Effects of Si-Miao-Yong-An decoction on myocardial I/R rats by regulating gut microbiota to inhibit LPS-induced TLR4/NF-κB signaling pathway.

BACKGROUND: Coronary Artery Disease (CAD) is primarily caused by inflammation which is closely linked to the gut microbiota. Si-Miao-Yong-An (SMYA) decoction is a traditional Chinese herbal formula with anti-inflammatory properties that found to be effective against CAD. However, it is still unclear whether SMYA can modulate gut microbiota and whether it contributes to the improvement of CAD by reducing inflammation and regulating the gut microbiota. METHODS: The identification of components in the SMYA extract was conducted using the HPLC method. A total of four groups of SD rats were orally administered with SMYA for 28 days. The levels of inflammatory biomarkers and myocardial damage biomarkers were measured through ELISA, while echocardiography was used to assess heart function. Histological alterations in the myocardial and colonic tissues were examined following H&E staining. Western blotting was performed to evaluate protein expression, whereas alterations in gut microbiota were determined by 16 s rDNA sequencing. RESULTS: SMYA was found to enhance cardiac function and decrease the expression of serum CK-MB and LDH. SMYA was also observed to inhibit the TLR4/NF-κB signaling pathway by downregulating the protein expression of myocardial TLR4, MyD88, and p-P65, leading to a reduction in serum pro-inflammatory factors. SMYA modified the composition of gut microbiota by decreasing the Firmicutes/Bacteroidetes ratio, modulating Prevotellaceae_Ga6A1 and Prevotellaceae_NK3B3 linked to the LPS/TLR4/NF-κB pathway, and increasing beneficial microbiota such as Bacteroidetes, Alloprevotella, and other bacterial species. Moreover, SMYA was found to safeguard the intestinal mucosal and villi structures, elevate the expression of tight junction protein (ZO-1, occludin), and reduce intestinal permeability and inflammation. CONCLUSIONS: The results indicate that SMYA has the potential to modulate the gut microbiota and protect the intestinal barrier, thereby reducing the translocation of LPS into circulation. SMYA was also found to inhibit the LPS-induced TLR4/NF-κB signaling pathway, leading to a decrease in the release of inflammatory factors, which ultimately mitigated myocardial injury. Hence, SMYA holds promise as a therapeutic agent for the management of CAD.

Network pharmacology-based approach to research the effect and mechanism of Si-Miao-Yong-An decoction against thromboangiitis obliterans.

BACKGROUND: Si-Miao-Yong-An decoction (SMYAD) is a conventional therapeutic formula for treat thromboangiitis obliterans (TAO), consisting of four Chinese herbs: Lonicerae japonicae Thunb. (Jinyinhua), Scrophularia ningpoensis Hemsl. (Xuanshen), Angelica sinensis (Oliv.) Diels (Danggui) and Glycyrrhiza uralensis Fisch. (Gancao). However, the mechanism of SMYAD in TAO treatment remains unclear. METHODS: Components, as well as potential targets of SMYAD in TAO therapy, were downloaded from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Subsequently, with the Database for Annotation, Visualization, and Integrated Discovery (DAVID) server, the gene ontology (GO) biological processes and the Kyoto encyclopedia of genes and genomes (KEGG) signalling pathways of the targets enrichment were performed. Next, based on STRING online database, the protein interaction network of vital targets was built and analysed. Molecular docking and calculation of the binding affinity were performed using AutoDock. The PyMOL software was employed to observe docking outcomes of active compounds and protein targets. Based on the predicted outcomes of network pharmacology, in vivo and in vitro tests were performed for validation. In vivo experiment, the TAO rats model was established using sodium laurate injection into the femoral artery. The symptoms as well as pathological changes of the femoral artery were observed. Besides, the predicted targets were verified by the RT-qPCR, in vitro experiment. The cell viability in LPS-induced human umbilical vein endothelial cells (HUVECs) was detected using CCK-8 kit, and the predicted targets were also verified by the RT-qPCR. RESULTS: In the network pharmacology analysis, we obtained 105 chemical components in SMYAD and 24 therapeutic targets. We found that the mechanism SMYAD in TAO therapy was primarily associated with inflammation and angiogenesis by constructing multiple networks. Quercetin, vestitol and beta-sitosterol were important compounds, and interleukin-6 (IL6), MMP9, and VEGFA were key targets. According to molecular docking, active compounds (quercetin, vestitol and beta-sitosterol) and targets (IL6, MMP9 and VEGFA) showed good binding interactions. In in vivo experiment, SMYAD ameliorated the physical signs and pathological changes, inhibited the expression of IL6 and MMP9, and enhanced the expression of VEGFA. In an in vitro experiment, SMYAD increased the cell viability of LPS-induced HUVECs and the expression of VEGFA, and reduced the expression of IL6 and MMP9. CONCLUSIONS: This study showed that SMYAD improves TAO symptoms and inhibits the development of TAO. The mechanism could be associated with anti-inflammatory and therapeutic angiogenesis.

Proteomic investigation and biomarker identification of lung and spleen deficiency syndrome in HIV/AIDS immunological nonresponders.

Background: Human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) immunological nonresponders (HIV/AIDS-INRs) whose CD4+ cell counts do not rebound after highly active antiretroviral therapy (HAART) treatment usually experience severely impaired immune function and high mortality. Traditional Chinese medicine (TCM) has many advantages in the field of AIDS, especially its promotion of patients' immune reconstitution. Accurate differentiation of TCM syndromes is a prerequisite for guiding an effective TCM prescription. However, the objective and biological evidence for identification of the TCM syndromes in HIV/AIDS-INRs remains lacking. Lung and spleen deficiency (LSD) syndrome, a typical HIV/AIDS-INR syndrome, was examined on in this study. Methods: We first performed a proteomic study of LSD syndrome in INRs (INRs-LSD) using tandem mass tag combined with liquid chromatography-tandem mass spectrometry (TMT-LC-MS/MS) and screened them against the healthy and undocumented identifiable groups. The TCM syndrome-specific proteins were subsequently validated based on bioinformatics analysis and enzyme-linked immunosorbent assay (ELISA). Results: A total of 22 differentially expressed proteins (DEPs) were screened in INRs-LSD compared to the healthy group. Based on bioinformatic analysis, these DEPs were found to be mainly associated with the immunoglobin A (IgA)-generated intestinal immune network. In addition, we examined the TCM syndrome-specific proteins alpha-2-macroglobulin (A2M) and human selectin L (SELL) with ELISA and found that they were both upregulated, which was consistent with the proteomic screening results. Conclusions: A2M and SELL were finally identified as potential biomarkers for INRs-LSD, providing a scientific and biological basis for identifying typical TCM syndromes in HIV/AIDS-INRs and an opportunity to build a more effective TCM treatment system for HIV/AIDS-INRs.

Epidemiological investigation and proteomic profiling of typical TCM syndrome in HIV/AIDS immunological nonresponders.

HIV/AIDS pandemic remains the world's most severe public health challenge, especially for HIV/AIDS immunological nonresponders (HIV/AIDS-INRs), who tend to have higher mortality. Due to the advantages in promoting patients' immune reconstitution, Traditional Chinese medicine (TCM) has become one of the mainstays of complementary treatments for HIV/AIDS-INRs. Given that effective TCM treatments largely depend on precise syndrome differentiation, there is an increasing interest in exploring biological evidence for the classification of TCM syndromes in HIV/AIDS-INRs. In our study, to identify the typical HIV/AIDS-INRs syndrome, an epidemiological survey was first conducted in the Liangshan prefecture (China), a high HIV/AIDS prevalence region. The key TCM syndrome, Yang deficiency of spleen and kidney (YDSK), was evaluated by using a tandem mass tag combined with liquid chromatography-tandem mass spectrometry (TMT-LC-MS/MS). A total of 62 differentially expressed proteins (DEPs) of YDSK syndrome compared with healthy people were screened out. Comparative bioinformatics analyses showed that DEPs in YDSK syndrome were mainly associated with response to wounding and acute inflammatory response in the biological process. The pathway annotation is mainly enriched in complement and coagulation cascades. Finally, the YDSK syndrome-specific DEPs such as HP and S100A9 were verified by ELISA, and confirmed as potential biomarkers for YDSK syndrome. Our study may lay the biological and scientific basis for the specificity of TCM syndromes in HIV/AIDs-INRs, and may provide more opportunities for the deep understanding of TCM syndromes and the developing more effective and stable TCM treatment for HIV/AIDS-INRs.

HJ11 decoction restrains development of myocardial ischemia-reperfusion injury in rats by suppressing ACSL4-mediated ferroptosis.

HJ11 is a novel traditional Chinese medicine developed from the appropriate addition and reduction of Si-Miao-Yong-An decoction, which has been commonly used to treat ischemia-reperfusion (I/R) injury in the clinical setting. However, the mechanism of action of HJ11 components remains unclear. Ferroptosis is a critical factor that promotes myocardial I/R injury, and the pathophysiological ferroptosis-mediated lipid peroxidation causes I/R injury. Therefore, this study explored whether HJ11 decoction ameliorates myocardial I/R injury by attenuating ACSL4-mediated ferroptosis. This study also explored the effect of ACSL4 expression on iron-dependent programmed cell death by preparing a rat model of myocardial I/R injury and oxygen glucose deprivation/reperfusion (OGD/R)-induced H9c2 cells. The results showed that HJ11 decoction improved cardiac function; attenuated I/R injury, apoptosis, oxidative stress, mitochondrial damage, and iron accumulation; and reduced infarct size in the myocardial I/R injury rat model. Additionally, HJ11 decoction suppressed the expression of ferroptosis-promoting proteins [Acyl-CoA synthetase long-chain family member 4 (ACSL4) and cyclooxygenase-2 (COX2)] but promoted the expression of ferroptosis-inhibiting proteins [ferritin heavy chain 1 (FTH1) and glutathione-dependent lipid hydroperoxidase glutathione peroxidase 4 (GPX4)] in the myocardial tissues of the I/R injury rat model. Similar results were found with the OGD/R-induced H9c2 cells. Interestingly, ACSL4 knockdown attenuated iron accumulation, oxidative stress, and ferroptosis in the OGD/R-treated H9c2 cells. However, ACSL4 overexpression counteracted the inhibitory effect of the HJ11 decoction on OGD/R-triggered oxidative stress and ferroptosis in H9c2 cells. These findings suggest that HJ11 decoction restrained the development of myocardial I/R injury by regulating ACSL4-mediated ferroptosis. Thus, HJ11 decoction may be an effective medication to treat myocardial I/R injury.

Biological differentiation of traditional Chinese medicine from excessive to deficient syndromes in AIDS: Comparative microRNA microarray profiling and syndrome-specific biomarker identification.

Traditional Chinese medicine (TCM) has been widely applied as a supplementary therapy of human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) in China. TCM has a positive effect on improving the quality of life, prolonging life, and ameliorating the symptoms of HIV/AIDS patients. Yang deficiency of spleen and kidney (YDSK) syndrome is a typical deficient TCM syndrome in AIDS patients, and accumulation of heat-toxicity (AHT) syndrome is a common excessive syndrome in the earlier stage of AIDS. Thus, accurate diagnosis of these two syndromes can improve the targeted treatment effect, and predict the prognosis of the disease. However, the scientific basis of TCM syndromes remains lacking, greatly hindering the accuracy of diagnosis and effectiveness of treatment. In this research, microRNA (miRNA) microarray and quantitative real-time polymerase chain reaction combined with bioinformatics were used for comparative analysis between YDSK and AHT patients. Significantly differential expressed miRNAs (SDE-miRNAs) of each TCM syndrome were identified, including hsa-miR-766-3p and hsa-miR-1260a and so on, as well hsa-miR-6124, hsa-let-7g-5p and so on, for YDSK and AHT, respectively. Biological differences were found between their SDE-miRNAs based on bioinformatics analyses, for example, ErbB signaling pathway mainly linked to AHT, while focal adhesion dominated in YDSK. Syndrome-specific SDE-miRNAs were further identified as potential biomarkers, including hsa-miR-30e-5p, hsa-miR-144-5p for YDSK and hsa-let-7g-5p, hsa-miR-126-3p for AHT, respectively. All of them have laid biological and clinical bases for TCM diagnosis and treatment of AIDS syndrome at the miRNA level, offering potential diagnostic indicators of immune reconstitution.

The efficacy of Qigong exercises for nonalcoholic fatty liver disease: A protocol for systematic review and meta-analysis.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases in the world that represents an important public health challenge nowadays. Lifestyle changes and exercise can reduce the development of fatty liver. The aim of this systematic review and meta-analysis is to evaluate the treatment efficacy of Qigong for NAFLD. METHODS: A detailed search for articles up to September 2020 will be performed to identify randomized controlled trials for Qigong in NAFLD. The following database will be used: PUBMED, Embase, Web of Science, Cochrane Library, Sino Med, Chinese National Knowledge Infrastructure (CNKI), Chinese Science and Technology Periodicals Database, and Wanfang Databas. Grey literature will be explored and the selection of studies, data extraction and validation will be performed independently by 2 reviewers using predefined selection criteria and quality indicators. Stata V.13.0 and Review manager 5.3 software will be used for data synthesis, sensitivity analysis, subgroup analysis, and risk of bias assessment. We will use the grading of recommendations assessment, development, and evaluation system to assess the quality of evidence. RESULTS: This research will provide a quantitative and standardized assessment of the treatment efficacy of Qigong for NAFLD. CONCLUSION: This systematic review will generate the latest evidence for determining whether Qigong has a positive treatment effect for NAFLD. REGISTRATION NUMBER: INPLASY202090034.

Pediatric tuina for the treatment of fever in children: A protocol for systematic review and meta-analysis.

BACKGROUND: Infantile fever is a common symptom of the pediatric diseases, which is often caused by cold, food accumulation, or other pathogenic factors. Pediatric tuina is regarded as an acceptable non-pharmaceutical therapy for children with optimal effects, which has been widely used for infantile fever around China. But there is still a lack of systematic evaluation and research on its safety and effectiveness during the treatment of infantile fever. Thus the protocol is to collect clinical evidence and demonstrate the efficacy and safety of antipyretic manipulation by pediatric tuina. METHODS: The systematic electronic search will be executed in Cochrane Library (1991-2020.6), EMBASE (1980-2020.6), PubMed (1996-2020.6), WHOICTRP (2004-2020.6), Web of Science (1900-2020.6), CNKI (1994-2020.6), CBM (1994-2020.6), WANFANG (1980-2020.6), and VIP (2000-2020.6) Database. The Review Manager (V.5.3) will be use to assess the risk of bias and data analyses. The methodological quality will be assessed by using the online GRADEpro tool. If the quality of numeric data is favorable, a meta-analysis will be carried out. RESULTS: A high-quality evidence of pediatric tuina for the treatment of infantile fever. CONCLUSION: The systematic review will provide a reliable basis for judging whether pediatric tuina is safe and effective in the treatment of pediatric fever. INPLASY REGISTRATION NUMBER: INPLASY202060032.