Comparative prototypes and metabolites of Du-zhi pill in normal and cerebral ischemia rats by UHPLC-Q-TOF-MS/MS method.

Du-Zhi pill (DZP) is widely used as a Chinese medicine in treating cerebral ischemia. UHPLC-Q-TOF-MS/MS techniques were used to detect and identify the metabolites in rat brain samples of normal and middle cerebral artery occlusion (MCAO) model rats administered with DZP. It was tentatively found that 43 prototypes and 93 metabolites could be identified in rat brain samples. Normal and MCAO model rat brain samples contained 19 prototype components. Eight prototype components were only detected in normal rat brain samples, while 16 were found only in MCAO model rat brain samples. It was determined that 47 metabolites had been identified in the normal rats, while 86 had been placed in MCAO model rats. There were 40 common metabolites in both normal and MCAO model rat brain samples. Seven metabolites were only detected in normal rat brain samples, while 46 were found only in MCAO rat brain samples. The comparison of metabolites in brain samples of normal and MCAO rats showed apparent differences. It was discovered that glucuronidation, methylation, acetylation, and sulfation are phase II metabolic routes of DZP, while hydrogenation, hydroxylation, and dehydroxylation are phase I metabolic routes. Moreover, hydrogenation, glucuronidation, hydroxylation, and methylation were the main metabolic pathways because of the number of metabolites identified in these metabolic pathways. The results provide a valuable reference for further research into effective substances of DZP for treating cerebral ischemia.

Shengmai san-derived compound prescriptions: A review on chemical constituents, pharmacokinetic studies, quality control, and pharmacological properties.

BACKGROUND: Shengmai San Formula (SMS), composed of Ginseng Radix et Rhizoma, Ophiopogon Radix and Schisandra chinensis Fructus, was a famous formula in Tradition Chinese Medicine (TCM). With the expansion of clinical applications, SMS was developed to different dosage forms, including Shengmai Yin Oral liquid (SMY), Shengmai Capsule (SMC), Shengmai Granule (SMG), Shengmai Injection (SMI) and Dengzhan Shengmai Capsule (DZSMC). These above SMS-derived compound prescriptions (SSCPs) play an important role in the clinical treatment. This review is aimed to providing a comprehensive perspective of SSCP. METHODS: The relevant literatures were collected from classical TCM books and a variety of databases, including PubMed, Google Scholar, Science Direct, Springer Link, Web of Science, China National Knowledge Infrastructure, and Wanfang Data. RESULTS: The chemical constituents of SSCPs, arrived from the individual medicinal materials including Ginseng Radix et Rhizoma, Ophiopogon Radix, Schisandra chinensis Fructus, Erigerontis Herba, were firstly summarized respectively. Then the pharmacokinetics studies, quality control, and pharmacological properties of SSCPs were all reviewed. The active compounds, pharmacokinetics characterizes, quality control markers, the effects and mechanisms of pharmacology of the different dosage forms of SSCPs were summarized. Furthermore, the research deficiencies of SSCPs and an innovative research paradigm for Chinese materia medica (CMM) formula were proposed. CONCLUSIONS: SMS, as a famous CMM formula, has great values in drug research and in clinical treatment especially for cardiocerebrovascular diseases. This article firstly make a comprehensive and systematic review on SMS.

Rapid characterization and identification of the chemical constituents and the metabolites of Du-zhi pill using UHPLC coupled with quadrupole time-of-flight mass spectrometry.

A reliable method using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was established to conduct a comprehensive analysis of the chemical constituents of Du-zhi pill (DZP) as well as their metabolites in rat plasma, urine and feces after gastric perfusion. The efficient on-line mass data acquisition modes combined the various off-line mass data mining strategy was applied. A full mass scan was performed, and then accurate MS/MS datasets were obtained through the use of a multiple mass defect filter (MMDF) and dynamic background subtraction (DBS)-dependent data acquisition method. Furthermore, post-acquisition data processing was conducted using various data-mining tools, including extracted ion chromatography (XIC), mass defect filtering (MDF), product ion filtering (PIF), and neutral loss filtering (NLF) (MetabolitePilot™). Finaly, a total of 176 compounds were identified or tentatively characterized in DZP. Moreover, a total of 233 components in vivo, which includes 92 prototype components and 141 metabolites, were unambiguously or tentatively identified in rat plasma, urine and feces. The metabolic pathways, including phase I reactions (hydroxylation, dehydroxylation and hydrogenation) and phase II reactions (acetylation, sulfation, glucuronidation and methylation), for the absorbed constituents, were explored and summarized. This is the first systematic study on the components of DZP and their metabolites in vivo. This study provide a valid analytical strategy for the characterization of chemical compounds and metabolites of TCM formulas. Moreover, an integrative strategy was proposed for the characterization and identification of chemical constituents and metabolites for additional TCM prescriptions.