Synergy最新文献

{"title":"Synergy: Easier to say than to prove","authors":"R. Verpoorte, H.K. Kim, Y.H. Choi","doi":"10.1016/j.synres.2018.10.004","DOIUrl":"https://doi.org/10.1016/j.synres.2018.10.004","url":null,"abstract":"","PeriodicalId":38079,"journal":{"name":"Synergy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.synres.2018.10.004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"137268019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The combination index (CI < 1) as the definition of synergism and of synergy claims","authors":"Ting-Chao Chou","doi":"10.1016/j.synres.2018.04.001","DOIUrl":"10.1016/j.synres.2018.04.001","url":null,"abstract":"<div><p>The unified theory of the median-effect equation (MEE) of the mass-action law (MAL) indicates that <em>dose</em> and <em>effect</em> are interchangeable, and <em>all</em> dose-effect <em>curves</em> can be transformed into <em>straight-lines</em> by the <em>median-effect plot.</em> Therefore, it allows pharmacodynamics (PD) analysis using small size experimentation for in vitro and in vivo studies. Further, extension of MEE has proven that the Combination Index Equation (CIE) which defines <strong>Synergism (CI &lt; 1),</strong> Additive Effect (CI = 1) and Antagonism (CI &gt; 1), can be automatically simulated by CompuSyn software within one second after data entries. With adequate experimental accuracy of measurements, the minimum number of only <strong>10 data points</strong> are required for quantitative synergy determination in two-drug combinations, even in animals or in clinical trials. Three articles introducing the CI method (in 1984), the review (2006), and the perspectives (2011) have been well recognized and cited 5516, 2382, and 1701 times in 1117, 768 and 530 biomedical journals, respectively (as of 2.10.2018) [<em>Google Scholar Citations- Ting-Chao Chou</em>]. However, the academic societies and governmental regulatory agencies are still lack of guideline on <em>synergy definition</em>, despite over 20 arbitrary, non-quantitative synergy definitions are still applied and reported. As drug combination is the most widely used therapies for the most dreadful diseases such as cancer and AIDS, a call for open forum on scientific credibility and accountability in these matters is warranted.</p></div>","PeriodicalId":38079,"journal":{"name":"Synergy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.synres.2018.04.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49505577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergy assessments of plant extracts used in the treatment of stress and aging-related disorders","authors":"Alexander Panossian ,&nbsp;Ean-Jeong Seo ,&nbsp;Thomas Efferth","doi":"10.1016/j.synres.2018.10.001","DOIUrl":"10.1016/j.synres.2018.10.001","url":null,"abstract":"","PeriodicalId":38079,"journal":{"name":"Synergy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.synres.2018.10.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45461010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring synergy in ayurveda and traditional Indian systems of medicine","authors":"Pulok K. Mukherjee,&nbsp;Subhadip Banerjee,&nbsp;Amit Kar","doi":"10.1016/j.synres.2018.10.003","DOIUrl":"10.1016/j.synres.2018.10.003","url":null,"abstract":"<div><p><span><span>Synergy is a phenomenon of life. It has been observed that combinatory treatments may achieve more stable “network responses’’ than single </span>drugs. </span>Drug combination treatments<span> are routinely applied in an increasing number of disciplines in medicine. Single drug treatments are less effective than drug combinations in complex treatment regimes. Plant derived herbal drugs<span><span> or phytopharmaceuticals<span> can be considered a natural “model” for combinatory treatments. Specific compositions of multi-component mixtures represent combined actions of single substances. Ayurveda, the </span></span>traditional medicine<span> of India has played an important role in disease management and health for many centuries, their present frequent use is challenged by the necessity to determine their complex composition and their multitarget mode of action. Ancient Ayurvedic literature like Sarangadhar Samhita focuses on the idea of synergy or ‘samyoga’. Network pharmacology research focuses on excellent systems biology techniques like protein interaction, genomic expression and mRNA expression data, which are employed to gain insight into the mechanism of action (MoA) prediction and validation. The following brief review provides valuable perspective regarding the bridge of Ayurveda and synergy research using network pharmacology as the tool to understand the molecular combination mechanism.</span></span></span></p></div>","PeriodicalId":38079,"journal":{"name":"Synergy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.synres.2018.10.003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48381808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of monocyte redox balance by 1,8-cineole (eucalyptol) controls oxidative stress and pro-inflammatory responses in vitro: A new option to increase the antioxidant effects of combined respiratory therapy with budesonide and formoterol?","authors":"Lisa Joy Juergens ,&nbsp;Izabela Tuleta ,&nbsp;Meinolf Stoeber ,&nbsp;Kurt Racké ,&nbsp;Uwe R. Juergens","doi":"10.1016/j.synres.2018.05.001","DOIUrl":"10.1016/j.synres.2018.05.001","url":null,"abstract":"<div><h3>Background</h3><p><span><span>Airway mucus hypersecretion is the typical feature of </span>COPD and asthma. Hypersecretion is caused by </span>reactive oxygen species<span> (ROS) and links the COPD-bronchitis phenotype to frequent exacerbations. Since the monoterpene<span> 1,8-cineole is known for its secretolytic activity, we studied the antioxidant activity of 1,8-cineole.</span></span></p></div><div><h3>Methods</h3><p><span><span>Using a culture model of fetal calf serum (FCS)-stimulated human </span>monocytes, we determined the effects of 1,8-cineole, at therapeutic concentrations (10</span>⁻¹⁰–10⁻⁵ M) on superoxide anions (O₂⁻<span>), superoxide dismutase (SOD), hydrogen peroxide (H</span>₂O₂<span><span>) and of LPS-stimulated 8-isoprostanes (8-IsoP) and TNF-α. The effect of formoterol (F), </span>budesonide (BUD), BUD + F without and with 1,8-cineole were determined on O</span>₂⁻-release.</p></div><div><h3>Results</h3><p>1,8-cineole (10⁻⁵ M) strongly inhibited O₂⁻ (−53%, p &lt; 0.001), partially inhibited SOD (−28%, p = 0.0039) and inhibited H₂O₂<span> in an undulating manner at 10</span>⁻¹⁰ M (−48%, p = 0.0274), while total cellular antioxidant activity as determined by inhibition of 8-IsoP increased dose-dependently from 10⁻⁶ M (−42%, p = 0.0288) to 10⁻⁵ M (−84%, p &lt; 0.0001) comparable to TNF-α. Only weak antioxidant and, at higher concentrations, even pro-oxidant effects were detectable for F and BUD, respectively, but no pro- or antioxidant effects of F + BUD. The antioxidant effects of 1,8-cineole were not substantially influenced during co-incubation with F + BUD.</p></div><div><h3>Conclusions</h3><p>We report an inhibition of superoxide anions, balancing partial dismutation of superoxide anions and independent inhibition of H₂O₂<span><span><span> by 1,8-cineole. These results suggest a non-specific combined, antioxidant and anti-inflammatory mode of action of 1,8-cineole as bifunctional drug for further </span>clinical evaluation in mild to severe COPD and as adjunctive therapy to control </span>disease progression.</span></p></div>","PeriodicalId":38079,"journal":{"name":"Synergy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.synres.2018.05.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49610772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of quercetin on myocardial potency of curcumin against ischemia reperfusion induced myocardial toxicity","authors":"Manodeep Chakraborty ,&nbsp;Mohammed Gulzar Ahmed ,&nbsp;Ananya Bhattacharjee","doi":"10.1016/j.synres.2018.09.001","DOIUrl":"10.1016/j.synres.2018.09.001","url":null,"abstract":"<div><h3>Background</h3><p><span>Curcumin<span> (CUR) is a well established cardioprotective phytoconstituent, but the poor bioavailability associated with it is providing a scope to do further research to improvise therapeutic efficacy of CUR. The present study was designed to address this challenge by combining with bio-enhancer like Quercetin (QUE) against </span></span>ischemia reperfusion injury (IRI) induced myocardial toxicity in rats.</p></div><div><h3>Materials and Methods</h3><p><span>Rats (n = 8) were treated with CUR (200 mg/kg, p.o.) alone and combination of CUR (200 mg/kg, p.o.) and QUE (10 mg/kg, p.o.) for 30 days. Twenty four hour after last treatment Ischemia reperfusion injury was induced by modified Lagendorff apparatus, and the effect of different treatments was evaluated by percentage recovery in terms of heart rate and developed tension, biomarkers, heart tissue antioxidant levels and histopathological examination. Influence of QUE on </span>pharmacokinetic of CUR was studied by HPLC method. Results obtained were assessed by one‑way analysis of variance followed by Tukey–Karmer multiple comparison test.</p></div><div><h3>Results</h3><p>CUR and QUE demonstrated significant myocardial potency compared to CUR alone‑treated group. Significant increase in bioavailability and half life, along with significant decrease in clearance was observed for CUR in combination group compared to CUR alone treated group.</p></div><div><h3>Conclusion</h3><p>From this study it can be concluded that combination of CUR and QUE exhibited profound protection compared to CUR alone treated group against IRI induced myocardial toxicity. Findings of pharmacokinetic interaction justified the results of pharmacodynamic interaction.</p></div>","PeriodicalId":38079,"journal":{"name":"Synergy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.synres.2018.09.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43550071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methotrexate induced cell death mechanisms in MCF-7 adenocarcinoma breast cancer cells: Enhanced cytotoxicity following dff45-siRNA pre-treatment","authors":"Fatemeh Kiani ,&nbsp;Negin Rasouli ,&nbsp;Tahereh Kashkoolinejad ,&nbsp;Shahrokh Safarian ,&nbsp;Seyed Jalal Zargar ,&nbsp;Nader Sheibani","doi":"10.1016/j.synres.2018.08.002","DOIUrl":"10.1016/j.synres.2018.08.002","url":null,"abstract":"<div><p><span>There are many efforts to diminish risks associated with the use of cancer chemotherapeutic agents through design and utilization of new strategies including gene therapy. We previously showed knockdown of </span><em>dff</em>45 or overexpression of <em>dff</em><span><span>40, the important apoptosis regulators, resulted in enhanced sensitization of </span>cancer cells to chemotherapeutic agents. Here we show that pre-treatment with </span><em>dff45-</em><span><span>siRNA additively increased the overall cytotoxic effects of </span>methotrexate<span> (MTX), at its partially safe concentration (30 μM with almost 37% of killing potency), up to 85%. This is approximately 51% greater than MTX treatment, and about 20% greater than siRNA treatment alone. The main mechanism of cell death by MTX treatment was through AIF-induced caspase-independent apoptosis, as well as the less common Atg5 and DRAM-induced apoptosis. Investigation of apoptosis with </span></span><em>dff45-</em>siRNA treatment showed the canonical caspase-dependent apoptosis as the main mechanism of cell death. This was also true for MTX+siRNA treatment. We did not observe a sharp increase in expression of autophagy genes in cells incubated with <em>dff45-</em>siRNA. However, treatment with MTX+siRNA may trigger autophagy via an Atg5-independent pathway.</p></div>","PeriodicalId":38079,"journal":{"name":"Synergy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.synres.2018.08.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42703457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Omega-3 fatty acids moderate oxidative and proinflammatory events in experimental hepatotoxicity in Wistar rats: comparison with livolin","authors":"Luqman Aribidesi Olayaki,&nbsp;Wale Johnson Adeyemi,&nbsp;Joseph Sunday Yinusa,&nbsp;Grace Amarachi Adedayo","doi":"10.1016/j.synres.2018.08.001","DOIUrl":"10.1016/j.synres.2018.08.001","url":null,"abstract":"<div><p><span>Dietary supplementation<span><span> with omega-3 fatty acids have been advocated because of the global preference for the omega-6 fatty acids - rich Western style diet. The study investigated the effects of omega-3 fatty acids (combination of N-3: eicosapentaenoic acid (EPA) and </span>docosahexaenoic acid (DHA); EPA/DHA ratio = 3/2) compared to livolin (Phosphatidylcholin + vitamins) on biochemical and haematological parameters in diclofenac (DF) - induced </span></span>hepatotoxicity<span><span> in male Wistar rats<span>. Twenty five rats were used. They were divided into 5 groups (n = 5) which included: Group 1-Control (untreated); Group 2-DF control; Group 3-DF + Low N-3; Group 4-DF+High N-3; and, Group 5-DF + Livolin. Group 2 received DF at 10 mg/kg b.w. (i.m.) during the first 7days of the experiment, thereafter; they were administered distilled water (0.1 ml) for three weeks. Groups 3, 4, and 5 were pre-treated with DF during the first 7days of the experiment, afterwards, they were post-treated with N-3 and livolin at 100, 300, and 5.2 mg/kg b.w. (p.o.) respectively for 21days.The results showed that DF caused significant increases in </span></span>MDA<span>, LDH<span><span>, proinflammatory markers, ALT, AST, and </span>ALP activities, but, significant decreases in antioxidant indices. However, post-treatment with N-3 or livolin corrected these deviations. Although there was evidence of the dose dependent effects of N-3, the high dose was not always the most effective. The histological results proved that livolin has a more hepatoprotective action than N-3, although the biochemical and haematological findings attested that both therapies have comparable effects. It was concluded that livolin proffers a more protective effect than N-3 in DF-induced hepatotoxicity.</span></span></span></p></div>","PeriodicalId":38079,"journal":{"name":"Synergy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.synres.2018.08.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46647279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergistic effects and their potential significance for the influence of natural intensities of environmental factors on cell growth","authors":"Ekaterina S. Evstratova,&nbsp;Vladislav G. Petin,&nbsp;Galina P. Zhurakovskaya","doi":"10.1016/j.synres.2017.12.001","DOIUrl":"10.1016/j.synres.2017.12.001","url":null,"abstract":"<div><h3>Background</h3><p>The assessment of the potential significance of synergistic interaction between adverse ecological factors acting together at the level of intensities found in the biosphere is still intriguing and unresolved problem.</p></div><div><h3>Objective</h3><p>This study aims to analyze synergistic effects for various biological objects, tests, and interacting agents to provide conclusive evidence of possible synergistic interactions of natural intensities of environmental factors on cell growth.</p></div><div><h3>Methods</h3><p>Four dose-effect curves were obtained for each object and interacting factors: after the individual action of agents, after their simultaneous action and theoretically expected curve after independent addition of the effects produced by each agent. The synergistic enhancement ratio (SER) and its dependence on intensities of agents were quantitatively estimated based on these curves.</p></div><div><h3>Results</h3><p>The extent of synergistic interaction was shown to be dependent on the intensity of physical factors or concentration of chemicals in such a manner that there were optimal conditions at which the greatest synergy may be achieved. The lesser the intensity of one of the agents applied, the smaller intensity of another agent has to be used to provide the highest synergistic interaction. In investigations where SER &gt; 1, CI &lt; 1.</p></div><div><h3>Conclusion</h3><p>The existence of optimal conditions providing the greatest synergistic effect and its dependence on the intensity of applied agents was demonstrated. Common patterns were identified. It is concluded that synergistic interactions are important for the evaluation of biological consequences and risk assessment from combined effects at low intensities of ionizing radiation, UV-light, electromagnetic fields, or small concentration of chemicals.</p></div>","PeriodicalId":38079,"journal":{"name":"Synergy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.synres.2017.12.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45919625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Curcumin synergizes with the endocannabinoid reuptake inhibitor OMDM-2 in human MCF-7 breast cancer and U-87 glioblastoma cells","authors":"R.M. Ammar ,&nbsp;G. Ulrich-Merzenich","doi":"10.1016/j.synres.2017.11.001","DOIUrl":"10.1016/j.synres.2017.11.001","url":null,"abstract":"<div><h3>Introduction</h3><p>Δ⁹-Tetrahydrocannabinol (THC), active constituent of <em>Cannabis sativa</em> L., possesses potential antitumor activity. Modulating the endogenous level of cannabinoids could be a sensible strategy to avoid adverse events presently limiting the use of direct agonists. We investigated the cytotoxicity of endocannabinoid reuptake inhibitor OMDM-2 alone and in combination with the polyphenol curcumin, an active compound of <em>Curcuma longa</em> L.</p></div><div><h3>Methods</h3><p>The <em>in-vitro</em> anti-proliferative activities of OMDM-2 alone/in combination with curcumin were evaluated in breast cancer (MCF-7) and glioblastoma (U-87) cells using the resazurin assay. The effect of curcumin on OMDM-2 was determined by comparing different inhibitory concentrations (IC) values of OMDM-2 in absence and presence of curcumin. The additive, synergistic or antagonistic activity of the combination was evaluated by the combination index (CI) and isobologram analyses.</p></div><div><h3>Results</h3><p>OMDM-2 by itself showed anti-proliferative effects against both MCF-7 and U-87 cells in a dose dependent manner with IC₅₀ values of 4.9<!--> <!-->μM and 2.7<!--> <!-->μM respectively. Isobol and CI analyses at different dose ratios revealed that the drug interaction was predominantly synergistic against MCF-7 cells (CI<!--> <!-->≤<!--> <!-->0.5 at IC₅₀). While in case of glioblastoma cells CI values varied between &lt;0.2 up to 1.1 at IC₇₀ depending on the ratio and concentration of the drugs.</p></div><div><h3>Conclusion</h3><p>These findings provide experimental support for the use of curcumin as a modulator of tumor cell pharmacointeraction in cannabinoid based therapies. To achieve synergism dose ratios should be established for each cell type and ratiometric dosing be considered.</p></div>","PeriodicalId":38079,"journal":{"name":"Synergy","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.synres.2017.11.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49633823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}