Integrated Systems Biology and Chemical Biology Approach to Exploring Mechanisms of Traditional Chinese Medicines

After thousands of years of development, traditional Chinese medicines (TCMs) have evolved into a complete scientific system characterized by multiple components, targets, and pathways, which mediates numerous pharmacological activities and efficacies. The development of “-omics” technology, including systems biology and network pharmacology, has enabled the illustration of TCMs from a more systematic view. Although the network adequately reflects the overall philosophy of TCMs, its complexity hinders the relevant research to a hover. In addition, the strategies involved appear to be in contrast to the original concise and efficacious disease therapy oriented focus on classic Chinese material medica (CMM). Based on the established holistic view and reductionism, in this review, we discuss an integrated systems biology and chemical biology research approach that will facilitate and accelerate the understanding of the mechanisms of TCMs. Furthermore, we are optimistic that it will elucidate the associated interactions between active natural products and their targets, and ultimately improve the strategies for complex disease therapies.     

Anti-infectious efficacy of essential oil from Caoguo(Fructus Tsaoko)

OBJECTIVE: To evaluate the anti-infectious efficacy of essential oil extracted from Caoguo(Fructus Tsaoko).METHODS: Minimum inhibitory concentrations(MICs) against clinical isolates of three extracts andthe essential oil from Caoguo(Fructus Tsaoko) were determined by the agar dilution method. The anti-infectious efficacy of the essential oil was evaluated using a mouse peritonitis model which was infected with Staphylococcus aureus or Escherichia coli. The chemical components of the essential oil were identified.RESULTS: The results showed that the essential oil exhibited strong antibacterial activity in vitro, with MICs ranging from 22.49 to 1438.91 μg/m L. The results of in vivo anti-infectious efficacy showed that the Caoguo(Fructus Tsaoko) essential oil can protect the mice from Staphylococcus aureus or Escherichia coli infection. The compositions of the essential oil and relative component percentages were examined. A total of 32 compounds, were identified. The major compounds of essential oil were 1,8-cineole(25.92%) and geraniol(13.69%).CONCLUSION: Our findings suggest that Caoguo(Fructus Tsaoko) essential oil has broad-spectrum antibacterial properties. It warrants further investigation as an antibacterial agent targeting some bacterium with multi-drug resistance.     

Potential efficacy and mechanism of eight mild-natured and bitter-flavored TCMs based on gut microbiota: A reviewOA

The mild-natured and bitter-flavored traditional Chinese medicines(MB-TCMs) are an important class of TCMs that have been widely used in clinical practice and recognized as safe long-term treatments for chronic diseases. However, as an important class of TCMs, the panorama of pharmacological effects and the mechanisms of MB-TCMs have not been systemically reviewed. Compelling studies have shown that gut microbiota can mediate the therapeutic activity of TCMs and help to elucidate the core princi...     

Efficacy and safety of Xinglouchengqi decoction for acute ischemic stroke with constipation: study protocol for a randomized controlled trial

OBJECTIVE: To investigate the efficacy and safety of Xinglouchengqi(XLCQ) decoction in treatment of acute ischemic stroke with constipation.METHODS: In this prospective, multicenter, assessor-blinded, randomized controlled trial, 360 eligible participants will be randomized to the XLCQ group or the control group. Participants in the XLCQ group will receive XLCQ decoction, while those in the control group will undergo clysis therapy using glycerin enemas or oral administration of lactulose solution. Both groups will undergo a treatment period of(5 ± 2) d and a 1-month follow-up.The primary outcome measure will be the Constipation Scale score. The secondary outcome measures will include scores on the National Institutes of Health Stroke Scale, the Traditional Chinese Medicine(TCM) Stroke Scale, the Diagnostic Scale for TCM Syndromes of Ischemic Stroke and TCM Scale for Syndrome of Phlegm-heat and Fu-organ Excess.Therapeutic mechanism outcomes and safety outcomes will also be assessed. Assessments will be conducted at baseline, at the end of the treatment period, and at the follow-up. Moreover, daily visits will be scheduled to grade the status of constipation during the treatment period.DISCUSSION: The results of this study will provide scientific and objective data with which to assess the efficacy and safety of XLCQ decoction for patients with acute ischemic stroke and constipation.     

Comparative chemical characters of Pseudostellaria heterophylla from geographical origins of China

Objective: Pseudostellaria heterophylla has been paid more attention in recent years, mainly as a medicine food homology plant. The content determination of P. heterophylla is not specified in the Chinese Pharmacopoeia (version 2020). The environmental conditions in different production areas could exert an influence on the quality of P. heterophylla. The purpose of this study is to discriminate P. heterophylla collected from different geographical origins of China. Methods: In this study, the content of polysaccharide in 28 batches of P. heterophylla was determined using phenol-sulfuric acid. HPLC fingerprints were established under optimised HPLC-PDA methods. Subsequently, the similarity analysis (SA) and the quantification of heterophyllin B were analyzed. The metabolites of P. heterophylla were identified and evaluated using UHPLC-Q Exactive HF orbitrap MS system. Principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), hierarchical cluster analysis (HCA) and orthogonal PLS-DA (OPLS-DA) were performed based on all peak areas. Results: The polysaccharide content in Guizhou and Jiangsu was higher than that of other production areas, which varied significant from different origins. While the content of heterophyllin B in Anhui and Jiangsu was high. The correlation coefficients of HPLC fingerprints for 28 batches samples ranged from 0.877 to 0.990, and the characteristic map can be used to identify and evaluate the quality of P. heterophylla. The samples from Fujian, Guizhou, Jiangsu provinces can be relatively separated using multivariate statistical analysis including PCA, PLS-DA, HCA, OPLS-DA, indicating that their metabolic compositions were significantly different. Ultimately, a total of 15 metabolites which were filtrated by a VIP-value > 1 and a P-value ＜ 0.05 associated with the separation of different origins were identified. Conclusion: HPLC fingerprint was established to evaluate the quality and authenticity of P. heterophylla. The present work showed that the difference of geographic distributions had an influence on the internal chemical compositions. A sensitive and rapid untargeted metabolomics approach by UHPLC-Q Exactive HF orbitrap MS was utilized to evaluate P. heterophylla from different origins in China for the first time. Overall, this study provides insights to metabolomics of P. heterophylla and supplies important reference values for the development of functional foods.     

Comparison of clinical effectiveness of acupuncture and a Western drug on allergic rhinitis： study protocol for a randomized controlled trial

OBJECTIVE： To compare the efficacy of an acu- puncture regimen for persistent allergic rhinitis （PER）, aimed at improving a patient＇s mind or Shen in Traditional Chinese Medicine, to that of a sec- ond-generation H-receptor antagonist, cetirizine hydrochloride. METHODS： This multicenter, randomized, con- trolled clinical trial on PER will be conducted at three institutions in China. The total study period will be 9 weeks. After a 1-week preparatory screen- ing period, 240 eligible participants with PER willbe randomized to receive acupuncture or pharma- cotherapy （1： 1） for 4 weeks with a 4-week fol- low-up. The primary outcome will be changes in 7-day average total nasal symptom score. Second- ary outcome measures include rhinoconjunctivitis quality of life questionnaire score and total non-na- sal symptom score. RESULTS： The presence and seriousness of psycho- logical and emotional impairments should be con- sidered in therapeutic programs for allergic rhinitis. No clinical trial for treating allergic rhinitis via acu- puncture regulation of psychological and emotion- al activities has been reported. CONCLUSION： The findings of the trial will allow us to determine the effects of the mind （Shen）-regula- tion treatment approach. We will also be able to confirm if the effects of acupuncture are equivalent to those of the conventional drug cetirizine hydro- chloride.     

Words for Cover Figure

正Traditional Chinese medicines (TCMs) has a long history of treating and preventing diseases,but due to its complexity,the approaches to determine their quality and the TCM theory and compatibility rules remains ambiguous.Nowadays,a widely and cogent tool-Network pharmacology can be used to reflect pharmacologically active effects,mechanism of action and toxic activity in the field of TCMs scientific research.According to active ingredients with the relationship of quality and biological response (effect and safety under TCM theory and function),an integrated approach     

Some Novel Viewpoints on Physiology and Pathology of TCM Sphygmology

In Traditional Chinese Medicine(TCM),pulse manifestation are an essential method for clinicians to make accurate diagnosis while researches on pulse manifestation are also an important direction for the modernization of TCM.According to the viewpoints of TCM,the abnormality of qi,xue,yin and yang will lead to some alterations of pulse manifestations while by detecting these alterations of pulse manifestation,TCM researchers can not only conclude the abnormality of the qi,xue,yin and yang in the patients,make exact diagnose in TCM but also afford the just therapies.Our past researches had abstracted all metabolisms in our body into to pathways:energy metabolism which should be regarded as yang and stem cell proliferation&differentiation(SCPD)which should be regarded as yin.These two pathways support the metabolisms of local tissue and organs while arteries play vital roles for transportation of energy agents and stem cells to local tissue and organs.By detecting the alterations of pulse manifestations,clinician can conclude the alterations of energy metabolism and SCPD in body.Moreover,many novel parameters should be taken into consideration for describing the pulse manifestations and uncovering the physiology and pathology of pulse manifestations.     

Quercetin-3-O-β-D-glucopyranosyl-（4→1）-α-L-rhamnoside metabolites in the rat using UPLC-Q-TOF/MS

Ultraperformance liquid chromatography/quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF/MS） and the MetabolynxTM software, combined with mass defect filtering, were applied to identity the metabolites of quercetin-3-O-β-D-glucopyranosyl-（4→1）-α-L-rhamnoside（QGR） in rats after intravenous administration. MSE was used for simultaneous acquisition of precursor ion information and fragment ion data at high and low collision energy in one analytical run, which facilitated the rapid structural characterization of eight metabolites in rat plasma, urine and bile. The results indicated that methylation and glucuronidation were the major metabolic pathways of QGR in vivo. The present study provided important information about the metabolism of QGR which will be useful for fully understanding the mechanism of action of this compound. Furthermore, this work demonstrated the potential of the UPLC-Q-TOF/MS approach using Metabolynx for rapid and automated research of the metabolites of natural products.     

植物来源的新的抗肿瘤药物(英文)

Plants remain an important source of new drugs,new drug leads and new chemical entities.Plant based drug discovery resulted mainly in the development of anticancer and anti-infectious agents,and continues to contribute to the new leads in clinical trials.Natural product drugs play a dominant role in pharmaceutical care.Several plant-derived compounds are currently successfully employed in cancer treatment.There are many classes of plant-derived cytotoxic natural products studied for further improvement and development of drugs.New anticancer drugs derived from research on plant antitumor agents will be continuously discovered.The basic aim of this review is to explore the potential of newly discovered anticancer compounds from medicinal plants,as a lead for anticancer drug development.It will be helpful to explore the medicinal value of plants and for new drug discovery from them for the researchers and scientists around the globe.     

Research progress of Chinese herbal medicine compounds and their bioactivities: Fruitful 2020

Traditional Chinese medicines (TCMs) have continued to be a treasure trove. The study of chemodiversity and versatility of bioactivities has always been an important content of pharmacophylogeny. There is amazing progress in the discovery and research of natural components with novel structures and significant bioactivities in 2020. In this paper we review 271 valuable natural products, including terpenoids, steroids, flavonoids, phenylpropanoids, phenolics, nitrogen containing compounds and essential oil, etc., isolated and identified from TCMs published in journals of Chinese Traditional and Herbal Drugs (Zhong Cao Yao) and Chinese Herbal Medicines (CHMs), and focus on their structures, source organisms, and relevant bioactivities, paying special attention to structural characteristics of novel compounds and newly revealed pharmacological properties of known compounds. It is worth noting that natural products with antitumor activity still constitute the primary object of research. Among the reported compounds, two new triterpenoids, i.e., ursolic acid 3-O-β-cis-caffeate and mollugoside E, display remarkable cytotoxicity against PC-9 and HL-60 cell lines, respectively. Three known phenolic compounds, i.e., pyoluteorin, 4-hydroxy-3-methoxy cinnamaldehyde and 3,7-dimethoxy-5-hydroxy-1,4-phenanthrenequinone, exhibit significant cytotoxicity against multiple cell lines. Numerous studies on the free radical scavenging activity of reported compounds are currently underway. In vitro, three known phenolic compounds, i.e., 3,4-O-dicaffeoylquinic acid methyl ester, 3,4,5-O-tricaffeoylquinic acid methyl ester and arbutin, had more considerable antioxidant activities than vitamin C. The anti-inflammatory, anti-diabetic, hypolipidemic, neuroprotective and antimicrobial activities of isolated compounds are also encouraging. The structural characteristics and bioactivities of TCM compounds highlighted here reflect the enormous progress of CHM research in 2020 and will play a positive role in the future drug discovery and development. According to pharmacophylogeny, the phylogenetic distribution of compounds with different natures and flavors can be explored, with view to better mining TCM resources.     

Pathophysiological Characteristics of Phlegm-stasis Cementation Syndrome in Coronary Heart Disease: a Review and Update

The pathophysiological characteristics of Phlegm-stasis Cementation Syndrome in Coronary Heart Disease (CHD) has been summarized in this article. According to epidemiological investigations, phlegm-stasis cementation syndrome has become a dominant syndrome in CHD along with the improvement in living and dietary condition. The interaction between blood stasis and phlegm turbidity that is called Phlegmstasis Cementation Syndrome exists in CHD and other diseases. The bridge linked blood stasis and phlegm turbidity lies in the adversely effects of lipid metabolism disorder on platelet activation, vascular function and hemorheology indexes. Lipid metabolism disorder also can induce persistent inflammation including monocyte/macrophage activation and oxidative stress. Inflammation also is an important stimulating factor for atherosclerosis and the biology that underlies the complications of CHD, which belonged to the concept of “toxin” in Traditional Chinese medicines (TCM). On the other hand, the important function of inflammatory process on abnormal hemorheology, platelet activation and vascular dysfunction can be used to elucidate the basic pathogenetic condition of the toxin inducing blood stasis in TCM. Therefore, it is this pathological process that can be used to address the basic pathogenetic theory of phlegm turbidity inducing the symptom of toxin and blood stasis, and subsequently phlegm-stasis cementation in TCM. We deduced that lipid metabolic disturbance, inflammation activation, vascular dyfunction and hemorheological disorders could be as pathophysiological characteristics of Phlegm-stasis cementation syndrome.     

Challenges and strategies in progress of drug delivery system for traditional Chinese medicine Salviae Miltiorrhizae Radix et Rhizoma (Danshen)

Traditional Chinese medicines(TCMs), with a history of thousands of years, are widely used clinically with effective treatment. However, the drug delivery systems(DDSs) for TCMs remains major challenges due to the characteristics of multi-components including alkaloids, flavones, anthraquinones, glycosides,proteins, volatile oils and other types. Therefore, the novel preparations and technology of modern pharmaceutics is introduced to improve TCM therapeutic effects due to instability and low bioavailability of active ingredients. Salviae Miltiorrhizae Radix et Rhizoma, the radix and rhizomes of Salvia miltiorrhiza Bunge(Danshen in Chinese), is a well known Chinese herbal medicine for protecting the cardiovascular system, with active ingredients mainly including lipophilic tanshinones and hydrophilic salvianolic acids.In this review, this drug is taken as an example to present challenges and strategies in progress of DDSs for TCMs. This review would also summary the characteristics of active ingredients in it including physicochemical properties and pharmacological effects. The purpose of this review is to provide inspirations and ideas for the DDSs designed from TCMs by summarizing the advances on DDSs for both singleand multi-component from Danshen.     

Discovery and identification of quality markers of Sparganii Rhizoma based on zebrafish thrombosis model

Objective: The aim of the present study was to determine the Q-markers of Sparganii Rhizoma against thrombus through an integration of investigations on its antithrombotic effect, content determination and spectrum-effect correlation analysis. Methods: Based on the concept of Q-Marker, Sparganii Rhizoma was investigated for the identification of chemical component. The pharmacological effects on arachidonic acid-induced thrombosis in zebrafish were also investigated. The material basis in ethanol extract was determined by HPLC-UV. Furthermore, the potential Q-markers were analyzed and predicted according to the effect-chemical correlation analysis. Finally, the anti-thrombotic Q-markers were verified through the anti-thrombotic test of monomer components. Results: The model of thrombosis zebrafish was established with larvae exposed to 100 μmol/L arachidonic acid for 1 h. Nine ingredients in Sparganii Rhizoma were identified as 5-hydroxymethylfurfural, vanillic acid, ferulic acid, p-hydroxybenzaldehyde, p-hydroxybenzoic acid, vanillin, protocatechuic acid, p-coumaric acid and isoferulic acid. According to the determination effect of zebrafish thrombosis model and HPLC content analysis results, all the other contents present positive correlation except 5-hydroxymethylfurfural, and the P values of three representative potential Q-markers (ferulic acid, protocatechuic acid and p-coumaric acid) were 0.002, 0.001 and 0.026, respectively. Conclusion: Sparganii Rhizoma showed a dose-dependent effect on the recovery of reducing cardiac red blood cell on zebrafish model. Three phenolic acids (ferulic acid, protocatechuic acid and p-coumaric acid) were proved to possess the anti-thrombotic effects which could be regarded as the potential Q-markers for quality assessment of Sparganii Rhizoma.     

Progress in the design and quality control of placeboes for clinical trials of traditional Chinese medicine

In recent years, new preparations of traditional Chinese medicines(TCMs) have been developed, increasing the need for their clinical trials. Using placeboes rather than control drugs is increasingly popular in clinical trials of TCMs, as the therapeutic effects of the tested TCMs can be more properly judged. The basic attributes of TCM placeboes include similarity, safety, applicability and controllability. In particular,it is necessary to have similarities in appearance, color, smell and taste ...     

CASE STUDIES OF THE TREATMENT OF HYPOTHYROIDISM BY MERIDIAN THEORY OF CHINESE MEDICINE

Some patients with hypothyroidism still remain symptom after prolonged treatment with thyroxine. Alternative treatment needs to be explored. The treatment is described as overlapof acupunture, supplemented with electric acupuncture, magnetic acupuncture, ear acupuncture, herbaltreatment, and acupressure of thyroid. The result of two case studies will be discussed in the presentation.The theoretical basis for the approach will also be explored.In Chinese medicine, hypothyroidismis often defined as spleen deficiency in the early stage and can be treated with ISRQ recipes (Invigorating the Spleen and Replenishing the Qi). In the chronic stage, hypothyroidism can be seen as kidneydeficiency and can be treated with KRR (Kidney Reinforcing Regimen). Hypthyroidism symptoms aresometimes diffcult to treat. However, TCM (Traditional Chinese Medicine) diagnosis and treatmentare based on an overall analysis of the illness according to patients' condition. After successful treamentof TCM, patients can stop taking Thy     

Formulation optimization and characterization of transdermal film of curcumin by response surface methodology

Objective:India is referred as goldmine of herbal drugs but still lack of optimization of herbal drugs,which has kept us on the back foot.The rationale of the study is to prepare optimized transdermal drug delivery system of curcumin employing response surface methodology to study the collective effect of independent variables like concentration of ethyl cellulose,hydroxyl propyl methyl cellulose and dibutyl phthalate which significantly influenced characteristics like percentage elongation and in vitro drug release.Method:Twenty formulations containing varying concentrations of polymers and permeation enhancer were prepared using solvent casting technique.Result:The study revealed that the effect of dibutyl phthalate(DBP) concentration was the highest on percentage elongation(P 0.0001),while hydroxy propyl methyl cellulose(HPMC) concentration exhibited pronounced effect on drug release(P 0.0001) through dialysis membrane.Linear model fitted the best for curcumin release and elongation for all formulations.According to Derringer's desirability prediction tool,the composition of optimized film was found to be 242.14% of HPMC,109.59% of ethyl cellulose(EC),and 1.03% of DBP.Under these conditions,the optimized patch exhibited a predicted value of%elongation and in vitro drug release of 94.35% and 80.0306%,respectively,which was comparable to the actual values of percent elongation and in vitro drug release i.e.95.02% and 81.03% respectively.FTIR and thermal studies were also performed which revealed no interaction or complexation between drug and excipients.The ex vivo study performed using rat skin showed that the cumulative drug release from the optimized patch showed flux of(30.68±18) μg/cm~2/h.Conclusion:It can be concluded that in future if proper optimization of herbal formulations is carried out,they can become the first choice for patients as compare to synthetic drugs.     

基于药代动力学和荧光光谱研究监测联合用药中游离态华法林

Objective: Monitoring the unbound drug concentration in blood in combination therapy is necessary,because its concentration determines the efficacy of drug therapy. This study was designed to explore the effect of Dan Hong Injection(DHI) on the unbound warfarin using two approaches including an in vivo pharmacokinetic and in vitro fluorescence studies.Methods: The effect of DHI on the pharmacokinetic properties of the unbound warfarin was investigated by a microdialysis sampling method coupled with LC–MS/MS. The effect of DHI and salvianolic acid B(Sa B) on warfarin binding with bovine serum albumin(BSA) was conducted by fluorescence spectrometry.Results: The AUC_(0-tn)of warfarin with DHI group was higher than that of warfarin alone group. The result showed that DHI could increase the concentration of unbound warfarin in rat blood, which may be due to the competition between warfarin and DHI as well as its components binding to serum albumin. The competition process was demonstrated by fluorescence study.Conclusion: Combination therapy of DHI with warfarin could enhance the release profile of warfarin from serum protein.     

Reduning Injection prevents carrageenan-induced inflammation in rats by serum and urine metabolomics analysis

Objective: To elucidate the anti-inflammatory mechanism of Reduning Injection (RDN) by analyzing the potential biomarkers and metabolic pathways of the carrageenan-induced inflammatory model from the overall metabolic level. Methods: Rat inflammatory model was established by carrageenan. UPLC-Q-TOF/MS was used to detect and analyze changes of endogenous metabolites in the serum and urine of carrageenan-induced inflammatory rats. Combined with multivariate analysis and databases analysis, inflammatory-related potential biomarkers were screened and identified to analyze possible metabolic pathways. The reliability and biological significance of these biomarkers was verified by metabolic network analysis and correlation analysis with pharmacodynamic indicators. Results: A total of 16 potential biomarkers were screened and identified by multivariate analysis and metabolite databases, among which 13 species could be adjusted by RDN. The metabolism pathway analysis revealed that histidine metabolism, sphingolipid metabolism, and tyrosine metabolism were greatly disturbed. Their biomarkers involved urocanic acid, sphingosine, and norepinephrine, all of which showed a callback trend after RDN treatment. The three biomarkers had a certain correlation with some known inflammatory-related small molecules (histamine, arachidonic acid, Leukotriene B4, and PGE2) and pharmacodynamic indicators (IL-6, IL-1β, PGE2 and TNF-α), which indicated that the selected biomarkers had certain reliability and biological significance. Conclusion: RDN has a good regulation of the metabolic disorder of endogenous components in carrageenan-induced inflammatory rats. And its anti-inflammatory mechanism is mainly related to the regulation of amino acid and lipid metabolism. This research method is conducive to the interpretation of the overall pharmacological mechanism of Chinese medicine.     

THE APPLICATION OF THE CODE MESSAGES THEORY IN ACUPUNCTURE AND MOXIBUSTION

The code message is the language of the human body communication systems.Each organ has a main code and each message has a special code. These codes resemble the computer codes. The messages can be from different kinds of energy:such as: Electrical, Magnetic, Electromagnetic,Chemical, Thermic, Gravity & antigravity, Light,Sound vibration and motor, etc. These messages are sent by specialized cells(transmitters)through the communication system tospecialized receptors which can perform the transformation and the transportation and code modifica-tion of the message energy and the message to another energy and code understandable by the masterof the human body "the Brain". "The Brain" will analyse the message and responds accordingly by sending order messages to dif-ferent parts of the body following the same role, i. e., by an electrical messages which can be trans-formed to another type of energy messages, like, chemical, motor, thermal, etc. by special receptorsand transmitters in the organ or the related tissues.