ABSTRACT
Qianggan capsule (QGC) is a complex preparation composed of 16 traditional Chinese medicines (TCM) that can clear heat and dampness, fortify the spleen and blood, typify qi and relieve depression. However, the chemical composition of QGC remains incompletely understood, despite its clinical use in treating chronic hepatitis and liver injury. The objective of this study was to explore the quality markers of QGC through qualitative and quantitative analysis of its chemical components. First, the chemical composition of QGC was qualitatively analyzed using UHPLC-Q-TOF-MS/MS. Subsequently, the LC-sMRM method was developed and optimized to accurately quantify various chemical components of 10 batches of QGC. Finally, the variations in chemical components between batches were analyzed via multivariate statistical analysis. UHPLC-Q-TOF-MS/MS analysis revealed 167 chemical constituents in QGC, comprised of 48 flavonoids, 32 terpenoids, 18 phenolic acids, 9 coumarins, 9 phenylpropanoids, and 51 nucleosides, sugars, amino acids, anthraquinones, and other compounds. The LC-sMRM method was established for the quantitative analysis of 42 chemical components in 10 batches of QGC. The ultrasonic-assisted extraction parameters were optimized using RSM. Compared with conventional MRM, sMRM demonstrated superior sensitivity and precision. PCA and OPLS-DA identified eight chemical components with content differences among batches. This study established the chemical composition of QGC, offering useful guidance for assessing its quality.
Subject(s)
Drugs, Chinese Herbal , Tandem Mass Spectrometry , Drugs, Chinese Herbal/chemistry , Tandem Mass Spectrometry/methods , Chromatography, High Pressure Liquid/methods , Flavonoids/analysis , Flavonoids/chemistry , Coumarins/chemistry , Coumarins/analysis , Terpenes/analysis , Hydroxybenzoates/analysis , Reproducibility of Results , Nucleosides/analysis , Capsules/chemistryABSTRACT
Piperlonguminine (PLG) is a major alkaloid found in Piper longum fruits. It has been shown to possess a variety of biological activities, including anti-tumor, anti-hyperlipidemic, anti-renal fibrosis and anti-inflammatory properties. Previous studies have reported that PLG inhibits various CYP450 enzymes. The main objective of this study was to identify reactive metabolites of PLG in vitro and assess its ability to inhibit CYP450. In rat and human liver microsomal incubation systems exposed to PLG, two oxidized metabolites (M1 and M2) were detected. Additionally, in microsomes where N-acetylcysteine was used as a trapping agent, N-acetylcysteine conjugates (M3, M4, M5 and M6) of four isomeric O-quinone-derived reactive metabolites were found. The formation of metabolites was dependent on NADPH. Inhibition and recombinant CYP450 enzyme incubation experiments showed that CYP3A4 was the primary enzyme responsible for the metabolic activation of PLG. This study characterized the O-dealkylated metabolite (M1) through chemical synthesis. The IC50 shift assay showed time-dependent inhibition of CYP3A4, 2C9, 2E1, 2C8 and 2D6 by PLG. This research contributes to the understanding of PLG-induced enzyme inhibition and bioactivation.
Subject(s)
Activation, Metabolic , Cytochrome P-450 CYP3A , Dioxolanes , Microsomes, Liver , Animals , Humans , Cytochrome P-450 CYP3A/metabolism , Microsomes, Liver/metabolism , Microsomes, Liver/drug effects , Rats , Dioxolanes/pharmacology , Dioxolanes/chemistry , Cytochrome P-450 CYP3A Inhibitors/pharmacology , Cytochrome P-450 Enzyme System/metabolism , Male , Piperidones , BenzodioxolesABSTRACT
A new myrsinol-type diterpene polyester, 14-deoxo-3ß-O-propinoyl-2α,5α,7ß,15ß-tetra-O-acetyl-14α-O-benzoyl-myrsinol (1), and its known analogue, 14-deoxo-3ß-O-prorionyl-5α,15ß-di-O-acetyl-7ß-O-nicotinoyl-myrsinol-14ß-acetate (2), together with a monoterpenoid, pubinernoid A (3), two indole alkaloids, neoechinulin A (4) and dihydroxyisoechinulin A (5), two benzene derivatives, siringin (6) and (3-methoxyphenyl) acetic acid (7), were isolated from the 70% acetone extract of the aerial parts of Euphorbia dracunculoides Lam. Their structures were elucidated on the basis of spectroscopic evidence and comparison with literature reports. The absolute configuration of 1 was deduced by comparing experimental and calculated ECD spectra. Among them, compounds 4 and 5 were first obtained from the plant source. In addition, the (13)C NMR data of compound 2 was reported for the first time.
Subject(s)
Diterpenes/chemistry , Euphorbia/chemistry , Plant Components, Aerial/chemistry , Polyesters/chemistry , Cell Line, Tumor/drug effects , Diterpenes/isolation & purification , Humans , Molecular Structure , Polyesters/isolation & purificationABSTRACT
Sixteen compounds including daphnoretin (1), isofraxidin (2), scopoletin (3), kaempferol (4), quercetin (5), guaijaverin (6), astragalin (7), quercetin-3-O-ß-D-glucopyranoside (8), naringenin-7-O-ß-D-glucopyranoside (9), 5-O-methylapi- genin-7-O-ß-D-glucopyranoside (10), methyl gallate (11), prionitiside A (12), (2S)-2,3-dihydroxypropyl-1,6,8-trihydroxy-3- methyl-9,10- dioxoanthracene-2-carboxylate (13), 3,3'-di-O-methyl ellagic acid (14), 3'-O-methyl-3,4-O,O-metheneellagic acid-4'-O-ß-D- glucopyranoside (15) and 3,4-methylenedioxy-3'-O-methylellagic acid (16), were isolated from the 70% acetone extract of Euphorbia dracunculoides Lam. Among them, compounds 1-3, 6-9, 11, and 14 were isolated from E. dracunculoides for the first time, and compounds 10, 12, 13, 15, and 16 were firstly obtained from the genus Euphorbia. Their structures were elucidated by spectroscopic analysis, including 1H-NMR, 13C-NMR, and ESI-MS.
