ABSTRACT
Jinlingzi San (JLZS), composed of Fructus Toosendan (FT) and Rhizoma Corydalis (RC), is a classical traditional Chinese medicine prescription for regulating Qi to relieve pain. The present study investigated the pharmacokinetic compatibility of FT and RC in JLZS. A fast, selective and sensitive UPLC-MS/MS method for simultaneous determination of one limonoid (toosendanin), four tertiary alkaloids (corydaline, tetrahydropalmatine, tetrahydrocoptisine, tetrahydroberberine) and two quaternary alkaloids (palmatine, dehydrocorydaline) in rat plasma was established and fully validated. The plasma samples were pretreated by a fast protein precipitation and chromatographed using a 1.7-µm C18 column and 0.1 % formic acid-water and acetonitrile via gradient elution with a run time of 3.7 min. Multiple reaction monitoring mode with positive electrospray ionization was adopted to detect the analytes and internal standard (diphenhydramine). The lower limits of quantification were 0.08-3.09 ng/mL using only 50 µL of plasma sample. Using the proposed method, the pharmacokinetic differences of seven bioactive components in rats after administration of JLZS and the single herb (FT or RC) were investigated. The results showed that the elimination of toosendanin and alkaloids decreased significantly in the JLZS group (p < 0.05) compared with the single herb group, and the exposure of the alkaloids increased in some degree. The study demonstrated the synergistic effect of combining FT with RC on the pharmacokinetics of seven bioactive components and provided new information for a better understanding of the compatibility mechanism of JLZS.
Subject(s)
Corydalis , Drugs, Chinese Herbal , Animals , Chromatography, High Pressure Liquid , Chromatography, Liquid , Rats , Rats, Sprague-Dawley , Reproducibility of Results , Tandem Mass SpectrometryABSTRACT
Objective To investigate the pharmacological components of "Szechwan Chinaberry Fruit-Rhizoma Corydalis" drug combination and its potential molecular mechanism in the treatment of liver cancer based on network pharmacology. Methods Related databases, such as TCMSP, Uniprot, and GeneCard, were used to obtain the effective components of Szechwan Chinaberry Fruit and Rhizoma Corydalis, their corresponding action targets, and the disease targets of liver cancer, and the intersecting targets of drugs and diseases were selected. In addition, STRING and Metascape databases were used to screen out the core targets of drug action and perform GO function and KEGG pathway enrichment analyses. Results There were 9 active components in Szechwan Chinaberry Fruit and 49 active components in Rhizoma Corydalis, with 1 common component between the two drugs; there were 181 action targets of Szechwan Chinaberry Fruit and 1097 action targets of Rhizoma Corydalis, with 143 common targets between the two drugs. There were 162 intersecting targets between the drug combination and liver cancer, and the main genes involved were IL6, TP53, VEGFA, TNF, and CASP3. KEGG analysis showed that the main pathways involved included cancer pathway, AGE-RAGE signaling pathway of diabetes complications, TNF signaling pathway, NF-κB signaling pathway, and thyroid hormone signaling pathway. Conclusion There are many different components in the drug combination of "Szechwan Chinaberry Fruit-Rhizoma Corydalis", which can exert a therapeutic effect on liver cancer by acting on related genes and signaling pathways.
ABSTRACT
Objective :1H NMR spectroscopy and principal component analysis (PCA) were used to investigate the mouse serum metabonomics and toxic mechanism after oral administration of Fructus Toosendan.
ABSTRACT
Objective 1H NMR spectroscopy and principal component analysis(PCA) were used to investigate the mouse serum metabonomics and toxic mechanism after oral administration of Fructus Toosendan. Methods In this study, mice were orally administered with the ethyl acetate extract of Fructus Toosendan before collecting serum samples. Then 1H NMR was utilized to identify the metabolites with the PCA. After the experimental model of toxicity was established and the data were collected, NMR spectral regions and the metabolites were identified and ranked according to their weight aline with the loading plot. Results The scores plot for classification within groups was clear and showed a great difference from the control group. Combining the body weight and biochemical results, the elevated levels of glucose, lactate, taurine, arginine, glycine and decreased levels of betaine, creatine, amino and neurotransmitters were observed. Conclusion Our current study indicated that the ethyl acetate extract of Fructus Toosendan has liver and kidney toxicity.
