Advances in Research Methods of Pharmacodynamic Substances in Traditional Chinese Medicines and Their Application in the Teaching of Traditional Chinese Medicine Analysi

With the continuous progress of science and technology,the research methods of pharmacodynamic substances in traditional Chinese medicine are developing,and the application of these methods in teaching is becoming more and more extensive.By introducing these research methods into the classroom,teachers can help students to deeply understand the nature and mechanism of action of pharmacodynamic substances in traditional Chinese medicine,and improve their interest in and knowledge of traditional Chinese medicine.This paper introduces the definition of pharmacodynamic substances in traditional Chinese medicine,research methods,and their application in the teaching of traditional Chinese medicine analysis.

Methodological survey of using Bayesian Network for predicting pharmacology-based bioactivities of Chinese medicines:a scoping review

Background:It seems to be numerous unclear black-box mechanisms of Chinese Medicines(CMs)with multiple bioactivities in the real-world clinical practice.Meanwhile,prior prediction is necessary before the implementation of pharmacodynamics-pharmacokinetics-based researches.With emergent ML techniques for TCM domain,Bayesian Network(BN)has shown its potentials for CM-bioactivity prediction and syndromes identification in Traditional Chinese Medicine(TCM),benefited from many advantages,such as flexibility in addressing,data-driven and probability-based inference under complex uncertainty.Although BN has been extensively used in TCM,the scarcity of researches on refining methodological features of BN-modelling for optimization poses a significant challenge.Our goal is to present methodological overview of BN-modelling for CM-bioactivities prediction towards pharmacology,which tends to acquire a sequence of intimations for boosting in-depth and optimized CM-BN collaboration based on detected gaps.Methods:We performed systematic search of 13 databases from their inception to November 10th 2022 regardless of language written,which excluded unindexed journals and clinical trial registries,using the 3 keywords(CM,Pharmacology,BN).And full-text original researches with the given subject were under consideration.Afterwards,selection of eligible studies,data refinement and inspection were totally conducted by 6 review authors.Results:A total of 7 studies involving 17 BN models were included for synthesis and refinement,based on existing literatures and databases with 2 modelling functions:regression and tagging.There were 3 prediction patterns:property-bioactivity,efficacy-bioactivity and constituent-bioactivity inference,covering 8 feature-utilized efficacies,5 feature-utilized properties and 10 feature-utilized constituents.Thereafter,without an independent validation dataset,established BNs were mostly utilized to predict the root-node probabilities of unknown data.Indeed,incomplete report on modelling samples,directed acyclic graphs,conditional probability tables and algorithms hindered us from gathering information.Conclusion:A spot of studies were found in this work.And current evidence suggested that some breakthroughs should be achieved in CM-BN integration in the future.At last,to our knowledge,we preliminarily proposed certain recommendations and elicited implications for future work.

The role of autophagy in the treatment of osteoporosis by Chinese medicines(natural)

Osteoporosis is one of the common orthopaedic diseases,characterised by increased bone fragility due to reduced bone mass and microstructural degeneration,posing a great threat to patients’quality of life and safety.In recent years,Chinese medicine(natural)has had a unique advantage in the treatment of osteoporosis and has shown good efficacy.Autophagy is an inherent cellular survival mechanism for the removal and recycling of damaged proteins and organelles and plays an important role in maintaining the stability of the intracellular environment and organ function.Therefore,this article aims to provide a comprehensive review of these Chinese medicines(natural)for the treatment of osteoporosis through autophagy.They have been intensively studied and reported to have effects such as promoting osteogenesis and anti-bone resorption.The Chinese medicines include plants such as Cistanche deserticola,Epimedium,Curculigo orchioides Gaertn,Achyranthes bidentata Blume,Leonurus japonicus Houtt,Ginseng,Chuanxiong Rhizome,Eucommia ulmoides,Morindae Officinalis Radix,Curcuma longa,Polygoni Cuspidati Rhizoma et Radix,Anemarrhena asphodeloides Bunge,Salvia miltiorrhiza Bge and Pueraria Lobata,thus providing evidence for the use of alternative herbal therapies for the effective treatment of osteoporosis.

Applications of HPLC/MS in the analysis of traditional Chinese medicines

In China, traditional Chinese medicines （TCMs） have been used in clinical applications for thousands of years. The successful hyphenation of high-performance liquid chromatography （HPLC） and mass spectrometry （MS） has been applied widely in TCMs and biological samples analysis. Undoubtedly, HPLC/MS technique has facilitated the understanding of the treatment mechanism of TCMs. We reviewed more than 350 published papers within the last 5 years on HPLC/MS in the analysis of TCMs. The present review focused on the applications of HPLC/MS in the component analysis, metabolites analysis, and pharmacokinetics of TCMs etc. 50% of the literature is related to the component analysis of TCMs, which show that this field is the most popular type of research. In the metabolites analysis, HPLC coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry has been demonstrated to be the powerful tool for the characterization of structural features and fragmentation behavior patterns. This paper presented a brief overview of the applications of HPLC/MS in the analysis of TCMs. HPLC/MS in the fingerprint analysis is reviewed elsewhere.

Insight into Medicinal Chemistry Behind Traditional Chinese Medicines: p-Hydroxybenzyl Alcohol-Derived Dimers and Trimers from Gastrodia elata

From an aqueous extract of“tian ma”(the steamed and dried rhizomes of Gastrodia elata),ten new compounds gastrodiben-zins A−D(1−4)and gastrotribenzins A−F(5−10),along with known analogues(11−20),having structure features coupling between two and three p-hydroxybenzyl-derived units via carbon-and/or ether-bonds,were isolated and characterized by spectroscopic data analysis.Meanwhile,the new compounds 5a,6a,8a,22,and 23,as well as the known derivatives 13a,14a,15,17−21,24,25,and p-hydroxybenzyl aldehyde were isolated and identified from a refluxed aqueous solution of p-hydroxybenzyl alcohol.Methylation of 5a and 6a in methanol and ethylation of 6a,8a,13a,and 14a in ethanol produced 5 and 6 and 7,8,13,and 14,respectively.using ultra-performance liquid chromatography high-resolution electrospray ioniza-tion mass spectrometry(UPLC-HRESIMS)analysis of the refluxed solutions of p-hydroxybenzyl alcohol and the refluxed extracts of the fresh G.elata rhizome and“tian ma”extracts indicated consistent production and variation of the dimeric and trimeric derivatives of p-hydroxybenzyl alcohol upon extracting solvents and refluxing time.In various assays,the dimeric and trimeric derivatives showed more potent activities than p-hydroxybenzyl alcohol itself and gastrodin,which are the main known active constituents of“tian ma”.These results revealed for the first time that the more effective dimers and trimers can be produced through condensation of the co-occurring p-hydroxybenzyl alcohol during processing and decocting of the G.elata rhizomes,demonstrating insights into medicinal chemistry behind application protocols of traditional Chinese medicines.

Screening potential mitochondria-targeting compounds from traditional Chinese medicines using a mitochondria-based centrifugal ultrafiltration/liquid chromatography/mass spectrometry method

Mitochondria regulate numerous crucial cell processes, including energy production, apoptotic cell death, oxidative stress, calcium homeostasis and lipid metabolism. Here, we applied an efficient mitochondria-based centrifugal ultrafiltration/liquid chromatography/mass spectrometry（LC/MS） method,also known as screening method for mitochondria-targeted bioactive constituents（SM-MBC）. This method allowed searching natural mitochondria-targeting compounds from traditional Chinese medicines（TCMs）, including Puerariae Radix（PR） and Chuanxiong Radix（CR）. A total of 23 active compounds were successfully discovered from the two TCMs extracts. Among these 23 hit compounds, 17 were identified by LC/MS, 12 of which were novel mitochondria-targeting compounds. Among these, 6 active compounds were analyzed in vitro for pharmacological tests and found able to affect mitochondrial functions. We also investigated the effects of the hit compounds on Hep G2 cell proliferation and on loss of cardiomyocyte viability induced by hypoxia/reoxygenation injury. The results obtained are useful for in-depth understanding of mechanisms underlying TCMs therapeutic effects at mitochondria level and for developing novel potential drugs using TCMs as lead compounds. Finally, we showed that SM-MBC was an efficient protocol for the rapid screening of mitochondria-targeting constituents from complex samples such as PR and CR extracts.

Isolation and screening of glucosidase inhibitors from Chinese medicines

Objective: To search for glucosidase inhibitors from Chinese medicines. Methods: Six kinds of widely-used Chinese medicines with the activity of decreasing blood glucose were prepared by the process of boiling, condensing, precipitating, exchanging with resins and rinsing. In vitro glucosidase inhibitory activities were examined by photometric bioassay derived from rats, yeast and almond of all the Chinese medicine extracts. Diabetic ICR mice models were established by intraperitoneal injection of STZ (200 mg/kg). To investigate the in vivo effect of lowering blood glucose, the mouse blood glucose level was assayed at 30 min after being given 2.5 g/kg starch and acarbose or varied concentrations of different constituents of some Chinese medicines by stomach tube. Results: The constituents of Sangye, Sangzhi, Sangbaipi, Dihuang and Yuzhu showed potent inhibitory activities against glucosidase. Furthermore, the first kind of constituents was proved to be beneficial in reducing blood glucose by in vivo glucose tolerance experiments. Conclusion: The constituents of Chinese medicines with reducing blood glucose effect have been discovered, thus providing a clue to novel drugs.

Clinical Observation on Influence of Chinese Medicines for Promoting Blood Circulation to Remove Blood Stasis on FIB and DD in Plasma of Patients with Cerebral Thrombosis

to study the influence of Chinese medicines for promoting blood circulation to remove blood stasis on fibrinogen(FIB)and D-dimer(DD)in plasma of patients with cerebral thrombosis. Method:73 inpatients with acute cerebral thrombosis were randomly divided into a control group of 34 cases and a treatment group of 39 cases.The content of FIB and DD in plasma was detected before treatment and on the 7th and 14th days after treatment.Result:FIB content in plasma after treatment was lower than that before treatment in the control group(P<0.01)and more remarkable in the treatment group(P<0.001).There was an obvious difference in DD content before and after treatment in both groups.DD content on the 7th and 14th days after treatment in the treatment group was obviously higher than that in the control group(P<0.01 and P<0.05 respectively). Conclusion:Chinese medicines for promoting blood circulation to remove blood stasis can reduce the FIB content in plasma of patients with cerebral thrombosis,raise the DD content in plasma, cause the peak of DD content appear earlier and obviously improve hypercoagulability of blood in patients with cerebral thrombosis.

Rapid bioluminescence assay for monitoring rat CES1 activity and its alteration by traditional Chinese medicines

In traditional Chinese medicine herbs(TCM),including Radix Salviae Miltiorrhizae(Danshen),Radix Puerariae Lobatae(Gegen),Radix Angelicae Sinensis(Danggui),and Rhizoma Chuanxiong(Chuanxiong)are widely used for the prevention and treatment of cardiovascular diseases and also often co-administered with Western drugs as a part of integrative medicine practice.Carboxylesterase 1(CES1)plays a pivotal role in the metabolisms of pro-drugs,Since(S)-2-(2-(6-dimethylamino)-benzothiazole)-4,5-dihydrothiazole-4-carboxylate(NLMe)has recently been identified by us as a selective CES1 bioluminescent sensor,we developed a rapid method using this substrate for the direct measurement of CES1 activity in rats.This bioluminescence assay was applied to determine CES1 activity in rat tissues after a two-week oral administration of each of the four herbs noted above.The results demonstrated the presence of CES1 enzyme in rat blood and all tested tissues with much higher enzyme activity in the blood,liver,kidney and heart than that in the small intestine,spleen,lung,pancreas,brain and stomach.In addition,the four herbs showed tissue-specific effects on rat CES1 expression.Based on the CES1 biodistribution and its changes after treatment in rats,the possibility that Danshen,Gegen and Danggui might alter CES1 activities in human blood and kidney should be considered.In summary,a selective and sensitive bioluminescence assay was developed to rapidly evaluate CES1 activity and the effects of orally administered TCMs in rats.

Clinical evidence and potential mechanisms of Chinese medicines for the treatment of diabetic retinopathy

Diabetic retinopathy is one of the main causes of visual impairment and blindness on a global scale. At present, thelimitations of anti-vascular endothelial growth factor agents, steroids, laser photocoagulation, and vitreous surgery haveled to a growing awareness of the role of Chinese medicines in the treatment of diabetic retinopathy. This review firstdescribes the ingredients and characteristics of the formulae including Chinese herbal formulaes, Chinese patent drugsand ancient processed drugs and summarizes the application of Chinese medicines and their mechanisms of action in thetreatment of diabetic retinopathy. Due to the complexity of Chinese medicines, in-depth mechanisms, side effects of herb,and drug interactions need to be elaborated in future research. Chinese medicines have the potencial to protect theresidual eyesight and delay the progression of disease, thereby offering a beneficial, exploitable option in thetreatment/prevention of diabetic retinopathy.

Ancient and modern medication laws of aromatic Chinese medicines in treating angina pectoris based on data mining

Objective To explore ancient and modern medication laws of aromatic Chinese medicines in treating angina pectoris, and to provide new ideas for the clinical treatment.Methods With “angina pectoris” as the key word, ancient books prescriptions and Chinese patent medicines related to angina pectoris were collected from China National Knowledge Infrastructure(CNKI), Traditional Chinese Medicine Database System, Chinese Medicine Prescription Database, New National Proprietary Chinese Medicine(2 nd edition), and Chinese Pharmacopoeia(2020 edition) from January 1, 2015 to December 31, 2021. Core highfrequency aromatic Chinese medicines were defined, and their potential medication rules were analyzed and summarized. Microsoft Access 2010 was used for data management. Data analysis software, including Excel and IBM SPSS Modeler 18.0 were used for drug association rule analysis, and Cytoscape 3.7.2 for visual display.Results There were 67 ancient books prescriptions and 258 Chinese patent medicines containing aromatic Chinese medicines treating angina pectoris collected from relevant databases. In ancient books prescriptions, there were nine aromatic Chinese medicines with the frequency ≥10, and the most commonly used medicine was Danggui(Angelicae Sinensis Radix), followed by Chenpi(Citri Reticulatae Pericarpium). There were 33 aromatic Chinese medicines with the frequency ≥10 in Chinese patent medicines, and the most commonly used medicine was Danshen(Salviae Miltiorrhizae Radix et Rhizoma), followed by Chuanxiong(Chuanxiong Rhizoma) and Sanqi(Notoginseng Radix et Rhizoma). In ancient books prescriptions, the medicines mainly belonged to intenal-warming medicines, Qi-regulating medicines, and blood circulation promoting and blood stasis removing medicines.There were eight medicine pairs with confidence equal to 100% in ancient books prescriptions, the most frequently used pairs were Chuanxiong(Chuanxiong Rhizoma) +Danggui(Angelicae Sinensis Radix), and Xiangfu(Cyperi Rhizoma) + Chenpi(Citri Reticulatae Pericarpium). In Chinese patent medicines, the aromatic Chinese medicine Chuanxiong(Chuanxiong Rhizoma) could be combined with many other Chinese medicines, among which the Confidence and Support of Chuanxiong(Chuanxiong Rhizoma) + Danshen(Salviae Miltiorrhizae Radix et Rhizoma) were at a high level.Conclusion Aromatic Chinese medicines for the treatment of angina pectoris of coronary heart disease are mainly warm, and the flavors are mainly pungent, sweet, and bitter. They mainly access to the liver, gallbladder, and pericardium meridians. The treatment of angina pectoris of coronary heart disease mainly focuses on warming heart pulse, and promoting blood circulation and removing blood stasis.

The Drug-carrier Interactions, Release Behaviors and Cell Responses of Hydroxyapaptite Containing Several Chinese Medicines

The present work shows drug-carrier interactions, release behaviors and cell responses of hydroxyapatite （HA） containing salvianolic acid B （Sal B）, astragalus polysaecharide （APS）, and naringin. X-ray diffraction （XRD） showed that the crystallinity and crystal size of HA decreased significantly when Sal B was added （p〈0.05）. Transmission electron microscope （TEM） confirmed that the nano-acicular crystals of HA containing Sal B were the most fine among all specimens. It was conjectured that Sal B preferentially adsorbed on the positively charged surface of HA crystals to inhibit their growth. In vitro release of HA containing Chinese medicines followed the first-order equation. The drug-carrier affinity between HA and Sal B might have prolonged the release of Sal B. The proliferation and differentiation of osteoblasts were promoted by Chinese medicines containing HA in the time and dosage dependent manner. The osteoblasts displayed a polygonal morphology with cell-cell junctions in all cases. It is suggested that the contained Chinese medicines would promote the activities of the osteoblasts.

Screening of new non-nucleoside reverse transcriptase inhibitors of HIV-1 based on traditional Chinese medicines database

HIV- 1 RT is an important target for the treatment of AIDS. There are two major classes of antiviral agents that inhibit HIV- 1 RT have been identified, nucleoside RT inhibitors （NRTIs） and non-nucleoside RT inhibitors （NNRTIs）. In this report, a noval class of non-nucleoside compound with potential RT inhibitory activity were found from the traditional Chinese medicines database （TCMD） using a combination of virtual screening, docking, molecular dynamic simulations, where results were ranked by scoring function of the docking tool. The result indicates that M4753 （a compound derived from TCMD） has not only the lowest bonding energy but also the best match in geometric conformation with the forthcoming NNRTIs. Accordingly M4753 might possibly become a promising lead compound of NNRTIs for AIDS therapy.

Selectivity of New β-Cyclodextrin Derivatives as CGC Stationary Phases and Application for the Analysis of Volatile Compounds in Traditional Chinese Medicines

New cyclodextrin derivatives （CDs）, heptakis（2, 6-di- O-methyl-3- O-methoxymethyl）-β-CD （ Ⅰ ） and heptakis（2, 3, 6-tri-O-methoxymethyl）-β-CD （ Ⅱ ）, were investigated for their chromatographic performance as stationary phases for capillary gas chromatography （CGC）. Both of the CDs exhibited good selectivity and satisfactory separation for test mixtures and aromatic positional isomers, and volatile compounds from Ligusticurn chuanxiong Hort. Additionally, the selectivity and elution orders of major compounds were compared with a well-recognized commercial column on the basis of the results by gas chromatography-mass spectrometry （GC-MS）. The present work demonstrates the good selectivity of the two new CDs and can be used as GC stationary phases for the separation of positional isomers and analytes in complex samples.

Metabonomics/metabolomics analysis technology and its application in quality control of traditional Chinese medicines

Chinese medicines are an important part of traditional Chinese medicines,but their'safe,effective,stable and controllable'issue still remains to be solved.The rise of metabonomics in 20th century,consistent with the overall adjustment concept of multi-component,multi-level,multi-target,multi-metabolic pathways of traditional Chinese medicines,is conducive to solve basic problems in their quality control.This paper systematically describes recent application and development of 1H-NMR metabonomics techniques,LC-MS metabonomics techniques and GC-MS metabonomics techniques in the quality control of traditional Chinese medicines.It provides a new reference for Chinese medicines and the identification and quality assessment of their products.

Advances in Research of Toxic Traditional Chinese Medicines in the Treatment of Malignant Tumors

Combating poison with poison is an important method of traditional Chinese medicine to treat malignant tumors.This study reviews the experimental research on anti-tumor effects of toxic traditional Chinese medicines in recent years.It summarizes the action mechanism of toxic traditional Chinese medicines for the treatment of malignant tumors,including:inhibiting tumor cell proliferation and angiogenesis,inducing tumor cell apoptosis and differentiation,reversing tumor cell multidrug resistance(MDR),inhibiting tumor cell invasion and metastasis,and enhancing the body's immune functions.Finally,it discusses the research and development prospects of toxic traditional Chinese medicines as new anti-tumor drugs.

Treatment of Irritable Bowel Syndrome by Oral Administration of Chinese Medicines and Retention-Enema——A Report of 50 Cases

Irritable bowel syndrome (IBS), a common disease of intestinal dysfunction, is also called emotional enteritis, mucous enteritis, irritable colon and so on1. It is often lingering with a long disease course and is easy to recur. The author has in recent years treated 50 cases of the disease by oral administration of Chinese medicines and retention-enema, with satisfactory results reported as follows.

The Potential Targets of Chinese Medicines in the Treatment of Parkinson＇s Disease： Old Wine in New Bottles

This article systematically reviews the present research situation of the pathogenesis of PD （Parkinson＇s disease） and our recent research over the past decade, to discuss the potential targets of many TCM （traditional Chinese medicines） in prevention and treatment of PD, such as against oxidative stress （Astragaloside, protocatechuic aldehyde, Liu-Wei-Di-Huang）, anti-apoptosis （Geniposide, Zhichan powder）, improve mitochondrial function （Paeoniflorin, Da-Bu-Yin-Wan）, inhibition of protein aggregation （Panax ginseng, Irisflorentin）, induce autophagy （piperine, Paeoniflorin）, and many other mechanisms and multiple effectiveness （Saponins, Acanthopanax）. With the research and development in PD pathogenesis and clarifying the targets of a variety of traditional Chinese medicine, especially its monomeric components, the development of traditional Chinese medicine in prevention and treatment of PD will have very broad application value and prospect.

Inhibition of Urogenital Chlamydia Trachomatis in Vitro by 12 Diuretic Traditional Chinese Medicines

Objective: To detect the inhibition of urogenitalchlamydia trachomatis (CT) by 12 traditional Chinesemedicines in vitro.Methods: The inhibition of CT isolates by these medicineswas detected by micro-culture technique with McCoy cellsin vitro. Results: All the diuretic traditional Chinese medicinesinhibited urogenital CT The minimum inhibitoryconcentrations (MICs) ranged from 0.122 mg ml^(-1) to 62.5mg ml^(-1). Diathus superbus L., Poria cocos (Shew.) Woft,Polyporus umbellatus (Pers.) Fries, and Artemisia capillariesThunb showed stronger inhibition than the other eighttraditional Chinese medicines. The numbers and sizes ofinclusions bodies reduced gradually and disappeared finallywith the increase of the concentrations. Conclusion: All the 12 diuretic traditional Chinesemedicines inhibited urogenital CT.

Status and Development Trend of Evaluation of Post-Marketing Traditional Chinese Medicines in China

Evaluation of traditional Chinese medicines after the market has achieved fruitful results after years of development.The real-world research concept has been first proposed by Chief Researcher Xie Yanming in 2010 and to 2020 with the approval of the National Medical Products Administration to use real-world evidence to support drug development and review in 2020.Real-world data application and transformation continue to cause heated discussions in the industry.Real-world research concepts have been added new motivation into the evaluation of Chinese medicines after they are marketed.The development of the Chinese patent medicine industry is facing unprecedented opportunities and challenges.