Model informed precision medicine of Chinese herbal medicines formulas-A multi-scale mechanistic intelligent model

Recent trends suggest that Chinese herbal medicine formulas(CHM formulas)are promising treatments for complex diseases.To characterize the precise syndromes,precise diseases and precise targets of the precise targets between complex diseases and CHM formulas,we developed an artificial intelligence-based quantitative predictive algorithm(DeepTCM).DeepTCM has gone through multilevel model calibration and validation against a comprehensive set of herb and disease data so that it accurately captures the complex cellular signaling,molecular and theoretical levels of traditional Chinese medicine(TCM).As an example,our model simulated the optimal CHM formulas for the treatment of coronary heart disease(CHD)with depression,and through model sensitivity analysis,we calculated the balanced scoring of the formulas.Furthermore,we constructed a biological knowledge graph representing interactions by associating herb-target and gene-disease interactions.Finally,we experimentally confirmed the therapeutic effect and pharmacological mechanism of a novel model-predicted intervention in humans and mice.This novel multiscale model opened up a new avenue to combine“disease syndrome”and“macro micro”system modeling to facilitate translational research in CHM formulas.

Analysis of Adverse Reactions in the Treatment of COVID-19 with Three Chinese Patent Medicines and Three Herbal Formulas

Objective To explore the rules and characteristics of the adverse drug reactions(ADRs)of three Chinese patent medicines and three herbal formulas for the treatment of COVID-19,and to provide a reference for clinical safe medication.Methods The cases and ADR reports of the three Chinese patent medicines and three herbal formulas in PubMed,Web of Science,Springer Link,CNKI,Wanfang and VIP database were retrieved from December 2019 to May 2021.Then we extracted and analyzed the effective information included in the literature.Results and Conclusion According to the pre-developed retrieval plan,a total of 136 documents were obtained,and a total of 6 documents met the inclusion criteria finally.553 patients used three Chinese patent medicines and three herbal formulas,and there were 133 cases of adverse reactions.The adverse reactions of patients taking the three Chinese patent medicines and three herbal formulas can all be explained under the theory of traditional Chinese medicine,and the adverse reactions can be eliminated by adding or subtracting the flavor of the medicine or stopping the medicine.

Progress on traditional Chinese medicine in improving hepatic fibrosis through inhibiting oxidative stress

Hepatic fibrosis is a common pathological process that occurs in the development of various chronic liver diseases into cirrhosis and liver cancer,characterized by excessive deposition of the extracellular matrix.In the past,hepatic fibrosis was thought to be a static and irreversible pathological process.In recent years,with the rapid development of molecular biology and the continuous in-depth study of the liver at the microscopic level,more and more evidence has shown that hepatic fibrosis is a dynamic and reversible process.Therefore,it is particularly important to find an effective,simple,and inexpensive method for its prevention and treatment.Traditional Chinese medicine(TCM)occupies an important position in the treatment of hepatic fibrosis due to its advantages of low adverse reactions,low cost,and multi-target effectiveness.A large number of research results have shown that TCM monomers,single herbal extracts,and TCM formulas play important roles in the prevention and treatment of hepatic fibrosis.Oxidative stress(OS)is one of the key factors in the occurrence and development of hepatic fibrosis.Therefore,this article reviews the progress in the understanding of the mechanisms of TCM monomers,single herbal extracts,and TCM formulas in preventing and treating hepatic fibrosis by inhibiting OS in recent years,in order to provide a reference and basis for drug therapy of hepatic fibrosis.

Comparison of Traditional Chinese Medicine with Western Medicine Cancer Therapy

The interactions among drugs,tumor and host are critical for a response to therapy and for outcome.Anticancer herbs used in Chinese medicine are classified into 4 groups based on their target (tumor,patient and drug) as follows:eliminating pathogenic factors,strengthening the body resistance,enhancing effects of chemotherapy and detoxication of chemotherapy. Correspondingly,anticancer drugs used in Western medicine can be classified into 4 groups as follows:cytotoxic drugs,biological response modifiers,chemosensitizers and chemoprotectants. Based on the theory of Chinese medicinal formulas,prescriptions are composed of four constituents,namely,primary constituent (main component of the formula prescription),minister constituent (second component of formula prescription),adjuvant constituent (adjuvant component of the formula prescription) and messenger constituent (component making the formula prescription targeting pathological tissues).To control the interaction among drugs and to modulate the interaction among the tumor,patient and drugs,we suggest that combined therapy for Western medicine might include 4 constituents,i.e.,primary,cooperative,adjuvant and modulatory constituent. Cytotoxic drugs frequently are used as primary and cooperative constituents,whereas biological response modifiers and biochemical modulators are usually regarded respectively as adjuvant drugs and modulatory constituents. We believe these new concepts may be helpful for the aim of appropriately designing,evaluating or providing combination therapy.

Prescription analysis of traditional chinese medicine for COVID-19treatment

Background:Coronavirus disease 2019 is still spreading all over the world and without any specific medicine.Traditional Chinese medicine has played an important role in the control of epidemics in China and accumulated many experiences.The aim of this study is to summarize the law of traditional Chinese medicine and provide reference for coronavirus disease 2019 traditional Chinese medicine treatment.Methods:We collected the treatment plans of traditional Chinese medicine for coronavirus disease 2019 in 24 provinces of China to evaluate the basic Chinese medicine formulas,and the efficacy types,frequency,“Four Characters”,“Five Tastes”,“Channel Tropism”of herbal medicines.Combination rules between medicines were calculated by Apriori algorithm and Clementine12.0.Results:The formulas for“Relieving Exterior Syndrome”,“Expelling Dampness”,“Clearing Heat”and“Supplementing”have highest proportion.In prevention period and medical observation period,the medicines mainly have effect for“Clearing Heat”,“Relieving Exterior Syndrome”and“Supplementing”.In treatment period,medicines for“Clearing Heat”,“Relieving Superficies”and“Relieving Dampness”had higher frequency.The“Four Characters”of Chinese medicines in all treatment plans were mainly“Cold”and“Warm”.Medicines in the treatment plans always belong to“Pungent Taste”,“Bitter Taste”and“Sweet Taste”.For“Channel Tropism”,most medicines turned over to the“Lung”,“Stoma”and“Spleen”.The common medicine combinations in the recommended formulas during the prevention period and medical observation period were medicines for“Qi-Supplementing”and“Relieving Superficies”.In treatment period(mild,moderate,severe/critical),medicines for“Dampness Expelling”,“Relieving Superficies”and“Qi-Supplementing”were combined in a high frequency.In recovery period,the medicines for“Dispelling Dampness”combined the medicines for“Promoting Blood Circulation”with highest frequency.Conclusions:We found the characteristics of medicine and prescription rules of traditional Chinese medicine for the treatment of coronavirus disease 2019 and provided scientificity and effectiveness of it.More importantly,it provides reference for the development of new clinical prescriptions for coronavirus disease 2019.

Research and Development of Skincare Products Based on the Theory of Traditional Chinese Medicine

The application of traditional Chinese medicine in skincare formula development was expounded from the views of“symptom,theory,method,prescription,medicine and effect”.Traditional Chinese medicine prescriptions were improved according to the laws and regulations for China’s cosmetic industry and by the modern scientific and technological means,which had important guiding significance for the research and development of plant-based functional skincare products.The problems in concept claim and quality control standard,and the problems of market confusion,which were ascribed to the lack of basic research in the application of Chinese herbal cosmetics,were pointed out.The future development direction of plant-based functional cosmetics guided by TCM theory was prospected.

Chinese herbal formulae defend against Mycoplasma gallisepticum infection

Mycoplasma gallisepticum HS strain(MG-HS)is a pathogen that causes chronic respiratory disease(CRD)in chicken,which is characterized by host respiratory inflammatory damage,brings huge economic losses to the poultry industry.Recently,emerging Chinese herbal medicines(CHM)have been used to treat CRD.This study was aimed to investigate the preventive and therapeutic effects and their potential mechanisms of Chinese herbal medicinal formulae(CHMF),which consisted of 10 kinds of Chinese herbal medicine including Scutellaria,Houttuynia cordate and licorice,on MGinduced CRD in chickens.With respect to the preventive effect,the results showed that CHMF could effectively recover the MG-induced decrease on body weight and feed conversion ratio.Histopathological analysis showed that both prevention and treatment of CHMF could significantly alleviate the severe respiratory inflammation induced by MG infection.Moreover,compared with the MG infection group,both the prevention groups and the treatment groups of CHMF could effectively reduce the expression of MG adhesion protein(p MGA1.2)to inhibit the proliferation of MG,and thus effectively inhibit the expression of MG-induced inflammatory factors interleukin-1β(IL-1β)and tumour necrosis factor-α(TNF-α).In summary,these findings confirm that CHMF can protect chickens from various tissue damage caused by MG infection and has no adverse effects on the performance of chickens in the short term.And its efficacy against MG is equal to or better than that of tiamulin.

The traditional Chinese medicines treat chronic heart failure and their main bioactive constituents and mechanisms

Chronic heart failure(CHF)is a severe public health problem with increasing morbidity and mortality,any treatment targeting a single session is insufficient to tackle this.CHF is characterized by reduced cardiac output resulting from neurohumoral dysregulation and cardiac remodeling,which might be related to oxidative stress,inflammation,endoplasmic reticulum stress,apoptosis,autophagy,mitochondrial function,and angiogenesis.These molecular mechanisms interact with each other through crosstalk.Historically,Chinese medicinal herbs have been widely applied in the treatment of CHF,and therapeutic effects of Chinese medicinal herbs and their ingredients have been scientifically confirmed over the past decades.Traditional Chinese medicine(TCM)with multiple components can confront the different pathogenesis of CHF through multiple targets.This review analyzes commonly used TCM patent drugs and TCM decoctions that are applicable to different stages of CHF based on clinical trials.Diverse bioactive ingredients in Chinese medicinal herbs have been found to treat CHF via multiple molecular mechanisms.This review comprehensively covers the key works on the effects and underlying mechanisms of TCM,herbal ingredients and synergistic effects of constituent compatibility in treating CHF,providing additional ideas to address this threat.

Effect of the Fu Zheng Method Applied by Hong-Feng CHEN on the Quality of Life in TNBC Patients and Empirical Research Based on Data Mining

Objective To preliminarily evaluate the efficacy of the Fu Zheng method(supporting resistance against pathogenic factors)applied by Professor Hong-Feng CHEN in improving the quality of life in patients with triple-negative breast cancer(TNBC)to collect and organize the traditional Chinese medicine(TCM)formulas applied by Professor Hong-Feng CHEN in the treatment of TNBC in order to explore the patterns in prescription.Methods The Functional Assessment of Cancer Therapy-Breast scale(FACT-B V4.0)were collected before and after treatment;the database and data mining platform for prescribed TCM formulas were constructed using Microsoft SQL Server 2005,and the patterns in drug pairing and combination were summarized by correlation analysis of data mining.Results The formulas improved the mean scores of the patients’physical well-being,social/family well-being,emotional well-being,physical function well-being and additional concerns(P<0.01);the drug combinations and pairs frequently used by Professor Hong-Feng CHEN were summarized.Conclusion The TCM formulas applied by Professor Hong-Feng CHEN can alleviate adverse physiological reactions,improve psychological conditions and improve function in patients.The formulas take spleen invigoration and stomach nourishment as well as blood circulation promotion and stagnation dissipation as the therapeutic principles,with simplicity in prescription and focus on care and protection the foundation of acquired constitution.

Network Pharmacology in Research of Chinese Medicine Formula: Methodology, Application and Prospective

Chinese medicine(CM) is usually prescribed as CM formula to treat disease. The lack of effective research approach makes it difficult to elucidate the molecular mechanisms of CM formula owing to its complicated chemical compounds. Network pharmacology is increasingly applied in CM formula research in recent years, which is identified suitable for the study of CM formula. In this review, we summarized the methodology of network pharmacology, including network construction, network analysis and network verification. The aim of constructing a network is to achieve the interaction between the bioactive compounds and targets and the interaction between various targets, and then find out and validate the key nodes via network analysis and network verification. Besides, we reviewed the application in CM formula research, mainly including targets discovery, bioactive compounds screening, toxicity evaluation, mechanism research and quality control research. Finally, we proposed prospective in the future and limitations of network pharmacology, expecting to provide new strategy and thinking on study for CM formula.

Traditional Chinese medicine for prevention and treatment of hepatocellular carcinoma: A focus on epithelial-mesenchymal transition

Hepatocellular carcinoma(HCC)is one of the most prevalent malignant cancers worldwide.Epithelialmesenchymal transition(EMT),which endows epithelial cells with mesenchymal properties,plays an important role in the early stages of metastasis.Conventional cancer therapies have promising effects,but issues remain,such as high rates of metastasis and drug resistance.Thus,exploring and evaluating new therapies is an urgent need.Traditional Chinese medicines(TCMs)have been acknowledged for their multi-target and coordinated intervention effects against HCC.Accumulating evidence indicates that TCM can inhibit the malignancy of cells and the progression of EMT in HCC.However,studies on the effects of TCM on EMT in HCC are scarce.In this review,we summarized recent developments in anti-EMT TCMs and formulae,focusing on their underlying pharmacological mechanisms,to provide a foundation for further research on the exact mechanisms through which TCM affects EMT in HCC.

An Overview of Epigenetics in Chinese Medicine Researches

Chinese medicine（CM） has contributed to human health care for several thousand years and is still popular in Asian countries. But the mechanisms underlying CM remain obscure, and need to be clarified by modern biological subjects and methods. Recently, CM researches on epigenetics have gained obvious improvement following rapidly developed molecular technologies. In this review, we revealed mutual characteristics of epigenetics and CM, such as holism, yin-yang dynamic nature, reversibility and balance, and visceral manifestation. Moreover, epigenetic modifications, including DNA methylation, histone post-transcriptional modifications, micro RNA interference, etc. may help explore the molecular basis of CM syndrome classification, and mechanisms of Chinese herbal medicine（CHM）, CHM compounds and Chinese herbal formulae activities. Meanwhile, CM and epigenetics might promote each other and jointly develop following the continuous progress of epigenetics in CM researches.

Interactions Between Traditional Chinese Medicine and Anticancer Drugs in Chemotherapy

Herbal medicines, including traditional Chinese medicines(TCMs), have been used in Eastern countries for treating diseases such as cancer for thousands of years. With the growing knowledge of tumorigenesis and cancer therapy, some natural compounds have been developed as clinical anticancer drugs. In addition, many compounds and TCMs have been characterized as complementary and alternative treatments,with synergetic effects on enhancing the efficacy or reducing the side effects of the therapeutics. In this review, we summarized the recent studies focusing on the combination of natural compounds or TCM decoction with chemotherapeutics. The detailed mechanisms of action of the combinations and the application of analytical methods on TCM development are also discussed.

Exploring Traditional Chinese Medicine by A Novel Therapeutic Concept of Network Target

Traditional Chinese medicine（TCM） holds a holistic theory, and specializes in balancing disordered human body using numerous natural products, particularly Chinese herbal formulae. TCM has certain treatment advantages for patients suffering from various complex diseases. However, due to the complex nature of TCM, it remains difficult to unveil such holistic medicine by the current reductionism research strategies, which treat both herbal ingredients and targets in isolation. Recently, an emerging network pharmacology approach has been introduced to tackle this bottleneck problem. A TCM-derived novel therapeutic concept, ＂network target＂, which is different from the Western medicine＇s ＂onetarget＂ concept, has been proposed from China. The network target strategy is able to illustrate the complex interactions among the biological systems, drugs, and complex diseases from a network perspective, and thus provides an innovative approach to access ancient remedies in a precision manner and at a systematic level, which also highlights TCM＇s potential in current medical systems.

Pharmacologic mechanisms mining and prediction of Xiaoer Qixing Cha Formulae in the treatment of infantile functional dyspepsia based on chemical analysis by UPLC-QTOF/MS and interactive network pharmacology

Objective: To explore the main chemical compounds in Xiaoer Qixing Cha Formulae (XQCF), and investigate its mechanisms for the treatment of infantile functional dyspepsia (IFD). Methods: The chemical components were identified by UPLC-QTOF/MS analytic technique. Targets of the compounds were screened from TCMSP and SWISS database, and disease targets were screened from OMIM and TTD online database. Candidate targets of compounds were mapped to the disease targets as predict therapeutic targets for XQCF. Several networks were constructed and analyzed by Cytoscape ver. 3.2.1. Meanwhile, prescription compatibility in XQCF was interpreted from the network perspective based on distribution of the number of targets. Furthermore, Gene Ontology (GO) enrichment analysis and KEGG pathway analysis were operated via Clue Go to illustrate complex relationships between the potential targets and pharmacological mechanisms. Results: A total of fifty-three compounds were recognized or tentatively characterized belonging to XQCF based on MS data and online chemical database. Sixty-three therapeutic targets were screened. AKT1, FOS, SLC6A4, COMT and 5-HT receptors were focused as therapeutic targets of XQCF. Pathways including carbohydrate digestion and absorption, serotonergic synapse, calcium signaling pathway and cAMP signaling pathway were predicted as significant regulatory pathways. The results indicated that the predicted targets and pathways related in brain-gut axis to a great extent, which could be potential pharmacological mechanism of XQCF for the treatment of IFD. Conclusions: The findings in this study provided the experimental and theoretical basis for further research for XQCF. Those also illustrated a reasonable method worth intensive study on pharmacodynamic mechanisms of TCM Formulae.

Dissecting the underlying pharmaceutical mechanism of Danggui Buxue decoction acting on idiopathic pulmonary fibrosis with network pharmacology

Backgroud:Danggui Buxue decoction(DBD),a classical prescription in traditional Chinese medicine,has been found to have protective effect on bleomycin-induced pulmonary fibrosis in rats by reducing alveolar inflammation and fibrosis.However,the biological activity of individual chemical components and mechanism of action of whole formula are not clear.Methods:Potential targets of active ingredients of DBD were collected through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and SymMap database.Target genes related to idiopathic pulmonary fibrosis were obtained from the Online Mendelian Inheritance in Man database,Therapeutic Targets Database and Gkb database.Then,the common targets were obtained by overlapping the potential targets of active ingredients in DBD and diseases related targets.The selected targets were subjected to Kyoto Encyclopedia of Genes and Genomes signaling pathway and Gene Ontology analysis,and the network map of active component-target-pathway was established using Cytoscape 3.7.1 software.The active components of DBD with most targets were selected for fibrosis-related marker verification.The mRNA and protein expression of fibrosis markers,α-smooth muscle actin,collagen 1 and fibronectin,were detected in TGF-β1-induced fibroblast cell line after treatment with the active components.Results:The 14 active ingredients,such as quercetin and kaempferol,were screened from DBD.It acts on 26 targets like estrogen receptor 2 and prostaglandin-endoperoxide synthase 2,and mainly involves 38 signaling pathways such as cell inflammation and autophagy.Kaempferol and quercetin are the two compounds with the highest network regulation,which can inhibit the transformation of fibroblasts into myofibroblasts and reduce the expression of fibrosis markersα-smooth muscle actin,collagen 1 and fibronectin.Conclusion:The integration mode of multi-component,multi-target,multi-channel and mechanism of DBD in the treatment of idiopathic pulmonary fibrosis are predicted by means of network pharmacology.Our study could indicate the direction of further anti-fibrotic mechanism research.

Is the Chinese Medicinal Formula Guipi Decoction(归脾汤) Effectiveas AnAdjunctive Treatment for Depression？AMeta-Analysis of Randomized Controlled Trials

Objectives： To evaluate the effectiveness and safety of Guipi Decoction（归脾汤, GPD） as an adjunctive in the treatment of depression. Methods： A review of all relevant studies retrieved from a search of the following databases were conducted without any language restriction： Excerpt Medica Database（EMBASE）, Pub Med, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure（CNKI）, VIP Information, Wanfang Data, and the Chinese Biomedical Literature Database. Papers published until February 2013 were taken into consideration. The analysis was performed using the Cochrane software Revman 5.1. Results： Nine randomized controlled trials involving 620 patients with depression were included in this review. The meta-analysis revealed that compared with antidepressant therapy alone, treatment with a combination of GPD and an antidepressant drug significantly improved the symptoms of depression [weighted mean difference（WMD）： –3.09; 95% confidence interval（CI）： –4.11 to –2.07] and increased the rates of effectiveness（OR： 4.75; 95% CI： 2.66–8.51） as well as recovery（OR： 1.73; 95% CI： 1.17–2.56）. The adverse effects of GPD were not found to be significant in these studies. Conclusions： The findings of this meta-analysis were in keeping with the notion that GPD formulations were effective in the treatment of depression without causing any severe adverse effects. However, currently available evidence was of low quality and therefore inadequate to justify a strong recommendation of using GPD formulations in the management of depression.

Effects of Qingre Huoxue Jiedu Formula on Nerve Growth Factor-Induced Psoriasis

Objective:To elucidate the mechanisms of 4 effective components from a Chinese medicine formula,namely Qingre Huoxue Jiedu Formula(QHJ heat-and toxin-clearing and blood-activating formula),in the treatment of nerve growth factor(NGF)-induced psoriasis.Methods:Keratinocyte proliferation and T cell proliferation models were developed using NGF.An NGF solution(NGF+DMEM,100 ng/mL)was added to all induced groups and treated groups and were cultured for 24 h,while a solution with NTRK1 antagonist(K252 a+DEME,300 nmol/L)was added and cultured for 1 h.The models were used to evaluate the effects of the treatment with each of the 4 components of QHJ,namely shikonin,paeonol,astilbin and ursolic acid.Cell apoptosis and proliferation were measured by flow cytometry analysis and CCK8 assay,respectively.The mRNA expression levels of Bax,Bcl-xl,and NGF receptor(NGFR)were assessed by quantitative real-time PCR(qRT-PCR)and Western blot analysis,respectively.Results:(1)All QHJ-treated groups showed significantly increased cell apoptosis and inhibition of cell proliferation compared with the NGF-induced groups(P<0.05).In addition,treatment with QHJ plus NTRK1 significantly enhanced cell apoptosis and inhibition of cell proliferation compared with cells treated with QHJ only(P<0.05),particularly in cells treated with ursolic acid.(2)QHJ-treated groups showed higher protein expression levels of Bax,Bcl-xl compared with other groups(P<0.05).Additionally,treatment with QHJ plus NTRK1 significantly increased the protein expression levels of Bax,Bcl-xl and NGFR compared with those treated with QHJ only(all P<0.05),especially in those treated with shikonin.Conclusion:The action mechanism of QHJ on psoriasis might be through enhancing cell apoptosis and inhibition of cell proliferation,and upregulating the expression level of Bax,Bcl-xl and NGFR.

Efficacy and Safety of Qiaoshao Formula(翘芍方) on Patients with Lifelong Premature Ejaculation of Gan(Liver) Depression and Shen(Kidney) Deficiency Syndrome:A Randomized Controlled Trial

Objective： To observe the efficacy and safety of Qiaoshao Formula（翘芍方, QSF） on patients with lifelong premature ejaculation（LPE） of Gan（Liver） depression and Shen（Kidney） deficiency syndrome. Methods： A total of 60 LPE patients were randomly divided into treatment（QSF） and control（dapoxetine） groups. The treatment group received QSF twice a day and the control group received dapoxetine 1 to 2 h prior to planned sexual intercourse for 4 weeks. The outcomes included intra-vaginal ejaculation latency time（IELT）, premature ejaculation diagnostic tool（PEDT）, clinical global impression of change（CGIC）, scores of Chinese medicine symptoms（CMSS）, sex life satisfaction（SLS） and adverse events（AEs）. Results： In the treatment group, the median IELT was 3 min vs. 1.5 min before and after treatment（P〈0.05）. PEDT in the treatment group was reduced to 11.76±1.68 from 15.83±2.30 after treatment（P〈0.05）. Besides, patient＇s SLS was improved from 1.30±0.05 to 6.30±0.04（P〈0.05）, and spouse＇s SLS was increased from 1.30±0.08 to 6.10±0.06（P〈0.05）; CMSS was decrease from 14.86±3.02 to 9.62±2.87（P〈0.05）. In addition, no significant AE was observed in both groups. Conclusion： QSF may be effective and safe on LPE patients with Gan depression and Shen deficiency syndrome.