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Non-infectious chronic diseases in human including diabetes, non-alcoholic fatty liver disease (NAFLD), atherosclerosis (AS), neurodegenerative diseases, osteoporosis, as well as malignant tumors may have some common pathogenic mechanisms such as non-resolved inflammation (NRI), gut microbiota dysfunction, endoplasmic reticulum stress, mitochondria dysfunction, and abnormality of the mammalian target of rapamycin (mTOR) pathway. These pathogenic mechanisms could be the basis for "homotherapy for heteropathy" in clinic. Some commonly used clinical drugs, such as metformin, berberine, aspirin, statins, and rapamycin may execute therapeutic effect on their targeted diseases,and also have the effect of "homotherapy for heteropathy". The mechanisms of the above drugs may include anti-inflammation, modulation of gut microbiota, suppression of endoplasmic reticulum stress, improvement of mitochondria function, and inhibition of mTOR. For virus infectious diseases, as some viruses need certain commonly used replicases, the inhibitors of the replicases become examples of "homotherapy for heteropathy" for antiviral therapy in clinic (for example tenofovir for both AIDS and HBV infection). Especially, in case of outbreak of new emerging viruses, these viral enzyme inhibitors such as azvudine and sofibuvir, could be rapidly used in controlling viral epidemic or pandemic, based on the principle of "homotherapy for heteropathy". In this review article, we show the research progress of the biological basis for "homotherapy for heteropathy" and the possible mechanisms of some well-known drugs, in order to provide insights and new references for innovative drug R&D.
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AIM: To predict the core targets and related signaling pathways of Yi-xin-yin oral liquid for the treatment of arrhythmia, heart failure and myocarditis based on UHPLC-Q-TOF/MS, network pharmacology, molecular docking methods, cell experiments, according to the“homotherapy for heteropathy”theory in traditional Chinese medicine. METHODS: UHPLC-Q-TOF / MS was used to analyze and identify the chemical composition of Yi-xin-yin oral liquid Extract and the blood-absorbing components of rats oral administrated with Yi-xin-yin oral liquid extract, which compounds were applied in the databases searching for the potential targets (TCMSP, SwissTargetPrediction) and disease targets (OMIM, Genecard). Venn diagram was used for target intersection, and the subsequent protein-protein interaction network obtained core targets by STRING11.5 database, and then construct a "disease-component-target" network by cytoscape3.9.0. Finally, DAVID database was used to analysis GO function and KEGG enrichment analysis of core targets, and molecular docking validation was performed using Autodock vina software. And, validated with H9c2 cells for potential active ingredients and targets. RESULTS: A total of 156 compounds were identified from Yi - xin-yin Oral Liquid extract; 34 compounds were identified from rat serum, including 6-gin-gerol, isoliquiritigenin, glycyrrhizic acid and other compounds, and 139 intersecting targets were obtained. The KEGG pathway enrichment analysis mainly involved the TNF signaling pathway, IL-17 signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway and so on. The TNF and IL-6 targets were selected for molecular docking with the main compounds, and the docking results were good (less than -5 kcal/mol). In vitro cellular experiments have shown that Yi-xin-yin oral liquid can exert therapeutic effects by regulating TNF and IL-6. CONCLUSION: The main potential active ingredients of Yi-xin-yin oral liquid may be isoliquiritigenin, glycyrrhetinic acid, calycosin-7-glucoside, salvianolic acid B, and 6-gingerol, which mainly act on TNF, IL-6 and other targets to regulate specific signaling pathways and exert therapeutic effects.
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Objective:To explore the material basis and mechanism of acute stroke treated with Rhei Radix et Rhizoma based on Homotherapy for Heteropathy using the analysis of proteomics and bioinformatics. Method:A total of 60 male Sprague-Dawley（SD）rats were randomly divided into ischemic stroke（IS） sham-operation group (Sham1), IS model group (IS), IS+ Rhei Radix et Rhizoma treatment group (DH1)，ICH sham-operation group (Sham2), intracerebral hemorrhage（ICH） model group (ICH), and ICH + Rhei Radix et Rhizoma treatment group (DH2), with 10 rats in each group. After cerebral perfusion, the brain tissues were quantified by proteomic analysis, and differentially expressed proteins (DEPs) were identified. Specimens of IS, Sham1, and DH1 groups were collected at 24 hours, while those of ICH, Sham2, and DH2 groups were collected at 48 hours. The common DEPs were analyzed by bioinformatics, and the relevant DEPs were verified by Western blot. Result:Rhei Radix et Rhizoma regulated 21 common DEPs associated with acute stroke (including 12 up-regulated and 9 down-regulated). According to Kyoto Encyclopedia of Genes and Genomes（KEGG） analysis, amyotrophic lateral sclerosis (ALS) pathway was enriched, and three proteins [Neurofilament light polypeptide (Nefl), Neurofilament medium polypeptide (Nefm), Neurofilament heavy polypeptide (Nefh)] involved in this pathway. Energy metabolism, ion homeostasis, regulation of synaptophysin, cell cycle and neurogenesis were the common mechanisms of "Homotherapy for Heteropathy". After treatment with Rhei Radix et Rhizoma, the expression levels of GTP binding protein REM2 (Rem2), tyrosine 3-monooxygena (Th), Nefl and neuromodulin (Gap43) were significantly higher than those of the corresponding model group (P<0.05). The expression of Nefl was down-regulated, while the expressions of Rem2，Th and Gap43 were up-regulated, which was consistent with the results of proteomics. Conclusion:Rhei Radix et Rhizoma-homotherapy-differential protein expression profile is established is study. Energy metabolism, ion homeostasis, regulation of synaptophysin, cell cycle and neurogenesis are the common mechanisms.
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Objective Urinary metabolomics associated with the histological progression of liver fibrosis (LF) and pulmonary fibrosis (PF) were utilized to explore common differential metabolites and their associated changes, and to explain the scientific connotation of the traditional Chinese medicine (TCM) theory of "homotherapy for heteropathy". Methods HE staining was used to monitor the histopathological changes in rats with LF and PF. Urinary metabolic profiling was performed by UPLC-Q-TOF/MS to analyze the metabolic profiles of LF and PF, as well as to clarify the common differential metabolites and their dynamic changes in LF and PF progression. Results Similar pathologic processes and trajectories of the PLS-DA score plots were observed in both the LF and PF models. Furthermore, 16 differential urine metabolites were found both in LF and PF. Among these, nine metabolites, including adrenochrome and 5-L-glutamyl-taurine, were key biomarkers which affect the development of LF and PF through oxidative damage, inflammation, and release of profibrogenic cytokines. Conclusion Metabonomic analysis revealed that LF and PF share common differential metabolites with the same changing trends and explained the scientific connotation of the TCM theory of "homotherapy for heteropathy".
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OBJECTIVE: To explore the molecular mechanism and targets with"Relieving the Depressed Liver" effectofemotional diseases treatment by Radix Bupleuri. METHOD: Systems pharmacology methodwas employed to exploring the ingredients, targets and diseases information which was related "Relieving the Depressed Liver" effect in Radix Bupleuri. Next, the "disease-target" network and "drug-target" network were built by Cytoscape 3.2.1 and we analyzed the network by using network topological analysis method and systems pharmacological data. RESULT: Twenty-five targets were found to be associated with emotional diseases. Eight core ingredients from 118 ingredients in Radix Bupleuri were directly related to these targets. The molecular mechanism of Radix Bupleuri treatment of emotional diseases is produced by the interactions between the 118 ingredients and 25 potential targets, and eight core compounds may play a central role in the process of this treatment mechanism. CONCLUSION: Through the construction of systems pharmacology models, the molecular mechanism of "Relieving the Depressed Liver" effect of Radix Bupleuri from the system level is we interpreted. Our study provides a theoretical foundation for the explanation of TCM treating mechanism and "treat different diseases with same Chinese medicine" phenomenon.