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Objective: To study the efficacy network and potential mechanism of Xiaochaihu Decoction (XCHD) in the treatment of coronavirus disease 2019 (COVID-19) with syndrome of pathogenic heat lingering in the lung and obstructive cardinalat, and analyze the active ingredients of XCHD with anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) efficacy. Methods: The correspondence between COVID-19 and XCHD was analyzed by literature consulting. Based on network pharmacology, Cytoscape 3.6.0 and other software were then used to construct XCHD efficacy network of “Chinese medicine prescription-active ingredient-key target” for pneumonia and immune regulation, in order to confirm anti-SARS-CoV-2 active ingredients in the prescription. Some softwares were used to analyze XCHD for COVID-19 treatment in multiple aspects. Results: A total of 48 active ingredients with potential anti-SARS-CoV-2 effect in herbs were collected; 140 active ingredients in XCHD for pneumonia treatment and immune regulation were analyzed, of which 12 ingredients had direct anti-SARS-CoV-2 activity including baicalein, formononetin, quercetin, etc. The active ingredients in XCHD exerted efficacy for pneumonia treatment and immunoregulation through 95 key targets such as IL-6, NOS2, and ESR1, involving multiple pathways such as the TNF signaling pathway, IL-17 signaling pathway, and influenza A. Analysis of gene co-expression and PPI interaction analysis found that ACE2 only co-expressed with NOS2 in the above targets, and also interacted with only five targets in the PPI interaction network. It is speculated that the ACE2 target only plays an important role when SARS-CoV-2 invaded the human body, and had little effect in the treatment of pneumonia after viral infection. Conclusion: The active ingredients in XCHD play a role in treating COVID-19 by inhibiting SARS-CoV-2 activity, blocking the SARS-CoV-2 invasion pathway, inhibiting cytokine storm, and regulating immunity. It is worth noting that drugs designed for the ACE2 target can block virus invasion, but may not be effective for diseases such as alveolar inflammation, Therefore, this study also provides a multi-target and multi-directional space for XCHD for early COVID-19 treatment. In addition, when XCHD is used in the early treatment of COVID-19, we should pay attention to the precise use of drugs based on syndrome accurate identification, one is to avoid adverse reactions, the other is to avoid cytokine damage caused by re-crown disease.
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The aim of this paper was to construct a rat model of acute pancreatitis(AP) with syndrome of liver depression and Qi stagnation, and provide evaluation tools for pharmacodynamic research and efficacy network verification of related traditional Chinese medicine in view of the etiology, pathogenesis and clinical manifestations of AP. According to the Chinese and Western medicine diagnosis and treatment guidelines for AP with syndrome of liver depression and Qi stagnation, etiology, pathogenesis and clinical syndromes in TCM, Meta-analysis results, and evaluation strategy of establishing an animal model combining disease and syndrome in our laboratory, the biological surrogate outcomes suitable for the evaluation of animal models of AP with syndrome of liver depression and Qi stagnation were extracted then. The chronic unpredictable stress(CUS) method and chronic unpredictable stress +L-arginine(CUS +L-Arg) method were used to construct the rat model, and the above biological surrogate outcomes were used to evaluate whether an AP rat model was established. During the experiment, the weight and syndrome scores of the rats were observed and recorded. At the end of the experiment, the rats' serum, organs and tissues were collected from the operation to detect the various indicators. As compared with the normal group, the syndrome scores of the CUS group and CUS +L-Arg group were significantly increased(P<0.01); the anti-syndrome medicine Chaihu Shugan Pills could significantly reduce the syndrome scores of the two groups of rats(P<0.01), indicating that both modeling methods can replicate the syndrome of liver depression and Qi stagnation in the rat model. As compared with the normal group, the serum amylase(AMY) activity level was increased by 3 times in the CUS +L-Arg group(P<0.01), and the AMY activity level was also increased in CUS group, but not up to 3 times of the normal value. As compared with the normal group, the le-vels of TNF-α and IL-6 mRNA in the pancreatic tissues of the CUS +L-Arg group were significantly increased(P<0.01); the levels of TNF-α mRNA in the pancreatic tissues of the CUS group were significantly increased(P<0.05), but IL-6 mRNA level only showed a rising trend, indicating that only the CUS + L-Arg method can be used to replicate the AP damage in the disease-syndrome combination model. The CUS + L-Arg method can be used for continuous modeling for 4 weeks to establish a disease-syndrome combination model of AP rats with syndrome of liver depression and Qi stagnation. The model has the characteristics of repeatability, stability after mode-ling, low animal mortality, and similar clinical pathogenesis. It can be used for the evaluation of traditional Chinese medicine efficacy and the verification of efficacy network.
Subject(s)
Animals , Rats , Acute Disease , Depression , Liver , Medicine, Chinese Traditional , Pancreatitis , Qi , SyndromeABSTRACT
Objective: Under the guidance of traditional Chinese medicine theory, this paper used network pharmacology model to explore the effective components and mechanism of “treating different diseases with same method” of Chaihu Guizhi Decoction (CHGZD) in treating gastric ulcer and epilepsy, which provided modern medical evidence for the theory of “treating different diseases with same method” of traditional Chinese medicine. Methods: The chemical constituents and potential targets of CHGZD were collected by TCMSP and TCMID databases. Disease targets of gastric ulcer and epilepsy were obtained in PubMed, CTD, and OMIM databases. Cytoscape 3.6.0 software was used to map CHGZD for gastric ulcer and epilepsy. The pharmacodynamic basis and molecular mechanism of the “treating different diseases with same method” network, and the functional and pathway enrichment analysis of gene targets was analyzed by DAVID 6.8 and KOBAS 3.0. Results: A total of 198 kinds of chemical constituents, 417 target targets, 114 gastric ulcer disease targets, and 461 epileptic disease targets were collected from CHGZD. Network analysis showed that 152 active components such as quercetin, beta-sitosterol, wogonin, kaempferol, and saikosaponin a in CHGZD played a role in the treatment of gastric ulcers and epilepsy through 17 common targets including PTGS2, VEGFA, TP53, IL6, and TNF, and 62 pathways such as pathways in cancer, and proteoglycans in cancer. Conclusion: The similar efficacy network composed of 17 common targets in gastric ulcer and epilepsy was the basis for CHGZD to play the role of “different disease and common treatment”. A total of 152 components work together through 62 pathways and 17 pathways to achieve the effect of “treating different diseases with same method”, which provides modern medical evidence for the traditional Chinese medicine to treat gastric ulcer and epilepsy from the liver and spleen.
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Objective: To study the effective components and mechanism of action of Dachaihu Decoction (DCHD) in the treatment of pancreatitis (syndrome of liver depression and qi stagnation). Methods: The PPI network and the multi-dimensional relationship network of “Chinese material medica prescription active ingredient key target” of DCHD in the treatment of pancreatitis with stagnation of liver qi. Based on network pharmacology, the software such as Cytoscape 3.6.0 was firstly used to construct the PPI interaction network of key targets in the Chinese material medica with the effect of soothing liver and regulating qi (“Shugan Liqi” in Chinese) and DCHD “Chinese material medica prescription-effective components-key target” multi-dimensional network for the treatment of pancreatitis, and then treat the two networks as an intersection to obtain the network of DCHD for the treatment of pancreatitis (syndrome of liver depression and qi stagnation) “Chinese material medica prescription-effective components-key target”, and finally analyzed with relevant software. Results: A total of 59 key targets for Shugan Liqi were obtained such as AKT1, VEGFA, and PRSS1; A total of 83 main active ingredients such as quercetin, kaempferol and baicalein were collected from DCHD. The treatment of pancreatitis (syndrome of liver depression and qi stagnation) involved 18 targets of Ganyu Qizhi such as PTGS2, DPP4, PRSS1, and 30 related biological processes and signaling pathways such as extracellular matrix degeadation, IL-17 signaling pathway, and AGE-RAGE signaling pathway in diabetic complications. Conclusion: The multi-component and multi-target in DCHD are the basis for its efficacy. It is worthwhile to deeply think about the use of network pharmacology in the context of syndrome research.