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Cnidii Fructus, derived from the dried ripe fruit of Cnidium monnieri (L.) Cuss, has the effect of warming kidneys and invigorating Yang. This study established the spectrum-effect relationships between ultra-high-performance liquid chromatography (UHPLC) fingerprints and the antitumor activities of Cnidii Fructus on human hepatocellular carcinoma (HepG2) cells. In UHPLC fingerprints, 19 common peaks were obtained, and 17 batches of herbs had similarity >0.948. In Cell Counting Kit-8 (CCK-8) test, 17 batches of Cnidii Fructus extract significantly inhibited the proliferation of HepG2 cells to different degrees, showing different half-maximal inhibitory concentration (IC50) values. Furthermore, gray correlation analysis, Pearson's analysis, and orthogonal partial least squares discriminant analysis were performed to screen out eight components. The analysis of mass spectrum data and a comparison with standards revealed that the eight components were methoxsalen, isopimpinellin, osthenol, imperatorin, osthole, ricinoleic acid, linoleic acid, and oleic acid. The verification experiments by testing single compounds indicated that these eight compounds were the major anti-hepatoma compounds in Cnidii Fructus. This work provides a model combining UHPLC fingerprints and antitumor activities to study the spectrum-effect relationships of Cnidii Fructus, which can be used to determine the principal components responsible for the bioactivity.
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Proliferación Celular , Cnidium , Cromatografía Líquida de Alta Presión/métodos , Humanos , Células Hep G2 , Proliferación Celular/efectos de los fármacos , Cnidium/química , Frutas/química , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Neoplasias Hepáticas/tratamiento farmacológico , Carcinoma Hepatocelular/tratamiento farmacológico , Extractos Vegetales/farmacología , Extractos Vegetales/química , Reproducibilidad de los Resultados , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/análisis , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/análisis , Furocumarinas/farmacología , Furocumarinas/análisis , Furocumarinas/químicaRESUMEN
Physochlainae Radix (PR) is an essential herbal medicine that has been generally applied for treating cough and asthma. In this study, a comprehensive strategy for quality evaluation of PR from different origins was established by integrating qualitative identification, quantitative analysis, and chemometric methods. A total of 58 chemical components were identified by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UHPLC-Q-TOF-MS/MS), and a sensitive and rapid UHPLC-QqQ-MS/MS method was established for the simultaneous determination of 12 compounds. In addition, multivariate statistical analysis was applied for discriminant analysis to compare the differences among 30 batches of PR samples. The results showed that the 30 batches of PR collected from four provinces could be clustered into three categories, in which scoparone, protocatechuic acid, tropic acid, and scopolin were important components to distinguish the primary and non-primary producing areas, as well as superior and inferior products of PR. Chemometric results were consistent and validated each other, and systematically explained the intrinsic quality characteristics of PR. This study first demonstrated that LC-MS combined with multivariate statistical analysis, provided a comprehensive and effective means for quality evaluation of PR.
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Medicamentos Herbarios Chinos , Espectrometría de Masas en Tándem , Espectrometría de Masas en Tándem/métodos , Quimiometría , Raíces de Plantas/química , Análisis Multivariante , Análisis Discriminante , Cromatografía Líquida de Alta Presión/métodos , Medicamentos Herbarios Chinos/análisisRESUMEN
Geo-authentic herbs refer to medicinal materials produced in a specific region with superior quality. Stephania tetrandra S. Moore (S. tetrandra) is cultivated in many provinces of China, including Anhui, Zhejiang, Fujian, Jiangxi, Hunan, Guangxi, Guangdong, Hainan, and Taiwan, among which Jiangxi is the geo-authentic origin. To explore habitat-related chemical markers of herbal medicine, an integrated chromatographic technique including gas chromatography-mass spectrometry (GC-MS), ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS) and ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS/MS) combined with chemometric analysis was established. The established methods manifested that they were clearly divided into two groups according to non-authentic origins and geo-authentic origins, suggesting that the metabolites were closely related to their producing areas. A total of 70 volatile compounds and 50 non-volatile compounds were identified in S. tetrandra. Meanwhile, tetrandrine, fangchinoline, isocorydine, magnocurarine, magnoflorine, boldine, and higenamine as chemical markers were accurately quantified and suggested importance in grouping non-authentic origins and geo-authentic origins samples. The discriminatory analysis also indicated well prediction performance with an accuracy of 80%. The results showed that the multiple chromatographic and chemometric analysis technique could be used as an effective approach for discovering the chemical markers of herbal medicine to fulfill the evaluation of overall chemical consistency among samples from different producing areas.
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Medicamentos Herbarios Chinos , Plantas Medicinales , Stephania tetrandra , Stephania tetrandra/química , Espectrometría de Masas en Tándem/métodos , Quimiometría , China , Cromatografía Líquida de Alta Presión/métodos , Plantas Medicinales/química , Medicamentos Herbarios Chinos/química , EcosistemaRESUMEN
Introduction: Pogostemon cablin (PC) is used in traditional Chinese medicine and food, as it exerts pharmacological effects, such as immune-modulatory, antibacterial, antioxidant, antitumor, and antiviral. Currently, the pharmacokinetics (PK) studies of PC mainly focus on individual components. However, research on these individual components cannot reflect the actual PK characteristics of PC after administration. Therefore, the simultaneous determination of multiple components in rat plasma using UPLC-MS/MS was used for the pharmacokinetic study after oral administration of PC extract in this study, providing reference value for the clinical application of PC. Methods: In the present study, a reliable and sensitive ultra-high performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the simultaneous determination of 15 prototype components (vanillic acid, vitexin, verbascoside, isoacteoside, hyperoside, cosmosiin, apigenin, ß-rhamnocitrin, acacetin, ombuin, pogostone, pachypodol, vicenin-2, retusin, and diosmetin-7-O-ß-D-glucopyranoside) in rat plasma after oral administration of the PC extract. Plasma samples were prepared via protein precipitation using acetonitrile, and icariin was used as the internal standard (IS). Results: The intra-day and inter-day accuracies ranged from -12.0 to 14.3%, and the precision of the analytes was less than 11.3%. The extraction recovery rate of the analytes ranged from 70.6-104.5%, and the matrix effects ranged from 67.4-104.8%. Stability studies proved that the analytes were stable under the tested conditions, with a relative standard deviation lower than 14.1%. Conclusion: The developed method can be applied to evaluate the PK of 15 prototype components in PC extracts of rats after oral administration using UPLC-MS/MS, providing valuable information for the development and clinical safe, effective, and rational use of PC.
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ETHNOPHARMACOLOGICAL RELEVANCE: The combination of Aconitum carmichaelii Debx (Chuanwu, CW) and Pinellia ternata (Thunb.) Breit (Banxia, BX) forms an herbal pair within the eighteen incompatible medicaments (EIM), indicating that BX and CW are incompatible. However, the scientific understanding of this incompatibility mechanism, especially the corresponding drug-drug interaction (DDI), remains complex and unclear. AIM OF THE STUDY: This study aims to explain the DDI and potential incompatibility mechanism between CW and BX based on pharmacokinetics and cocktail approach. MATERIALS AND METHODS: Ultraperformance liquid chromatography-tandem mass spectrometry methods were established for pharmacokinetics and cocktail studies. To explore the DDI between BX and CW, in the pharmacokinetics study, 10 compounds were determined in rat plasma after administering CW and BX-CW herbal pair extracts. In the cocktail assay, the pharmacokinetic parameters of five probe substrates were utilized to assess the influence of BX on cytochrome P450 (CYP) isoenzyme (dapsone for CYP3A4, phenacetin for CYP1A2, dextromethorphan for CYP2D6, tolbutamide for CYP2C9, and omeprazole for CYP2C19). Finally, the DDI and incompatibility mechanism of CW and BX were integrated to explain the rationality of EIM theory. RESULTS: BX not only enhances the absorption of aconitine and benzoylaconine but also accelerates the metabolism of mesaconitine, benzoylmesaconine, songorine, and fuziline. Moreover, BX affects the activity of CYP enzymes, which regulate the metabolism of toxic compounds. CONCLUSIONS: BX altered the activity of CYP enzymes, consequently affecting the metabolism of toxic compounds from CW. This incompatibility mechanism may be related to the increased absorption of these toxic compounds in vivo.
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Aconitum , Interacciones de Hierba-Droga , Pinellia , Ratas Sprague-Dawley , Aconitum/química , Pinellia/química , Animales , Masculino , Ratas , Sistema Enzimático del Citocromo P-450/metabolismo , Espectrometría de Masas en Tándem , Extractos Vegetales/farmacocinética , Extractos Vegetales/farmacología , Extractos Vegetales/química , Medicamentos Herbarios Chinos/farmacocinética , Medicamentos Herbarios Chinos/química , Interacciones FarmacológicasRESUMEN
Chebulae Fructus, was extensively used as a food supplement and medicinal herb, which contained two medicinal forms corresponding to the mature fruit of Chebulae Fructus (CF) and CF pulp. They were widely used in the Chinese clinical medicine and it played a significant role in the Mongolian and Tibetan medicine for the treatment of sore throat, asthma, diarrhea and other diseases. Both of them were recorded in the 2020 Edition (Volume I) of the Chinese Pharmacopoeia. However, the chemical components of CF and CF pulp have not been holistically explored, which seriously hindered its quality evaluation. This study investigated the overall chemical profile of the CF and CF pulp using ultra high-performance liquid chromatography coupled with quadrupole time of flight mass spectrometry (UHPLC-Q-TOF/MS) and ultra high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Sixty-four chemical components were tentatively identified, and 13 components were quantified in Chebulae Fructus. Furthermore, multivariate chemometric methods were applied to compare the differences among CF samples, and all samples were classified by orthogonal partial least squares-discriminant analysis (OPLS-DA) based on the 13 quantified compounds. The results showed that CF and CF pulp were clustered in two different areas. Ellagic acid, chebulagic acid, chebulinic acid, corilagin and pentagalloyl glucose were selected as the significant constituents to different of CF and CF pulp. LC-MS coupled with chemometrics strategy analysis could comprehensively evaluate the holistic quality of CF, which provided a necessary information for the rational development and utilization of CF and CF pulp resource.