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.

An Energy Metabolism Study on the Efficacy of Naoxintong Capsules against Myocardial Infarction in a Rat Model.

Background: In myocardial ischemia, optimizing the myocardial metabolic phenotype to improve cardiac function is critical. Naoxintong capsules (NXT) are widely prescribed in Chinese medicine for the treatment of cerebrovascular and cardiovascular diseases. Methods: In this study, a rat model of myocardial infarction was established by ligation of the left anterior descending coronary artery. The structure and function of the heart were evaluated using echocardiography. The pathological changes of the rat myocardium and the myocardial volume collagen fraction (CVF) were examined using hematoxylin-eosin (HE) and Masson's trichrome staining (Masson). The expression of TNF-α and IL-6 were detected by immunohistochemistry. The level of cTnT was also measured to evaluate myocardial injury. In order to study the changes in energy metabolism in myocardial infarction and the effects of NXT, a targeted analysis method for detecting the 29 energy metabolites in cardiac muscle tissue was developed based on UPLC-QQQ-MS. Western blotting was used to detect the expression of proteins related to energy metabolism in myocardia. Results: In the rat model of myocardial infarction, NXT showed obvious effects, such as improving heart function and increasing LVEF and LVFS. HE staining, Masson staining, and immunohistochemical results revealed that NXT decreased inflammatory infiltration, improved myocardial fibrosis, and reduced infarct size. In addition, NXT significantly reduced the level of serum cTnT. The levels of the 29 energy metabolites in cardiac muscle tissue were analyzed using a newly developed targeted analysis method. Compared to the sham group, the levels of 17 metabolites from different energy metabolic pathways, including four compounds in glycolysis metabolism, four compounds in TCA cycle, three compounds in oxidative phosphorylation, four compounds in purine metabolism, and two compounds in glutathione metabolism, displayed obvious changes induced by myocardial ischemia. Expressions of SIRT1, PGC-1α, and ATP5D proteins related to energy metabolism were decreased after myocardial infarction. These perturbations could all be reversed by NXT intervention, suggesting that the therapeutic effects of NXT were partially due to interferences with energy metabolisms. Conclusion: This study provides a useful approach for investigating the mechanism of myocardial infarction and evaluating the efficacy of NXT from energy metabolism.