Couplet Medicines Research Articles

Application of association rules and simulated annealing algorithms in optimizing traditional Chinese medicine placement schemes

Background and aimChina has used traditional Chinese medicine (TCM) to treat diseases for more than 2000 years. Traditionally, TCMs in medicine cabinets are arranged alphabetically or on the basis of experience, but this arrangement greatly affects dispensing efficiency. However, owing to the unique properties and qualities of TCM, very few automatic approaches or systems have specifically addressed TCM dispensing problems. Therefore, it is necessary to establish a method of optimizing the traditional Chinese medicine placement scheme (TCMPS) via computer algorithms to improve the work efficiency of pharmacists.MethodsA prescription dataset from a hospital in 2022 was obtained, and the association rule algorithm (ARA) was used to calculate the frequency of use for each type of TCM and the associations between different types of TCMs. On the basis of these association and frequency data, the optimal TCMPS was calculated using the simulated annealing algorithm (SAA) and then verified using the prescription dataset from 2023.ResultsA total of 10,601 prescriptions were collected in 2022, involving 360 different TCMs, and each prescription contained an average of 9.485 TCMs, with Danggui (3628) being the most frequently used. When the threshold of support was set to 0.05 and the confidence was set to 0.8, 78 couplet medicines used in orthopedics clinics were found through ARA. When the threshold value of support was set to 0, the confidence was set to 0, and the rule length was 2, a total of 129,240 rules were obtained, indicating support between all pairwise TCMs. The TCMPS, calculated using SAA, had a correlation sum of 14.183 and a distance sum of 3.292. The TCMPS was verified using a prescription dataset from 2023 and theoretically improved the dispensing efficiency of pharmacists by approximately 50%.ConclusionsIn this study, the ARA and SAA were successfully applied to pharmacies for the first time, and the optimal TCMPS was calculated. This approach not only significantly improves the dispensing efficiency of pharmacists and reduces patient waiting time but also enhances the quality of medical services and patient satisfaction, and provides a valuable reference for the development of smart medicine.

Herb couplet medicines (Erxian) protect osteoblasts from high glucose-induced damage by reducing cell apoptosis in diabetic osteoporosis: A network pharmacology and experimental verification-based study

IntroductionTraditional Chinese medicine (TCM) has unique advantages in treating diabetic osteoporosis (DOP). This study aimed to explore the mechanisms underlying the protective effects of herb couplet medicines (Erxian) on DOP using network pharmacology and verify these mechanisms using cell experiments. MethodsWe used chromatography to analyze the bioactive components of serum containing Erxian couplet medicines (ECMs) and searched for possible targets of the active ingredients in the Traditional Chinese Medicine Systems Pharmacology database. The target proteins of DOP were retrieved from the GeneCards and Online Mendelian Inheritance in Man databases. A component-target network diagram was then constructed using the screened drug components and target information for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. In vitro, cell morphological changes were observed using alkaline phosphatase staining, and the effect of the ECMs on osteoblast viability was assessed using a cell counting kit-8 assay. Finally, the pathway information predicted by network pharmacology was validated using flow cytometry, real-time polymerase chain reaction, and western blot experiments. ResultsTwelve types of active ingredients in serum containing ECMs were obtained via chromatography, and 96 potential targets were identified using network pharmacology analysis. Furthermore, GO and KEGG pathway enrichment analyses revealed that the ECMs might participate in the apoptosis signaling pathway in the treatment of DOP. In vitro tests showed that treatment with ECM serum increased osteoblasts’ survival rate and improved the HG group's cell morphology (P < 0.05). BCL2-associated X protein (BAX) expression increased in the HG group but decreased after ECM serum addition (P < 0.05). The expression of B-cell lymphoma-2 (BCL-2) was found to be reduced in the HG group but increased after ECM serum addition (P < 0.05). ConclusionECMs can treat DOP via multiple targets and multiple signaling pathways. Moreover, the mechanism underlying the effects of ECMs on osteoblasts was verified by inhibiting apoptotic. The complete signaling pathway requires future study.

Effects of Extraction Methods on Volatile Oil Profiles of Cinnamomi ramulus–Zingiberis rhizoma recens Couplet Medicines

Cinnamomi ramulus (CR, Guizhi in Chinese) and Zingiberis rhizoma recens (ZRR, Shengjiang in Chinese) are couplet medicines (drug pairs or drug combinations) in traditional Chinese medicine prescriptions. They contain a high amount of volatile oils which endow them with unique flavors and pharmacological activities. Extraction methods have a great influence on the extraction efficiency and composition of volatile oils. Firstly, the volatile oils of CR and ZRR were extracted by steam distillation (SD) and analyzed by GC-MS to obtain their chemical profiles. In total, 35 and 55 compounds were identified in the volatile oils of CR and ZRR, respectively. In order to find a suitable extraction method for the couplet medicine CR-ZRR, subsequently, steam distillation (SD), azeotropic distillation (AD) and supercritical fluid extraction (SFE) were applied to extract the volatile oils from CR-ZRR. The average extraction yields by SD, AD and SFE were 0.573%, 0.62% and 2.135%, respectively. The chemical composition of the volatile oils was then analyzed by GC-MS. In total, 73, 59 and 71 compounds were identified from the extracts obtained by SD, AD and SFE, respectively. Principal component analysis (PCA) and OPLS-DA showed that citral, (E)-cinnamaldehyde dimethyl acetal, zingiberene, cinnamaldehyde and β-sesquiphellandrene were the main contributors to distinguish the volatile oils that were obtained by different processes. Considering the chemical diversity and the total content of the main bioactive components of the volatiles oils, SD was more suitable for CR-ZRR volatile oil extraction. This study provides a basis for elucidating the chemical composition and suitable extraction method for the volatile oils of CR-ZRR.

Extract of Sophorae flavescentis radix-Cnidii fructus couplet medicines treats vulvovaginal candidiasis by affecting the vaginal mucosal barrier.

Aim: This study investigated the inhibition of extract of Sophorae flavescentis radix-Cnidii fructus couplet medicines (ESCC) on Candida albicans (C. albicans) in vitro and the effect of ESCC on the vaginal mucosal barrier in vivo. Materials & methods: Susceptibility testing was performed with C. albicans SC5314. A vulvovaginal candidiasis mouse model was successfully established. The plate method, Gram staining, hematoxylin and eosin staining and ELISA were used to detect relevant inflammatory indexes: IFN-γ, IL-1 and TNF-α. Quantitative real-time PCR and western blot were used to detect mucosal immune-related factors: MUC1, MUC4, DEFB1 and DEFB2. Results: ESCC was able to inhibit the proliferative activity of C. albicans, and it affected inflammation-related factors and indicators of vaginal mucosal immunity. Conclusion: ESCC showed potential value in the treatment of vulvovaginal candidiasis.

Exploring the molecular mechanism of Huangqin-Jinyinhua couplet medicines for the treatment of hand-foot and mouth disease using network pharmacology, molecular docking and bioinformatics databases

BackgroundHuangqin-Jinyinhua couplet medicines (HQJYH) were often used to treat hand-foot and mouth disease (HFMD), although its mechanism remains unclear. This study investigated the active ingredients in HQJYH and their mechanism when treating HFMD by network pharmacology and molecular docking. MethodsThe TCMSP database obtained the principal active ingredients found in HQJYH. The GeneCards, CTD, PharmGkb and DisGeNet databases were used to obtain the main targets involved in HFMD, and the merged targets were obtained by R software and the Venn package. The DAVID database performed GO and KEGG enrichment analyses on the intersection targets. We also used Cytoscape software to construct an “HQJYH-Active Ingredients-Targets” network and used the STRING platform to conduct protein–protein interaction (PPI) analyses on the intersection targets. Molecular docking of core active ingredients-core targets interactions were modeled using AutoDock Vina software. Results56 active ingredients were found in HQJYH, corresponding to 212 targets, 5323 HFMD targets, and 156 intersection targets. KEGG enrichment analysis found that genes were mainly enriched in the PI3K-Akt signaling pathway, MAPK signaling pathway and other pathways. Cytoscape showed that the core active ingredients were quercetin, luteolin, kaempferol, beta-sitosterol, stigmasterol, wogonin, baicalein and acacetin. The PPI network showed that the core targets involved were TP53, CASP3, AKT1, IL6, MAPK14, EGFR, and HIF1A. The molecular docking results indicated key binding activity between Baicalein-AKT1, quercetin-AKT1, wogonin-AKT1, kaempferol-AKT and wogonin-MAPK14. ConclusionThis study was based on network pharmacology and revealed the potential molecular mechanisms involved in treating HFMD by HQJYH.

Biomarker identification and pathway analysis of Astragalus membranaceus and Curcuma zedoaria couplet medicines on adenine-induced chronic kidney disease in rats based on metabolomics.

Background: Chronic kidney disease (CKD) is usually insidious, and most affected individuals are asymptomatic until the disease becomes advanced. The effective treatment of CKD would rely on the incorporation of multidisciplinary approaches. Astragalus membranaceus (AM) and Curcuma zedoaria (CZ) have been widely used in the treatment of CKD. However, the mechanism of AM and CZ in the treatment of CKD is still unclear. Methods: This study was designed to evaluate the effects of AM and CZ on adenine-induced rats and to investigate the underlying mechanism by using metabolomic analysis. Addition of 0.75% adenine to the diet of rats for 3weeks induced the animal model of CKD. The rats in the treatment group were treated with AM and CZ (2.1g/kg/day) for 4weeks. Blood and kidney samples were collected for biochemical and histological examination. Ultra-high-performance liquid chromatography/Q Exactive HFX mass spectrometer (UHPLC-QE-MS) was applied to analyze metabolic profiling variations in the kidney. Results: The results showed that AM and CZ could significantly reduce serum creatinine (Scr) and blood urea nitrogen (BUN) levels in CKD rats and alleviate renal pathological injury. By comparing the endogenous components of the normal group and the model group in positive ion mode and negative ion mode, a total of 365 and 155 different metabolites were screened, respectively. A total of 117 and 73 metabolites with significantly different expressions were identified between model group and AM and CZ group in positive ion mode and negative ion mode, respectively. The pivotal pathways affected by AM and CZ included nicotinate and nicotinamide metabolism, and glycine, serine and threonine metabolism. Furthermore, significant changes in metabolites in CKD rats after AM and CZ therapies were observed, including L-Threonine, D-pantothenic acid, and nicotinamide. Moreover, we found that AM and CZ significantly reduced renal fibrosis and inflammation in CKD rats, which may be related to the regulation of SIRT1/JNK signaling pathway. Conclusion: In conclusion, AM and CZ significantly reduced renal fibrosis and inflammation in CKD rats, which may be related to the regulation of SIRT1/JNK signaling pathway. Furthermore, L-Threonine, D-pantothenic acid, and nicotinamide may be potential biomarkers for the progression and treatment of CKD.

Chondroprotective Mechanism of Eucommia ulmoides Oliv.-Glycyrrhiza uralensis Fisch. Couplet Medicines in Knee Osteoarthritis via Experimental Study and Network Pharmacology Analysis.

Knee osteoarthritis (KOA) is the primary prevalent disabling joint disorder among osteoarthritis (OA), and there is no particularly effective treatment at the clinic. Traditional Chinese medicine (TCM) herbs, such as Eucommia ulmoides Oliv. and Glycyrrhiza uralensis Fisch. (E.G.) couplet medicines, have been reported to exhibit beneficial health effects on KOA, exact mechanism of E.G. nevertheless is not fully elucidated. We assess the therapeutic effects of E.G. on KOA and explore its underlying molecular mechanism. UPLC-Q-TOF/MS technique was used to analyze the active chemical constituents of E.G. The destabilization of the medial meniscus model (DMM) was employed to evaluate the chondroprotective action of E.G. in KOA mice using histomorphometry, μCT, behavioral testing and immunohistochemical staining. Additionally, network pharmacology and molecular docking were used to predict potential targets for anti-KOA activities of E.G., which was further verified through in vitro experiments. In vivo studies have shown that E.G. could significantly ameliorate DMM-induced KOA phenotypes including subchondral bone sclerosis, cartilage degradation, gait abnormality and thermal pain reaction sensibility. E.G. treatment could also promote extracellular matrix synthesis to protect articular chondrocytes, which was indicated by Col2 and Aggrecan expressions, as well as reducing matrix degradation by inhibiting MMP13 expression. Interestingly, network pharmacologic analysis showed that PPARG might be a therapeutic center. Further study proved that E.G.-containing serum (EGS) could up-regulate PPARG mRNA level in IL-1β-induced chondrocytes. Notably, significant effects of EGS on the increment of anabolic gene expressions (Col2, Aggrecan) and the decrement of catabolic gene expressions (MMP13, Adamts5) in KOA chondrocytes were abolished due to the silence of PPARG. E.G. played a chondroprotective role in anti-KOA by inhibiting extracellular matrix degradation, which might be related to PPARG.

Carrier-free Chinese herbal small molecules self-assembly with 3D-porous crystal framework as a synergistic anti-AD agent

Alzheimer's disease (AD) is a devastating neurodegenerative disease caused by multiple factors. Single-target drugs have limited efficacy for AD treatment. Therefore, multi-target intervention strategy has great potential. Traditional Chinese medicine (TCM) is mostly used in the form of compound prescription, which has the polypharmacology behavior. Rhizoma Coptidis and Radix et Rhizoma Rhei are frequently used as the couplet medicines of TCM for AD therapy. In this study, the novel carrier-free nanoassembly with 3D-porous frame crystal structure has formulated from supramolecular self-assembly of berberine (BER) and rhein (RHE), the main active components of Rhizoma Coptidis and Radix et Rhizoma Rhei, respectively. Combining with the spectral data and single crystal structure, the self-assembly process was clarified as dominated by electrostatic interaction and π-π stacking. In vitro release property, cholinesterase (ChE) inhibition, β-amyloid (Aβ) aggregation regulation, radical elimination, metal ions chelation and cytotoxicity assay indicated that the obtained BER-RHE assembly had the Fickian diffusion-controlled sustained release ability, synergistic biological activities and virtually no neurotoxicity. In addition, in vivo reactive oxygen species (ROS) level evaluation showed that the assembly could reduce the accumulation of intracellular ROS in Caenorhabditis elegans (C. elegans). Meanwhile, BER-RHE assembly could also be used as a novel potential carrier for drug delivery due to its superior 3D-porous frame. This green and facile strategy for carrier-free nanoassembly microscopic construction via supramolecular self-assembly might provide inspiration for the development of multi-target therapy for AD and the design of the novel drug delivery system.

Exploring the mechanism of Epimedii folium and notoginseng radix against vascular dementia based on network pharmacology and molecular docking analysis: pharmacological mechanisms of EH-PN for VD.

To explore the mechanism of Epimedii Folium (HF) and Notoginseng Radix (NR) intervention in vascular dementia (VD). This study used the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database to collect the active ingredients and potential drug targets of HF and NR, the Uniprot database to convert drug target names into gene names, GeneCards, Drugbank, Therapeutic Target Database, and Online Mendelian Inheritance in Man database to collect the potential disease targets of VD, and then combined them with the drug targets to construct the HF-NR-VD protein-protein interaction (PPI) network by Search Tool for the Retrieval of Interacting (STRING). Cytoscape (version 3.7.1) was used to perform cluster analysis of the PPI network. Metascape database was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The potential interaction of the main components of the HF-NR couplet medicine with core disease targets was revealed by molecular docking simulations. There were 23 predicted active ingredients in HF and NR, and 109 common drug targets that may be involved in the treatment of VD. Through PPI network analysis, 30 proteins were identified as core proteins owing to their topological importance. GO functional analysis revealed that the primary biological processes were mainly related to inflammation, apoptosis, and the response to oxidative stress. KEGG pathway enrichment analysis revealed that TNF and PI3K/Akt signaling pathways may occupy the core status in the anti-VD system. Molecular docking results confirmed that the core targets of VD had a high affinity for the main compounds of the HF-NR couplet medicine. We demonstrated the multi-component, multi-target, and multi-pathway characteristics of HF-NR couplet medicine for the treatment of VD and provided a foundation for further clinical application and experimental research.

A novel saponin liposomes based on the couplet medicines of Platycodon grandiflorum–Glycyrrhiza uralensis for targeting lung cancer

Liposomes have been widely used for targeted drug delivery, but the disadvantages caused by cholesterol limit the application of conventional liposomes in cancer treatment. The compatibility basis of couplet medicines and the compatibility principle of the traditional Chinese medicine principle of ‘monarch, minister, assistant and guide’ are the important theoretical basis of Chinese medicine in the treatment of tumor and the important method to solve the problem of high toxicity. In this study, the active ingredients of the couplet medicines Platycodon grandiflorum and Glycyrrhiza uralensis were innovatively utilized, and glycyrrhizic acid (GA) was encapsulated in liposomes constructed by mixing saponin and lecithin, and cholesterol was replaced by platycodin and ginsenoside to construct saponin liposomes (RP-lipo) for the drug delivery system of Chinese medicine. Compared with conventional liposomes, PR-lipo@GA has no significant difference in morphological characteristics and drug release behavior, and also shows stronger targeting of lung cancer cells and anti-tumor ability in vitro, which may be related to the pharmacological properties of saponins themselves. Thus, PR-lipo@GA not only innovatively challenges the status of cholesterol as a liposome component, but also provides another innovative potential system with multiple functions for the clinical application of TCM couplet medicines.

SHENG Can-ruo's experience in treatment of goiter with integrated acupuncture and herbal medication

The paper introduces professor SHENG Can-ruo's experience in treatment of goiter with the combination of acupuncture and herbal medication. Professor SHENG believes that this disease is mostly related with emotional injury, improper diet and geographical and climatic factors, as well as body constitution. Qi stagnation, phlegm retention, blood stagnation and interaction of phlegm and stasis are the essential pathogenesis of goiter. Either acupuncture or herbal medication should focus on "phlegm and stasis" in treatment. Besides, the theory of western medicine should also be considered. In western medicine, thyroid enlargement is classified into Ⅰ, Ⅱ and Ⅲ degrees of struma, thus, the pathogenesis and treatment with Chinese medicine should be adjusted accordingly. The created "four throat points", combined with acupuncture at distal points, relieve the local masses. The basic herbal formula is prepared and the couplet medicines are modified based on syndrome differentiation. The integrated acupuncture and herbal medication regulates emotions and provides a comprehensive treatment for goiter.

Radix Bupleuri-Radix Paeoniae Alba couplet medicine in the treatment of type 2 diabetes mellitus - A network pharmacology and cellular experimental assessment

The increasing global incidence of type 2 diabetes mellitus(T2DM) requires new drug interventions. For more than two thousand years, the combination of Radix Bupleuri and Radix Paeoniae Alba couplet medicine (BPCM) has provided beneficial activities in the treatment of diabetes. The object of this network pharmacology study was explore their combined mechanisms with verification In vitro . The chemical compounds and potential targets of BPCM were analyzed through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Gene information related to T2DM was collected using GeneCards and OMIM database. The core targets were obtained through Venn Diagram, and the protein interaction network (PPI) was constructed using the STRING database. The networks of compound-target and drug-compound-common target-disease were constructed by Cytoscape. Gene ontology (GO) term enrichment analysis and biological pathway (KEGG) enrichment analysis were performed using R language. SYBYL docking for key compounds with targets were performed to explore their binding modes, which was further verified through cell experiments. The study identified 17 active ingredients in Radix Bupleuri and 13 active ingredients in Radix Paeoniae Alba . There were 23 targets related to type 2 diabetes, including caspase 3 (CASP3), peroxisome proliferation-activated receptor γ (PPARG) and intercellular adhesion molecule-1 (ICAM1). Further analysis identified 403 GO biological processes and 76 related signal pathways. It was found that CASP3-kaempferol, CASP3-quercetin, and ICAM1-stigmasterol had high binding activities. In the palmitic acid-induced HepG2 cells, BPCM improved lipid aggregation and up-regulated the levels of p-ACC and p-AMPK. Importantly, experimental verification results showed that BPCM increased the expression of PPARG and decreased the levels of CASP3 and ICAM1. Through network pharmacology, molecular docking and vitro experiments, the study found that BPCM may treat T2DM by promoting AMPK/ACC conduction and inhibiting lipid accumulation.

Effecacy of Biejia (Carapax Trionycis) and Ezhu (Rhizoma Curcumae Phaeocaulis) couplet medicine on epithelial-mesenchymal transition, invasion and migration of MDA-MB-231 triple negative breast cancer cells via PI3K/Akt/mTOR signaling pathway.

To investigate the efficacy of Biejia (Carapax Trionycis) and Ezhu (Rhizoma Curcumae Phaeocaulis) couplet medicine on epithelial-mesenchymal transition (EMT), invasion and migration of MDA-MB-231 triple negative breast cancer (TNBC) cells based on PI3K/Akt/mTOR signaling pathway. MDA-MB-231 cells were treated with different medicated serum as Biejia-, Ezhu-, Biejia-Ezhu (BJ-, EZ-, BJ-EZ-) groups, intervened with no drug rat serum and paclitaxel with final concentration of 33 nM (IC50) as negative and positive control (NC and PC) groups. CCK-8 assay, scratch test, and Transwell assay were used to examine cell proliferation, invasion, and migration. The expression of E-cadherin, N-cadherin, Vimentin, MMP-2, MMP-9, PI3K, Akt, p-Akt, mTOR, and p-mTOR was determined by Western blot, and the mRNA expression of PI3K, Akt and mTOR was determined by real-time polymerase chain reaction. BJ-EZ group inhibited proliferation after 24, 48, and 72 h compared with the NC group (P < 0.05, < 0.01 or < 0.001) and reduced the invasion and migration of MDA-MB-231 cells (P < 0.01 or < 0.001). In addition, BJ-EZ group upregulated the expression of E-cadherin, downregulated the expression of N-cadherin, Vimentin, MMP-2, and MMP-9 (P < 0.05, P < 0.01 or P < 0.001), and inhibited the mRNA and protein expression of PI3K, Akt (p-Akt), mTOR (p-mTOR) (P < 0.05, < 0.01 or < 0.001). Biejia (Carapax Trionycis) and Ezhu (Rhizoma Curcumae Phaeocaulis) couplet medicine can inhibit the proliferation, invasion, migration and EMT of MDA-MB-231 cells through PI3K/Akt/mTOR signaling pathway, and the effect is better than that of Biejia (Carapax Trionycis) or Ezhu (Rhizoma Curcumae Phaeocaulis) alone.

Exploratory Compatibility Regularity of Traditional Chinese Medicine on Osteoarthritis Treatment: A Data Mining and Random Walk-Based Identification.

Osteoarthritis (OA) is a degressive and complex disease which is a growing public health problem on a global scale. On basis of an in-house database consisting of clinical records of 13,083 OA patients, the Traditional Chinese Medicine (TCM) was divided into 4 categories of medicines on the basis of the curative properties of herbs. Due to the lack of depth and internal relationship in the calculation results of TCM compatibility law data mining methods such as statistics and frequency analysis, we use a variety of multidimensional complex network methods that can efficaciously find the compatibility law of TCM, including similarity measure, graphical visualization of network diagram, random walking, and propensity score methods. We summarize common couplet medicines utilized for the treatment of osteoarthritis. The similarity measure method was used to investigate the commonly used drugs for the treatment of osteoarthritis. The method of association rule analysis is used to recognize the compatibility between the components. On basis of the propensity score methods, the evaluation displayed that, compared with single drug, the drug group increased ESR, CRP, C3, C4, IgG, and IgA more efficiently. Concluding, a random walk model was constructed to assess drug efficacy. After applying a random walk model, while revealing the compatibility among different components of TCM, their therapeutic efficacy against OA is analyzed. We obtained four groups of drug combination clusters by similarity measure and 11 pairs of highly connected drugs by association rules, which are cardinal drug combinations in the prescription for the treatment of OA. We also found that different traditional drug pairs were associated with different laboratory indexes, and drug combinations could better optimize laboratory indexes. This study presented that the TCM constituents complement one another. Besides, the therapeutic effects resulting from a variety of combinations of these constituents are quite different.

Network Pharmacology-Based Analysis on the Mechanism of Action of Ephedrae Herba-Cinnamomi Ramulus Couplet Medicines in the Treatment for Psoriasis.

BackgroundThis study explored the mechanism of action of Ephedrae Herba-Cinnamomi Ramulus couplet medicine (MGCM) at the pharmacological level in the treatment of psoriasis.Material/MethodsThe active ingredients in MGCM were mined through literature retrieval and the BATMAN-TCM database, and potential targets were predicted. In addition, targets associated with psoriasis were acquired using multiple disease-related databases. Thereafter, an interaction network between candidate MGCM targets and the known psoriasis-associated targets was constructed based on the protein–protein interaction (PPI) data, using the STRING database. Then, the topological parameter degree was determined for mining the core targets for MGCM in the treatment of psoriasis, which also represented the major hubs within the PPI network. In addition, the core networks of targets and ingredients were constructed using Cytoscape software to apply MGCM in the treatment for psoriasis. These core targets were then analyzed for Gene Ontology biological processes and Kyoto Encyclopedia of Genes and Genomes pathway enrichment using OmicShare.ResultsThe ingredient-target core network of MGCM for treating psoriasis was constructed; it contained 52 active ingredients and corresponded to 19 core targets. In addition, based on enrichment analysis, these core targets were majorly enriched for several biological processes (immuno-inflammatory responses, leukocyte differentiation, energy metabolism, angiogenesis, and programmed cell death) together with the relevant pathways (Janus kinase-signal transducer and activator of transcription, toll-like receptors, nuclear factor κB, vascular endothelial growth factor, and peroxisome proliferator-activated receptor), thus identifying the possible mechanism of action of MGCM in treating psoriasis.ConclusionsThe present network pharmacology study indicated that MGCM alleviates various pathological factors of psoriasis through multiple compounds, multiple targets, and multiple pathways.

Exploring active ingredients and function mechanisms of Ephedra-bitter almond for prevention and treatment of Corona virus disease 2019 (COVID-19) based on network pharmacology

BackgroundCOVID-19 has caused a global pandemic, and there is no wonder drug for epidemic control at present. However, many clinical practices have shown that traditional Chinese medicine has played an important role in treating the outbreak. Among them, ephedra-bitter almond is a common couplet medicine in anti-COVID-19 prescriptions. This study aims to conduct an exploration of key components and mechanisms of ephedra-bitter almond anti-COVID-19 based on network pharmacology.Material and methodsWe collected and screened potential active components of ephedra-bitter almond based on the TCMSP Database, and we predicted targets of the components. Meanwhile, we collected relevant targets of COVID-19 through the GeneCards and CTD databases. Then, the potential targets of ephedra-bitter almond against COVID-19 were screened out. The key components, targets, biological processes, and pathways of ephedra-bitter almond anti-COVID-19 were predicted by constructing the relationship network of herb-component-target (H-C-T), protein-protein interaction (PPI), and functional enrichment. Finally, the key components and targets were docked by AutoDock Vina to explore their binding mode.ResultsEphedra-bitter almond played an overall regulatory role in anti-COVID-19 via the patterns of multi-component-target-pathway. In addition, some key components of ephedra-bitter almond, such as β-sitosterol, estrone, and stigmasterol, had high binding activity to 3CL and ACE2 by molecular docking simulation, which provided new molecular structures for new drug development of COVID-19.ConclusionEphedra-bitter almonds were used to prevent and treat COVID-19 through directly inhibiting the virus, regulating immune responses, and promoting body repair. However, this work is a prospective study based on data mining, and the findings need to be interpreted with caution.

Application and Pharmacological Properties of Chinese Herb Danggui: A System Review

History of the usage of Angelica sinensis (Danggui in Chinese) is glorious, it often acts as monarch drug compatible in various classical formulations. Angelica sinensis can be widely used in treatment of gynecologic diseases and all kinds of blood-deficiency fever by tonifying blood and repairing vitality. It contains abundant volatile oil, organic acid and Angelica sinensis polysaccharide, coumarin, trace elements and amino acids, which possesses extensive pharmacological activities include resistant to cancer and tumour, regulation of blood system, hepatoprotective effects, anti-inflammatory action, antioxidant activity, protection of nervous system, as well as cardioprotective effects. Based on numerous reports and the published scientific literature recent years, an extensive review of research on chemical components, pharmacological activities and the compatibility application of Angelica sinensis were conducted. The relationship between active ingredients and the corresponding pharmacological effects, as well as commonly used couplet medicines and the utility in clinic were simultaneously summarized.

Study on the mechanism of two related Chinese herbs Danggui-Baishao in treating cardiovascular diseases based on network pharmacology

Objective By adopting network pharmacology to study the mechanism of the two classical Chinese herbs Danggui-Baishao in treating cardiovascular diseases. Methods By searching from TCMSP and related literature, together with the databases of TCMSP, SWISS and STITCH, potential active compounds of Danggui-Baishao were collected, while the targets for cardiovascular diseases were obtained from TTD, OMIM and DrugBank databases. Then the PPI network was screened for the major targets. The KEGG Pathway annotation analyses of major targets were performed by using the DAVID database. The ingredient-major target-key pathway network was constructed by Cytoscape. Results There were 17 compounds and 54 major targets in the ingredient-target-pathway network, as well as 10 key pathways, including inflammation-related pathway (TNF signaling pathway), pathways related to cardiovascular system (such as PI3K-Akt signaling pathway, FoxO signaling pathway, VEGF signaling pathway, Rap1 signaling pathway), prolactin signaling pathway and estrogen signaling pathway. Conclusions The study verified the characteristics of multi-components, multi-targets and integral regulation for Danggui-Baishao with the application of network pharmacology. It predicted that Dangui-Baishao couldtreat cardiovascular diseases mainly by regulating angiogenesis, inflammatory response and apoptosis. Key words: Angelica sinensis; Paeoniae radix alba; Couplet medicines; Cardiovascular diseases; Network pharmacology

Couplet medicines of leech and centipede granules improve erectile dysfunction via inactivation of the CaSR/PLC/PKC signaling in streptozotocin-induced diabetic rats.

Erectile dysfunction (ED) is one of the significant complications of diabetes mellitus (DM), and CASR plays an important role in cellular antiapoptosis and NO production in the vascular endothelium by activating PKC. The present study was aimed to investigate the efficacy of Leech and Centipede Granules (LCG) through the CaSR/PLC/PKC signaling. Fifty male Sprague-Dawley rats were treated with streptozotocin to induce the DM model. After 10 weeks, an apomorphine test was used to confirm DMED. Rats with DMED were administrated with LCG and U73122 for 4 weeks. Fasting blood glucose, body weight, insulin and glucagon levels were measured. Erectile function in rats was assessed by apomorphine. Serums were measured using enzyme-linked immunosorbent assay and flow cytometry, and penile tissues were harvested for histologic and the expression of related targets analyses. After treatment, fasting blood glucose, body weight, insulin, glucagon levels, and erectile function were significantly ameliorated in the LCG groups. The LOX-1, NOX, and EMPs concentrations were significantly decreased with LCG treatment. LCG also continuously increased NO and decreased ET-1 content in penile tissues. LCG and U73122 administration also improved penile fibrosis by significantly decreasing VCAM-1, ICAM-1, and CD62P. The data also showed that LCG reduced the apoptosis level in the penis. Furthermore, the inhibited activation of the CaSR/PLC/PKC pathway was observed in DMED rats with LCG treatment. Collectively, LCG significantly ameliorated erectile function of DMED rats via increased NO generation, inhibiting endothelial cells apoptosis and penile fibrosis, which might benefit from the suppression of CaSR/PLC/PKC pathway in DMED rats.

Prescription and treatment rules for the prescriptions containing Poria cocos and Atractylodes macrocephala couplet medicine based on traditional Chinese Medicine inheritance support platform

Prescription and treatment rules for the prescriptions containing Poria cocos and Atractylodes macrocephala couplet medicine based on traditional Chinese Medicine inheritance support platform