Homotherapy for heteropathy: Interleukin-41 and its biological functions.

Interleukin-41 (IL-41) is a newly discovered cytokine, named Cometin, Subfatin, meteorin-like transcription (Metrnl), and so forth. It is widely expressed in animals and can exert its biological roles through autocrine and paracrine forms. It has functions such as anti-inflammatory, improving body metabolism, regulating immunity, regulating fat metabolism and participates in the process of autoimmune disease or inflammatory injury. It plays an important role in psoriasis, diabetes, Crohn's disease (CD), osteoarthritis, Kawasaki disease (KD), Graves' disease, autoimmune hepatitis, infertility, obesity, sepsis, cardiovascular diseases and respiratory diseases. This paper reviews the biological functions of IL-41, the relationship between IL-41 and diseases, the effects of IL-41 in the cytokine network and the possible signalling pathways. In order to explore the same target or the same drug for the treatment of different diseases from the perspective of homotherapy for heteropathy, cytokine strategies based on IL-41 have been put forward for the precise treatment of immune diseases and inflammatory diseases. It is worth noting that IL-41 related preparations for lung protection and smoking cessation are interesting research fields.

Homotherapy-for-heteropathy of Bupleurum Chinense DC.-Scutellaria baicalensis Georgi in treating depression and colorectal cancer: A network pharmacology and animal model approach.

ETHNOPHARMACOLOGICAL RELEVANCE: Bupleurum chinense DC.-Scutellaria baicalensis Georgi (BS) is a classic drug pair that has good clinical effects on depression and many tumors. However, the concurrent targeting mechanism of how the aforementioned drug pair is valid in the two distinct diseases, has not been clarified yet. AIM OF THE STUDY: The components of BS were detected by LC-MS, combined with network pharmacology to explore the active ingredients and common targeting mechanism of its multi-pathway regulation of BS in treating depression and CRC, and to validate the dual effects of BS using the CUMS mice model and orthotopic transplantation tumor mice model of CRC. RESULTS: Twenty-nine components were screened, 84 common gene targets were obteined, and the top 5 key targets including STAT3, PIK3R1, PIK3CA, AKT1, IL-6 were identified by PPI network. GO and KEGG analyses revealed that PI3K/AKT and JAK/STAT signaling pathways might play a crucial role of BS in regulating depression and CRC. BS significantly modulated CUMS-induced depressive-like behavior, attenuated neuronal damage, and reduced serum EPI and NE levels in CUMS model mice. BS improved the pathological histological changes of solid tumors and liver tissues and inhibited solid tumors and liver metastases in tumor-bearing mice. BS significantly decreased the proteins' expression of IL-6, p-JAK2, p-STAT3, p-PI3K, p-AKT1 in hippocampal tissues and solid tumors, and regulated the levels of IL-2, IL-6 and IL-10 in serum of two models of mice. CONCLUSION: BS can exert dual antidepressant and anti-CRC effects by inhibiting the expression of IL-6/JAK2/STAT3 and PI3K/AKT pathway proteins and regulating the release of inflammatory cytokines.

Biological principles for "homotherapy for heteropathy" / 药学学报

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.

Mechanism of Yi-xin-yin oral liquid according to homotherapy for heteropathy theory based on UHPLC-Q-TOF/MS combined with network pharmacology and molecular docking techniques / 中国临床药理学与治疗学

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.

The common regulatory pathway of COVID-19 and multiple inflammatory diseases and the molecular mechanism of cepharanthine in the treatment of COVID-19.

Background: Similar pathogenesis makes Corona Virus Disease 2019 (COVID-19) associated with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and gouty arthritis (GA), and it is possible to introduce common drugs for the treatment of RA, AS and GA into the treatment of COVID-19. That is, "homotherapy for heteropathy", especially cytokine inhibitors. But little is known about the specific link between the diseases. In addition, "new use of old drugs" is an important short-term strategy for the treatment of COVID-19. Cepharanthine (CEP), a monomer component of traditional Chinese medicine (TCM), is mainly used in the treatment of leukopenia and has recently been proved to have a good therapeutic effect on COVID-19, but its specific molecular mechanism has not been clearly explained. The purpose of this work is to explore the common targets and signaling pathways among COVID-19, RA, AS, and GA by means of network pharmacology (NP), and to infer the potential mechanism of CEP in the treatment of COVID-19. Methods: Firstly, SwissTargetPrediction was used to predict the targets of CEP, and the pathogenic targets of COVID-19, RA, AS and GA were searched in GeneCards, OMIM, TTD, PharmGKB database and literature, respectively. Then, the protein interaction network of CEP and COVID-19 cross targets and the common targets of COVID-19, RA, AS and GA was constructed. Cytosscape 3.7.2 software was used to construct CEP-common targets-signaling pathways-COVID-19 network, module function analysis, gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG). Finally, the molecular docking of hub targets and CEP was carried out by AutoDock software. Results: The results showed that the common targets of the four diseases were tumor necrosis factor (TNF), interleukin (IL)-6 and IL-1ß, and involved Coronavirus disease, IL-17 signaling pathway and TNF signaling pathway. CEP has a good binding force with AKT Serine/Threonine Kinase 1 (AKT1), phosphatidylinositol 3-kinase (PIK3) CA, PIK3CD and Angiotensin-converting enzyme 2 (ACE2), and plays a role in the treatment of COVID-19 by regulating PI3K-Akt signaling pathway, Relaxin signaling pathway, VEGF signaling pathway and HIF-1 signaling pathway. Conclusion: Therefore, this study not only confirmed the potential mechanism of CEP in the treatment of COVID-19 at the molecular level, but also found that TNF and IL-17 inhibitors, which are commonly used in the treatment of RA, AS and GA, may also affect the treatment of COVID-19, which provides new clues and theoretical basis for the rapid discovery of effective therapeutic drugs for COVID-19.

Homotherapy for heteropathy active components and mechanisms of Qiang-Huo-Sheng-Shi decoction for treatment of rheumatoid arthritis and osteoarthritis.

Qiang-Huo-Sheng-Shi decoction (QHSSD), a classic traditional Chinese herbal formula, which has been reported to be effective in rheumatoid arthritis (RA) and osteoarthritis (OA). However, the concurrent targeting mechanism of how the aforementioned formula is valid in the two distinct diseases OA and RA, which represents the homotherapy-for-heteropathy principle in traditional Chinese medicine (TCM), have not yet been clarified. In the present study, network pharmacology was adopted to analyze the potential molecular mechanism, and therapeutic effective components of QHSSD on both OA and RA. A total of 153 active ingredients in QHSSD were identified, 142 of which associated with 59 potential targets for the two diseases were identified. By constructing the protein-protein interaction network and the compound-target-disease network, 72 compounds and 10 proteins were obtained as the hub targets of QHSSD against OA and RA. The hub genes of ESR1, PTGS2, PPARG, IL1B, TNF, MMP2, IL6, CYP3A4, MAPK8, and ALB were mainly involved in osteoclast differentiation, the NF-κB and TNF signaling pathways. Moreover, molecular docking results showed that the screened active compounds had a high affinity for the hub genes. This study provides new insight into the molecular mechanisms behind how QHSSD presents homotherapy-for-heteropathy therapeutic efficacy in both OA and RA. For the first time, a two-disease model was linked with a TCM formula using network pharmacology to identify the key active components and understand the common mechanisms of its multi-pathway regulation. This study will inspire more innovative and important studies on the modern research of TCM formulas.

Brain Material Basis and Relevant Mechanism of Acute Stroke Treated with Rhei Radix et Rhizoma Based on Homotherapy for Heteropathy Using Proteomics / 中国实验方剂学杂志

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.

Scientific connotation of TCM theory of "homotherapy for heteropathy" in treatment of liver and pulmonary fibrosis based on metabonomics / 中草药

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".

Systems pharmacology based researching of Radix Bupleuri in treatment of different emotional diseases / 中国药学杂志

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.