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Synergistic Therapeutic Effects and Immunoregulatory Mechanism of Maxing Shigan Decoction Combined with Sijunzi Decoction on Viral Pneumonia in Mice.

ABSTRACT: Influenza is defined in traditional Chinese medicine (TCM) as an epidemic febrile illness and is usually treated with herbal compound formulas under the guidance of the "Qu Xie and Fu Zheng" theories. Ma Xing Shi Gan Tang (MXSGD) is a prominent remedy for clearing heat and detoxifying toxins in the clinical treatment of influenza in TCM, playing the role of "Qu Xie." Si Jun Zi Tang (SJZD) is recognized as one of the "Fu Zheng" formulas for strengthening the spleen and nourishing the stomach, with immunomodulatory effects. In this study, we followed the principles of "Qu Xie and Fu Zheng" to explore the effects of MXSGD combined with SJZD on viral pneumonia and its mechanism. Results showed that the couse of MXSGD and SJZD was effective in reducing the mortality rates and severity of lung pathology in lethally infected FM1 mice compared to the use of either drug alone. Moreover, further research demonstrated that the combined use suppressed TLRs and NLRP3 inflammatory signaling pathways at 4 dpi while promoting them at 7 dpi. At 10 dpi, there was a significant increase in CD11c⁺ and CD103⁺ DCs in the lungs. Together, SJZD improved the therapeutic effectiveness of MXSGD in treating influenza virus pneumonia than when used alone. MXSGD and SJZD exhibit synergistic effects in the treatment of influenza, as evidenced by the inhibition of TLR7 and NLRP3 inflammatory pathways early in the infection and facilitation of the response later. They also increase CD11c⁺ and CD103⁺ DC levels, as well as balancing Th1/Th2 cytokines.

SUBMITTER: Huang H

PROVIDER: S-EPMC11364478 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature

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Synergistic Therapeutic Effects and Immunoregulatory Mechanism of Maxing Shigan Decoction Combined with Sijunzi Decoction on Viral Pneumonia in Mice.

Huang Huimin H Yang Huanhua H Zhang Zurong Z Song Yunlong Y Li Li L Li Ke K Zhang Junjie J Qi Xiaoyu X Wu Ying Y

The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale 20240823

Influenza is defined in traditional Chinese medicine (TCM) as an epidemic febrile illness and is usually treated with herbal compound formulas under the guidance of the "Qu Xie and Fu Zheng" theories. Ma Xing Shi Gan Tang (MXSGD) is a prominent remedy for clearing heat and detoxifying toxins in the clinical treatment of influenza in TCM, playing the role of "Qu Xie." Si Jun Zi Tang (SJZD) is recognized as one of the "Fu Zheng" formulas for strengthening the spleen and nourishing the stomach, wit ...[more]

PMID: 39221016

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Project description:BackgroundHuangqi Sijunzi decoction (HQSJZD) is a commonly used conventional Chinese herbal medicine prescription for invigorating Qi, tonifying Yang, and removing dampness. Modern pharmacology and clinical applications of HQSJZD have shown that it has a certain curative effect on Alzheimer's disease (AD).MethodsThe active components and targets of HQSJZD were searched in the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The genes corresponding to the targets were retrieved using UniProt and GeneCard database. The herb-compound-target network and protein-protein interaction (PPI) network were constructed by Cytoscape. The core targets of HQSJZD were analysed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The main active compounds of HQSJZD were docked with acetylcholinesterase (AChE). In vitro experiments were conducted to detect the inhibitory and neuroprotective effects of AChE.ResultsCompound-target network mainly contained 132 compounds and 255 corresponding targets. The main compounds contained quercetin, kaempferol, formononetin, isorhamnetin, hederagenin, and calycosin. Key targets contained AChE, PTGS2, PPARG, IL-1B, GSK3B, etc. There were 1708 GO items in GO enrichment analysis and 310 signalling pathways in KEGG, mainly including the cAMP signalling pathway, the vascular endothelial growth factor (VEGF) signalling pathway, serotonergic synapses, the calcium signalling pathway, type II diabetes mellitus, arginine and proline metabolism, and the longevity regulating pathway. Molecular docking showed that hederagenin and formononetin were the top 2 compounds of HQSJZD, which had a high affinity with AChE. And formononetin has a good neuroprotective effect, which can improve the oxidative damage of nerve cells.ConclusionHQSJZD was found to have the potential to treat AD by targeting multiple AD-related targets. Formononetin and hederagenin in HQSJZD may regulate multiple signalling pathways through AChE, which might play a therapeutic role in AD.

Project description:BackgroundAsthma is a chronic inflammatory disease of the airways with recurrent attacks, which seriously affects the patients' quality of life and even threatens their lives. The disease can even threaten the lives of patients. Sijunzi decoction (SJZD), a classical Chinese medicine formula with a long history of administration, is a basic formula used for the treatment of asthma and demonstrates remarkable efficacy. However, the underlying mechanism has not been elucidated.Materials and methodsWe aimed to integrate network pharmacology and intestinal flora sequencing analysis to study the mechanism of SJZD in the treatment of allergic asthmatic mice. The active compounds of SJZD and their asthma-related targets were predicted by various databases. We performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses to identify potentially relevant pathways for target genes. Furthermore, the active compound-target and target-signaling pathway network maps were constructed by using Cytoscape 3.8.2. These results were combined with those of the intestinal flora sequencing analysis to study the influence of SJZD on airway inflammation in allergic asthmatic mice.ResultWe obtained 137 active compounds from SJZD and associated them with 1445 asthma-related targets acquired from the databases. A total of 109 common targets were identified. We visualized active compound-target and target-signaling pathway network maps. The pathological analysis and inflammation score results suggested that SJZD could alleviate airway inflammation in asthmatic mice. Sequencing analysis of intestinal flora showed that SJZD could increase the relevant abundance of beneficial bacterial genus and maintain the balance of the intestinal flora. The core toll-like receptor (TLR) signaling pathway was identified based on network pharmacology analysis, and the important role TLRs play in intestinal flora and organismal immunity was also recognized. The analysis of the correlation between environmental factors and intestinal flora revealed that beneficial bacterial genera were negatively correlated with TLR2 and positively correlated with the TLR7 expression. Furthermore, they were positively correlated with IFN-γ and IL-10 levels and negatively correlated with IL-4 and IL-17 levels.ConclusionSJZD alleviated the airway inflammation state in asthmatic mice. The findings suggest that increasing the relevant abundance of beneficial intestinal bacteria in mice with asthma, regulating intestinal flora, interfering with the level of TLR2 and TLR7 expression to adjust the secretion of inflammatory factors, and alleviating asthmatic airway inflammation may be the possible mechanism involved in the treatment of asthma by SJZD, providing a basis for further studies on SJZD.

Project description:Ethnopharmacological relevanceSince the occurrence of coronavirus disease 2019 (COVID-19) in Wuhan, China in December 2019, COVID-19 has been quickly spreading out to other provinces and countries. Considering that traditional Chinese medicine (TCM) played an important role during outbreak of SARS and H1N1, finding potential alternative approaches for COVID-19 treatment is necessary before vaccines are developed. According to previous studies, Maxing Shigan decoction (MXSGD) present a prominent antivirus effect and is often used to treat pulmonary diseases. Furthermore, we collected 115 open prescriptions for COVID-19 therapy from the National Health Commission, State Administration of TCM and other organizations, MXSGD was identified as the key formula. However, the underlying molecular mechanism of MXSGD against COVID-19 is still unknown.Aim of the studyThe present study aimed to evaluate the therapeutic mechanism of MXSGD against COVID-19 by network pharmacology and in vitro experiment verification, and screen the potential components which could bind to key targets of COVID-19 via molecular docking method.Materials and methodsMultiple open-source databases related to TCM or compounds were employed to screen active ingredients and potential targets of MXSGD. Network pharmacology analysis methods were used to initially predict the antivirus and anti-inflammatory effects of MXSGD against COVID-19. IL-6 induced rat lung epithelial type Ⅱ cells (RLE-6TN) damage was established to explore the anti-inflammatory damage activity of MXSGD. After MXSGD intervention, the expression level of related proteins and their phosphorylation in the IL-6 mediated JAK-STAT signaling pathway were detected by Western blot. Molecular docking technique was used to further identify the potential substances which could bind to three key targets (ACE2, Mpro and RdRp) of COVID-19.ResultsIn this study, 105 active ingredients and 1025 candidate targets were selected for MXSGD, 83 overlapping targets related to MXSGD and COVID-19 were identified, and the protein-protein interaction (PPI) network of MXSGD against COVID-19 was constructed. According to the results of biological enrichment analysis, 63 significant KEGG pathways were enriched, and most of them were related to signal transduction, immune system and virus infection. Furthermore, according the relationship between signal pathways, we confirmed MXSGD could effectively inhibit IL-6 mediated JAK-STAT signal pathway related protein expression level, decreased the protein expression levels of p-JAK2, p-STAT3, Bax and Caspase 3, and increased the protein expression level of Bcl-2, thereby inhibiting RLE-6TN cells damage. In addition, according to the LibDock scores screening results, the components with strong potential affinity (Top 10) with ACE2, Mpro and RdRp are mainly from glycyrrhiza uralensis (Chinese name: Gancao) and semen armeniacae amarum (Chinese name: Kuxingren). Among them, amygdalin was selected as the optimal candidate component bind to all three key targets, and euchrenone, glycyrrhizin, and glycyrol also exhibited superior affinity interactions with ACE2, Mpro and RdRp, respectively.ConclusionThis work explained the positive characteristics of multi-component, multi-target, and multi-approach intervention with MXSGD in combating COVID-19, and preliminary revealed the antiviral and anti-inflammatory pharmacodynamic substances and mechanism of MXSGD, which might provide insights into the vital role of TCM in the prevention and treatment of COVID-19.

Dataset Information

Synergistic Therapeutic Effects and Immunoregulatory Mechanism of Maxing Shigan Decoction Combined with Sijunzi Decoction on Viral Pneumonia in Mice.

Publications

Synergistic Therapeutic Effects and Immunoregulatory Mechanism of Maxing Shigan Decoction Combined with Sijunzi Decoction on Viral Pneumonia in Mice.

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