Dataset Information

Deciphering the Pharmacological Mechanisms of Ma Xing Shi Gan Decoction against COVID-19 through Integrating Network Pharmacology and Experimental Exploration.

ABSTRACT: The outbreak of new infectious pneumonia caused by SARS-CoV-2 has posed a significant threat to public health, but specific medicines and vaccines are still being developed. Traditional Chinese medicine (TCM) has thousands of years of experience in facing the epidemic disease, such as influenza and viral pneumonia. In this study, we revealed the efficacy and pharmacological mechanism of Ma Xing Shi Gan (MXSG) Decoction against COVID-19. First, we used liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) to analyze the chemical components in MXSG and identified a total of 97 components from MXSG. Then, the intervention pathway of MXSG based on these components was analyzed with network pharmacology, and it was found that the pathways related to the virus infection process were enriched in some of MXSG component targets. Simultaneously, through literature research, it was preliminarily determined that MXSG, which is an essential prescription for treating COVID-19, shared the feature of antiviral, improving clinical symptoms, regulating immune inflammation, and inhibiting lung injury. The regulatory mechanisms associated with its treatment of COVID-19 were proposed. That MXSG might directly inhibit the adsorption and replication of SARS-CoV-2 at the viral entry step. Besides, MXSG might play a critical role in inflammation and immune regulatory, that is, to prevent cytokine storm and relieve lung injury through toll-like receptors signaling pathway. Next, in this study, the regulatory effect of MXSG on inflammatory lung injury was validated through transcriptome results. In summary, MXSG is a relatively active and safe treatment for influenza and viral pneumonia, and its therapeutic effect may be attributed to its antiviral and anti-inflammatory effects.

SUBMITTER: Li Q

PROVIDER: S-EPMC7725906 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Ma Xing Shi Gan Decoction (MXD), a classical traditional Chinese medicine prescription, is widely used for the treatment of upper respiratory tract infection. However, the effect of MXD against particulate matters with diameter of less than 2.5 ?m (PM2.5) induced lung injury remains to be elucidated. In this study, rats were stimulated with PM2.5 to induce lung injury. MXD was given orally once daily for five days. Lung tissues were harvested to assess pathological changes and edema. Myeloperoxidase (MPO) activity and malonaldehyde (MDA) content in lung were determined to evaluate the degree of injury. To assess the barrier disruption, the bronchoalveolar lavage fluid (BALF) was collected to determine the total protein content and count the number of neutrophils and macrophages. For evaluating the activation of macrophage in lung tissue, CD68 was detected using immunohistochemistry (IHC). The levels of inflammatory factors including tumor necrosis factor-alpha (TNF-?), interleukin-1beta (IL-1?), and interleukin-6 (IL-6) in BALF and serum were measured. In vitro, a PM2.5-activated RAW 264.7 macrophages inflammatory model was introduced. To evaluate the protective effect of MXD-medicated serum, the cell viability and the release of inflammatory factors were measured. The effects of MXD on the High mobility group box-1/Toll-like receptor 4/Nuclear factor-kappa B (HMGB1/TLR4/NF?B) pathway in lung tissue and RAW 264.7 cells were assessed by Western blot. For further confirming the protective effect of MXD was mediated by inhibiting the HMGB1/TLR4/NF?B pathway, RAW 264.7 cells were incubated with MXD-medicated serum alone or MXD-medicated serum plus recombinant HMGB1 (rHMGB1). MXD significantly ameliorated the lung injury in rats, as evidenced by decreases in the pathological score, lung edema, MPO activity, MDA content, CD68 positive macrophages number, disruption of alveolar capillary barrier and the levels of inflammatory factors. In vitro, MXD-medicated serum increased cell viability and inhibited the release of inflammatory cytokines. Furthermore, MXD treatment was found to inhibit HMGB1/TLR4/NF?B signal pathway both in vivo and in vitro. Moreover, the protection of MXD could be reversed by rHMGB1 in RAW 264.7. Taken together, these results suggest MXD protects rats from PM2.5 induced acute lung injury, possibly through the modulation of HMGB1/TLR4/NF?B pathway and inflammatory responses.

Project description:Le-Cao-Shi (LCS) has long been used as a folk traditional Chinese medicine formula against liver injuries, whereas its pharmacological mechanisms remain elusive. Our study aims to investigate the underlying mechanism of LCS in treating liver injuries via integrated network pharmacology, metabonomics, and experimental validation. By network pharmacology, 57 compounds were screened as candidate compounds based on ADME parameters from the LCS compound bank (213 compounds collected from the literature of three single herbs). According to online compound-target databases, the aforementioned candidate compounds were predicted to target 87 potential targets related to liver injuries. More than 15 pathways connected with these potential targets were considered vital pathways in collectively modulating liver injuries, which were found to be relevant to cancer, xenobiotic metabolism by cytochrome P450 enzymes, bile secretion, inflammation, and antioxidation. Metabonomics analysis by using the supernatant of the rat liver homogenate with UPLC-Q-TOF/MS demonstrated that 18 potential biomarkers could be regulated by LCS, which was closely related to linoleic acid metabolism, glutathione metabolism, cysteine and methionine metabolism, and glycerophospholipid metabolism pathways. Linoleic acid metabolism and glutathione metabolism pathways were two key common pathways in both network pharmacology and metabonomics analysis. In ELISA experiments with the CCl4-induced rat liver injury model, LCS was found to significantly reduce the levels of inflammatory parameters, decrease liver malondialdehyde (MDA) levels, and enhance the activities of hepatic antioxidant enzymes, which validated that LCS could inhibit liver injuries through anti-inflammatory property and by suppressing lipid peroxidation and improving the antioxidant defense system. Our work could provide new insights into the underlying pharmacological mechanisms of LCS against liver injuries, which is beneficial for its further investigation and modernization.

Project description:Background: Ganghuo Kanggan decoction (GHKGD) is a clinical experience prescription used for the treatment of viral pneumonia in the Lingnan area of China, and its clinical effect is remarkable. However, the mechanism of GHKGD in influenza is still unclear. Objective: To predict the active components and signaling pathway of GHKGD and to explore its therapeutic mechanism in influenza and to verified it in vivo using network pharmacology. Methods: The potential active components and therapeutic targets of GHKGD in the treatment of influenza were hypothesized through a series of network pharmacological strategies, including compound screening, target prediction and pathway enrichment analysis. Based on the target network and enrichment results, a mouse model of influenza A virus (IAV) infection was established to evaluate the therapeutic effect of GHKGD on influenza and to verify the possible molecular mechanism predicted by network pharmacology. Results: A total of 116 candidate active compounds and 17 potential targets were identified. The results of the potential target enrichment analysis suggested GHKGD may involve the RLR signaling pathway to reduce inflammation in the lungs. In vivo experiments showed that GHKGD had a protective effect on pneumonia caused by IAV-infected mice. Compared with the untreated group, the weight loss in the GHKGD group in the BALB/c mice decreased, and the inflammatory pathological changes in lung tissue were reduced (p < 0.05). The expression of NP protein and the virus titers in lung were significantly decreased (p < 0.05). The protein expression of RIG-I, NF-kB, and STAT1 and the level of MAVS and IRF3/7 mRNA were remarkably inhibited in GHKGD group (p < 0.05). After the treatment with GHKGD, the level of Th1 cytokines (IFN-?, TNF-?, IL-2) was increased, while the expression of Th2 (IL-5, IL4) cytokines was reduced (p < 0.05). Conclusion: Through a network pharmacology strategy and in vivo experiments, the multi-target and multi-component pharmacological characteristics of GHKGD in the treatment of influenza were revealed, and regulation of the RLR signaling pathway during the anti-influenza process was confirmed. This study provides a theoretical basis for the research and development of new drugs from GHKGD.

Project description:Taohe-Chengqi decoction (THCQ), a classical traditional Chinese medicinal (TCM) formula, has been extensively used for treating chronic kidney disease (CKD). However, the biological activity and mechanisms of action of its constituents against renal fibrosis have not yet been investigated thoroughly. This study was aimed at devising an integrated strategy for investigating the bioactivity constituents and possible pharmacological mechanisms of the n-butanol extract of THCQ (NE-THCQ) against renal fibrosis. The n-butanol extract of THCQ was prepared by the solvent extraction method. The components of NE-THCQ were analyzed using UPLC-Q/TOF-MS/MS techniques and applied for screening the active components of NE-THCQ according to their oral bioavailability and drug-likeness index. Then, we speculated the potential molecular mechanisms of NE-THCQ against renal fibrosis through pharmacological network analysis. Based on data mining techniques and topological parameters, gene ontology, and pathway enrichment, we established compound-target (C-T), protein-protein interaction (PPI) and compound-target-pathway (C-T-P) networks by Cytoscape to identify the hub targets and pathways. Finally, the potential molecular mechanisms of NE-THCQ against renal fibrosis, as predicted by the network pharmacology analyses, were validated experimentally in renal tubular epithelial cells (HK-2) in vitro and against unilateral ureteral obstruction models in the rat in vivo. We identified 26 components in NE-THCQ and screened seven bioactive ingredients. A total of 118 consensus potential targets associated with renal fibrosis were identified by the network pharmacology approach. The experimental validation results demonstrated that NE-THCQ might inhibit the inflammatory processes, reduce ECM deposition and reverse EMT via PI3K/AKT/mTOR and HIF-1α/VEGF signaling pathways to exert its effect against renal fibrosis. This study identified the potential ingredients of the NE-THCQ by UPLC-Q/TOF-MS/MS and explained the possible mechanisms of NE-THCQ against renal fibrosis by integrating network pharmacology and experimental validation.

Dataset Information

Deciphering the Pharmacological Mechanisms of Ma Xing Shi Gan Decoction against COVID-19 through Integrating Network Pharmacology and Experimental Exploration.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets