Discovery and Development of Artemisinin and Related Compounds

Artemisinin is isolated from the plant Artemisia annua, sweet wormwood, an herb employed in traditional Chinese medicine. Prof. You-you Tu discovered artemisinin in the 1960s, so she was awarded the 2015 Nobel Prize in Physiology or Medicine. Artemisinin and its semi-synthetic derivatives are a group of drugs that possess the most rapid action of all current drugs against Plasmodium falciparum malaria. In this review, the author investigated history on discovery of artemisinin, ethnopharmacology of Artemisia plants, chemistry and pharmacological activities of the relative compounds, and introduced Tu and other Chinese and world scientists’ contribution, development of artemisinin and the related compounds and registered and marketed artemisinin drugs in China, UK, and USA. The author also recalled the studies on the mechanism of action of artemisinins and artemisinin combination therapies and summed up the resistance issues. In Current Recommendations and the Global Plan for Insecticide Resistance Management in Malaria Vectors (GPIRM), that the WHO prevents the development and manages the spread of insecticide resistance is summarized in the technical basis for coordinated action against insecticide resistance: preserving the effectiveness of modern malaria vector control. Prof. Tu re-emphasized the artemisinin resistant on five principles to the WHO. She called on the world''s scientists to pay attention to the study of drug resistance, and hopes scientists to contribute to break resistance of artemisinins.     

Anticancer and multidrug-resistance reversing potential of traditional medicinal plants and their bioactive compounds in leukemia cell lines

Multidrug resistance remains a serious clinical problem in the successful therapy of malignant diseases. It occurs in cultured tumor cell lines, as well as in human cancers. Therefore, it is critical to develop novel anticancer drugs with multidrug-resistance modulating potential to increase the survival rate of leukemia patients. Plant-derived natural products have been used for the treatment of various diseases for thousands of years. This review summarizes the anticancer and multidrug-resistance reversing properties of the extracts and bioactive compounds from traditional medicinal plants in different leukemia cell lines. Further mechanistic studies will pave the road to establish the anticancer potential of plant-derived natural compounds.     

Network pharmacology unveils spleen-fortifying effect of Codonopsis Radix on different gastric diseases based on theory of ‘‘same treatment for different diseases” in traditional Chinese medicine

Objective: "Same treatment for different diseases" is a unique treatment strategy under the guidance of traditional Chinese medicine(TCM) theory.Codonopsis Radix(Codonopsis pilosula,Dangshen in Chinese)with spleen-fortifying effect was employed to understand the strategy of "Same treatment for different diseases",based on its common mechanism in the treatment of gastric diseases including gastric ulcer,gastritis and gastric cancer via network pharmacology research.Methods:Network pharmacology research methods were used to analyze the interaction network and potential mechanisms of Dangshen in treating gastric ulcer,gastritis and gastric cancer.The active components and their target proteins of Dangshen were integrated from TCMSP,BATMAN-TCM databases.The targets of gastric ulcer,gastritis and gastric cancer were collected through GeneCards,PubMed,TDD and DisGeNET Database.Through screening,the key components and the key targets of Dangshen in treating gastric ulcer,gastritis and gastric cancer were obtained.After KEGG pathway analysis and GO analysis,the important pathways and biological processes were analyzed.Results:Through data and literature mining,the common and specific pharmaceutical effects and mechanism of Dangshen were summarized in these three gastric lesions.It was shown that Dangshen mainly acted on gastric ulcer,gastritis and gastric cancer through the overall regulation of the PI3K-AkT signaling pathway.With the development of the disease,it will gradually increase the control of inflammation through TNF,NF-κB and other inflammation-related signaling pathways to reduce inflammatory damage.For tumorigenesis,it pays more attention to inhibiting the ErbB signaling pathways to reduce the proliferation and migration of tumor cells.In addition,Dangshen's regulation of HIF-1 signaling pathway may also be beneficial for the treatment of gastric ulcer,gastritis and gastric cancer.Conclusion:Dangshen achieves spleen-fortifying effect on gastric diseases including gastric ulcer,gastritis and gastric cancer through multiple targets in multiple pathways,especially PI3K-AKT pathway and HIF-1 pathway.It could provide a scientific basis for understanding the strategy of "Same treatment for different diseases" in traditional Chinese medicine.     

A Preliminar y Study on Combination Therapy of Artemisinin Dimer Oxime and Topotecan against Nonsmall Cell Lung Cancer in Mice

Background: Artemisinin dimer oxime – dimer molecule synthesized from artemisinin possesses high bioavailability and marked in vitro anticancer activities against solid tumor?derived cell lines, endothelial cell proliferation, migration, and angiogenic processes. Numerous murine models have been developed to study human cancer. The most widely used models are the human tumor xenograft mouse model. Materials and Methods: In this study, human tumor cells(NCI?H640, 1 × 107 in 100 μL) are implanted subcutaneously, or 1 × 107 in 50 μL in the thoracic cavity, in athymic nude mice(nu/nu). The implanted cells were allowed to grow for 10 days before initiation of drug treatment(dimer oxime and topotecan, ip). Tumor volume and thoracic/body weight ratio were recorded. Results: We successfully established subcutaneous and thoracic xenografts with human nonsmall cell lung cancer cell line xenografts in athymic nude mice in only 10 days. Using these models, we attempted treatment of xenografts with topotecan – a known anticancer drug and artemisinin dimer oxime or combination of these two drugs. Combination therapy showed a significant reduction in tumor volume and tumor/body weight. Treatments with combination of topotecan and dimer oxime resulted in the reduced mortality rates in comparison with untreated mice. Conclusions: Xenograft tumor models are useful for preclinical screening of new pharmacophores. From this preliminary study, it appears that combination of dimer oxime and topotecan may be used as chemotherapeutic agents against nonsmall cell lung cancer. Further studies are needed to evaluate other combination treatment regimens as well as the mechanism(s) of action.     

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.     

Delineation on Therapeutic Significance of Transporters as Molecular Targets of Drugs

Transporters are membrane proteins mediating permeation of organic and inorganic solutes through the plasma membrane and membranes of intracellular organella.They play essential roles in the epithelial absorption and cellular uptake of nutrients as well as absorption,distribution,metabolism,and excretion of drugs.Because transporters contribute to determining the distribution of compounds in the body in concert with metabolic/synthetic enzymes,the drugs that affect the functions of transporters are expected to alter the distribution of compounds in the body and to ameliorate disrupted homeostasis.In this context,drugs targeting transporters have been used clinically.Such drugs include antidepressants targeting monoamine transporters,diuretics targeting inorganic ion transporters of renal tubules,and uricosuric agents targeting renal urate transporters.Now new transporter-targeting drugs designed based on post-genome drug development strategy have been in the process of clinical trials or basic/clinical researches.For example,the inhibitors of renal Na+/glucose cotransporter SGLT2 have been proved for their efficacy in the treatment of diabetes mellitus.The cancer L-type amino acid transporter 1(LAT1) has been considered as a target of cancer diagnosis and therapeutics.The transporter-targeting drugs are expected to provide new rationale in the therapeutics of various diseases.     

Molecular Insight into the Therapeutic Promise of Xuebijing Injection againstCoronavirus Disease 2019

Background: The potential human?to?human transmission of the coronavirus pneumonia (coronavirus disease 2019 [COVID?19]) has caused an outbreak of acute respiratory illness. Xuebijing injection is recommended as first?line treatment for the severe and critical patients with COVID?19. The aim of presentstudy isto interpret the pharmacological mechanisms and molecular connections of Xuebijing injection against COVID-19 by utilizing the approaches of network pharmacology and molecular docking. Materials and Methods: Active ingredients of Xuebijing injection were collected by Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, and putative therapeutic targets were screened from TCMSP, SwissTargetPrediction, and STITCH databases. Moreover, the protein–protein interactions, topological analysis, and pathway enrichment were established to distinguish the hub targets and pathways by employing STRING database, Cytoscape software, DAVID database, respectively. In addition, the potential interaction and binding activity of candidate ingredients in Xuebijing injection with core targets were revealed by molecular docking simulation (AutoDock software). Results: A total of 115 bioactive components in Xuebijing injection were collected, and?416 targets including AKT1, TP53, VEGFA, ALB, TNF and so on were responsible for treating COVID?19. Bioinformatics analysis revealed that matching core targets were closely associated with the inhibition of cytokine storm for its clinical beneficial effects in severe cases. The results of enrichment analysis indicated that PI3K?Akt signaling pathway, human T?cell leukemia virus type 1 infection, mitogen?activated protein kinase signaling pathway, tuberculosis, focal adhesion, TNF signaling pathway, and small?cell lung cancer were represented pathways of Xuebijing injection against COVID?19 in terms of lung inflammation, virus infection, and lung injury. Meanwhile, the active ingredients of Xuebijing injection exerted superior binding activities with 3CLpro and angiotensin?converting enzyme 2 as observed via molecular docking simulation. Conclusions: Through the comprehensive analysis of network pharmacology, the current research preliminarily elaborated the molecular regulation of therapeutic mechanisms for Xuebijing injection against COVID?19 and binding activity between active components and core targets, which provided scientific evidence to facilitate the development of Xuebijing injection and clinical treatment for COVID-19.     

The forecast of anticancer targets of cryptotanshinone based on reverse pharmacophore-based screening technology

Anticancer targets of cryptotanshinone were evaluated and rapidly forecasted with PharmMapper, a reverse pharmacophore-based screening platform, as well as drug target databases, including PDTD, DrugBank and TTD. The pathway analyses for the collection of anticancer targets screened were carried out based on the KEGG pathway database, followed by the forecast of potential pharmacological activities and pathways of the effects of cryptotanshinone, and verification of some of the targets screened using whole cell tests. The results showed that a total of eight targets with anticancer potential were screened, including MAP2K1, RARα, RXRα, PDK1, CHK1, AR, Ang-1 R, and Kifll. These targets are mainly related to four aspects of the cancer growth： the cell cycle, angiogenesis, apoptosis, and androgen receptor. The cell tests showed that cryptotanshinone can inhibit the viability of human hepatoma cells SMMC-7721, which is related to the reduction of expression of MAP2K1 mRNA. This method provides a strong clue for the study of the anticancer effects and mechanisms of action of cryptotanshinone in the future.     

Network pharmacology-based prediction and verification of the molecular targets and pathways for schisandrin against cerebrovascular disease

AIM： To illuminate the molecular targets for schisandrin against cerebrovascular disease based on the combined methods of network pharmacology prediction and experimental verification. METHOD： A protein database was established through constructing the drug-protein network from literature mining data. The protein-protein network was built through an in-depth exploration of the relationships between the proteins. The computational platform was implemented to predict and extract the sensitive sub-network with significant P-values from the protein-protein network. Then the key targets and pathways were identified from the sensitive sub-network. The most related targets and pathways were also confirmed in hydrogen peroxide （H202）-induced PC 12 cells by Western blotting. RESULTS： Twelve differentially expressed proteins （gene names： NFKB1, RELA, TNFSF10, MAPK1, CHUK, CASP8, PIGS2, MAPK 14, CREBI, IFNG, APR and BCL2） were confirmed as the central nodes of the interaction network （45 nodes, 93 edges）. The NF-KB signaling pathway was suggested as the most related pathway of schisandrin for cerebrovascular disease. Furthermore, schisandrin was found to suppress the expression and phosphorylation of 1KKct, as well as p50 and p65 induced by H2O2 in PC12 cells by Western blotting. CONCLUSION： The computational platform that integrates literature mining data, protein-protein interactions, sensitive sub-network, and pathway results in identification of the NF-arB signaling pathway as the key targets and pathways for schisandrin.     

Mechanism underlying treatment of diabetic kidney disease using Traditional Chinese Medicine based on theory of Yin and Yang balance

The pathogenic mechanism of diabetic kidney disease(DKD) is complex. The development of DKD cannot be fully explained by a single mechanism.Traditional Chinese Medicine(TCM) has been applied extensively for the treatment of DKD in China.However, studying the mechanism of DKD using theories and methods that are appropriate for TCM characteristics and searching for theoretical bases for TCM clinical application are topics that still need to be explored and researched. Activation of the transforming growth factor(TGF)-β1/Smad and PI3 K/Akt/mTOR signaling pathways functions as a self-protection mechanism against renal microinflammation in DKD. However, the persistent abnormal overactivation of reactions causes secondary cell dysfunction, cell apoptosis, increased extracellular matrix(ECM) secretion, and eventually renal fibrosis. During this process, the dysregulation of self-balance among a variety of signaling pathways and the loss of self-feedback regulatory mecha-nisms downstream of these signaling pathways are critical causes of the occurrence and development of DKD. TCM may both inhibit the expression or activation of "hyperactive" signaling pathways(NFB, Smad3, and PI3 K/Akt/mTOR) and increase the expression or activation of "deficient" signaling pathways(Smad7 and PTEN) to restore balance to cells with an abnormal pathophysiological status and achieve the goal of DKD treatment.     

Effect of Yinlai Decoction on the metabolic pathways in the lung of high-calorie diet-induced pneumonia rats

Objective:To search for specific metabolites in the lungs of pneumonia rats fed with a high-calorie diet,as well as explore the changes in the lung metabolites of young rats treated with Yinlai Decoction(YD)and its effects on inflammation-related metabolic pathways.Methods:Lipopolysaccharides(LPS)and a special high-calorie diet were used to induce Sprague Dawley(SD)rats to simulate the intestinal state of infant pneumonia.Liquid chromatography-mass spectrometry technology(LC-MS/MS)was used to detect metabolites in each group.Supervised orthogonal partial least squares discriminant analysis(OPLS-DA)model values were used for the detection results to find the differential metabolites.The metabolic pathways that are involved with the differential metabolites were clarified through enrichment analysis and topological analysis.Finally,the T cell receptor signaling pathway(TCR)signal conversion was analyzed by the network pharmacology method.Results:In the high-calorie diet combined with pneumonia group(M3),a total of 55 metabolites were determined to be different from the normal group(N).A total of 36 metabolites were determined to be different from those in the lung metabolites of the YD treatment group(T1).YD had a regulatory effect on glutathione metabolism,arginine and proline metabolism,ascorbic acid and aldehyde metabolism and phenylalanine metabolism.And the small molecule metabolites could act on the FYN and lymphocytespecific protein tyrosine kinase(LCK)target proteins in the TCR signaling pathway,thereby affecting the immune function of the lungs.Conclusion:A high-calorie diet can cause abnormal sphingolipid metabolism in the lungs of young rats,thereby creating chronic lung inflammation in young rats.YD has a beneficial effect when used to treat young rats with LPS-induced pneumonia fed on high-calorie diets.Its mechanisms of action may affect the body’s immune pathways by regulating the oxidative stress pathway affected by glutathione metabolism.     

Anticancer activity of Sargassum wightii Greville on Dalton’s ascitic lymphoma简

AIM： Sargassum wightii Greville is a marine brown alga belonging to the Sargassaceae family which has about 200 species. The ethanolic extract of the whole dry plant powder contained numerous phytoconstituents, including flavonoids. The study was fo- cused on the anticancer activity ofSargassum wightii in mice. METHOD： The ethanolic extract ofSargassum wightii （EESW） at two dose levels was used to examine the anticancer activity in mice using DAL cell lines to induce cancer. The body weight, viable and non-viable tumor cell count, mean survival time, increase in life span, and hematological parameters were observed for anticancer activity of EESW. RESULTS： The intraperitoneal inoculation of DAL cells in mice significantly increased cancer cell count. The decrease in the cancer cell number observed in the EESW-treated group cancer animals indicates that the test drug has a significant inhibitory ef- fect on the tumor cell proliferation. Treatment with EESW also showed a significant decrease in tumor weight, and hence increased the lifespan of DAL-treated mice. In addition, EESW administration significantly restored the hematological parameters in DAL-treated mice. CONCLUSION： The present study results suggest that administration of extract offers enhanced antioxidant potential. Therefore it can be concluded from this study that EESW possesses anticancer activity.     

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...     

Nanocarriers to Enhance Solubility, Bioavailability, and Efficacy of Artemisinins

The therapeutic potential of artemisinin (ART) and its derivatives (ARTs) is not limited to malaria but has been recently expanded to other infections with protozoans, trematodes, or viruses as well as to cancer. Due to their limited poor water and oil solubility, rapid degradation by the liver, and short half-life, they have a low bioavailability after oral administration. Consequently, there is a pressing necessity to formulate new ART preparations to raise its bioavailability and efficacy. Nanosized drug delivery systems represent important tools in modern medicine with wide clinical applications, because of their potential modulation of pharmacokinetic and biodistribution. This review focuses on polymer-based systems, lipid?based systems, and inorganic nanoparticles loaded with ARTs. The overall goal of this field of research is to enhance their solubility and stability to improve bioavailability at much lower doses and to increase long-term safety. In addition, the opportunity to reach highly specific site?targeted delivery by these nanocarriers confers a high medicinal value. Remarkably, most of the reported nanoparticulate drug delivery systems are biologically inactive or marginally immunogenic, generating no antigenic or pyrogenic reactions but only partial intrinsic toxicity. As clinical studies in human patients are available so far, there is a pressing need to translate preclinical results on ART-based nanosystems into clinical settings.     

Study of the anti-MRSA activity of Rhizoma coptidis by chemical fingerprinting and broth microdilution methods

AIM： Methicillin-resistant Staphylococcus aureus （MRSA） is a pathogenic bacterium that causes both hospital- and community-acquired infections, and for which single-drug treatments are becoming less efficient. Rhizoma coptidis has been used for more than two thousand years in China to treat diarrhea, fever, and jaundice. In this study, the anti-MRSA activity of Rhizoma coptidis is examined and its effective components sought. METHODS： The mecA and norA genes were determined by PCR amplification and sequencing. Drug susceptibility of Staphylococcus aureus ATCC43300 was performed using the VITEK2 compact system. The chemical fingerprint of Rhizoma coptidis was investigated using HPLC and preparative liquid chromatography, and the anti-MRSA activity was determined using an improved broth microdilution method. RESULTS： The drug susceptibility test revealed that the penicillin-binding protein phenotype of the strain changed in comparison to penicillin-sensitive Staphylococcus aureus. Ten batches of Rhizoma coptidis showed anti-MRSA activity on the norA-negative Staphylococcus aureus strain, as well as the strain that contained a norA gene. The spectrum-effect relationship revealed that the berberine alkaloids were the effective components, within which berberine, coptisine, palmatine, epiberberine,, and jatrorrhizine were the major components. CONCLUSION： This study lays a foundation for in vivo studies of Rhizoma eoptidis and for the development of multi-component drugs.     

Network Pharmacology Approach to Determine Active Compounds and Potential Targets Associated with the Anti‑Abortion Effects of Scutellariae Radix

Background:It is widely accepted that the causes andmechanisms of abortion are very complicated.InChina, ScutellariaeRadix (SR)(Scutellaria baicalensis Georgi) is widely used as a traditional Chinese herbal medicine with anti?abortion effects. However, the chemical components and pharmacologic profiles of SR have not been elucidated. The network pharmacology approach can provide a system?level perspective to explore the components, targets, and mechanism of herbal medicines. Thus, this approach was employed to identify the absorbable compounds, potential targets, and signaling pathways associated with SR. Materials and Methods: In this study, we used the Lipinski rule and an oral bioavailability of >30% to identify the bioactive compounds in SR. Targets of the anti?abortion activity of SR were obtained from the PharmMapper website server database. The Search Tool for the Retrieval of Interacting Genes and DAVID databases were utilized to perform protein–protein interaction analysis and pathway enrichment analysis, respectively. Finally, Cytoscape software was used to visualize the active compound–target–Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway network of SR. Results: In total, 286 chemical compounds were identified in SR; of these, 27 compounds could be absorbed into the blood, and 10 compounds that had a high docking score with their corresponding targets were determined. These potentially active compounds of SR regulated 142 targets and clearly affected 29 KEGG pathways. From these targets, a total of 11 targets, which were expressed in the breast and female reproductive system, were associated with the anti?abortion effects of SR: EGFR, HRAS, HSP90AA1, ESR1, PRKACA, SRC, GSK3B, JAK2, IGF1R, CDK2, and AR. In the KEGG pathway analysis, five pathways were related to the anti?abortion effect of SR, including the estrogen signaling pathway, the prolactin signaling pathway, progesterone?mediated oocyte maturation, and oocyte meiosis. Conclusions: The network pharmacology approach used in our study attempted to explain the mechanism of the anti?abortion effects of SR and has provided an alternative approach for the investigation of the effects of this complex compound.     

Assessment of pulmonary infectious disease treatment with Mongolian medicine formulae based on data mining, network pharmacology and molecular docking

Objective: Pulmonary infectious diseases (PID) include viral pneumonia (VP) and pulmonary tuberculosis (PT). Mongolian medicine (MM) is an effective treatment option in China, however, the core group medicines (CGMs) in the treatment of PID and their underlying therapeutic mechanisms remain unclear. In this study, through the method of data mining, the CGMs of MM for the treatment of PID were excavated, and the possible mechanism of action of the CGMs in the treatment of PID was explored by using network pharmacology. Methods: First, 89 MM formulae for the treatment of pulmonary infectious diseases collected from Gan Lu Si Bu, Meng Yi Jin Kui, People''s Republic of China Ministry of Health Drug Standards (Mongolian Medicine Volume), Standard of Mongolian Medicine Preparations in Inner Mongolia (2007 Edition), and Standard of Mongolian Medicine Preparations in Inner Mongolia (2014 Edition). The CGMs of MM for PID were excavated through association rule analysis and cluster analysis. Then, the active ingredients and potential targets of the CGMs were obtained from TCMSP, TCMIP, BATMAN-TCM databases. PID targets information was collected from OMIM, GeneCards, and DrugBank databases. The possible targets of CGMs treatment for PID were obtained by intersection. The PPI network was constructed through the STRING database, and the topology analysis of the network was performed. Through the enrichment analysis of the intersection targets by R language, the main action pathways and related target proteins of CGMs in the treatment of PID were screened out. The results were verified by molecular docking. Results: A total of 89 formulae were included, involving 164 MM herbs. The efficacy of the drugs was mainly cough-suppressing and panting-calming herbs, and heat-clearing herbs. The nature and flavor were mainly bitter and cold. The CGMs of MM to treatment of PID was excavated as the classic famous formula Sanzi Decoction (Toosendan Fructus-Chebulae Fructus-Gardeniae Fructus). A total of 28 candidate components and 237 predicted targets of CGMs were collected, and 61 common targets with PID were obtained, including key compounds such as quercetin, kaempferol, β-sitosterol and stigmastero and key targets such as VEGFA, IL6, TP53, AKT1. KEGG enrichment analysis yielded AGE-RAGE signaling pathways, IL-17 signaling pathways, and TNF signaling pathways. Molecular docking results showed that the key targets were well matched with the potential active ingredients of CGMs. Conclusion: This study found that MM commonly used cough-suppressing and panting-calming herbs in combination with heat-clearing herbs to treat PID, and the CGMs for the treatment of PID is “Toosendan Fructus-Chebulae Fructus-Gardeniae Fructus”. CGMs mainly play a role in the treatment of PID by acting on VEGFA, IL6, TP53, AKT1 and other targets, regulating AGE-RAGE signaling pathways, IL-17 signaling pathways, and TNF signaling pathways.     

Research progress in the use of leeches for medical purposes

Leeches are invertebrates that have a long history of application in the development of human medicine in both the East and the West.This paper comprehensively analyzes and evaluates current research and the latest progress with regard to the application of leeches,their medical value,and their application prospects from various perspectives,so as to provide a reference for new viewpoints and directions for research on leeches.Modern research has revealed that leeches contain various bioactive components,which have pharmacological effects such as anticoagulation,antithrombosis,blood viscosity reduction,and anti-atherosclerosis.Leech therapy is an important treatment approach for venous congestion after microsurgery and is also an effective adjuvant treatment for diabetic feet,chronic pain,and tumors.Therefore,leeches are of importance for the research and development of new drugs,the restoration of blood supply after surgery,and the adjuvant treatment of diseases accompanied by blood blocking.In addition,leeches can also be used as model organisms for research in evolutionary biology and invertebrate neurophysiology as well as in neurophysiological,behavioral,and functional studies.