Nrf2 signaling by western blotting. MA or MK efficiently depressed O2-, H2O2 and HOCl levels, platelet activation and aggregation and H2O2-enhanced ICAM-1 and VCAM-1 expression in the endothelial cells. FeCl3 significantly increased NFB p65, 3-nitrotyrosine, CHOP and ICAM-1 expression, and decreased nuclear Nrf2 translocation and induces arterial thrombus formation. MA or MK pretreatment significantly elongated the level of FeCl3-induced TTO compared to TTO group, significantly decreased proinflammatory NF-B/ICAM-1 signaling, endoplasmic reticulum stress CHOP expression and decreased thrombotic area. MA or MK significantly preserved nuclear Nrf2 translocation. MA and MK exerted a similar protective effect in attenuating thrombus formation. We suggest MA is better than MK to improve FeCl3-induced arterial thrombosis. Through the study about Monascus Adlay (MA) and Antrodia cinnamomea, we found that anti-inflammatory and anti-oxidative effect are one of the main mechanism of Traditional herbal medicine. We can explore more about the mechanisms of the other traditional herbal medicine to discover the secret of Chinese Medicine.