A multi-module structure labelled molecular network orients the chemical profiles of traditional Chinese medicine prescriptions: Xiaoyao San, as an example.

Ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS) technology has emerged as a crucial tool for identifying components in traditional Chinese medicine (TCM). However, the characterization of the chemical profiles of TCM prescriptions (TCMPs) which often consist of multiple herbal medicines and contain diverse structural types, presents several challenges, such as component overlapping and time-consuming. In this study, a novel strategy known as the multi-module structure labelled molecular network (MSLMN), which integrates molecular networking, database annotation, and cluster analysis techniques, has been successfully proposed, which facilitates the identification of chemical constituents by leveraging a high-structural similarity ion list derived from the MSLMN. It has been effectively applied to analyze the chemical profile of Xiaoyao San (XYS), a classical TCMP. Through the MSLMN method, a total of 302 chemical constituents were identified, covering nine structural types in XYS. Furthermore, a validated and quantitative analytical method using UHPLC-QqQ-MS/MS technology was developed for 31 identified chemicals, encompassing all eight herbal medicines present in XYS, and the developed analytical approach was applied to investigate the content distribution across 40 different batches of commercially available XYS. In total, the proposed strategy has practical significance for improving the insight into the chemical profile of XYS and serves as a valuable approach for handling complex system data based on UHPLC-MS, particularly for TCMPs.

Do B Vitamins Enhance the Effect of Omega-3 Polyunsaturated Fatty Acids on Cardiovascular Diseases? A Systematic Review of Clinical Trials.

Studies have suggested that B vitamins or omega-3 polyunsaturated fatty acids (PUFAs) may deter the development of cardiovascular disease (CVD). This systematic review aims to examine whether the combined supplementation of both B vitamins and omega-3 PUFAs could provide additional beneficial effects to prevent CVD beyond the effect of each supplement based on clinical trials published up to December 2021. The overall findings are inconsistent and inconclusive, yet the combined supplementation of these two nutrients may be more effective at reducing plasma homocysteine, triglyceride, and low-density lipoprotein-cholesterol than the individual components. The underlying mechanisms mainly include alleviating endothelial dysfunction, inhibiting atherosclerosis and lesion initiation, reducing oxidative stress, suppressing activation of pro-inflammatory cytokines, regulating endothelial nitric oxide synthase, and interfering with methylation of genes that promote atherogenesis. Although biologically plausible, the existing literature is insufficient to draw any firm conclusion regarding whether B vitamins can further enhance the potential beneficial effects of omega-3 PUFA intake on either primary or secondary prevention of CVD. The inconsistent findings may be largely explained by the methodological challenges. Therefore, well-designed high-quality trials that will use the combined supplementation of B vitamins and omega-3 PUFAs or dietary patterns rich in these two types of nutrients are warranted.

Combined association of early exposure to long-chain n-3 polyunsaturated fatty acids, mercury and selenium with cognitive performance in 1-year-old infants.

BACKGROUND: Previous studies on long-chain n-3 polyunsaturated fatty acids (LCn3PUFAs) and infant neurodevelopment did not consider effect modifications of mercury (Hg) and selenium (Se). OBJECTIVES: To examine the joint association of prenatal LCn3PUFAs, Hg and Se with infant cognitive performance, and to explore whether DNA methylation may explain this potential association. METHODS: A total of 484 newborns were enrolled from the Shanghai Birth Cohort with available data on cord blood LCn3PUFA, nail Hg and Se during 2015-2016. Cord blood LCn3PUFA concentrations were assessed by gas chromatography, and nail Hg and Se concentrations were measured using clippings collected within 6 months of birth by inductively coupled plasma mass spectrometry. Five aspects of infant neurodevelopment (communication, gross motor, fine motor, problem-solving, and personal-social skills) were assessed using the Age and Stage Questionnaire (ASQ) at ages 6 and 12 months. Multivariable-adjusted generalized estimating equations models were performed to examine the associations between cord blood LCn3PUFA concentrations and ASQ test scores, and these associations were stratified by nail Hg and Se levels. Epigenome-wide DNA methylation in cord blood was compared in a random subgroup consisting of 19 infants from the highest and 21 from the lowest decile of LCn3PUFA concentrations. RESULTS: LCn3PUFAs were not significantly associated with any ASQ test scores. However, in the subgroup with lower Hg (

Chemical profile and potential mechanisms of Huo-Tan-Chu-Shi decoction in the treatment of coronary heart disease by UHPLC-Q/TOF-MS in combination with network pharmacology analysis and experimental verification.

Huo-Tan-Chu-Shi Decoction (HTCSD), a traditional Chinese medicine (TCM) prescription within Guangdong Provincial TCM Hospital (the largest TCM hospital in China), is used for effective clinical treatment of coronary heart disease (CHD) caused by phlegm-dampness syndrome with high incidence in the hot and humid climate of Lingnan region. However, its chemical components responsible for the therapeutic effects remain unclear, which restricts its application and further development. Hence, a detailed workflow, combing with UHPLC-Q/TOF-MS, network pharmacology analysis and experimental verification, was proposed and applied to characterize the chemical profile and potential mechanism of HTCSD against CHD. As a result, a total of 130 components from all six composed herbal medicines were characterized in a rapid and sensitive manner through UHPLC-Q/TOF-MS, of which 33 compounds were unambiguously confirmed with reference standards. Consequently, based on the integrated pharmacology network of "herbs-chemicals-targets-pathways-therapeutic effects", four chemicals (magnoflorine, menisperine, 13-hydroxyberberine, luteolin) with four CHD related targets (SRC, MAPK1, EGFR and AKT1) were considered as the key components and targets of HTCSD in the treatment of CHD. Furthermore, the effect of HTCSD was confirmed in animal experiments by enhancing the phosphorylation of MAPK, and the published literature and molecular binding results suggested that magnoflorine and luteolin tended to be the critical compounds involved in the process. Taken together, the characterization of chemical profile combined with network pharmacology analysis and experimental verification not only provided an efficient insight into the overall chemical profile of HTCSD but also revealed the potential pharmacological components and mechanisms of HTCSD against CHD, which laid a necessary chemical and biological basis for the discovery of in vivo bioactive components and the further revelation of functionary mechanism.

The discovery of Q-markers of Qiliqiangxin Capsule, a traditional Chinese medicine prescription in the treatment of chronic heart failure, based on a novel strategy of multi-dimensional "radar chart" mode evaluation.

BACKGROUND: Qiliqiangxin Capsule (QLQX), a traditional Chinese medicine (TCM) prescription, is especially used for clinical treatment of chronic heart failure (CHF) in China. However, the holistic quality control of QLQX has not been well established due to lack of system research on the quality marker (Q-marker). PURPOSE: In this study, a new strategy of multi-dimensional "radar chart" mode was proposed to overcome the problem that traditional methods cannot evaluate the multiple properties of Q-markers comprehensively and visually, and the strategy was successfully applied to discover the Q-markers of QLQX. METHODS: First, nineteen prototypes that entered the in vivo systemic circulation were selected out as the candidate Q-markers based on our previous studies of chemical and in vivo metabolic profiles. Then, their contents in QLQX were quantitatively analyzed by UHPLC-MS/MS, and the bioactivities on the H9c2 cardiomyocytes cell model was evaluated. The network of in vivo component-target closely related to CHF was further constructed. Finally, a multi-dimensional "radar chart" mode was developed and corresponding Regression Area (RA) and Coefficient Variation (CV) were calculated after data standardization and integration visually based on the Q-marker related multiple characteristics (including the compatibility contribution of herbal medicines, the content, the bioactivity, the in vivo predicted bioavailability and the degree of network pharmacology of candidate components in the TCM prescription). RESULTS: By comparison of RA and CV of the chemicals in the "radar chart", seven compounds mainly from King and Minister herbs (songorin, calycosin-7-O-ß-D-glucopyranoside, astragaloside, tanshinone IIA, ginsenoside Re, hesperidin and alisol A) were screened out as the Q-markers of QLQX, showing the reasonable compatibility contribution and high content in QLQX, preferable pharmacological effect on CHF, as well as good bioavailable characteristics and high target hits in system pharmacology. CONCLUSION: The Q-marker discovery of QLQX in this study laid an important foundation for its quality control improvement, and the mode standardized the abstract definitions of Q-marker and realized the comprehensive assessment of multiple properties of Q-marker in TCM prescriptions, which has a reference value for revealing the Q-marker in the quality control researches of TCM prescriptions.

Intakes of Folate, Vitamin B6, and Vitamin B12 in Relation to Diabetes Incidence Among American Young Adults: A 30-Year Follow-up Study.

OBJECTIVE: To prospectively examine intakes of folate, vitamin B6, and vitamin B12 in relation to diabetes incidence in a large U.S. cohort. RESEARCH DESIGN AND METHODS: A total of 4,704 American adults aged 18-30 years and without diabetes were enrolled in 1985-1986 and monitored until 2015-2016 in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Dietary assessment was conducted by a validated dietary history questionnaire at baseline, in 1992-1993, and in 2005-2006. The cumulative average intakes of folate, vitamin B6, and vitamin B12 were used in the analyses. Incident diabetes was ascertained by plasma glucose levels, oral glucose tolerance tests, hemoglobin A1c concentrations, and/or antidiabetic medications. RESULTS: During 30 years (mean 20.5 ± 8.9) of follow-up, 655 incident cases of diabetes occurred. Intake of folate, but not vitamin B6 or vitamin B12, was inversely associated with diabetes incidence after adjustment for potential confounders. Compared with the lowest quintile of total folate intake, the multivariable-adjusted hazard ratios (95% CI) in quintiles 2-5 were 0.85 (0.67-1.08), 0.78 (0.60-1.02), 0.82 (0.62-1.09), and 0.70 (0.51-0.97; P trend = 0.02). Higher folate intake was also associated with lower plasma homocysteine (P trend < 0.01) and insulin (P trend < 0.01). Among supplement users, folate intake was inversely associated with serum C-reactive protein levels (P trend < 0.01). CONCLUSIONS: Intake of folate in young adulthood was inversely associated with diabetes incidence in midlife among Americans. The observed association may be partially explained by mechanisms related to homocysteine level, insulin sensitivity, and systemic inflammation.

Ethanol extracts from Hemerocallis citrina attenuate the decreases of brain-derived neurotrophic factor, TrkB levels in rat induced by corticosterone administration.

ETHNOPHARMACOLOGICAL RELEVANCE: Hemerocallis citrina, a traditional herbal medicine, has been used for the improvement of behavioral and emotional status in Eastern-Asia countries. AIM OF THE STUDY: Our previous studies have demonstrated that the ethanol extracts of H. citrina flowers (HCE) reversed the behavioral alterations and monoamine neurotransmitter dysfunctions in stressed mice. However, the relation of its antidepressant-like action with neurotrophic molecular expressions remains unknown. MATERIALS AND METHODS: To clarify this, we explored the effect of HCE (32.5, 65, 130mg/kg, p.o.) on the behavior, brain-derived neurotrophic factor (BDNF) and its receptor (TrkB) in depression-like rats induced by exogenous administration of the stress hormone corticosterone (40mg/kg, s.c.). RESULTS: It was observed that repeated administration of corticosterone induced an elevation on the serum corticosterone levels, which caused the abnormalities observed in the sucrose preference test and forced swimming test (FST). Administration of HCE (65 and 130mg/kg) reversed the changes above and up-regulated the BDNF and TrkB receptor protein expressions in the brain region of frontal cortex and hippocampus. CONCLUSION: These findings confirm that HCE produce an antidepressant-like effect in corticosterone-induced depression-like model of rats and this effect is at least partly mediated by BDNF-TrkB signaling in the frontal cortex and hippocampus.