An investigation of the antidepressant-like effect of Jiaotaiwan in rats by nontargeted metabolomics based on ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry.

Depression is a mental disorder characterized by persistent unhappiness, lack of interest, with cognitive and sleep disorders. Jiaotaiwan is a traditional Chinese medicine for the treatment of insomnia and depressive-like symptoms. In this study, the major chemical components in Jiaotaiwan were qualitatively analyzed using ultra high performance liquid chromatography quadrupole time-of-flight mass spectrometry, and a model of depression in rats was subsequently established with chronic unpredictable mild stress followed by Jiaotaiwan intervention. Next, the metabolic profile of rat serum samples was analyzed using nontargeted metabolomics, wherein changes in the metabolites in serum samples before and after Jiaotaiwan administration were measured by multiple statistical approaches. Principal component analysis and partial least squares discriminant analysis indicated that the Jiaotaiwan treatment improved the metabolic phenotype depression. Moreover, the heatmap analysis identified the most important ten biomarkers involved in depression. According to the pathway analysis, the therapeutic effect of Jiaotaiwan on depression may involve the regulation of amino acid metabolism, glycerophospholipid metabolism, and energy metabolism. These findings help us understand the pathogenesis of depression in-depth, and discover targets for clinical diagnosis and treatment. And it also lays a foundation for the use of Jiaotaiwan as an antidepressant agent.

Danlou tablet inhibits the inflammatory reaction of high-fat diet-induced atherosclerosis in ApoE knockout mice with myocardial ischemia via the NF-κB signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Danlou tablet (DLT), a traditional herbal formula, has been used to treat chest discomfort (coronary atherosclerosis) in China. Although the anti-inflammatory activities of DLT have been proposed previously, the mechanisms of DLT in treating atherosclerosis with myocardial ischemia (AWMI) remain unknown. AIM OF THE STUDY: Atherosclerosis can result in heart disease caused by stenosis or occlusion of the lumen, resulting in myocardial ischemia, hypoxia, or necrosis. In recent years, changes in people's diets, increased stress, and secondary fatigue and obesity etc. have resulted in increases in the number of patients with atherosclerosis. In cases where the condition has further developed, patients may suffer from myocardial ischemia, hypoxia, or necrosis. Many traditional Chinese medicine compounds have been prescribed for the treatment of AWMI. DLT has been used to treat chest discomfort (coronary atherosclerosis) in China. Based on previous research, the aim of this study was to further investigate the effect of DLT on AWMI, and describe the underlying mechanisms. MATERIALS AND METHODS: To achieve this, an animal model of AWMI was established using apolipoprotein E (ApoE-/-) mice fed a high fat diet combined with isoprenaline (ISO) injection. For comparison, mouse models of only atherosclerosis and only myocardial ischemia were included. In the treatment groups, mice were treated daily with DLT at 700 mg/kg for four weeks. Echocardiographic evaluation, hematoxylin and eosin (H&E) staining, oil red O staining, ELISAs, Western blots, and immunohistochemical analyses were subsequently used to investigate the mechanism of DLT based on the NF-κB signaling pathway. RESULTS: The results indicate that the use of DLT is effective, to varying degrees, for the treatment of atherosclerosis, myocardial ischemia, and AWMI in mice. After DLT treatment, the left ventricular structure and morphology of the mice, the histopathology of cardiac tissue, and atherosclerotic plaques in the aortas all improved to varying degrees. DLT could play a therapeutic role by regulating the NF-κB signaling pathway related to inflammatory factors, including TNF-α, IL-6, IL-1ß, IL-8, MMP-1 and MMP-2, as well as protein expression of NF-κB p-50 and IκB-α, and positive cell expression of NF-κB p-50, IκB-α and phospho-NF-κB p-50 in the model mice. CONCLUSION: These preliminary results indicate that the therapeutic efficacy of DLT on high-fat diet-induced atherosclerosis in ApoE-/- mice with myocardial ischemia could be exerted at least in part by regulating the NF-κB signaling pathway.

Adjuvant treatment of coronary heart disease angina pectoris with Chinese patent medicine: A prospective clinical cohort study.

BACKGROUND: Patients with coronary heart disease (CHD) angina pectoris are in critical condition, which can cause sudden death, myocardial infarction, and other adverse events, and bring serious burden to families and society. Timely treatment should be given to improve the condition. Western medicine treatment of angina pectoris failed to meet the demand of angina symptom control. OBJECTIVE: It is hoped that the research method with higher evidential value will be adopted to compare the short-term, medium-term, and long-term effects of Chinese patent medicine combined with conventional western medicine and conventional western medicine alone in the treatment of CHD angina pectoris, so as to tap the clinical efficacy advantages of traditional Chinese medicine (TCM) and provide reliable data support for its clinical application. METHODS: A prospective cohort study was conducted among patients with CHD angina pectoris who were treated with oral Chinese patent medicine and conventional western medicine. The patients were divided into exposed group and nonexposed group according to whether or not the patients with CHD angina pectoris were treated with Chinese patent medicine. The exposed group was treated with TCM combined with conventional western medicine, while the nonexposed group was treated with conventional western medicine alone. Patients need to be hospitalized for 2 weeks as the introduction period and whether to enter the group is determined according to the treatment and medication conditions of the patients. The follow-up time points were 0th, 4th, 12th, 24th, and 48th weeks. The main events and secondary events were used as the evaluation criteria for clinical efficacy of CHD angina pectoris. In the experimental study, we will use strict indicators to detect standard operation procedure for multinomics and bacterial flora detection. CONCLUSION: This study will provide evidence for the clinical efficacy advantages of Chinese patent medicine and reliable support for its clinical application through test data.

Anti-inflammatory and antioxidative effects of Dan-Lou tablets in the treatment of coronary heart disease revealed by metabolomics integrated with molecular mechanism studies.

ETHNOPHARMACOLOGICAL EVIDENCE: The Dan-Lou tablet (DLT), a well-known Chinese prescription, has definitive clinical efficacy in the treatment of precordial discomfort and pain caused by coronary heart disease (CHD). However, the pharmacological mechanism of DLT in the treatment of CHD has not been clearly elucidated and needs to be further explored. AIM OF THE STUDY: We aimed to identify relevant biological pathways by assessing changes in biomarkers in response to DLT intervention in CHD to reveal the potential biological mechanism of DLT treatment for CHD. MATERIALS AND METHODS: The major chemical components in DLT were qualitatively analyzed using ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS), and a model of CHD in rats was subsequently established with a high-fat diet and left anterior coronary artery ligation (LADCA) followed by DLT intervention. Next, the metabolic profile of rat serum samples was analyzed using nontargeted metabolomics, wherein changes in the metabolites in serum samples before and after DLT administration were measured by PLS-DA, and two pathways of DLT treatment for CHD were predicted. Finally, predicted metabolomic pathways were verified by detecting and analyzing tissues from the rat model, revealing the mechanism of DLT in the treatment of CHD. RESULTS: Forty-five major chemical components were identified by the chemical characterization of DLT. In terms of metabolism, 17 biomarkers of CHD in rats were identified. Among these biomarkers, linoleic acid, γ-linolenic acid and lysophosphatidylcholines (LPCs) were found to play an important role in energy metabolism and glycerophospholipid metabolism. Protein analysis revealed that EGFR phosphorylation was inhibited in CHD rats after DLT treatment, which lowered the expression of TNF-α, IL-6 and MMP9, decreased the expression levels of ox-LDL and MDA, and increased the expression of SOD. CONCLUSION: The mechanism of DLT in the treatment of CHD involves inhibiting the expression of EGFR and the activation of the MAPK signaling pathway by regulating glycerophospholipid metabolism (LPCs) and energy metabolism (linoleic acid and γ-linolenic acid). Therefore, inflammation-related (TNF-α, IL-6, MMP9) and oxidative stress-related (ox-LDL, MDA, SOD) indicators are affected, leading to the regulation of the oxidative stress state and anti-inflammatory effects.

Antidepressant-like effects of the Radix Bupleuri and Radix Paeoniae Alba drug pair.

The Radix Bupleuri and Radix Paeoniae Alba drug pair plays a pivotal role in Xiaoyaosan, a famous Chinese herbal preparation that is popular in clinical medicine. To investigate the antidepressant-like effects and potential mechanism of action of the Radix Bupleuri and Radix Paeoniae Alba drug pair, we carried out the forced swim test (FST) and tail suspension test (TST), as the mouse models of depression; and the open field test (OFT) to exclude false-positive results. Subsequently, ptosis and hypothermia induced by reserpine were assessed. Finally, the concentrations of monoamine neurotransmitters and their metabolites, namely epinephrine (NE), 5-hydroxytryptamine (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) in the hippocampal and cortical tissues of mice were detected with HPLC with electrochemical detector. The Radix Bupleuri and Radix Paeoniae Alba (1:1) drug pair at low, medium, and high doses decreased immobility time in both the FST and TST, and counteracted hypothermia induced by reserpine in mice. After the administration of reserpine, the concentrations of 5-HT and NE in the hippocampal and cortical tissues were decreased; however, pre-treatment with the Radix Bupleuri and Radix Paeoniae Alba drug pair significantly elevated the concentrations of 5-HT and NE in the hippocampal and cortical tissues. The results suggested that, compared with single dose of fluoxetine and the drugs used individually, the Radix Bupleuri and Radix Paeoniae Alba drug pair had an excellent antidepressant-like effect. These data revealed a possible mechanism of action, as the regulation of the central monoaminergic neurotransmitter system in the hippocampal and cortical tissues.