Study On Pharmacodynamics And Metabonomics Of Caulophyllum Robustum Maxim. In The Treatment Of CIA Rats

Caulophyllum robustum Maxim(CRM)is the root and rhizome of Berberidaceae.It is also known as "Hong Mao Qi,Wei Yan Xian and Sou Shan Mao",and it has a long history in the folk.According to the record of the Chinese medicine dictionary,it has the effect of regulating qi,relieving the wind and activating blood,and it has remarkable curative effect in the treatment of rheumatoid arthritis,tonsillitis and injury.Based on the effective parts of CRME(CRME)as the research object,collagen-induced arthritis(CIA)was used as pharmacodynamic model and characteristic efficacy index were studied.The metabonomics was used to investigate the CRME to CIA rats urine and plasma metabolic spectrum interference effect,based on the endogenous metabolites of potential targets and pathways for the treatment of CRME against RA.1.Pharmacodynamic study of the CRME in the treatment of CIA model mice.The bovine type Ⅱ collagen was used to induced DBA/1 mice to establish CIA model.Inflammatory cytokines which contains TNF-α,IL-6,IL-1β and PGE2 content were used as quantitative indicators to evaluat anti-inflammatory immune function,meanwhile,the body weight of mice,paw swelling,arthritis score and visceral index,histopathological and immunohistochemical results as auxiliary measure.The results showed that the different doses of CRME could significantly improve the arthritis symptoms in CIA mice,and the high CRME was better than that of tripterygium and methotrexate.CRME also had a certain immunosuppressive effect by inhibiting inflammatory cytokines.Therefore,high doses of CRME had the best anti-inflammatory and immunological effects.2.The urine metabolomics of the CRME in the treatment of CIA model rats.The paper used urine as the samples,the metabonomics method of using UPLC-TOF-MS with principal component analysis(PCA)and partial least squares-discriminant analysis(PLS-DA)for the treatment of CRME against CIA.A total of 56 potential biomarkers and 20 metabolic pathways were identified which related to CIA rats.After the CRME intervention,16 endogenous metabolites were changed,17-β-estradiol-3-glucuronide,5b-cholestanol,5b-choIestanol-3a,7a,12a-triol,stigmastanol,D-ribose,monoisobutyl phthalic acid,α-CEHC,2,4-diaminobutyric acid and 7-hydroxy-3-oxocholanoic acid were increased,hydroquinone,2-indolecarboxylic acid,indoxyl,L-tyrosine,hippuric acid,benzoic acid and N1-methyl-4-pyridone-3-formamide were decreased.These metabolites involved 8 metabolic pathways,including tryptophan metabolism,nicotinic acid and nicotinamide metabolism,tyrosine metabolism,phenylalanine metabolism,energy metabolism and cholesterol metabolism.The changes of these biomarkers indicated that CRME played a therapeutic role by regulating the metabolism of amino acids,energy metabolism and lipid metabolism.3.The plasma metabonomics of the CRME in the treatment of CIA model rats.The paper used plasma as the samples,the metabonomics method of using UPLC-TOF-MS with principal component analysis(PCA)and partial least squares-discriminant analysis(PLS-DA)for the treatment of CRME against CIA.A total of 34 potential biomarkers and 17 metabolic pathways associated with CIA were identified.After the CRME intervention,16 endogenous metabolites were changed,11b-hydroxyprogesterone,phosphatidylethanolamine,phosphatidylcholine,phosphatidyl serine,lysophosphatidylethanolamine,lysophosphatidylcholine,phosphatidyl inositol,carbatrienoic acid,3,4-dihydrofuranone,tetrahydrofolate,and 9-deoxy-methylene-prostagland E2 have a significant regulatory effect,estrogen metabolism,glycine,serine and threonine metabolism,glycerin phospholipid metabolism,arachidonic acid metabolism and biosynthesis pathway of unsaturated fatty acids.The changes of these biomarkers indicated that CRME played a therapeutic role by regulating amino acid metabolism and fatty acid metabolism.Above all,CRME have anti-inflammatory and immune suppression effect on CIA model mice,the metabonomics had been studied by adjusting the metabolism of amino acids,vitamin metabolism,energy metabolism and lipid metabolism pathway.This study may provide a new explanation of the treatment of CRME against RA through these potential targets points and pathways.