Mechanism of Guigan Longmu Decoction in the Treatment of Arrhythmias Based on Network Pharmacology and Untargeted Metabolomics Assays.

BACKGROUND: Guigan longmu decoction (GGLM), a traditional Chinese medicine compound, has demonstrated efficacy in treating rapid arrhythmia clinically. Nevertheless, its mechanism of action remains elusive. This study aims to elucidate the molecular mechanism underlying the efficacy of GGLM in treating arrhythmia utilizing non-targeted metabolomics, widely-targeted metabolomics, and network pharmacology, subsequently validated through animal experiments. METHODS: Initially, network pharmacology analysis and widely-targeted metabolomics were performed on GGLM. Subsequent to that, rats were administered GGLM intervention, and nontargeted metabolomics assays were utilized to identify metabolites in rat plasma postadministration. The primary signaling pathways, core targets, and key active ingredients of GGLM influencing arrhythmia were identified. Additionally, to validate the therapeutic efficacy of GGLM on arrhythmia rat models, a rat model of rapid arrhythmia was induced via subcutaneous injection of isoproterenol, and alterations in pertinent pathogenic pathways and proteins in the rat model were assessed through qRT-PCR and Western blot following GGLM administration. RESULTS: The results of network pharmacology showed that 99 active ingredients in GGLM acted on 249 targets and 201 signaling pathways, which may be key to treating arrhythmia. Widelytargeted metabolic quantification analysis detected a total of 448 active ingredients in GGLM, while non-targeted metabolomics identified 279 different metabolites and 10 major metabolic pathways in rats. A comprehensive analysis of the above results revealed that the core key active ingredients of GGLM in treating arrhythmia include calycosin, licochalcone B, glabridin, naringenin, medicarpin, formononetin, quercetin, isoliquiritigenin, and resveratrol. These active ingredients mainly act on the relevant molecules and proteins upstream and downstream of the MAPK pathway to delay the onset of arrhythmia. Animal experimental results showed that the heart rate of rats in the model group increased significantly, and the mRNA and protein expression of p38, MAPK, JNK, ERK, NF-kb, IL-1ß, and IL-12 in myocardial tissue also increased significantly. However, after intervention with GGLM, the heart rate of rats in the drug group decreased significantly, while the mRNA and protein expression of p38 MAPK, JNK, ERK1, NF-kb, IL-1ß, and IL-12 in myocardial tissue decreased significantly. CONCLUSION: GGLM, as an adjunctive therapy in traditional Chinese medicine, exhibits favorable therapeutic efficacy against arrhythmia. This can be attributed to the abundant presence of bioactive compounds in the formulation, including verminin, glycyrrhizin B, glabridine, naringenin, ononin, quercetin, isorhamnetin, and kaempferol. The metabolites derived from these active ingredients have the potential to mitigate myocardial inflammation and decelerate heart rate by modulating the expression of proteins associated with the MAPK signaling pathway in vivo.

[Source Appointment and Assessment of Heavy Metal Pollution in Surface Dust in the Main District Bus Stops of Tianshui City].

In this study, a PMF model was used to identify the sources and pollution level of heavy metals in the surface dust of a bus station. On the basis of the traditional heavy metal pollution evaluation methods, the Hakanson toxicity response coefficient was used to modify the traditional weight. The matter-element extension theory was introduced to reflect the toxicological properties and hazard degree of the heavy metals, and the matter-element extension model was established to evaluate the pollution level of heavy metals in the surface dust of the study area. The results were compared with Igeo, PN, and RI. ① Except for Co and V, the other heavy metals were higher than the Gansu soil background values by 1.29-9.30 times. The points of Cu and Pb exceeded the rate by 100%, and Cr, Ni, and As exceeded the rate by 96.15%, 94.23%, and 96.15%, respectively. ② PMF showed that source 1 was a natural source, and its contribution rate to V was 32.12%. Source 2 was natural-traffic pollution sources, contributing 51.50% and 33.37% to Cu and Co, respectively. Source 3 was a construction waste pollution source, with contribution rates of 45.06% and 44.70% for Cr and Ni, respectively, and source 4 was a coal-traffic mixed source, with contribution rates of 49.89% and 75.25% for As and Pb, respectively. ③ The matter-element evaluation results showed that the surface dust of the bus stops was mainly class IV (moderately polluted), and 13% of sample points were still clean, 37% were moderately polluted, and 25% were slightly and heavily polluted. The results of this method were quite different from the PN results and were more consistent with the RI results, indicating that its evaluation results were more sensitive and can be used for heavy metal pollution assessment.

Adjunctive folate for major mental disorders: A systematic review.

OBJECTIVES: This is a meta-analysis of randomized controlled trials (RCTs) to examine the efficacy and safety of adjunctive folate for three major mental disorders (schizophrenia, bipolar disorder, and major depressive disorder (MDD)). METHODS: Review Manager Program Version 5.3 was used to analyze data. RESULTS: Fourteen studies with 16 RCTs (n = 1,520) on folate for schizophrenia (4 RCTs, n = 210), mood disorders (i.e., unipolar and bipolar depression) (1 RCT, n = 60), bipolar disorder (2 RCTs, n = 189) and MDD (9 RCTs, n = 1,061) were analyzed separately by diagnosis. For schizophrenia, adjunctive folate was not superior to placebo in terms of total psychopathology (standardized mean difference (SMD) = -0.14, 95% confidential interval (CI): -0.67, 0.39; I2 = 30%, P = 0.60), and positive (SMD = 0.09, 95% CI: -0.44, 0.62; I2 = not applicable, P = 0.74), negative (SMD = -0.39, 95% CI:-0.84, 0.05; I2 = 50%, P = 0.08), and general symptom scores (SMD = -0.33, 95%CI:-0.87, 0.20; I2 = not applicable, P = 0.22). For bipolar and unipolar depression, adjunctive folate was significantly superior to placebo in improving depressive symptoms. For bipolar disorder, adjunctive folate was effective in treating the acute phase of mania in bipolar disorder, but not in the acute phase of depression. For MDD, adjunctive folate was significantly superior to placebo in improving depressive symptoms (SMD = -0.38, 95%CI: -0.66, -0.09; I2 = 71%, P = 0.01), which was confirmed in 5 of the 10 subgroups. Discontinuation due to any reason and adverse drug reactions were similar between folate and placebo in each diagnostic category. CONCLUSION: This systematic review found adjunctive folate appeared to be effective and safe for MDD and bipolar manic episode, but it was not effective in treating schizophrenia.