Xie Xin Tang Effective Component Of Anti-toxin Efficacy And Mechanism Study

The early research had found that the couple of Dahuang-Huangqin had the strongest antiendotoxic activity which even excelled the activity of whole recipe(Xie-Xin Decoction),the high polarity chemical compositions of Dahuang-Huangqin couple and the low polarity chemical compositions of Radix et Rhizoma Rhei are the main antiendotoxic effective fractions,such as the total free and conjuncted anthraquinone of Radix et Rhizoma Rhei,total flavonoids of Radix Scutellariae.The NO release was inhibited obviously by these effective fractions,the effect of compatibility of conjunct anthraquinone and total flavonoids was slight stronger than compatibility of free anthraquinone and total flavonoids,but no statistical difference.The early work had explored the antiendotoxic mechanism of the compatibility of conjunct anthraquinone and total flavonoids,this study used in vivo experiments to certificate the effect of the compatibility of free anthraquinone and total flavonoids,and explored its mechanism,for comprehensive evaluation the antiendotoxic effects of effective fractions.This will provide the evidences for the compatibility of Xie-Xin Decoction to use reasonable and its further development, and also provide new thinking and model for the research of compatibility mechanism of the traditional Chinese medicine prescription.In the study,endotoxin challenged mice,LPS-induced fever rabbits and rats were used to certificate the antiendotoxic effect of the compatibility of free anthraquinone and total flavonoids;and the antiendotoxic mechanism of the effective fractions of Xie-Xin Decoction were studied by RT-PCR,Western blotting from TLR4 signal pathway in LPS-induced lung injury rats.The results were showed as follows:1 Total flavonoids and total free anthraquinone according to the ratio of A1 could protect BCG-primed mice from LPS-induced lethality,inhibit LPS induced rabbits and rats fervescence,and also reduce the content of endotoxin in serum, suggesting it exactly have the role of anti-endotoxin.2 The effective fraction of xie-xin decoction and their different compatibilities can reduce the wet/dry weight ratio of lung tissues,the WBC,PMN and protein in BALF,they all had protect effects on LPS-induced lung injury rats,but the best one was the compatibilities of total flavonoids and total free anthraquinone,it can down regulation the expression of TLR4 and CD14,inhibite the NF-κB nuclear translocation and IκB degradation,decrease the release of TNF-α,IL-1β,IL-6 and NO.Overall,total flavonoids and total free anthraquinone according to the ratio of A1 have the effect of anti-endotoxin,its mechanism is affecting the TLR4- NF-κB-inflammatory factor signal pathway:down regulation the expression of TLR4 and CD14,sequentially inhibite the NF-κB nuclear translocation and IκB degradation, decrease the release of inflammatory factor.