Compatibility Of Radix Aconiti Kusnezoffi Preparata And Radix Glycyrrhizae On The Treatment Of Rheumatoid Arthritis Rats And Metabolic Study On Rhizoma Paridis Saponins

The purpose of this study is to evaluate the pharmacological effects of compatibility ofRadix Aconiti Kusnezoffi Preparata (ZCW) and Radix Glycyrrhizae (GC) on RheumatoidArthritis. In rat biological samples after oral administration of the ethanol extract of ZCW-GC,the activities were analyzed and the influence of herbs on the pharmacokinetics of maincomponents and pharmacology related to anti-inflammation and analgesic activities werestudied to elucidate the compatibility in the formulae. In order to explain the rational use ofRadix Aconiti Kusnezoffi Preparata and Radix Glycyrrhizae, the effects of ZCW-GC onCYP450activities were evaluated by using a multiple-drug-probe cocktail. The detailedresults were listed as follows:The anti-inflammatory effects of the ethanol extract of Radix Aconiti KusnezoffiPreparata and Radix Glycyrrhizae were examined by using albumin egg-induce paw edema inmice assay and xylene-induced ear edema in mice method. Analgesic activity was evaluatedby three models including acetic acid-induced writhing, formalin test and hot-plate test. Therheumatoid arthritis activity was evaluated by injection of Freund‘s complete adjuvant. Inaddition, we used LC/MSnto investigat the serum pharmacochemistry after oraladministration of the ethanol extract of ZCW-GC composed of15known components,including flavanone, triterpene and alkaloids. The result suggested that the ethanol extract ofZCW-GC possesses excellent anti-inflammatory activity as well as peripheral and centralanalgesic properties. Flavanone, triterpene and alkaloids may be the active ingredients. It alsoshowed that the ethanol extract of ZCW-GC would be a valuable candidate for furtherinvestigation as a new anti-arthritic drug.After oral administration of ethanol extract of ZCW-GC, the pharmacokineticscharacteristics of alkaloid in Radix Aconiti Kusnezoffi Preparata and triterpene&flavonoidsingredients in Radix Glycyrrhizae have been changed. The absorption of alkaloid, triterpeneand flavonoids was decreased dramatically after the compatibility of two herbs, the AUC ofmesaconine and aconitine were decreased40.5%and14.1%, respectively.In this study, a―Cocktail‖approach in rats by HPLC was established and validated toevaluate the inductive or inhibitory effects on CYP3A, CYP1A2, CYP2A6bypharmacokinetic parameters of four probe drugs containing phenacetin, dapsone, coumarinand midazolam. The results suggested that Radix Aconiti Kusnezoffi Preparata and Radix Glycyrrhizae (ZCW-GC) could induce CYP3A and CYP1A2, but had no influence onCYP2A6.An accurate, sensitive and rapid method, LC-MS/MS, was developed and validated forthe simultaneous determination of Rhizoma Paridis saponins in rat plasma. The establishedanalytical method has been successfully applied to the pharmacokinetic studies of RhizomaParidis saponins in rats after oral administration and we investigated the metablism ofRhizoma Paridis saponins in rat using UPLC/Q-TOF/MS. Metabolism of RPS in rat fecesafter oral administration indicated that deglycosylation was the reaction in RPS.