RESUMO
Danggui Buxue Decoction is a classic formula for replenishing qi and nourishing blood. Despite its widespread use, its dynamic metabolism involved remains unclear. Based on the sequential metabolism strategy, blood samples from different metabolic sites were obtained via in situ closed intestine ring integrated with a jugular venous continuous blood supply technique. An ultra-high-performance liquid chromatography-linear triple quadruple-Orbitrap-tandem mass spectrometry method was developed for the identification of prototypes and metabolites in rat plasma. The dynamic absorption and metabolic landscape of flavonoids, saponins, and phthalides were characterized. Flavonoids could be deglycosylated, deacetylated, demethylated, dehydroxylated, and glucuronicated in the gut and then absorbed for further metabolism. Jejunum is an important metabolic site for saponins biotransformation. Saponins that are substituted by Acetyl groups tend to lose their acetyl groups and convert to Astragaloside IV in the jejunum. Phthalides could be hydroxylated and glucuronidated in the gut and then absorbed for further metabolism. Seven components serve as crucial joints in the metabolic network and are potential candidates for the quality control of Danggui Buxue Decoction. The sequential metabolism strategy described in this study could be useful for characterizing the metabolic pathways of Chinese medicine and natural products in the digestive system.
Assuntos
Medicamentos de Ervas Chinesas , Saponinas , Ratos , Animais , Espectrometria de Massas em Tandem , Medicamentos de Ervas Chinesas/análise , Cromatografia Líquida de Alta Pressão/métodos , Flavonoides/análise , Saponinas/análiseRESUMO
Danggui Buxue Decoction is a classic formula containing Astragali Radix and Angelicae Sinensis Radix in a 5:1 ratio and has been extensively used to treat blood deficiency for thousands of years. The aim of the study was to investigate the differences in plasma protein binding, pharmacokinetics, and tissue distribution of Danggui Buxue Decoction in normal and blood-deficient rats by ultra-performance liquid chromatography-tandem mass spectrometry. The effects on peripheral blood routine were verified. The compounds exhibited higher plasma protein binding and absorption in the model group compared to the control group, except formononetin. The six ingredients were distributed widely, and the highest concentrations were detected in the heart and uterus. As has been demonstrated in the previous study of the effect of Danggui Buxue Decoction, its potential is to serve as an effective traditional Chinese medicine formula for treating cardiovascular diseases and impacting estrogenic properties, which reveals the potential target organs of Danggui Buxue Decoction the heart and uterus. Our findings suggested that the absorption and distribution of different components in Danggui Buxue Decoction varies depending on the pathological state, molecular weight, lipid solubility, transporter-mediated efflux, and other factors.
Assuntos
Medicamentos de Ervas Chinesas , Espectrometria de Massas em Tandem , Feminino , Ratos , Animais , Medicamentos de Ervas Chinesas/química , Cromatografia Líquida , Administração OralRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Coptis chinensis Franch. (CC), as a commonly used heat-clearing and toxin-resolving traditional Chinese herbal medicine, has gained increased attention for its anti-tumor activity. However, little is known about the anti-tumor angiogenesis effect of CC and its possible bioactive components. Also, it has been shown that temperature affects the quality of CC, albeit whether and how it affects the anti-angiogenic activity of CC is currently unknown. AIM OF THE STUDY: To determine the processing temperatures (40, 60, 80, 120, 140, 150, 160 and 200⯰C) at which CC has the strongest anti-angiogenic effect and speculate the possible bioactive components. MATERIALS AND METHODS: The q-CAM model was constructed to explore the anti-angiogenesis agents of CC. The angiogenesis inhibition effects of CC samples at different processing temperatures and its seven alkaloids were determined based on morphological observation and vascular area proportion analysis. UPLC-MS/MS was employed to screen the potent active components of CC on anti-angiogenesis. RESULTS: All the intervention by CC at different processing temperatures and its seven alkaloids could inhibit angiogenesis on q-CAM vessels, as evidenced by a poor vasular development in morphological observation and a low vascular area proportion in vascular quantitative analysis, most evident in CC processed at 40⯰C and palmatine. LC-MS revealed that palmatine displayed strongest inhibitory effect on q-CAM vessels with a high absorption due to its stable structure. And the maternal nucleus transformation phenomenon of CC alkaloids was found in the quail embryo metabolism. CONCLUSIONS: The q-CAM models in conjunction with the UPLC-MS/MS technique could be a useful tool for assessing tumor angiogenesis and screening tumor-targeted medicines. Processing temperature can affect the anti-angiogenesis effect of CC because of its function on the content of alkaloids, and palmatine can be considered as a prospective anti-angiogenic drug.