Sulfanilamide, sulfadiazine, and dapsone were the first sulfonamides to be used to treat malaria by disrupting the folate biosynthesis process, which is essential for parasite survival. Therefore, we aimed to synthesize novel N-(2-arylaminophenyl)-2,3-diphenylquinoxaline-6-sulfonamide derivatives through a rational drug design approach.
Methods
All compounds were synthesized by the conventional method, and the products were characterized by spectral analysis (1H NMR and mass spectrometry). The progression of the reaction was monitored using thin-layer chromatography (TLC). All the derivatives were analyzed for their effective binding mode in the allosteric site of the plasmodium cysteine protease falcipain-2. Antibacterial and antifungal activities were determined using the broth dilution method.
Results
S6 (N-(2-thiazol-4yl)-acetyl-aminophenyl)-2,3-diphenylquinoxaline-6-sulfonamide and S9 (N-(1H-benzo[d]imidazol-2-yl)aminophenyl)-2,3-diphenylquinoxaline-6-sulfonamide formed five hydrogen bonds; S8 (N-(2-1H-imidazol-2yl)aminophenyl)-2,3-diphenylquinoxaline-6-sulfonamide and S10 (N-(1H-benzo[d]imidazol-5-yl)aminophenyl)-2,3-diphenylquinoxaline-6-sulfonamide formed four hydrogen bonds with the allosteric site of the enzyme. Considering the docking scores and formation of hydrogen bonds with the target enzyme, the novel derivatives were processed for wet lab synthesis. All the newly synthesized derivatives were subjected to in vitro antimalarial, antifungal, and antibacterial activities. All the derivatives exhibited sufficient sensitivity to the Plasmodium falciparum strain compared to the standards. Moreover, compounds S9 and S10 showed the most potent dual antimicrobial and antimalarial activities. They also exhibited powerful molecular interactions in molecular docking studies.
Conclusion
Based on the above results, it was concluded that N-(2-arylaminophenyl)-2,3-diphenylquinoxaline-6-sulfonamide derivatives have excellent biological potential to act as antimalarial, antifungal, and antibacterial agents.
{"title":"Rational drug design, synthesis, and biological evaluation of novel N-(2-arylaminophenyl)-2,3-diphenylquinoxaline-6-sulfonamides as potential antimalarial, antifungal, and antibacterial agents","authors":"Ahmed Hassen Shntaif , Sharuk Khan , Ganesh Tapadiya , Anand Chettupalli , Shweta Saboo , Mohd Sayeed Shaikh , Falak Siddiqui , Ramkoteswra Rao Amara","doi":"10.1016/j.dcmed.2021.12.004","DOIUrl":"https://doi.org/10.1016/j.dcmed.2021.12.004","url":null,"abstract":"<div><h3>Objective</h3><p>Sulfanilamide, sulfadiazine, and dapsone were the first sulfonamides to be used to treat malaria by disrupting the folate biosynthesis process, which is essential for parasite survival. Therefore, we aimed to synthesize novel N-(2-arylaminophenyl)-2,3-diphenylquinoxaline-6-sulfonamide derivatives through a rational drug design approach.</p></div><div><h3>Methods</h3><p>All compounds were synthesized by the conventional method, and the products were characterized by spectral analysis (<sup>1</sup>H NMR and mass spectrometry). The progression of the reaction was monitored using thin-layer chromatography (TLC). All the derivatives were analyzed for their effective binding mode in the allosteric site of the plasmodium cysteine protease falcipain-2. Antibacterial and antifungal activities were determined using the broth dilution method.</p></div><div><h3>Results</h3><p>S6 <em>(N-(2-thiazol-4yl)-acetyl-aminophenyl)-2,3-diphenylquinoxaline-6-sulfonamide</em> and S9 <em>(N-(1H-benzo[d]imidazol-2-yl)aminophenyl)-2,3-diphenylquinoxaline-6-sulfonamide</em> formed five hydrogen bonds; S8 <em>(N-(2-1H-imidazol-2yl)aminophenyl)</em>-<em>2,3-diphenylquinoxaline-6-sulfonamide</em> and S10 <em>(N-(1H-benzo[d]imidazol-5-yl)aminophenyl)-2,3-diphenylquinoxaline-6-sulfonamide</em> formed four hydrogen bonds with the allosteric site of the enzyme. Considering the docking scores and formation of hydrogen bonds with the target enzyme, the novel derivatives were processed for wet lab synthesis. All the newly synthesized derivatives were subjected to <em>in vitro</em> antimalarial, antifungal, and antibacterial activities. All the derivatives exhibited sufficient sensitivity to the <em>Plasmodium falciparum</em> strain compared to the standards. Moreover, compounds S9 and S10 showed the most potent dual antimicrobial and antimalarial activities. They also exhibited powerful molecular interactions in molecular docking studies.</p></div><div><h3>Conclusion</h3><p>Based on the above results, it was concluded that N-(2-arylaminophenyl)-2,3-diphenylquinoxaline-6-sulfonamide derivatives have excellent biological potential to act as antimalarial, antifungal, and antibacterial agents.</p></div>","PeriodicalId":33578,"journal":{"name":"Digital Chinese Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589377721000483/pdfft?md5=f7a7585ef0153b08ed0356457e8fdddd&pid=1-s2.0-S2589377721000483-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"137389761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-12-01DOI: 10.1016/j.dcmed.2021.12.003
Luo Xiaoying , Yang Yang , Mao Xinyong , Song Gengqing , Liu Qian , Jiang Tianyuan , Wei Wei
Objective
To evaluate the efficacy and safety of traditional Chinese medicine (TCM) compounds for the treatment of functional dyspepsia (FD).
Methods
The PubMed, Embase, Cochrane Library, Web of Science, Chinese Biomedical Database (CBM), Wanfang Data, China National Knowledge Infrastructure (CNKI), and China Science and Technology Journal Database (VIP) were searched to collect randomized, double-blind, and placebo-controlled trials of FD treated with TCM compounds. The search duration was from the establishment of the database to March 2, 2021. After two researchers independently screened the literature, extracted the data, and evaluated the bias risk included in the study, they used RevMan 5.4 software for meta-analysis.
Results
A total of 23 clinical trials were included, including 2 898 patients. Meta-analysis showed that the overall remission rate of FD treated with TCM compounds was significantly higher than that of placebo (73.8% vs. 46.2%) [RR = 1.50, 95% CI (1.29, 1.76), P < 0.000 01]. Among the single symptoms, TCM compounds were superior to the placebo in improving epigastric pain [MD =-0.99, 95% CI (-1.37,-0.61), P < 0.000 01], epigastric burning sensation [MD =-0.32, 95% CI (-0.59,-0.05), P = 0.02], postprandial fullness discomfort [MD = -1.59, 95% CI (-1.96, -1.21), P < 0.000 01], and early satiety symptoms [MD = -0.93, 95% CI (-1.32, -0.54), P < 0.000 01]. Compared with the placebo, TCM compounds treatment can obviously improve TCM syndrome in patients with FD [MD = -5.58, 95% CI (-7.55,-3.61), P < 0.000 01], gastric emptying rate [MD = 12. 22, 95% CI (8.90, 15.55), P < 0.00001], and helped to improve patients' quality of life [MD = 11.27, 95% CI (0.10, 22.43), P = 0.05]. No severe adverse events were reported between the two groups [RR = 1.34, 95% CI (0.91, 1.96), P = 0.14].
Conclusion
Our results showed that TCM compounds treatment could significantly alleviate FD symptoms, improve gastric emptying in FD patients, and help to improve their quality of life. No severe adverse reactions have been reported in clinical applications. Due to the limitation of the quantity and quality of the included studies, the above conclusions need to be verified by more high-quality studies.
目的评价中药复方治疗功能性消化不良(FD)的疗效和安全性。方法检索PubMed、Embase、Cochrane图书馆、Web of Science、中国生物医学数据库(CBM)、万方数据、中国知网(CNKI)和中国科技期刊数据库(VIP)，收集中药复方治疗FD的随机、双盲和安慰剂对照试验。检索时间为数据库建立至2021年3月2日。两位研究者独立筛选文献、提取资料、评估纳入研究的偏倚风险后，使用RevMan 5.4软件进行meta分析。结果共纳入23项临床试验，纳入患者2 898例。meta分析显示，中药复方治疗FD的总缓解率显著高于安慰剂组(73.8% vs 46.2%) [RR = 1.50, 95% CI (1.29, 1.76)， P <0.000 01]。在单一症状中，中药复方在改善胃脘痛方面优于安慰剂[MD =-0.99, 95% CI (-1.37，-0.61)， P <0.000 01]、上胃烧灼感[MD =-0.32, 95% CI (-0.59，-0.05)， P = 0.02]、餐后饱腹不适[MD = -1.59, 95% CI (-1.96， -1.21)， P <0.000 01]和早期饱腹症状[MD = -0.93, 95% CI (-1.32， -0.54)， P <0.000 01]。与安慰剂相比，中药复方治疗可明显改善FD患者中医证候[MD = -5.58, 95% CI (-7.55，-3.61)， P <0.000 01]，胃排空率[MD = 12]。22, 95% CI (8.90, 15.55)， P <0.00001]，有助于改善患者的生活质量[MD = 11.27, 95% CI (0.10, 22.43)， P = 0.05]。两组间无严重不良事件发生[RR = 1.34, 95% CI (0.91, 1.96)， P = 0.14]。结论中药复方治疗可明显缓解FD患者的症状，改善FD患者的胃排空，提高患者的生活质量。临床应用中未见严重不良反应的报道。由于纳入研究的数量和质量的限制，上述结论需要更多高质量的研究来验证。
{"title":"Traditional Chinese medicine compounds for the treatment of functional dyspepsia: an updated meta-analysis of randomized, double-blind, placebo-controlled trials","authors":"Luo Xiaoying , Yang Yang , Mao Xinyong , Song Gengqing , Liu Qian , Jiang Tianyuan , Wei Wei","doi":"10.1016/j.dcmed.2021.12.003","DOIUrl":"10.1016/j.dcmed.2021.12.003","url":null,"abstract":"<div><h3>Objective</h3><p>To evaluate the efficacy and safety of traditional Chinese medicine (TCM) compounds for the treatment of functional dyspepsia (FD).</p></div><div><h3>Methods</h3><p>The PubMed, Embase, Cochrane Library, Web of Science, Chinese Biomedical Database (CBM), Wanfang Data, China National Knowledge Infrastructure (CNKI), and China Science and Technology Journal Database (VIP) were searched to collect randomized, double-blind, and placebo-controlled trials of FD treated with TCM compounds. The search duration was from the establishment of the database to March 2, 2021. After two researchers independently screened the literature, extracted the data, and evaluated the bias risk included in the study, they used RevMan 5.4 software for meta-analysis.</p></div><div><h3>Results</h3><p>A total of 23 clinical trials were included, including 2 898 patients. Meta-analysis showed that the overall remission rate of FD treated with TCM compounds was significantly higher than that of placebo (73.8% vs. 46.2%) [RR = 1.50, 95% CI (1.29, 1.76), <em>P</em> < 0.000 01]. Among the single symptoms, TCM compounds were superior to the placebo in improving epigastric pain [MD =-0.99, 95% CI (-1.37,-0.61), <em>P</em> < 0.000 01], epigastric burning sensation [MD =-0.32, 95% CI (-0.59,-0.05), <em>P</em> = 0.02], postprandial fullness discomfort [MD = -1.59, 95% CI (-1.96, -1.21), <em>P</em> < 0.000 01], and early satiety symptoms [MD = -0.93, 95% CI (-1.32, -0.54), <em>P</em> < 0.000 01]. Compared with the placebo, TCM compounds treatment can obviously improve TCM syndrome in patients with FD [MD = -5.58, 95% CI (-7.55,-3.61), <em>P</em> < 0.000 01], gastric emptying rate [MD = 12. 22, 95% CI (8.90, 15.55), <em>P</em> < 0.00001], and helped to improve patients' quality of life [MD = 11.27, 95% CI (0.10, 22.43), <em>P</em> = 0.05]. No severe adverse events were reported between the two groups [RR = 1.34, 95% CI (0.91, 1.96), <em>P</em> = 0.14].</p></div><div><h3>Conclusion</h3><p>Our results showed that TCM compounds treatment could significantly alleviate FD symptoms, improve gastric emptying in FD patients, and help to improve their quality of life. No severe adverse reactions have been reported in clinical applications. Due to the limitation of the quantity and quality of the included studies, the above conclusions need to be verified by more high-quality studies.</p></div>","PeriodicalId":33578,"journal":{"name":"Digital Chinese Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589377721000471/pdfft?md5=d6dd4248d94f0d283fe5a6d3eb1826d3&pid=1-s2.0-S2589377721000471-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83795238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-10-01DOI: 10.1016/j.dcmed.2021.09.003
Subhash R. Yende , Sapan K. Shah , Sumit K. Arora , Keshav S. Moharir , Govind K. Lohiya
Objective
Rheumatoid arthritis (RA) is an autoimmune disease involving the synovial lining of the major joints. Current therapies have noteworthy side effects. Our study involved in silico evaluation of Ehretia laevis (E. laevis) phytoconstituents targeting tumor necrosis factor-α (TNF-α).
Methods
Molecular docking studies performed to investigate the binding pattern of the plant E. laevis phytoconstituents along with the crystal structure of TNF-α (PDB ID: 2AZ5) using AutoDock Vina followed by a study of interacting amino acid residues and their influence on the inhibitory potentials of the active constituents. Further the pharmacokinetic profile and toxicity screening carried out using SwissADME and pkCSM.
Results
The docked results suggest that lupeol (− 9.4 kcal/mol) and α-amyrin (− 9.4 kcal/mol) has best affinity towards TNF-α compared to standard drug thalidomide (− 7.4 kcal/mol). The active chemical constituents represents better interaction with the conserved catalytic residues, leading to the inhibition/blockade of the TNF-α-associated signaling pathway in RA. Furthermore, pharmacokinetics and toxicity parameters of these phytochemicals were within acceptable limits according to ADMET studies.
Conclusion
The binding potential of phytoconstituents targeting TNF-α showed promising results. Nonetheless, it encourages the traditional use of E. laevis and provides vital information on drug development and clinical treatment.
{"title":"In silico prediction of phytoconstituents from Ehretia laevis targeting TNF-α in arthritis","authors":"Subhash R. Yende , Sapan K. Shah , Sumit K. Arora , Keshav S. Moharir , Govind K. Lohiya","doi":"10.1016/j.dcmed.2021.09.003","DOIUrl":"10.1016/j.dcmed.2021.09.003","url":null,"abstract":"<div><h3>Objective</h3><p>Rheumatoid arthritis (RA) is an autoimmune disease involving the synovial lining of the major joints. Current therapies have noteworthy side effects. Our study involved <em>in silico</em> evaluation of <em>Ehretia laevis</em> (<em>E. laevis</em>) phytoconstituents targeting tumor necrosis factor-<em>α</em> (TNF-<em>α</em>).</p></div><div><h3>Methods</h3><p>Molecular docking studies performed to investigate the binding pattern of the plant <em>E. laevis</em> phytoconstituents along with the crystal structure of TNF-<em>α</em> (PDB ID: 2AZ5) using AutoDock Vina followed by a study of interacting amino acid residues and their influence on the inhibitory potentials of the active constituents. Further the pharmacokinetic profile and toxicity screening carried out using SwissADME and pkCSM.</p></div><div><h3>Results</h3><p>The docked results suggest that lupeol (− 9.4 kcal/mol) and <em>α</em>-amyrin (− 9.4 kcal/mol) has best affinity towards TNF-<em>α</em> compared to standard drug thalidomide (− 7.4 kcal/mol). The active chemical constituents represents better interaction with the conserved catalytic residues, leading to the inhibition/blockade of the TNF-<em>α</em>-associated signaling pathway in RA. Furthermore, pharmacokinetics and toxicity parameters of these phytochemicals were within acceptable limits according to ADMET studies.</p></div><div><h3>Conclusion</h3><p>The binding potential of phytoconstituents targeting TNF-<em>α</em> showed promising results. Nonetheless, it encourages the traditional use of <em>E. laevis</em> and provides vital information on drug development and clinical treatment.</p></div>","PeriodicalId":33578,"journal":{"name":"Digital Chinese Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589377721000318/pdfft?md5=4b53abc9a35b066bd74795d91b60a0cc&pid=1-s2.0-S2589377721000318-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87946680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-10-01DOI: 10.1016/j.dcmed.2021.09.004
SHENG Mengke , LIU Xing , LIAO Yuyao , LI Zhixun , LYU Lijing , YANG Jiaqi , SHI Xinyuan
Objective
To investigate the active components and mechanism of Sanao Decoction (三拗汤, SAD) in treating chronic cough based on network pharmacology and molecular docking.
Methods
Active components and their targets were obtained from the Traditional Chinese Medicine Systems and Pharmacology Database and Analysis Platform (TCMSP), Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine (BATMAN-TCM) database, and the literature. The component-target regulatory network and protein-protein interaction (PPI) network were constructed by Cytoscape 3.7.2, and a bioinformatics analysis was performed to identify the significant pathways and their relevant targets. Molecular docking of the core active components and relevant targets was performed.
Results
A total of 98 active components of SAD and the corresponding 113 drug targets were identified. The component-target regulatory network and PPI network were successfully established. Results of the bioinformatics analysis indicated that 2 281 Gene Ontology (GO) terms were enriched in chronic cough, including 2 062 terms were in biological processes, 77 in cellular components, and 142 in molecular functions, and top 20 significant pathways in Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Molecular docking study demonstrated that quercetin, luteolin, kaempferol, and naringenin were in good agreement with the corresponding targets.
Conclusion
The active compounds of SAD, such as quercetin, luteolin, kaempferol, and naringenin, may act on AKT1, MAPK1, RELA, EGFR, and Bcl-2 and regulate the PI3K-Akt signaling pathway, AGE-RAGE signaling pathway, and fluid shear stress and atherosclerosis pathway to exert the effects of anti-inflammatory, anti-airway remodeling, anti-oxidant stress effects, and repair airway damage, thus treating chronic cough.
{"title":"Investigation of the active components and mechanism of Sanao Decoction in treating chronic cough by network pharmacology and molecular docking","authors":"SHENG Mengke , LIU Xing , LIAO Yuyao , LI Zhixun , LYU Lijing , YANG Jiaqi , SHI Xinyuan","doi":"10.1016/j.dcmed.2021.09.004","DOIUrl":"10.1016/j.dcmed.2021.09.004","url":null,"abstract":"<div><h3>Objective</h3><p>To investigate the active components and mechanism of Sanao Decoction (三拗汤, SAD) in treating chronic cough based on network pharmacology and molecular docking.</p></div><div><h3>Methods</h3><p>Active components and their targets were obtained from the Traditional Chinese Medicine Systems and Pharmacology Database and Analysis Platform (TCMSP), Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine (BATMAN-TCM) database, and the literature. The component-target regulatory network and protein-protein interaction (PPI) network were constructed by Cytoscape 3.7.2, and a bioinformatics analysis was performed to identify the significant pathways and their relevant targets. Molecular docking of the core active components and relevant targets was performed.</p></div><div><h3>Results</h3><p>A total of 98 active components of SAD and the corresponding 113 drug targets were identified. The component-target regulatory network and PPI network were successfully established. Results of the bioinformatics analysis indicated that 2 281 Gene Ontology (GO) terms were enriched in chronic cough, including 2 062 terms were in biological processes, 77 in cellular components, and 142 in molecular functions, and top 20 significant pathways in Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Molecular docking study demonstrated that quercetin, luteolin, kaempferol, and naringenin were in good agreement with the corresponding targets.</p></div><div><h3>Conclusion</h3><p>The active compounds of SAD, such as quercetin, luteolin, kaempferol, and naringenin, may act on AKT1, MAPK1, RELA, EGFR, and Bcl-2 and regulate the PI3K-Akt signaling pathway, AGE-RAGE signaling pathway, and fluid shear stress and atherosclerosis pathway to exert the effects of anti-inflammatory, anti-airway remodeling, anti-oxidant stress effects, and repair airway damage, thus treating chronic cough.</p></div>","PeriodicalId":33578,"journal":{"name":"Digital Chinese Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S258937772100032X/pdfft?md5=b2541462617e60f926cfb53fdd773ac5&pid=1-s2.0-S258937772100032X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89951095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-10-01DOI: 10.1016/j.dcmed.2021.09.008
CHEN Cong , LIU Yang , TONG Qiaozhen , ZHANG Yi , HU Xudong , LIAO Jing
Objective
To investigate the protective effects of Jiawei Danshen Decoction (加味丹参饮, JWDSD) on myocardial ischemia-reperfusion injury (MIRI) via the regulation of serum Hydrogen sulfide (H2S) and cardiac Beclin1, light Chain 3A/B (LC3A/B), p62, and autophagy protein5 (ATG5).
Methods
Seventy specific pathogen free (SPF) Sprague-Dawley (SD) rats were randomly assigned to seven groups (n = 10 in each group), including normal control, sham operation, MIRI model (model), ischemic preconditioning, NaHS, JWDSD, and JWDSD +CSE inhibitor (JWDSD + PPG) groups, and orally administered the indicated drugs for 14 d. Two hours after the last administration, the left anterior decreased branch of the coronary artery of each rat in model, NaHS, JWDSD, and JWDSD + PPG groups was ligated for 30 min and subsequently reperfused for 90 min to establish the MIRI model, and the rats in the sham operation group were only exposed to the thorax after surgery without coronary ligation. Blood samples were collected to detect H2S levels using an enzyme-linked immunosorbent assay (ELISA). Heart tissues were harvested for histopathological and immunohistochemical examination and quantitative reverse transcription polymerase chain reaction analysis of Beclin1 and ATG5 mRNA expression and Western blot analysis of Beclin1, LC3A/B, and p62 protein expression.
Results
(1) The serum H2S content in model group rats was significantly reduced (P < 0.01), JWDSD significantly increased the serum H2S content of model group rats (P < 0.01), and the CSE inhibitor (PPG) significantly reduced H2S levels in the JWDSD group rats (P < 0.01). (2) Compared with the normal control group, the myocardial tissue necrosis and cell destruction occurred in the MIRI model group, and JWDSD could alleviate the myocardial tissue necrosis of model rats, but the ameliorative effect of JWDSD could be reversed by PPG. (3) Beclin1, LC3A/B, and p62 expression levels in the heart tissues of the model group were significantly increased (P < 0.001), whereas decreased by JWDSD (P < 0.05, P < 0.01, and P < 0.001, respectively), and the inhibitory effects of JWDSD on Beclin1, LC3A/B, and p62 expression were partially reversed by PPG (P < 0.01, P < 0.05, and P < 0.01, respectively). (4) The expression levels of autophagy-related genes Beclin1 and ATG5 were significantly increased in the model group (P < 0.001). JWDSD clearly downregulated the expression levels of Beclin1 and ATG5 (P < 0.05 and P < 0.001, respectively), which were reversed by PPG (P < 0.001).
Conclusion
Our experimental data show that JWDSD can exhibit an anti-MIRI role by increasing endogenous H2S generation, and downregulating
目的探讨加味丹参汤通过调节血清硫化氢(H2S)和心肌Beclin1、轻链3A/B (LC3A/B)、p62和自噬蛋白5 (ATG5)对心肌缺血再灌注损伤(MIRI)的保护作用。方法70只SPF级SD大鼠随机分为正常对照组、假手术组、MIRI模型组(模型)、缺血预处理组、NaHS组、JWDSD组和JWDSD +CSE抑制剂(JWDSD + PPG)组，每组10只，分别口服指定药物14 d。末次给药2 h后，NaHS组、JWDSD组、JWDSD组、JWDSD + PPG组结扎30 min后再灌注90 min建立MIRI模型，假手术组术后只暴露胸腔，不结扎冠状动脉。采集血样，采用酶联免疫吸附试验(ELISA)检测H2S水平。取心脏组织进行组织病理学和免疫组织化学检查，定量逆转录聚合酶链反应分析Beclin1、ATG5 mRNA表达，Western blot分析Beclin1、LC3A/B、p62蛋白表达。结果(1)模型组大鼠血清H2S含量显著降低(P <0.01)， JWDSD显著提高模型组大鼠血清H2S含量(P <0.01)， CSE抑制剂(PPG)显著降低JWDSD组大鼠H2S水平(P <0.01)。(2)与正常对照组比较，MIRI模型组心肌组织坏死和细胞破坏，JWDSD可减轻模型大鼠心肌组织坏死，但PPG可逆转JWDSD的改善作用。(3)模型组大鼠心脏组织Beclin1、LC3A/B、p62表达水平显著升高(P <0.001)，而JWDSD降低(P <0.05, P <0.01, P <PPG部分逆转了JWDSD对Beclin1、LC3A/B和p62表达的抑制作用(P <0.01, P <0.05, P <分别为0.01)。(4)模型组大鼠自噬相关基因Beclin1、ATG5表达水平显著升高(P <0.001)。JWDSD明显下调Beclin1和ATG5的表达水平(P <0.05和P <0.001)，而PPG逆转了这一趋势(P <0.001)。结论JWDSD通过增加内源性H2S的生成，下调Beclin1、LC3A/B、p62和ATG5的表达，具有抑制自噬信号通路的抗miri作用。
{"title":"The therapeutic effect of Jiawei Danshen Decoction on myocardial ischemia-reperfusion injury by inhibiting H2S-mediated autophagy signaling pathway","authors":"CHEN Cong , LIU Yang , TONG Qiaozhen , ZHANG Yi , HU Xudong , LIAO Jing","doi":"10.1016/j.dcmed.2021.09.008","DOIUrl":"10.1016/j.dcmed.2021.09.008","url":null,"abstract":"<div><h3>Objective</h3><p>To investigate the protective effects of Jiawei Danshen Decoction (加味丹参饮, JWDSD) on myocardial ischemia-reperfusion injury (MIRI) via the regulation of serum Hydrogen sulfide (H<sub>2</sub>S) and cardiac Beclin1, light Chain 3A/B (LC3A/B), p62, and autophagy protein5 (ATG5).</p></div><div><h3>Methods</h3><p>Seventy specific pathogen free (SPF) Sprague-Dawley (SD) rats were randomly assigned to seven groups (<em>n</em> = 10 in each group), including normal control, sham operation, MIRI model (model), ischemic preconditioning, NaHS, JWDSD, and JWDSD +CSE inhibitor (JWDSD + PPG) groups, and orally administered the indicated drugs for 14 d. Two hours after the last administration, the left anterior decreased branch of the coronary artery of each rat in model, NaHS, JWDSD, and JWDSD + PPG groups was ligated for 30 min and subsequently reperfused for 90 min to establish the MIRI model, and the rats in the sham operation group were only exposed to the thorax after surgery without coronary ligation. Blood samples were collected to detect H<sub>2</sub>S levels using an enzyme-linked immunosorbent assay (ELISA). Heart tissues were harvested for histopathological and immunohistochemical examination and quantitative reverse transcription polymerase chain reaction analysis of Beclin1 and ATG5 mRNA expression and Western blot analysis of Beclin1, LC3A/B, and p62 protein expression.</p></div><div><h3>Results</h3><p>(1) The serum H<sub>2</sub>S content in model group rats was significantly reduced (<em>P</em> < 0.01), JWDSD significantly increased the serum H<sub>2</sub>S content of model group rats (<em>P</em> < 0.01), and the CSE inhibitor (PPG) significantly reduced H<sub>2</sub>S levels in the JWDSD group rats (<em>P</em> < 0.01). (2) Compared with the normal control group, the myocardial tissue necrosis and cell destruction occurred in the MIRI model group, and JWDSD could alleviate the myocardial tissue necrosis of model rats, but the ameliorative effect of JWDSD could be reversed by PPG. (3) Beclin1, LC3A/B, and p62 expression levels in the heart tissues of the model group were significantly increased (<em>P</em> < 0.001), whereas decreased by JWDSD (<em>P</em> < 0.05, <em>P</em> < 0.01, and <em>P</em> < 0.001, respectively), and the inhibitory effects of JWDSD on Beclin1, LC3A/B, and p62 expression were partially reversed by PPG (<em>P</em> < 0.01, <em>P</em> < 0.05, and <em>P</em> < 0.01, respectively). (4) The expression levels of autophagy-related genes Beclin1 and ATG5 were significantly increased in the model group (<em>P</em> < 0.001). JWDSD clearly downregulated the expression levels of Beclin1 and ATG5 (<em>P</em> < 0.05 and <em>P</em> < 0.001, respectively), which were reversed by PPG (<em>P</em> < 0.001).</p></div><div><h3>Conclusion</h3><p>Our experimental data show that JWDSD can exhibit an anti-MIRI role by increasing endogenous H<sub>2</sub>S generation, and downregulating ","PeriodicalId":33578,"journal":{"name":"Digital Chinese Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589377721000367/pdfft?md5=794f0af6bd6532557e98bcfae2b0b4ec&pid=1-s2.0-S2589377721000367-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73453577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-10-01DOI: 10.1016/j.dcmed.2021.09.005
LEI Zhiqiang , WANG Chaoping , Abid Naeem , YIN Ning , CAO Meifang , LUO Jing
Objective
To explore the pharmacodynamic material basis and mechanism of action of volatile oil from Chuanxiong (Chuanxiong Rhizoma) - Suhexiang (Styrax) - Bingpian (Borneolum) (hereinafter referred to as C-S-B volatile oil) in treating angina pectoris based on network pharmacology and to detect its protective effects against rat myocardial damage.
Methods
Gas chromatography-mass spectrometry (GC-MS) was used to determine the constituents of volatile oils from Chuanxiong (Chuanxiong Rhizoma), Suhexiang (Styrax), and Bingpian (Borneolum), and the targets of the three main constituents were found predicted and screened using the PharmMapper server, and GeneCards and CooLGeN databases. The STRING database and Cytoscape software were used to draw the protein-protein interaction (PPI) network, RStudio software was used to analyze Gene Ontology (GO) and Kyoto Encyclopedia of Genome and Genome (KEGG) pathways, and Cytoscape software was used to construct the component-target-pathway-disease network. The rat model of myocardial injury was established by intraperitoneal injection of a large dose of isoprenaline hydrochloride. After continuous intervention with C-S-B volatile oil for 14 d, the ejection fraction (EF) and short axis shortening rate (FS) of the left ventricle were detected. The indices of myocardial damage were detected after hematoxylin-eosin (HE) staining.
Results
Fifteen volatile oil components from the C-S-B formula were identified. There are 470 targets of these volatile oil components and 401 angina-related genes. There are 28 core targets, including CHRM4, ADRA1A, FGFR1, CHRM2, CYP2A6, CHRM5, CHRM1, CHRM3, HDAC2, and MPO, etc.. The results of the KEGG analysis indicated that the C-S-B formula probably interferes with the following pathways: neuroactive ligand-receptor interactions, calcium signaling, cytochrome P450 metabolism of heteropoietin, among others. The results of animal experiments showed that the C-S-B formula essential oil could significantly improve the following myocardial indices in rats with myocardial injury: EF, FS, left ventricular end-systolic diameter (LVIDs), left ventricular end-diastolic diameter (LVIDd), and stroke volume (SV), and all the differences were statistically significant (P < 0.01).
Conclusion
The mechanism of action of volatile oil components in the C-S-B formula in treating angina pectoris was analyzed using multi-component, multi-target and multi-pathway systems, which has laid a foundation for further revealing its mechanism of action. Animal experiments have shown that the volatile oil of the C-S-B formula can improve EF, FS, and other indices of myocardial damage in a rat model, thus relieving myocardial damage caused by heart hyperactivity, improving cardiac function, and protecting against myocardial damage.
{"title":"Mechanism of volatile oil from Chuanxiong (Chuanxiong Rhizoma) - Suhexiang (Styrax) - Bingpian (Borneolum) in treating angina pectoris based on network pharmacology and its protective effects on myocardial damage in rats","authors":"LEI Zhiqiang , WANG Chaoping , Abid Naeem , YIN Ning , CAO Meifang , LUO Jing","doi":"10.1016/j.dcmed.2021.09.005","DOIUrl":"10.1016/j.dcmed.2021.09.005","url":null,"abstract":"<div><h3>Objective</h3><p>To explore the pharmacodynamic material basis and mechanism of action of volatile oil from Chuanxiong (Chuanxiong Rhizoma) - Suhexiang (Styrax) - Bingpian (Borneolum) (hereinafter referred to as C-S-B volatile oil) in treating angina pectoris based on network pharmacology and to detect its protective effects against rat myocardial damage.</p></div><div><h3>Methods</h3><p>Gas chromatography-mass spectrometry (GC-MS) was used to determine the constituents of volatile oils from Chuanxiong (Chuanxiong Rhizoma), Suhexiang (Styrax), and Bingpian (Borneolum), and the targets of the three main constituents were found predicted and screened using the PharmMapper server, and GeneCards and CooLGeN databases. The STRING database and Cytoscape software were used to draw the protein-protein interaction (PPI) network, RStudio software was used to analyze Gene Ontology (GO) and Kyoto Encyclopedia of Genome and Genome (KEGG) pathways, and Cytoscape software was used to construct the component-target-pathway-disease network. The rat model of myocardial injury was established by intraperitoneal injection of a large dose of isoprenaline hydrochloride. After continuous intervention with C-S-B volatile oil for 14 d, the ejection fraction (EF) and short axis shortening rate (FS) of the left ventricle were detected. The indices of myocardial damage were detected after hematoxylin-eosin (HE) staining.</p></div><div><h3>Results</h3><p>Fifteen volatile oil components from the C-S-B formula were identified. There are 470 targets of these volatile oil components and 401 angina-related genes. There are 28 core targets, including CHRM4, ADRA1A, FGFR1, CHRM2, CYP2A6, CHRM5, CHRM1, CHRM3, HDAC2, and MPO, etc.. The results of the KEGG analysis indicated that the C-S-B formula probably interferes with the following pathways: neuroactive ligand-receptor interactions, calcium signaling, cytochrome P450 metabolism of heteropoietin, among others. The results of animal experiments showed that the C-S-B formula essential oil could significantly improve the following myocardial indices in rats with myocardial injury: EF, FS, left ventricular end-systolic diameter (LVIDs), left ventricular end-diastolic diameter (LVIDd), and stroke volume (SV), and all the differences were statistically significant (<em>P</em> < 0.01).</p></div><div><h3>Conclusion</h3><p>The mechanism of action of volatile oil components in the C-S-B formula in treating angina pectoris was analyzed using multi-component, multi-target and multi-pathway systems, which has laid a foundation for further revealing its mechanism of action. Animal experiments have shown that the volatile oil of the C-S-B formula can improve EF, FS, and other indices of myocardial damage in a rat model, thus relieving myocardial damage caused by heart hyperactivity, improving cardiac function, and protecting against myocardial damage.</p></div>","PeriodicalId":33578,"journal":{"name":"Digital Chinese Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589377721000331/pdfft?md5=d112cbb8a31245e38b6801c5729ff17a&pid=1-s2.0-S2589377721000331-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78428463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-10-01DOI: 10.1016/j.dcmed.2021.09.007
HAN Jun , ZHENG Qinfang , FANG Liangzi , HUANG Xiaolong
Objective
To screen for α-glucosidase inhibitor active compounds in the total saponins of Baibiandou (Lablab Semen Album) based on UHPLC-Q-Exactive Orbitrap MS technology and to evaluate its hypoglycemic activity in vivo.
Methods
Acarbose was used as the positive control, and the median inhibitory concentration (IC50) was used as the evaluation index of α-glucosidase inhibitory activity to establish an in vitro α-glucosidase inhibition model. Further, UHPLC-Q-Exactive Orbitrap MS technology was used to screen and identify the active compounds of α-glucosidase inhibitors in the total saponins of Baibiandou (Lablab Semen Album) in order to further verify the activity of the main active monomer and to perform homologous modeling and molecular docking of yeast-derived α-glucosidase and human-derived α-glucosidase, while the hypoglycemic activity was evaluated in diabetic mice.
Results
This study successfully identified 15 compounds with potential α-glucosidase inhibitory activity, including Chikusetsusaponin IVa, from the total saponins of Baibiandou (Lablab Semen Album). Simultaneously, we verified the activity of the main active monomer Chikusetsusaponin IVa, and showed that it has strong α-glucosidase inhibitory activity. The α-glucosidase inhibitory concentration IC50 was (565.2 ± 1.026) μg/mL, and the IC50 of acarbose, which was lower than the positive control, was (706.6 ± 1.058) μg/mL. The docking energies of Chikusetsusaponin IVa were – 6.1 and – 7.7 kcal/mol with yeast-derived α-glucosidase and human-derived α-glucosidase molecules, respectively. Both showed strong binding activity, and the levels of alanine aminotransaminase (ALT), aspartate aminotransaminase (AST), UREA, Creatinine (CREA), and cholesterol (CHO) were significantly decreased by Chikusetsusaponin IVa (P < 0.05). In addition, it could repair damaged liver and pancreas cells of diabetic mice to some extent.
Conclusion
This study provides a basis for screening α-glucosidase inhibitors and structural modifications of the total saponins of Baibiandou (Lablab Semen Album).
{"title":"Screening and functional evaluation of the glucose-lowering active compounds of total saponins of Baibiandou (Lablab Semen Album)","authors":"HAN Jun , ZHENG Qinfang , FANG Liangzi , HUANG Xiaolong","doi":"10.1016/j.dcmed.2021.09.007","DOIUrl":"10.1016/j.dcmed.2021.09.007","url":null,"abstract":"<div><h3>Objective</h3><p>To screen for <em>α</em>-glucosidase inhibitor active compounds in the total saponins of Baibiandou (Lablab Semen Album) based on UHPLC-Q-Exactive Orbitrap MS technology and to evaluate its hypoglycemic activity <em>in vivo</em>.</p></div><div><h3>Methods</h3><p>Acarbose was used as the positive control, and the median inhibitory concentration (IC<sub>50</sub>) was used as the evaluation index of <em>α</em>-glucosidase inhibitory activity to establish an <em>in vitro α</em>-glucosidase inhibition model. Further, UHPLC-Q-Exactive Orbitrap MS technology was used to screen and identify the active compounds of <em>α</em>-glucosidase inhibitors in the total saponins of Baibiandou (Lablab Semen Album) in order to further verify the activity of the main active monomer and to perform homologous modeling and molecular docking of yeast-derived <em>α</em>-glucosidase and human-derived <em>α</em>-glucosidase, while the hypoglycemic activity was evaluated in diabetic mice.</p></div><div><h3>Results</h3><p>This study successfully identified 15 compounds with potential <em>α</em>-glucosidase inhibitory activity, including Chikusetsusaponin IVa, from the total saponins of Baibiandou (Lablab Semen Album). Simultaneously, we verified the activity of the main active monomer Chikusetsusaponin IVa, and showed that it has strong <em>α</em>-glucosidase inhibitory activity. The <em>α</em>-glucosidase inhibitory concentration IC<sub>50</sub> was (565.2 ± 1.026) μg/mL, and the IC<sub>50</sub> of acarbose, which was lower than the positive control, was (706.6 ± 1.058) μg/mL. The docking energies of Chikusetsusaponin IVa were – 6.1 and – 7.7 kcal/mol with yeast-derived <em>α</em>-glucosidase and human-derived <em>α</em>-glucosidase molecules, respectively. Both showed strong binding activity, and the levels of alanine aminotransaminase (ALT), aspartate aminotransaminase (AST), UREA, Creatinine (CREA), and cholesterol (CHO) were significantly decreased by Chikusetsusaponin IVa (<em>P</em> < 0.05). In addition, it could repair damaged liver and pancreas cells of diabetic mice to some extent.</p></div><div><h3>Conclusion</h3><p>This study provides a basis for screening <em>α</em>-glucosidase inhibitors and structural modifications of the total saponins of Baibiandou (Lablab Semen Album).</p></div>","PeriodicalId":33578,"journal":{"name":"Digital Chinese Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589377721000355/pdfft?md5=19474449944a55d991135d44e7360e37&pid=1-s2.0-S2589377721000355-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81448622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-10-01DOI: 10.1016/j.dcmed.2021.09.006
Liu Deguo , Li Zirong , Chen Qihua , Wang Yuhong , Xiao Changjiang
Objective
This study aimed to analyze the mechanism of action of the Pingyang Jiangya Formula (平阳降压方, PYJYF) in treating hypertension, based on network pharmacology, and to verify the subsequent predictions through animal experiments.
Methods
The active components and related target genes of PYJYF were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM), Encyclopedia of Traditional Chinese Medicine (ETCM), and DrugBank databases and available literature. The hypertension target genes were screened based on Therapeutic Target Database (TTD), GeneCards, Online Mendelian Inheritance in Man (OMIM), UniProt, and relevant literature. The component-disease-target network intersection target genes were inputted into the STRING database, and the key target genes were selected according to the degree algorithm. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to explore the multitarget mechanism of action and molecular regulatory network of PYJYF in the treatment of hypertension. To verify this prediction, we used PYJYF to intervene in spontaneously hypertensive rats (SHRs) and Wistar–Kyoto rats (WKY) as normal control, and the noninvasive tail artery manometry method was used to measure systolic blood pressure (SBP) in the rat tail before PYJYF intervention. After drug intervention, the SBP of each group rats were measured and compared every week. Enzyme-linked immunosorbent assay (ELISA) was used to test plasma renin, angiotensin II (Ang II), and aldosterone (Ald) levels, and hematoxylin-eosin (HE) staining was used to observe pathological damage to the renal vessels in each group of rats. Western blot and reverse transcription real-time quantitative PCR (RT-PCR) were used to detect the protein and mRNA expression levels of PI3K, AKT1, BAX, and Bcl-2, respectively.
Results
A total of 4 123 hypertension targets were obtained from related databases. From the TCMSP and chemical databases, 78 active components of PYJYF and the corresponding 401 drug targets were retrieved. Data analysis revealed that 208 drug targets directly interacted with the hypertension targets in PYJYF. The 10 targets most closely related to hypertension target proteins in PYJYF were directly retrieved from relevant databases. GO analysis revealed that 10 direct target proteins were involved in all aspects of the antihypertensive effects of PYJYF, as well as molecular biological processes, such as the regulation of blood pressure, renin-angiotensin-aldosterone system (RAAS), angiotensin-mediated ligand reactions, and biological stimulation of cardiomyocyte apoptosis. KEGG pathway enrichment analysis revealed that PYJYF directly affected 20 signaling pathways associated with hypertension. In animal
{"title":"Mechanism of Pingyang Jiangya Formula in treating hypertension based on network pharmacology and in vivo study","authors":"Liu Deguo , Li Zirong , Chen Qihua , Wang Yuhong , Xiao Changjiang","doi":"10.1016/j.dcmed.2021.09.006","DOIUrl":"10.1016/j.dcmed.2021.09.006","url":null,"abstract":"<div><h3>Objective</h3><p>This study aimed to analyze the mechanism of action of the Pingyang Jiangya Formula (平阳降压方, PYJYF) in treating hypertension, based on network pharmacology, and to verify the subsequent predictions through animal experiments.</p></div><div><h3>Methods</h3><p>The active components and related target genes of PYJYF were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM), Encyclopedia of Traditional Chinese Medicine (ETCM), and DrugBank databases and available literature. The hypertension target genes were screened based on Therapeutic Target Database (TTD), GeneCards, Online Mendelian Inheritance in Man (OMIM), UniProt, and relevant literature. The component-disease-target network intersection target genes were inputted into the STRING database, and the key target genes were selected according to the degree algorithm. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to explore the multitarget mechanism of action and molecular regulatory network of PYJYF in the treatment of hypertension. To verify this prediction, we used PYJYF to intervene in spontaneously hypertensive rats (SHRs) and Wistar–Kyoto rats (WKY) as normal control, and the noninvasive tail artery manometry method was used to measure systolic blood pressure (SBP) in the rat tail before PYJYF intervention. After drug intervention, the SBP of each group rats were measured and compared every week. Enzyme-linked immunosorbent assay (ELISA) was used to test plasma renin, angiotensin II (Ang II), and aldosterone (Ald) levels, and hematoxylin-eosin (HE) staining was used to observe pathological damage to the renal vessels in each group of rats. Western blot and reverse transcription real-time quantitative PCR (RT-PCR) were used to detect the protein and mRNA expression levels of PI3K, AKT1, BAX, and Bcl-2, respectively.</p></div><div><h3>Results</h3><p>A total of 4 123 hypertension targets were obtained from related databases. From the TCMSP and chemical databases, 78 active components of PYJYF and the corresponding 401 drug targets were retrieved. Data analysis revealed that 208 drug targets directly interacted with the hypertension targets in PYJYF. The 10 targets most closely related to hypertension target proteins in PYJYF were directly retrieved from relevant databases. GO analysis revealed that 10 direct target proteins were involved in all aspects of the antihypertensive effects of PYJYF, as well as molecular biological processes, such as the regulation of blood pressure, renin-angiotensin-aldosterone system (RAAS), angiotensin-mediated ligand reactions, and biological stimulation of cardiomyocyte apoptosis. KEGG pathway enrichment analysis revealed that PYJYF directly affected 20 signaling pathways associated with hypertension. In animal","PeriodicalId":33578,"journal":{"name":"Digital Chinese Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589377721000343/pdfft?md5=bea7367fac2a14d4d42c86ee1d00a60d&pid=1-s2.0-S2589377721000343-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72791319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-10-01DOI: 10.1016/j.dcmed.2021.09.001
Christian Bailly
Phytolacca
(Shanglu) is a well-known traditional herbal medicine that has been used for thousands of years in China. Phytolacca is also used worldwide in different traditional phyto-medicines and homeopathic preparations. The present work reviewed advances in the traditional uses, plant origin, chemical constituents, pharmacology, and medicinal properties of Phytolacca. Phytolacca is usually made from the roots of Phytolacca acinosa and P. esculenta, but the invasive plant P. americana (American pokeweed) is also widely used. Different types of medicinal products made with Phytolacca are available, as well as various types of Phytolacca extracts, showing a range of pharmacological activities including antioxidant, anti-inflammatory, anti-parasitic, antifungal, anticancer, and insecticidal effects. The marked anti-inflammatory activity of Phytolacca extracts supports its use in treating diseases such as arthritis, nephritis, and rheumatism, as well as in combatting cancer. Several bioactive natural products have been identified from Phytolacca, including glycosylated saponins such as esculentosides and phytolaccosides, as well as a few flavones (cochliophilin A) and phytosterols (α-spinasterol), which contribute to Phytolacca’s anti-inflammatory and/or anticancer effects. A quality evaluation of Phytolacca-based extracts and products is highly recommended; nevertheless, the use of Phytolacca can be encouraged to help regulate cytokine production and combat inflammatory diseases.
{"title":"Medicinal properties and anti-inflammatory components of Phytolacca (Shanglu)","authors":"Christian Bailly","doi":"10.1016/j.dcmed.2021.09.001","DOIUrl":"10.1016/j.dcmed.2021.09.001","url":null,"abstract":"<div><h3>Phytolacca</h3><p>(Shanglu) is a well-known traditional herbal medicine that has been used for thousands of years in China. <em>Phytolacca</em> is also used worldwide in different traditional phyto-medicines and homeopathic preparations. The present work reviewed advances in the traditional uses, plant origin, chemical constituents, pharmacology, and medicinal properties of <em>Phytolacca</em>. <em>Phytolacca</em> is usually made from the roots of <em>Phytolacca acinosa</em> and <em>P. esculenta</em>, but the invasive plant <em>P. americana</em> (American pokeweed) is also widely used. Different types of medicinal products made with <em>Phytolacca</em> are available, as well as various types of <em>Phytolacca</em> extracts, showing a range of pharmacological activities including antioxidant, anti-inflammatory, anti-parasitic, antifungal, anticancer, and insecticidal effects. The marked anti-inflammatory activity of <em>Phytolacca</em> extracts supports its use in treating diseases such as arthritis, nephritis, and rheumatism, as well as in combatting cancer. Several bioactive natural products have been identified from <em>Phytolacca</em>, including glycosylated saponins such as esculentosides and phytolaccosides, as well as a few flavones (cochliophilin A) and phytosterols (<em>α</em>-spinasterol), which contribute to <em>Phytolacca</em>’s anti-inflammatory and/or anticancer effects. A quality evaluation of <em>Phytolacca</em>-based extracts and products is highly recommended; nevertheless, the use of <em>Phytolacca</em> can be encouraged to help regulate cytokine production and combat inflammatory diseases.</p></div>","PeriodicalId":33578,"journal":{"name":"Digital Chinese Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S258937772100029X/pdfft?md5=b2236085c17d38f9794af6a425fd5f55&pid=1-s2.0-S258937772100029X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75364959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-10-01DOI: 10.1016/j.dcmed.2021.09.002
XIA Yu , LI Xin , MAN Rongyong , WANG Aibing , CAO Jianzhong
Objective
There are many clinical reports on traditional Chinese medicine (TCM) combined with nucleoside (acid) analogues (NAs) for the treatment of chronic hepatitis B (CHB), but its efficacy and safety are not completely clear. This meta-analysis aims to evaluate the clinical efficacy and safety thus providing evidence for clinical applications.
Methods
We searched Chinese databases the China National Knowledge Infrastructure (CNKI), Wanfang Data, and China Science and Technology Journal Database (VIP), as well as English databases PubMed and Cochrane Library, from time of establishment to April 14, 2021. Literature quality was evaluated according to the bias risk assessment criteria of Cochrane Collaboration network. RevMan 5.3 and Stata 12.0 software were used to perform this research.
Results
A total of 23 articles, 3 282 patients, and 25 TCM prescriptions were included in this study. NAs plus TCM remarkably improved the clinical total effective rate [Odds ratio (OR) = 3.92, P < 0.000 01], TCM syndrome score (Mean difference = − 3.73, P < 0.000 01), hepatitis B virus (HBV) DNA negative conversion rate (OR = 1.49, P = 0.000 1), hepatitis Be antigen (HBeAg) negative conversion rate (OR = 2.03, P < 0.000 01), alanine aminotransferase levels [Std mean difference (SMD) = − 0.95, P < 0.000 01], and aspartate aminotransferase levels (SMD = − 0.70, P = 0.000 4). Adverse reaction rates did not increase in the combined treatment group (OR = 0.97, P = 0.84). A comprehensive analysis of the 25 TCM prescriptions suggested that the combination of spleen-strengthening prescriptions with NAs showed better effects than other prescriptions.
Conclusion
TCM in combination with NAs, demonstrated better clinical efficacy against CHB than NAs alone. In addition, the combination of spleen-strengthening prescriptions and NAs was identified as the best therapeutic strategy. However, more randomized controlled trials of high quality are needed to provide more reliable clinical basis for the application of TCM.
目的中药联合核苷(酸)类似物治疗慢性乙型肝炎(CHB)的临床报道较多，但其疗效和安全性尚不完全清楚。本荟萃分析旨在评价其临床疗效和安全性，为临床应用提供依据。方法检索中国知网(CNKI)、万方数据、中国科技期刊库(VIP)等中文数据库，以及PubMed、Cochrane Library等英文数据库，检索时间为研究成立至2021年4月14日。根据Cochrane协作网的偏倚风险评估标准评价文献质量。本研究采用RevMan 5.3和Stata 12.0软件进行。结果共纳入文献23篇，患者3 282例，中药处方25个。NAs联合中药显著提高临床总有效率[优势比(OR) = 3.92, P <0.000 01]，中医证候评分(平均差异= - 3.73,P <乙型肝炎病毒(HBV) DNA阴性转换率(OR = 1.49, P = 0.000 1)、乙型肝炎抗原(HBeAg)阴性转换率(OR = 2.03, P <0.000 01)，丙氨酸转氨酶水平[Std平均差(SMD) = - 0.95, P <[0.000 01]、天冬氨酸转氨酶水平(SMD = - 0.70, P = 0.000 4)。联合治疗组不良反应发生率未增加(OR = 0.97, P = 0.84)。综合分析25个中药方剂，健脾方与NAs合用疗效优于其他方剂。结论中药联合NAs治疗慢性乙型肝炎的临床疗效优于单用NAs。此外，健脾方联合NAs是最佳治疗策略。然而，需要更多高质量的随机对照试验，为中医药的应用提供更可靠的临床依据。
{"title":"Clinical efficacy and safety of TCM prescriptions combined with nucleoside (acid) analogues in treating chronic hepatitis B: a meta-analysis","authors":"XIA Yu , LI Xin , MAN Rongyong , WANG Aibing , CAO Jianzhong","doi":"10.1016/j.dcmed.2021.09.002","DOIUrl":"10.1016/j.dcmed.2021.09.002","url":null,"abstract":"<div><h3>Objective</h3><p>There are many clinical reports on traditional Chinese medicine (TCM) combined with nucleoside (acid) analogues (NAs) for the treatment of chronic hepatitis B (CHB), but its efficacy and safety are not completely clear. This meta-analysis aims to evaluate the clinical efficacy and safety thus providing evidence for clinical applications.</p></div><div><h3>Methods</h3><p>We searched Chinese databases the China National Knowledge Infrastructure (CNKI), Wanfang Data, and China Science and Technology Journal Database (VIP), as well as English databases PubMed and Cochrane Library, from time of establishment to April 14, 2021. Literature quality was evaluated according to the bias risk assessment criteria of Cochrane Collaboration network. RevMan 5.3 and Stata 12.0 software were used to perform this research.</p></div><div><h3>Results</h3><p>A total of 23 articles, 3 282 patients, and 25 TCM prescriptions were included in this study. NAs plus TCM remarkably improved the clinical total effective rate [Odds ratio (OR) = 3.92, <em>P</em> < 0.000 01], TCM syndrome score (Mean difference = − 3.73, <em>P</em> < 0.000 01), hepatitis B virus (HBV) DNA negative conversion rate (OR = 1.49, <em>P</em> = 0.000 1), hepatitis Be antigen (HBeAg) negative conversion rate (OR = 2.03, <em>P</em> < 0.000 01), alanine aminotransferase levels [Std mean difference (SMD) = − 0.95, <em>P</em> < 0.000 01], and aspartate aminotransferase levels (SMD = − 0.70, <em>P</em> = 0.000 4). Adverse reaction rates did not increase in the combined treatment group (OR = 0.97, <em>P</em> = 0.84). A comprehensive analysis of the 25 TCM prescriptions suggested that the combination of spleen-strengthening prescriptions with NAs showed better effects than other prescriptions.</p></div><div><h3>Conclusion</h3><p>TCM in combination with NAs, demonstrated better clinical efficacy against CHB than NAs alone. In addition, the combination of spleen-strengthening prescriptions and NAs was identified as the best therapeutic strategy. However, more randomized controlled trials of high quality are needed to provide more reliable clinical basis for the application of TCM.</p></div>","PeriodicalId":33578,"journal":{"name":"Digital Chinese Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589377721000306/pdfft?md5=0dc3e341b7edc153cf3e8facef3ebff5&pid=1-s2.0-S2589377721000306-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88730574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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