To explore the anti-depression effect of Suanzaoren Decoction(SZRD), the regulatory effects on endogenous metabolites in the liver of rats with depression induced by chronic unpredictable mild stress(CUMS) were analyzed by using LC-MS metabolomics. The rats were randomly divided into normal control group, model group, low-dose SZRD group, high-dose SZRD group, and positive drug group. The CUMS depression model was replicated by applying a variety of stimuli, such as fasting and water deprivation, ice water swimming, hot water swimming, day and night reversal, tail clamping, and restraint for rats. Modeling and treatment were conducted for 56 days. The behavioral indexes of rats in each group, including body weight, open field test, sucrose preference test, and tail suspension test, were observed. Plasma samples and liver tissue samples were collected, and the contents of 5-hydroxytryptamine(5-HT), dopamine(DA), and norepinephrine(NE) in plasma were measured using enzyme-linked immunosorbent assay(ELISA). Meanwhile, the regulatory effects of SZRD on the liver metabolic profile of CUMS model rats were analyzed by the LC-MS metabolomics method. The results show that SZRD can significantly improve the depression-like behavior of CUMS model rats and increase the neurotransmitter levels of 5-HT, DA, and NE in plasma. A total of 24 different metabolites in the rats' liver are identified using the LC-MS metabolomics method, and SZRD can reverse 13 of these metabolites. Metabolic pathway analysis indicates that nine metabolic pathways are found to be significantly associated with depression, and in the low-dose SZRD group, four pathways can be regulated, including pentose phosphate pathway, purine metabolism, inositol phosphate metabolism, and sphingolipid metabolism. In the high-dose SZRD group, two metabolic pathways can be regulated, including sphingolipid metabolism and glycerol glycerophospholipid metabolism. Sphingolipid metabolism is a metabolic pathway that can be regulated by SZRD at different doses, so it is speculated that it may be the primary pathway through which SZRD can alleviate metabolic disturbances in the liver of CUMS model rats.
Animals ; Rats ; Drugs, Chinese Herbal/administration & dosage* ; Metabolomics ; Depression/metabolism* ; Male ; Liver/drug effects* ; Rats, Sprague-Dawley ; Antidepressive Agents/administration & dosage* ; Serotonin/blood* ; Humans ; Disease Models, Animal ; Behavior, Animal/drug effects*

Suhuang Zhike Capsules are widely used in clinical practice for the treatment of respiratory diseases and have been included in Medicine Catalogue for National Basic Medical Insurance, Work Injury Insurance, and Maternity Insurance and National Essential Medicines List. However, problems remain, such as unclear definitions of treatment courses and unidentified contraindications for certain populations. Therefore, this consensus was developed collaboratively by clinical experts in traditional Chinese medicine(TCM) related to pulmonary diseases, respiratory, and critical care medicine, as well as methodology and pharmacy experts, adhering strictly to the consensus development procedures established by the China Association of Chinese Medicine for clinical application of Chinese patent medicines, with the aim to guide the correct clinical use of Suhuang Zhike Capsules for the treatment of cough variant asthma, post-infectious cough, and other respiratory diseases. This consensus employed questionnaire surveys and expert interviews to identify clinical concerns based on the PICOS principle and conduct evidence evaluation and GRADE grading. Utilizing nominal group techniques and GRADE networking methods, it resulted in 17 recommendations and consensus suggestions. The consensus further clarifies the indications, TCM syndromes, usage, and clinical safety of Suhuang Zhike Capsules in the treatment of cough variant asthma and post-infectious cough, aiming to promote standardized medication use and facilitate the rational clinical application of Suhuang Zhike Capsules.
Humans ; Drugs, Chinese Herbal/administration & dosage* ; Consensus ; Capsules ; Respiratory Tract Diseases/drug therapy* ; Medicine, Chinese Traditional

Cardiac fibrosis(CF) is a cardiac pathological process characterized by excessive deposition of extracellular matrix(ECM). When the heart is damaged by adverse stimuli, cardiac fibroblasts are activated and secrete a large amount of ECM, leading to changes in cardiac fibrosis, myocardial stiffness, and cardiac function declines and accelerating the development of heart failure. There is a close relationship between heart yin deficiency and cardiac fibrosis, which have similar pathogenic mechanisms. Heart Yin deficiency, characterized by insufficient Yin fluids, causes the heart to lose its nourishing function, which acts as the initiating factor for myocardial dystrophy. The deficiency of body fluids leads to stagnation of blood flow, resulting in blood stasis and water retention. Blood stasis and water retention accumulate in the heart, which aligns with the pathological manifestation of excessive deposition of ECM, as a tangible pathogenic factor. This is an inevitable stage of the disease process. The lingering of blood stasis combined with water retention eventually leads to the generation of heat and toxins, triggering inflammatory responses similar to heat toxins, which continuously stimulate the heart and cause the ultimate outcome of CF. Considering the syndrome of heart Yin deficiency, traditional Chinese medicine capable of nourishing Yin, activating blood, and promoting urination can reduce myocardial cell apoptosis, inhibit fibroblast activation, and lower the inflammation level, showing significant advantages in combating CF.
Humans ; Fibrosis/drug therapy* ; Animals ; Yin Deficiency/metabolism* ; Myocardium/metabolism* ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/therapeutic use*

This article aims to explore the effect and mechanism of Liujunzi Pills on the intestinal microbiota of rats with spleen Qi deficiency syndrome. The raw Rhei Radix et Rhizoma water extract(1 g·mL~(-1)) was used to prepare spleen Qi deficiency rat models. A total of 44 SD male rats were randomly divided into a control group, a model group, Liujunzi Pills groups at high(3.24 g·kg~(-1)), medium(1.62 g·kg~(-1)), low(0.81 g·kg~(-1)) doses, and Shenling Baizhu San(2.50 g·kg~(-1)) group. The drug effect was evaluated by observing the following aspects: spleen index, fecal water content, body weight, and intestinal propulsion index. Gut microbiota analysis and 16S rRNA gene sequencing were conducted on feces. Enzyme-linked immunosorbent assay(ELISA) and UV spectrophotometry were used to detect interleukin-1β(IL-1β) and adenosine triphosphate(ATP) levels in small intestine tissues. Hematoxylin-eosin staining and transmission electron microscopy were employed to observe changes in intestinal pathology and microstructure. The results show that, compared with the control group, fecal moisture content is significantly increased while spleen index, body weight, and intestinal propulsion index are significantly reduced in rats of the model group, indicating the successful establishment of the model. The above symptoms can be improved by both Shenling Baizhu San and Liujunzi Pills. Compared with the control group, in the model group, the gut microbiota abundance is changed with an unbalanced development: the abundance of beneficial bacteria within the Bacteroidetes phylum is reduced, accompanied by a significantly decreased Shannon index, and reduced signal levels of nicotinamide adenine dinucleotide phosphate(NADPH)-related enzymes relevant to mitochondria. However, Liujunzi Pills and Shenling Baizhu San can significantly improve the Bacteroidetes phylum abundance in gut microbiota, microbial diversity, and NADPH activity in the model group. Additionally, compared with the control group, the ATP level is decreased and the IL-1β level is increased in small intestinal tissues of the model group, with shorter small intestinal epithelial villi and decreased mitochondrial number. The above symptoms can be improved by Liujunzi Pills and Shenling Baizhu San. In conclusion, Liujunzi Pills can treat spleen Qi deficiency syndrome by enhancing mitochondrial function to regulate gut microbiota balance and diversity.
Animals ; Gastrointestinal Microbiome/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Male ; Rats, Sprague-Dawley ; Rats ; Qi ; Spleen/metabolism* ; Splenic Diseases/metabolism* ; Humans ; Interleukin-1beta/genetics* ; Bacteria/drug effects* ; Feces/microbiology* ; Adenosine Triphosphate/metabolism*

OBJECTIVE: Pneumoconiosis, a lung disease caused by irreversible fibrosis, represents a significant public health burden. This study investigates the causal relationships between gut microbiota, gene methylation, gene expression, protein levels, and pneumoconiosis using a multi-omics approach and Mendelian randomization (MR). METHODS: We analyzed gut microbiota data from MiBioGen and Esteban et al. to assess their potential causal effects on pneumoconiosis subtypes (asbestosis, silicosis, and inorganic pneumoconiosis) using conventional and summary-data-based MR (SMR). Gene methylation and expression data from Genotype-Tissue Expression and eQTLGen, along with protein level data from deCODE and UK Biobank Pharma Proteomics Project, were examined in relation to pneumoconiosis data from FinnGen. To validate our findings, we assessed self-measured gut flora from a pneumoconiosis cohort and performed fine mapping, drug prediction, molecular docking, and Phenome-Wide Association Studies to explore relevant phenotypes of key genes. RESULTS: Three core gut microorganisms were identified: Romboutsia ( OR = 0.249) as a protective factor against silicosis, Pasteurellaceae ( OR = 3.207) and Haemophilus parainfluenzae ( OR = 2.343) as risk factors for inorganic pneumoconiosis. Additionally, mapping and quantitative trait loci analyses revealed that the genes VIM, STX8, and MIF were significantly associated with pneumoconiosis risk. CONCLUSIONS This multi-omics study highlights the associations between gut microbiota and key genes ( VIM, STX8, MIF) with pneumoconiosis, offering insights into potential therapeutic targets and personalized treatment strategies.
Humans ; Male ; East Asian People/genetics* ; Europe ; Gastrointestinal Microbiome ; Lung ; Macrophage Migration-Inhibitory Factors/metabolism* ; Mendelian Randomization Analysis ; Multiomics ; Pneumoconiosis/microbiology* ; Intramolecular Oxidoreductases

Objective:To investigate the effect of betaine in oxygen-glucose deprivation injury of rat brain microvascular endothelial cells(BMECs),and to clarify the regulatory effect of betaine on phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)pathway.Methods:Five SD rats aged 7 d were selected and the rat BMSEs were obtained.The oxygen-glucose deprivation model of rat BMECs was prepared under hypoxic and hypoglycemic conditions;the experiment was divdided into model group,and low dose,medium dose,and high dose of betaine groups and positive control group,at the same time,blank control group(without modeling)was set up.The BMECs in blank control group and model group were treated with fresh medium,the BMECs in positive control group were given a final concentration of 10 μmnol·L-1 nimodipine,and the BMECs in low,medium and high doses of betaine groups were treated with betaine at final concentration of 0.5,1.0 and 2.0 mmol·L-1,respectively.The survival rates of BMECs in various groups were determined by CCK-8 method at 12,24 and 48 h after culture;the activities of lactate dehydrogenase(LDH)and the levels of adenine ribonucleoside triphosphate(ATP)in the rat BMECs in various groups were determined using kits,and the levels of tumor necrosis factor-α(TNF-α),interleukin(IL)-6,IL-1β,and IL-18 in supernatants of the BMECs in various groups were determined by enzyme-linked immunosorbent assay(ELISA);the activities of superoxide dismutase(SOD)and levels of malondialdehyde(MDA)in the BMECs in various groups were determined by kits;the transendothelial resistance(TEER)values of rat BMSCs in various groups were determined by TEER analyzer,and the horseradish peroxidase(HRP)permeabilities of BMECs in various groups were determined by an insertion cell culture apparatus.TUNEL staining was used to determine the apoptotic rates of rat BMECs in vaisous groups,and Western blotting method was used to determine the ratios of phosphory lated PI3K(p-PI3K)/PI3K and phosphorylated AKT(p-AKT)/AKT in the rat BMECs in various groups.Results:Compared with blank control group,the survival rate of BMECs,activity of SOD,and level of ATP,value of TEER,and ratios of p-PI3K/PI3K and p-AKT/AKT of the rat BMECs in model group were significantly decreased(P＜0.05),while the activity of LDH,the levels of TNF-α,IL-6,IL-1β,IL-18,and MDA,the apoptotic rate of the BMECs,and HRP permeability were significantly increased(P＜0.05).Compared with model group,the survival rates of the BMECs,activities of SOD,and levels of ATP,values of TEER,and ratios of p-PI3K/PI3K and p-AKT/AKT of the BMECs in low,medium,and high doses of betaine groups and positive control group were significantly increased(P＜0.05),while the activities of LDH,the levels of TNF-α,IL-6,IL-1β,IL-18,and MDA,the apoptotic rates of BMECs and HRP permeabilities were significantly decreased(P＜0.05).Conclusion:Betaine can significantly repair the oxygen-glucose deprivation/reperfusion injury in the rat BMECs,inhibit the oxidative damage and apoptosis of BMECs,and improve the permeability of the cells;its mechanism may be related to the regulation of the PI3K/AKT pathway.