Comparative Pharmacokinetic Profiles of Three Protoberberine-type Alkaloids from Raw and Bile-processed Rhizoma coptidis in Heat Syndrome Rats.

BACKGROUND: The Bile-processed Rhizoma coptidis (BRC), which has a colder drug property than Rhizoma coptidis (RC), is widely used for the treatment of heat syndrome. We compared the pharmacokinetics of the protoberberine-type alkaloids in BRC and RC in rats with heat syndrome to elucidate the bile-processing mechanism. MATERIAL AND METHODS: We established a rapid and sensitive method for simultaneously determining three alkaloids: berberine, palmatine, and jatrorrhizine, in rat plasma based on ultra-performance liquid chromatography/tandem mass spectrometry. The separation was carried out on a Waters ACQUITY BEA C18 column. The mobile phase consisted of acetonitrile (containing 0.1% formic acid) and water (containing 0.1% formic acid and 10 mmol/L ammonium acetate) and carbamazepine was used as an internal standard. The detection was carried out in a multiple reaction monitoring mode (MRM) using electrospray ionization in the positive ion mode. RESULTS: Pharmacokinetic profiles indicated that the Cmax of berberine and palmatine increased two times and the Tmax of the three alkaloids decreased three times after bile processing. AUC0→∞ and AUC0→t of the alkaloids were similar between RC and BRC. CONCLUSION: The results suggest that bile processing could increase the absorption rate of alkaloids. This study broadens our understanding of Chinese herbal medicine processing. SUMMARY: Contents of berberine, palmatine and jatrorrhizine, in heat syndrome rats' plasma between the raw and bile-processed Rhizoma coptidis (RC) were determined by UPLC-MS/MS.The whole pharmacokinetic profiles of three alkaloids in the bile-processed Rhizoma coptidis (BRC) were similar to those of RC.The shorter Tmax and increased 2-fold Cmax were obtained after RC bile-processing.Bile-processing could promote the absorption rate of alkaloids in a certain degree. Abbreviation Used: RC: Rhizoma coptidis, BRC: Bile-processed Rhizoma coptidis, HPLC: high-performance liquid chromatography, UPLC-MS/MS: ultra-performance liquid chromatography-mass spectrometry/ mass spectrometry, LC-MS: liquid chromatography-mass spectrometry, MRM: multiple reaction monitoring mode, QC: quality control, RE: relative error, RSD: relative standard deviation, Cmax: maxium of drug concentration, Tmax: time for maxium of drug concentration, AUC: area under concentration-time curve, LLOQ: Linearity and lower limits of quantification, t1/2: half-life, Clz: body clearance.

Correlation between integrated pharmacokinetics and pharmacodynamics of bile processed Rhizoma Coptidis in febrile rats / 药学学报

This study was designed to validate the correlation between integrated pharmacokinetic and therapeutic effects of alkaloids using bile processed Rhizoma Coptidis (BRC). Rats were divided into three groups: normal, disease model, model+BRC. Rats were induced to have an excessive heat syndrome. Rectal temperatures were collected at 0, 3, 6 and 9 h after single oral administration of the drugs. The plasma concentrations of three alkaloids were quantified at different times by UPLC-MS/MS after the administration of BRC. An approach of self-defined weighting coefficiency was created to the holistic pharmacokinetic profiles of alkaloids in BRC. The classified and integrated synthetic concentrations were obtained, and then the pharmacokinetic parameters of alkaloids were calculated from non-compartmental model analysis. The potential relationship between the integrated mean concentration of alkaloids and the antifebrile efficacy was investigated. The holistic t(max) of alkaloids was 1.11 h, the antifebrile effect of BRC at 3 h was improved over the model group. Double peaking appeared in the integrated blood concentration-time curve, the second t(max) of alkaloids was 4.82 h. The antifebrile effects of BRC at 3-6 h were significant, and the antifebrile effects at 6-9 h was decreased significantly. Dynamic variation of alkaloids of BRC in the body exhibited the similarity to the pattern of its antifebrile effect.

Determination of four coumarin constituents before and after Angelicae Dahuricae Radix stewed with yellow rice wine and research on its mutual transformation mechanism / 中国中药杂志

To determine the contents of oxypeucedanin, oxypeucedanin hydrate, byakangelicol and byak-angelicin both before and after Angelicae Dahuricae Radix was stewed with yellow rice wine by high-performance liquid chromatography, and study the mutual transformation mechanisms of oxypeucedanin into oxypeucedanin hydrate, as well as byakangelicol into byak-angelicin. The research results indicated that the contents of oxypeucedanin and byakangelicol were decreased, but the contents of oxypeucedanin hydrate and byak-angelicin were increased after Angelicae Dahuricae Radix was processed with yellow rice wine. The contents' changes of these chemical compounds were due to the ring opening reaction of epoxy compounds, such as oxypeucedanin and byakangelicol under the weak acidity and heating conditions of yellow rice wine. This research could provide a scientific basis for the processing mechanism of Angelicae Dahuricae Radix with yellow rice wine stewing.

Differences in effective mechanisms of Coptidis Rhizoma and bile processed Coptidis Rhizoma on heat syndrome based on urinary metabonomics / 中国中药杂志

A urinary metabonomics method based on ultra-performance liquid chromatography coupled with LTQ-Orbitrap-mass spectrometry (UPLC/LTQ-Orbitrap-MS) was developed to study the difference of action mechanism of Coptidis Rhizoma (CR) and bile processed CR on the heat syndromein rats, and reveal the scientificity of CR processing method. The heat syndrome rat models were established by intragastric administration of water decoction of Aconiti Lateralis Radix Preparata, Zingiberis Rhizoma and Cinnamomi Cortex for 15 days combined with subcutaneous injection of dry yeast suspension. After administration for 15 days, the urine of rats in each group was collected at 0-6 h after modeling, 6-12 h after modeling and 12-24 h after modeling; principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were used for data treatment. Good separation was observed between the normal groups and model group at 0-6 h and 6-12 h, but overlapped at 12-24 h with no separation trend. Obvious separation was achieved in urine samples between CR group, BCR group and model groups at 0-6 h, close to the normal group. Separation trend occurred between CR group and BCR group at 0-6 h and 6-12 h. Thirty potential biomarkers related with heat syndrome were identified by PLS-DA approach. The results showed that the overall therapeutic effect of CR for heat syndrome had been changed after being processed with pig bile. Bile processed CR has the characteristics of multiple targets, rapid onset and strong effects, mainly playing a role of antipyretic effect through regulating cholinergic neurotransmitter, amino acid metabolism and purine metabolism.

Correlation between integrated pharmacokinetics and pharmacodynamics of bile processed Rhizoma Coptidis in febrile rats / 药学学报

This study was designed to validate the correlation between integrated pharmacokinetic and therapeutic effects of alkaloids using bile processed Rhizoma Coptidis (BRC). Rats were divided into three groups: normal, disease model, model+BRC. Rats were induced to have an excessive heat syndrome. Rectal temperatures were collected at 0, 3, 6 and 9 h after single oral administration of the drugs. The plasma concen­trations of three alkaloids were quantified at different times by UPLC-MS/MS after the administration of BRC. An approach of self-defined weighting coefficiency was created to the holistic pharmacokinetic profiles of alkaloids in BRC. The classified and integrated synthetic concentrations were obtained, and then the pharma­cokinetic parameters of alkaloids were calculated from non-compartmental model analysis. The potential relationship between the integrated mean concentration of alkaloids and the antifebrile efficacy was investigated. The holistic tmax of alkaloids was 1.11 h, the antifebrile effect of BRC at 3 h was improved over the model group. Double peaking appeared in the integrated blood concentration-time curve, the second tmax of alkaloids was 4.82 h. The antifebrile effects of BRC at 3-6 h were significant, and the antifebrile effects at 6-9 h was decreased significantly. Dynamic variation of alkaloids of BRC in the body exhibited the similarity to the pattern of its antifebrile effect.

Study on mechanism of combined administration of Coptidis Rhizoma and Rehmanniae Radix in treating type II diabetes mellitus / 中国中药杂志

To make a preliminary study on the mechanism of Coptidis Rhizoma(CR) and Rehmanniae Radix(RR) before and after the combined administration in treating type II diabetes mellitus. The type I diabetes animal model in rats was established by fat emulsion and intraperitoneal injection with streptozotocin, in order to compare the hpyerglycemic and hypolipidemic effects of CR, RR and their combined administration of different ratio. The urinary metabolic profiling in rats of Coptidis Rhizoma and Rehmanniae Radix before and after the combined administration was analyzed by using the gas chromatography-mass spectrometry. The differences among groups in metabolome were analyzed by the principal component analysis (PCA). The biochemical index results indicated that both CR and RR before and after the combined administration could lower high blood glucose, hypertriglyceride and high cholesterol. According to the analytical results of PCA of the rats' urine samples, the CR group was the most close to the normal group, with no significant difference in CR and RR group of different combination ratios. Twelve differentiated metabolites were identified to be related to type II diabetes. Compared with the normal group, the CR-treated group showed significant increase in seven differentiated metabolites. Among CR and RR drugs with different combination ratios, CR played a major role and thus acted as the monarch drug. Whereas RR served as the ministerial drug and assisted CR to show the efficacy. This study laid a foundation for the explanation of the combination mechanism of traditional Chinese medicines.

Comparing analysis of components in volatile oils of nutmeg and prepared nutmeg by GC-MS / 中国中药杂志

<p><b>OBJECTIVE</b>To compare components in volatile oils of nutmeg and prepared nutmeg.</p><p><b>METHOD</b>Volatile oil from nutmeg and prepared nutmeg were extracted by vapor distillation. The chemical components in two kinds of volatile oils were determined and indentified by GC-MS.</p><p><b>RESULT</b>The change in quantity and quality of components in volatile oils were observed after processing. 13 new components occurred and 4 components disappeared in volatile oils after processing. The contents of methyleugenol and methylisoeugenol that are active ingredients were increased. The contents of myristicin and safrol that are toxic ingredients in volatile oils were decreased.</p><p><b>CONCLUSION</b>The processing method of nutmeg by soaking with water and roasting with bran is scientific.</p>