Maxing Shigan Decoction Research Articles

Evaluation of Treatment Effect of Maxing Shigan Decoction and Qianjin Weijing Decoction for Severe Pneumonia

Evaluation of Treatment Effect of Maxing Shigan Decoction and Qianjin Weijing Decoction for Severe Pneumonia

Positive effects of Lianhuaqingwen granules in COVID-19 patients: A retrospective study of 248 cases

Ethnopharmacological relevanceLianhuaqingwen (LHQW) is a Chinese medicine, developed from appropriate addition and reduction of combined traditional Chinese medicine (TCM) Yinqiao San and Maxing Shigan decoction. LHQW has been used in routine influenza treatment for decades and plays a role in a broad-spectrum therapy on various influenza viruses.Aims of the study: The therapeutic effects of LHQW in coronavirus disease 2019 (COVID-19) have not been fully elucidated. A retrospective study was conducted in patients with COVID-19 to evaluate the influence of LHQW on laboratory results related to the disease, and to provide evidence for the clinical practice of TCM. Materials and methodsWe retrospectively collected 248 patients who met the moderate type COVID-19 diagnostic criteria, and received treatment in Tongji Hospital. Patients were divided into control (158 cases, standard treatment) and LHQW treatment (90 cases, standard treatment combined with LHQW) groups according to the different treatments administered. All laboratory data were obtained after 5–7 days’ treatment. ResultsIn this study, the average patient age was 58.95 years and 131 patients were male. The two groups were comparable in demographic characteristics, symptoms, and treatment. Compared with in the control group, D-dimer and erythrocyte sedimentation rate were significantly lower in the LHQW treatment group (2.47 ± 4.67 vs. 1.68 ± 3.61; 44.47 ± 30.24 vs. 35.39 ± 27.43; both P < 0.05). Lymphocyte counts, albumin and hemoglobin levels were higher in the LHQW treatment group than those in the control group (1.00 ± 0.46 vs. 1.13 ± 0.5; 34.39 ± 5.2 vs. 35.71 ± 4.76; 127.03 ± 16.58 vs. 131.11 ± 14.66; both P < 0.05). ConclusionThe study showed that LHQW significantly improved laboratory results of patients with COVID-19 and could be effectively applied alongside standard treatment of patients with moderate type COVID-19, providing preliminary clinical research evidence for the use of TCM in treatment of this disease.

Clinical trials for Traditional Chinese Medicine against coronavirus disease 2019 (COVID-19): Interpretation based on bibliometric analysis

<p indent="0mm">The coronavirus disease 2019 (COVID-19) has been spreading worldwide, posing a significant threat to human health. Currently, vaccines are available, but there is still no reliable cure for this disease. Traditional Chinese Medicine (TCM) has played an important role in addressing this epidemic, and several clinical studies have emerged regarding treatments for COVID-19 by TCM; status of those treatments, and patterns regarding these are worth summarizing and interpreting systematically. A comprehensive search of clinical trials was performed in various platforms, including PubMed, Embase, Web of Science, medRxiv, China National Knowledge Infrastructure, WanFang Data, and SinoMed, from January 1, 2020 to March 1, 2021. Analyzed information included language, received date, quantity, citations, affiliation, number of authors, research type (randomized controlled trial or non-randomized controlled trial), trial registry information, disease severity, sample size, specific interventions, outcomes, and adverse reactions, among others. Based on the aforementioned information, a quantitative and qualitative literature analysis was done. A total of 47 articles were retrieved, most of which were published in Chinese (42 articles, 89.36%). Based on the results of the number of trial registrations (12 articles), the number of citations (the maximum for a single article was 62), and the modified Chalmers scale (total: 100 points, average: 61.40 points), the overall study quality still needs improvement. Most patients presented with the mild and common type of COVID-19 and were recruited in Hubei Province, while researchers from these studies were from all over the country (135 institutions). TCM interventions included 66 different formulas and 134 herbs, of which Armeniacae semen amarum (Kuxingren), Agastache rugosa (Huoxiang), Ephedra sinica stapf (Mahuang), Gypsum fibrosum (Shigao), Glycyrrhizae radix et rhizome (Gancao), and Gtractylodes rhizoma (Cangzhu) appeared at high frequencies. Highlighted outcomes from these studies included the following: Clinical symptoms (fever, cough, fatigue, etc.), progression rate from normal stage to heavy stage, laboratory indices including leukocyte and lymphocyte counts, and c-reactive protein levels, imaging diversity of lung computed tomography (CT), and recorded adverse reactions. With a certain number of published clinical trials, the landscape of TCM clinical trials for COVID-19 was established. Most studies have a relatively low quality and impact, and standardized implementation of evidence-based research in TCM was lacking. The mainstay TCM treatment for COVID-19 involved clearing heat, releasing the exterior, and resolving its dampness. Additionally, the Maxing Shigan Decoction was one of the most common classical prescriptions for COVID-19, and the “three drugs and three perceptions” were also widely used. Some symptoms, laboratory indicators, and imaging diversity of lung CT were found to have significantly improved after taking these decoctions. Overall, TCM is safe, and no serious adverse reactions have been reported. Through multiple mechanisms, TCM has shown great clinical effects, but its underlying mechanisms and patterns should be further explored. It is of great practical significance to enhance the level of clinical and evidence-based research for TCM application in the prevention and treatment of acute and emergent infectious diseases. Furthermore, such research will help strengthen clinical expertise in this field and further standardize the implementation of evidence-based TCM medical research.

Lianhuaqingwen capsule inhibits influenza-induced bacterial adhesion to respiratory epithelial cells through down-regulation of cell adhesion molecules

Ethnopharmacological relevanceInfluenza virus infection is widely believed to cause mild symptoms, but can lead to high mortality and severe disease complicated by secondary bacterial pneumonia. Traditional Chinese medicine (TCM) has been proposed as a promising agent to treat respiratory viral infections. A herbal formula Lianhuaqingwen capsule (LHQW) comprising two prescriptions: Maxing Shigan decoction and Yinqiao San, has been used clinically to treat respiratory infection with immune regulatory effects. However, little is known about the capacity of LHQW against influenza-induced secondary bacterial pneumonia. Aim of studyThis study aimed to evaluate the efficacy and underlying mechanism of LHQW on influenza A virus A/PR/8/34 (PR8) secondary methicillin-resistant Staphy-lococcus aureus (MRSA) infection. MethodsThe anti-adhesion activity of LHQW against PR8-induced MRSA infection was assessed in human lung epithelial (A549) cells and the effect of LHQW on the expression of intracellular adhesion molecule 1 (ICAM-1) was detected. Also, the mRNA expression levels of inflammatory cytokines upon lipopolysaccharide (LPS) stimulation in PR8-infected A549 cells were determined. The body weight change, survivals, viral titers, colonies and the pathological parameters after LHQW treatment in severe pneumonia model have all been systematically determined. ResultsLHQW significantly reduced the adhesion of MRSA to PR8-infected A549 cells in a dose-dependent manner by suppressing the up-regulation of bacterial receptors. LHQW also markedly declined the overexpression of IL-6, IL-8, and TNF-α induced by LPS stimulated-A549 cells following influenza virus infection. Furthermore, the abnormal changes of lung index in dual-infection mice were relieved after administered with LHQW in preventive and therapeutic mode, but with no significantly difference (P > 0.05). LHQW could not effectively improve survival rate or prolong the survival time of mice (P > 0.05). LHQW (1000 mg/kg/d) administered prophylactically significantly decreased the lung viral titers (P < 0.05), slightly downregulated IL-6 but TNF-α, IL-1β levels and improved lung pathological inflammation including neutrophil infiltration, necrosis, which is consistent with the expression of inflammatory factors. ConclusionsLHQW inhibited influenza-induced bacterial adhesion by down-regulating the adhesion molecules with the improvement trend on severe pneumonia, indicating that it can be used as an adjuvant medication in severe viral-bacterial pneumonia therapy rather than as a single medication.

Systematic review of randomized controlled trial of Maxing Shigan Decoction in treatment of community acquired pneumonia

To systemically evaluate the efficacy and safety of Maxing Shigan Decoction in the treatment of community acquired pneumonia(CAP) and provide a reference for the treatment of CAP. Databases of CNKI, Wanfang, VIP, SinoMed, EMbase, Cochrane Library, Web of Science and PubMed were searched(from inception to May 30, 2020) to screen the randomized controlled trials(RCTs) of Maxing Shigan Decoction in treating CAP. Two authors independently screened and selected relevant literature and extracted data based on the inclusion and exclusion criteria. Any disagreement or differences was resolved through discussion. The bias risk assessment tool recommended by Cochrane handbook was used to evaluate the quality of the included studies, and RevMan 5.3 software was used for data analysis. Seventeen RCTs were finally included, involving 1 309 patients. Meta-analysis showed that Maxing Shigan Decoction combined with conventional Western medicine treatment could improve clinical efficacy in patients with CAP more effectively as compared with conventional Western medicine treatment alone, mainly in terms of anti-inflammatory effects, a decrease in C-reactive protein(CRP) content(MD=-6.01, 95%CI[-10.95,-1.06], P=0.02)and white blood cell(WBC) count, a decrease in procalcitonin(PCT) level(MD=-0.74, 95%CI[-0.77,-0.71], P&lt;0.000 1), and shortened recovery time of cough and fever. Maxing Shigan Decoction has certain curative effect on CAP, but there are problems in the methodology of included studies. High-quality stu-dies are still needed for further verification.

Maxing Shigan Decoction Mitigates Mycoplasma pneumonia-Induced Pyroptosis in A549 Cells via the NLRP3 Inflammasome.

BackgroundMycoplasma pneumoniae is a predominant cause of community-acquired respiratory infections. We recently discovered the clinical efficacy of Maxing shigan decoction (MXSG) in M. pneumoniae infection and designed a study to explore the mechanism of action.MethodsSerum IL-1β, IL-18, and TNF-α, and transcript expression of the NLR Family, Pyrin Domain Containing Protein 3 (NLRP3) were measured in the peripheral blood mononuclear cells (PBMCs) of 30 children with M. pneumoniae infection and 30 healthy donors. An in vitro model of M. pneumoniae infection in A549 cell culture was used to explore the curative effects and mechanisms of MXSG. Pyroptosis was measured by flow cytometry with activated caspase-1 and propidium iodide staining. IL-1β, IL-18, and TNF-α, and NLRP3 transcript expression were measured by qRT-PCR. Protein expression of NLRP3, Caspase-1, pro-caspase-1, IL-1β, pro-IL-1β, and GSDMD-N was determined by Western blotting. Experimental confirmation was performed in NLRP3-overexpressing A549 cells and in the presence of an NLRP3 inhibitor, INF39.ResultsM. pneumoniae infection-induced IL-1β, IL-18, TNF-α, and mRNA expression of NLRP3 in PBMCs and promoted pyroptosis in A549 cells. It also induced IL-1β, IL-18, TNF-α, and up-regulated NLRP3, ro-IL-1β, Caspase-1, Pro-Caspase-1, and GSDMD-N in culture. Similar to the NLRP3 inhibitor INF39, MXSG (0.1, 0.2, and 0.4 mg/mL) suppressed pyroptosis induced by M. pneumoniae infection and decreased IL-1β (P < 0.001), IL-18, TNF-α in culture. MXSG down-regulated NLRP3, pro-IL-1β, Caspase-1, pro-Caspase-1, and GSDMD-N in infected cultures and mitigated NLRP3 overexpression-induced pyroptosis.ConclusionMXSG mitigates M. pneumoniae-induced pyroptosis in A549 cells via the NLRP3 inflammasome.

Prospective: Evolution of Chinese Medicine to Treat COVID-19 Patients in China.

During the outbreak of the novel coronavirus disease (COVID-19), the Chinese government took a series of public health measures to tackle the outbreak and recommended six traditional Chinese medicine (TCM) evolved formulas, collectively referred to as “3-drugs-3-formulas”, for the treatment. In this prospective article, we will discuss how these six formulas evolved from TCM and what their underlying mechanisms of actions may be by evaluating the historical usage of the component formulas, the potential targeted pathways for the individual herbs used by STAR (signal transduction activity response) database from our laboratory, and the pathogenesis of COVID-19. Five of the six recommended formulas are administered orally, while the sixth is taken as an injection. Five classic categories of herbs in the six formulas including “Qing-Re”, “Qu-Shi”, “Huo-Xue”, “Bu-Yi” and “Xing-Qi” herbs are used based on different stages of disease. All five oral formulas build upon the core formula Maxingshigan Decoction (MD) which has anti-inflammatory and perhaps antiviral actions. While MD can have some desired effects, it may not be sufficient to treat COVID-19 on its own; consequently, complementary classic formulas and/or herbs have been added to potentiate each recommended formula’s anti-inflammatory, and perhaps anti-renin-angiotensin system (RAS)-mediated bradykinin storm (RBS) and antiviral effects to address the unique medical needs for different stages of COVID-19. The key actions of these formulas are likely to control systemic inflammation and/or RBS. The usage of Chinese medicine in the six formulas is consistent with the pathogenesis of COVID-19. Thus, an integrative systems biology approach—combining botanical treatments of conventional antiviral, anti-inflammatory or anti-RBS drugs to treat COVID-19 and its complications – should be explored.

Treatment strategy and thought on classical herbal formulae for coronavirus disease 2019

Coronavirus disease 2019(COVID-19) refers to the pneumonia caused by novel coronavirus(2019-nCoV) infection in 2019. It is highly infectious, with quick spreading and a wide range of impact. It has been broken out in many countries around the world and has become a public health emergency of international concern. Chinese medicine has a long history in treating plague, and viral disease is the clinical advantage in Chinese medicine. Under the premise that there is currently no specific drug treatment, Chinese medicine has achieved certain effects in the treatment of COVID-19, which has attracted much attention and has been upgraded to a national strategy. Regarding the treatment of COVID-19 with Chinese medicine, it is believed that in terms of the name of Chinese medicine, the modern connotation of &quot;uniform of typhoid and febrile disease&quot; should be re-recognized, and it is advisable to use drugs based on specific clinical prescriptions and indications. In terms of pathogenesis, the COVID-19 has the pathogenesis rules including from the mild to severe conditions, from the surface to the inside, from the excess syndrome to the deficiency syndrome. We should pay attention to the Taiyang syndrome damaged by wet disease in initial stage, Shaoyang syndrome complicated with Yangming syndrome in the middle stage, phlegm-heat obstructing lung in critical period, lung and spleen deficiency in the recovery stage. In terms of clinical treatment strategies, Dayuan Yin is recommended to induce sweat and disperse the stasis in early stage. Xiaochaihu Decoction and Maxing Shigan Decoction is used to relieve both exterior and interior symptoms in middle stage. In critical stage, Tingli Dazao Xiefei Decoction, Weijing Decoction, Xuanbai Chengqi Decoction, Xiaoxianxiong Decoction, and Sanzi Yangqin Decoction are considered to reduce phlegm and clear heat. We should pay attention to nourishing Qi and strengthening the spleen by Zhuye Shigao Decoction, Sha-shen Maidong Decoction, and Liujunzi Decoction in the later recovery period. It shall be noted that, no matter in the initial mild stage, the middle and critical stages, or in the later recovery stage, Chinese medicine plays an important role, including preventing mild to severe disease, shortening the fever time, improving cough symptoms, increasing blood oxygen saturation and reducing mortality. Many studies have shown that the classical herbal formulae can alleviate the cytokine storm, regulate the immune imbalance, and produce the potential effect of synergistic treatment for COVID-19 through multiple components, multiple targets, and multiple pathways.

Potential effect of Maxing Shigan decoction against coronavirus disease 2019 (COVID-19) revealed by network pharmacology and experimental verification

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.

Analysis of Clinical Efficacy of Xuebijing Combined with Maxing Shigan Decoction in Treating Severe Pneumonia

This research aims to discuss the clinical efficacy of Xuebijing joint Maxing Shigan decoction treatment in severe pneumonia patients, in the meantime to discuss the effects of drugs combination on inflammation indicators, arterial blood gases and clinical safety. We chose 120 patients with severe pneumonia in our hospital as the study cohort. Divided them into control group (n=60) and observation group (n=60). Control group received antibiotics. observation group received antibiotics as well but combined with Xuebijing and Maxing Shigan decoction. Compared both groups in clinical effective rate, inflammation index, arterial blood gas and the incidence of drug related complications after treatment. After treatment, observation group's inflammation indexes (C-reactive protein, procalcitonin), arterial blood gas changes (partial pressure of oxygen, partial pressure of carbon dioxide) and traditional Chinese medicine syndrome scores were significantly reduced (p<0.05). The clinical efficacy of observation group was higher than the other (p<0.05), it possessed no remarkable difference in both groups complications rate (p>0.05) and it was of no statistical difference. Xuebijing combined with Maxing Shigan decoction can effectively treat patients with severe pneumonia. The clinical symptoms are significantly improved, and inflammation indicators and arterial blood gas conditions can be improved without increasing the adverse incidence and complications of drugs. The combined use is worthwhile for patients with severe pneumonia.

Efficacy and safety of Maxing Shigan Decoction in the treatment of chronic obstructive pulmonary disease: A protocol for a systematic review and meta-analysis.

Background:Chronic Obstructive Pulmonary Disease (COPD) is currently the fourth leading cause of death in the world but is projected to be the 3rd leading cause of death by 2030. Chronic obstructive pulmonary disease is an important public health challenge, which can be prevented and treated. COPD is an important public health challenge, both preventable and treatable. In China, Maxing Shigan Decoction (MSD) has been used as a traditional Chinese medicine compound for the treatment of respiratory diseases for thousands of years. In order to evaluate the efficacy and safety of MSD in the treatment of COPD, we need to conduct meta-analysis and systematic reviews.Methods:The data comes from 7 publicly published databases, including: PubMed, The Cochrane Central Register of Controlled Trials (CENTRAL), EMbase, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Database(CBM), VIP Database, and Wanfang database. We will include randomized controlled trials (RCTs) to evaluate the effectiveness and safety of MSD in the treatment of COPD. Result measurement indicators include: TCM syndrome scores, lung function indicators, serum inflammatory factors, blood gas indicators, adverse reactions. RevMan 5.0 will be used for meta-analysis.Results:This study will provide high-quality evidence for the effectiveness and safety of traditional Chinese medicine therapy for COPD.Conclusion:The results of this study will help us determine whether MSD can effectively treat COPD.Ethics and dissemination:All analyses in this study are based on previously published research, so this study does not require ethical approval or patient consent. We will disseminate our findings electronically or in print by publishing results in peer-reviewed journals.OSF registration number:DOI 10.17605/OSF.IO/H5UNB.

Maxingshigan decoction for treating COVID-19: A protocol for systematic review and meta analysis.

Background:Coronavirus disease 2019 (COVID-19) is a rapidly spreading disease that has been in a public health emergency of international concern since its outbreak in 2020. Due to the complex pathogenesis and susceptibility of COVID-19, many commonly used drugs for the treatment of COVID-19 have not shown excellent clinical effects. Traditional Chinese medicine has a long clinical history of preventing and treating this respiratory infectious disease. Maxingshigan Decoction (MXSG) is widely used in China to treat COVID-19. However, there is no comprehensive and systematic evidence on the effectiveness and safety of Maxingshigan Decoction.Methods:PubMed, EMBASE, Clinical Trials, the Cochrane Library, Sino Med, and China National Knowledge Infrastructure up to September 2020. This study only screens clinical randomized controlled trials on MXSG for COVID-19 to evaluate its efficacy and safety. Data were extracted by 1 investigator and checked by an independent investigator. Review Manager 5.3 software was used for the data analysis. The dichotomous data is represented by relative risk, and the continuous is expressed by mean difference or standard mean difference, eventually the data is synthesized using a fixed effect model or a random effect model depending on whether or not heterogeneity exists.Results:The time from a positive diagnosis to a negative result of 2 consecutive nucleic acid tests (not on the same day), cure rate. The results of our research will be published in a peer-reviewed journal.Conclusion:The purpose of this systematic review is to provide new evidence for the effectiveness and safety of Maxingshigan decoction in the treatment of COVID-19.PROSPERO registration number:CRD42020211962.

Exploring the potential therapeutic effect of traditional Chinese medicine on coronavirus disease 2019 (COVID-19) through a combination of data mining and network pharmacology analysis

IntroductionHistorically traditional Chinese medicine (TCM) has been used as treatment during epidemics. During the recent COVID-19 pandemic patients evidence suggests that the use of TCM has provided health benefits and has been successfully used to control the spread of the disease in China. The aim of this study was to systematically explore the TCM formulae which have been used for the prevention and treatment of pneumonia or ‘pestilence’ to investigate their compatibility with the Chinese materia medica (CMM) and understand their potential mechanisms in the treatment of COVID-19. MethodsFrequency analysis was performed to identify high-frequency CMM and CMM groups. Association rules analysis was applied to investigate the compatibility law of CMMs and generate the commonly used CMM groups. ResultsA total of 173 prescriptions were collected. The frequency analysis showed that seven out of ten high-frequency CMMs overlapped with Lianhua Qingwen Capsules (LHQWC), and five high-frequency pair-CMMs and four triple-CMMs were included in LHQWC, respectively. Then three groups of CMM were generated from association rules analysis, one of which is Ma Xing Shi Gan Decoction (MXSGD). The results of the protein-protein interaction network and enrichment analysis showed that the potential therapeutic mechanisms of the generated prescriptions were involved in the anti-inflammatory, anti-viral, and neuroprotective effects. ConclusionThis study showed the importance of systematic research on TCM prescriptions and provided candidate CMM groups that have the potential to treat COVID-19. In vitro and in vivo experiments should be conducted to validate these network pharmacology results, which can provide more information for the development of potential antiviral drugs from TCM prescriptions. The combination of TCM treatment and modern medical approaches will benefit patients with COVID-19 and help to overcome the current epidemic.

A Network Pharmacology Study on the Effects of Ma Xing Shi Gan Decoction on Influenza

ObjectivePharmacological methods were used to screen targets and signaling pathways of Ma Xing Shi Gan Decoction (MXSGD) during influenza treatments, and mechanisms underlying anti-influenza effects were elucidated. MethodsThe Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and relevant literature were searched under predefined conditions to identify the main compounds and their targets. Interactions between the target proteins were predicted using the STRING database. Gene Ontology (GO) functional enrichment analyses and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed on the core targets involved in the influenza protein-protein interaction (PPI) network, using WebGestalt and the reactome database. iGEMDOCK was used for molecular docking of receptors and ligands to produce docking scores, and the results were visualized using Autodock and PyMOL. ResultsIn total, 126 major compounds and their respective targets were screened. 355 influenza target proteins and 1 221 influenza protein interactions were predicted using the STRING database. Influenza-related signaling pathways were strongly enriched in pharmacodynamic targets of MXSGD such as cytokine signaling in immune system and signaling by inter-leukin. The main biological process was response to the stimulates. Molecular docking results showed that RELA-Licochalcone A docking elicited by MXSGD, was superior to that of other target proteins and active compounds, suggesting that the docking site is also the main effector site of MXSGD during influenza treatments. Conclusions The results showed that MXSGD exerts anti-influenza effects by interfering with virus adsorption, inhibiting virus proliferation, influencing immune functions and protecting host cells, which may prevent inflammation-induced tissue damage.

Ma xing shi gan decoction eliminates PM2.5-induced lung injury by reducing pulmonary cell apoptosis through Akt/mTOR/p70S6K pathway in rats.

The present study was designed to investigate the anti-apoptosis effect of Ma xing shi gan decoction (MXD) on PM2.5-induced lung injury via protein kinase B (Akt)/mTOR/p70S6K pathway. A UPLC-MS/MS system was introduced for component analysis of MXD. Rats were instilled with PM2.5 solution suspension intratracheally to induce acute lung injury. The rats were then orally administered with MXD (16, 8, and 4 g/kg) once a day for 7 consecutive days. The therapeutic effects of MXD were evaluated by Hematoxylin and Eosin (HE) staining. The apoptotic cell death was analyzed by terminal-deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) assay. The alterations in cytochrome c (Cytc) and cleaved-caspase-3 (C-caspase-3) were measured by immunohistochemistry (IHC). The expressions of Bax, B-cell lymphoma 2 (Bcl-2), p-Akt, p-mTOR and p-p70S6K were detected by Western blot. In vitro, PM2.5 exposure model was introduced in A549 cell, followed by incubation with MXD-medicated serum. Hoechst staining was used to determine apoptotic rate. The levels of Bax, Bcl-2, p-Akt, p-mTOR and p-p70S6K were detected by Western blot. Our results in vivo indicated that treatment with MXD decreased histopathological changes score, TUNEL-positive cells rate, expressions of Cytc and C-caspase-3. The in vitro results revealed that incubation with MXD-mediated serum decreased apoptotic rate. Both results in vivo and in vitro demonstrated that MXD inhibited pro-apoptotic protein Bax and promoted anti-apoptotic protein Bcl-2 expression. Likewise, MXD activated Akt/mTOR/p70S6K signal pathway, which was also confirmed by Western immunoblotting. In conclusion, MXD attenuates lung injury and the underlying mechanisms may relate to regulating the apoptosis via Akt/mTOR/p70S6K signaling pathway activation.

Systematic Pharmacological Strategies to Explore the Regulatory Mechanism of Ma Xing Shi Gan Decoction on COVID-19

ObjectiveTo use systematic pharmacological strategies to explore the regulatory mechanisms of Ma Xing Shi Gan Decoction (MXSGD) against the coronavirus disease 2019 (COVID-19). MethodsData on the compounds and targets of MXSGD were collected from the Traditional Chinese Medicene Systems Parmacology Database and Analysis Platform (TCMSP) and TCM Databases@Taiwan. Data on ACE2-related targets and the protein-protein interaction (PPI) were collected from the String database. The Cytoscape 3.7.2 was used to construct and analyze the networks. The DAVID platform was used for Gene Ontology (GO) and pathway enrichment analyses. ResultsData on 272 MXSGD targets and 21 SARS-CoV-2 potential targets were collected. Four networks were constructed and analyzed based on the data: (1) compound-target network of MXSGD; (2) MXSGD-SARS-CoV-2-PPI network; (3) cluster of MXSGD-SARS-CoV-2-PPI network; (4) Herb-Pathway-Target network. The core targets included AKT1, MAPK3, IL-6, TP53, VEGFA, TNF, CASP3, EGFR, EGF and MAPK1. The antiviral biological processes were inflammatory responses (inflammatory cells, inflammatory cytokines and their signaling pathways), immune responses (T cells, monocytes, B cells and other immune cells), immune factors (IFN-γ, TNF-α and so on), virus defense, humoral immunity and mucosal innate immune response. The antivirus-related signaling pathways included TNF, NOD-like receptor, FoxO, PI3K-AKT and Toll-like receptor signaling pathways. ConclusionsMXSGD can control disease progression by regulating multiple compounds and targets; it can reduce inflammation and balance immunity by regulating several proteins that interact with ACE2 and signaling pathways closely related to disease development.

Analysis of medication characteristics of traditional Chinese medicine in treating COVID-19 based on data mining

To analysis the medication characteristics of the prescriptions issued via open channel by the National and Provincial Health Committee and the State Administration of Traditional Chinese Medicine in treating coronavirus disease 2019 (COVID-19). We collected the data of traditional Chinese medicine related to treatment plans published by the National and Provincial Health Committee and the State Administration of Traditional Chinese Medicine from the start of COVID-19 outbreak to February 19, 2020. The frequency analysis, cluster analysis and association analysis were performed. The study collected 4 national and 34 regional prevention and treatment plans, 578 items, 84 traditional Chinese formulations, 60 Chinese patent medicines, and 230 Chinese herbs. The high frequently used herbs were Liquorice, Scutellariabaicalensis, Semen armeniacaeamarae, and Gypsum. The commonly used traditional formulations included Maxing Shigan decoction, Yin Qiao powder, and Xuanbai Chengqi decoction. The Chinese patent drugs included Angong Niuhuang pill, Xuebijing injection, and Lianhua Qingwen capsule. The most common paired medications were Ephedra and Semen armeniacaeamarae, Fructusforsythiae and Liquorice. Two core combinations and one novel formula were discovered in the study. Yin Qiao powder and Huopo Xialing decoction are the basic formulations for Weifen syndrome of COVID-19. In addition, Maxing Shigan decoction, Liang Ge powder, Qingwen Baidu decoction and Da Yuan decoction are the basic formulations for Qifen syndrome of COVID-19. The main medication characteristics are clearing heat, entilating lung, removing toxicity and removing turbidity. It shows that removing toxicity and eliminating evil are the prescription thought in treating epidemic disease of traditional Chinese medicine.

Treatment of COVID-19 guided by holistic view of traditional Chinese medicine--therapy aimed at both viral and host

The global outbreak of coronavirus disease 2019(COVID-19) has further spread, and there is an increasing number of confirmed cases in many countries. On February 28, 2020 of Geneva time, the World Health Organization has raised global risk level to the very high level in view of outbreak of COVID-19. Since some patients' condition appeared to deteriorate rapidly after infection of this 2019 novel coronavirus(2019-nCoV), a variety of treatments should be considered. Holistic view and syndrome differentiation are the two characteristics of traditional Chinese medicine(TCM). Therefore, under the guidance of the holistic view, syndrome diffe-rentiation of TCM has achieved good effects in the treatment of COVID-19. This treatment mainly aimed at eliminating pathogens and strengthening overall health, regulating the balance of body and coordinating various of functions of Zangfu organs. In addition, modern medical proposes host-directed therapy(HDT), a strategy aims to interfere with host cell mechanism, enhance immune responses, and reduce exacerbated inflammation. To some extent, the combined application of HDT and antiviral therapy is highly consistent with the therapeutic concept of the holistic view of TCM. Therefore, under the guidance of the holistic view, syndrome differentiation of TCM uses treatments, such as clearing heat, detoxification, relieving asthma, clearing damp and phlegm, together with Lianhua Qingwen Capsules, Maxing Shigan Decoction, and Haoqin Qingdan Decoction under the guidance of these therapeutic methods. These therapeutic methods and prescriptions intervened with both virus and host at the same time in the treatment of COVID-19, which has important implications for the effective clinical treatment of COVID-19.

Study on screening potential traditional Chinese medicines against 2019-nCoV based on Mpro and PLP

With the rapid outbreak of COVID-19, traditional Chinese medicine(TCM) has been playing an active role against the epidemic. However, the screening of TCM is limited by the development cycle and laboratory conditions, which greatly limits the screening speed. This study established optimization docking models and virtual screening to discovery potential active herbs for the prevention and treatment of the novel coronavirus based on molecular docking technology. The crystal structures of 3 CL protease(Mpro) and papain-like protease(PLP) were obtained from PDB database and homologous modeling respectively, and were used to conduct virtual screening of TCMD 2009 database by CDOCKER program. The ingredients scored in the top 100 were selected respectively, and the candidate herbs were ranked by the numbers of hit molecules. Based on Mpro inhibitors screening, 12 322 potential active components were obtained, and the representative active components included aster pentapeptide A, ligustrazine, salvianolic acid B, etc., and Zingiberis Rhizoma Recens, Asteris Radix et Rhizoma, Notoginseng Radix et Rhizoma, Chuanxiong Rhizoma, Salviae Miltiorrhizae Radix et Rhizoma, Zingiberis Rhizoma, Dianthi Herba, Rhei Radix et Rhizoma, Cistanches Herba were obtained. While 11 294 potential active ingredients were obtained by PLP inhibitor screening, representative active ingredients included gingerketophenol, ginkgol alcohol, ferulic acid, etc., and Codonopsis Radix, Notopterygii Rhizoma et Radix, Zingiberis Rhizoma Recens, Ginkgo Semen, Chuanxiong Rhizoma, Trichosanthis Fructus, Paeoniae Radix Alba, Psoraleae Fructus, Sophorae Flavescentis Radix, Notoginseng Radix et Rhizoma, Angelicae Sinensis Radix were chosen. By combining the diagnosis and treatment scheme of Hunan province's and angiotensin converting enzyme 2(ACE2) inhibitors screening from literature, present study also discussed the rational application of candidate herbs to this epidemic situation. Trichosanthis Fructus obtained by PLP inhibitors screening and Fritillaria verticillata obtained by ACE2 inhibitors screening were parts of the Sangbei Zhisou Powder and Xiaoxianxiong Decoction, which might be applicable to the syndromes of cough and dyspnea. Rhei Radix et Rhizoma screened by Mpro and Trichosanthis Fructus screened by PLP were contained in Maxing Shigan Decoction and Xuanbai Chengqi Decoction, and could be applied to the syndromes of epidemic virus blocking lung. Mori Folium, Lonicerae Japonicae Flos and Forsythiae Fructus obtained by ACE2 inhibitors screening were included in the Sangju Decoction and Yinqiaosan, which might be applicable to the syndromes of warm pathogen attacking lung and cough and dyspnea. The results of this study are intended to provide a reference for the further development of traditional Chinese medicine to deal with the new epidemic.

Ma Xing Shi Gan Decoction Protects against PM2.5-Induced Lung Injury through Suppression of Epithelial-to-Mesenchymal Transition (EMT) and Epithelial Barrier Disruption.

This research was designed to explore the effect of Ma Xing Shi Gan decoction (MXD) in alleviating particulate matter less than 2.5 μm in diameter (PM2.5) induced lung injury from the perspective of epithelial barrier protection and inhibition of epithelial-to-mesenchymal transition (EMT). Rats were exposed to PM2.5 to establish a lung injury model in vivo, and a PM2.5-stimulated primary cultured type II alveolar epithelial cell model was introduced in vitro. Our results indicated that MXD alleviated the weight loss and pathologic changes and improved the epithelial barrier dysfunction. MXD also significantly inhibited the TGF-β/Smad3 pathway, increased the level of ZO-1 and claudin-5, and reversed the EMT process. Notably, the protection of MXD was abolished by TGF-β in vitro. Our results indicated that MXD has a protection against PM2.5-induced lung injury. The proposed mechanism is reversing PM2.5-induced EMT through inhibiting TGF-β/Smad3 pathway and then upregulating the expression of tight-junction proteins.