Synergy最新文献

Many countries in the world face the new challenge of having human coronavirus infection to manage commendably - the large affliction of human health. Together, each country has modern drugs and a variety of medicinal products developed from their traditional medical practitioners to treat a common cold. In this review, we describe potentially synergistic therapeutics of traditional and complementary medicine available for common cold which might be useful for prevention or for the adjuvant treatment of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Further, we provide a phylogenetic overview of SARSCoV-2 based on a complete genome sequence of common cold viruses. We suggest modern and traditional medicine and preventive strategies which might control the disease to offer more suitable and acceptable common cold management including coronavirus. A substantial proportion of medicinal products developed by traditional medicine against common cold as well as modern medicine mainly focus on symptoms suppression. The recombinant interferon alpha-2b and lactoferrin derived from modern medicine in combination with herbal based products from traditional medicine may support the prevention of novel coronavirus infections. An integrated approach against common cold viruses to establish efficacy and safety through modern and traditional medicine and regular physical exercise along with preventive dietary sources is proposed.

The medicinal properties of Daniella oliveri are attributed to its different parts. Several parts of the plants are used in forklore medicine to treat various diseases such as liver diseases, inflammation, fever and pain. The present study evaluated the antioxidant and hepatoprotective activities of ethanol extract of Daniella oliveri (EEDO) stem bark. The hepatoprotective activity was investigated using carbon tetrachloride (CCl₄)-induced hepatotoxicity in Wistar rats. The antioxidant activity was determined using both in vitro and in vivo models. The pre-treatment with extract (100, 200, and 300 mg/kg) and silymarin (100 mg/kg) produced a significant (p < 0.05) increase in hepatoprotective activity when compared with the negative control (CCl₄) group. The 2, 2-diphenyl-1-picrylhydrazine (DPPH) radical scavenging activity of the plant extract increased with increasing concentration of the extract with IC₅₀ value of 0.05 mg/mL. The extract at 200 mg/kg showed a significant (p < 0.05) increase in level of GSH and activities of SOD, CAT, and GPx when compared with CCl₄ group. The histopathological observations supported the biochemical evidences of hepatoprotection of EEDO. The present study suggests that EEDO stem bark has a potent hepatoprotective effect that may be linked to its antioxidant potential and validates its use in the traditional management of liver diseases.

Background

Diabetes mellitus type 2 is a common metabolic disorder characterized by an impaired insulin release, an insulin resistance followed by an altered metabolism. The use of plant based antidiabetic drugs attains an increased importance in recent days due to their potentially reduced side effects. Naregamia alata Wight & Arn. is a small plant extensively referred in Indian traditional medicine to treat various diseases including diabetes.

Aim

Evaluation of the antidiabetic activity of the methanolic extract (ME) and fractions (petroleum ether (PE), dichloromethane (DCM) and residual methanol (RM)) of N. alata.

Methods

Determination of the blood glucose, body weight and biochemical parameters (serum) in addition to the evaluation of the free radical generation, liver glycogen content and regeneration of pancreatic β-islets. An attempt was also made to investigate the major classes of phytochemicals responsible for the antidiabetic activity of N. alata.

Results

The dichloromethane fraction of N. alata showed a significant hypoglycemic effect along with improvements in the body weight (P < 0.01) and biochemical parameters (Serum protein, urea, creatinine, total cholesterol (TC), triglycerides (TG), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein (LDL), very low density lipoprotein (VLDL)). Increased liver glycogen content and a reversal of serum and liver antioxidant levels in diabetic rats treated with the dichloromethane fraction were seen. The histopathological studies showed an improvement in the architecture of kidney and liver and a regeneration of pancreatic islets. The first phytochemical analyses revealed the presence of a significantly high amount of terpenes in the dichloromethane fraction of N. alata.

Conclusion

N. alata extracts showed hypoglycemic effect in STZ induced diabetic rats. Further studies to isolate the potent antidiabetic compound(s) and to identify synergistic, antagonistic or additive effects of the active ingredients are under progress.

Combating multiple drug resistant ovarian cancer is a major challenge. Combined chemotherapy of platinum drugs with phytochemicals (e.g. paclitaxel) introduce new options for oncologists in overcoming drug resistance. The objective of the present study was to investigate the activity of cisplatin in combination with emetine and patulin within ovarian cancer models. Antitumour activity of the cisplatin, emetine and patulin as a single drug was determined against human ovarian cancer cell lines (A2780 and A2780^CisR) by using the MTT reduction assay. Combination indices obtained from Chou-Talalay method were used to express combined drug actions. Proteomics was also carried out to identify the proteins which were responsible for the synergistic effects of the drug combinations. Cisplatin in combination with emetine produced synergism against ovarian cancer models depending on dose and sequence of drug administration. Patulin also demonstrated synergism when combined cisplatin at different doses and sequence of administrations. Eight proteins (e.g. VIME, ENPL, GRP78, CARL, NACA, COF1, PPIA and RSSA) were considered for combined drug actions of cisplatin plus emetine. Synergistic activity of the combination of cisplatin with patulin could be attributed to the downregulation of VIME, COF1 and CH10 as well as upregulation of CISY. Combinations of cisplatin with emetine and cisplatin with patulin led to dose reductions of cisplatin in the ovarian cancer cell line A2780. These combinations could be warranted for further evaluation using suitable in vitro and animal models in the context of overcoming drug resistance.

Background

Breast cancer is one of the leading causes of cancer deaths among women worldwide. Cisplatin is a broad-spectrum anticancer drug used in the treatment of breast cancer. Recent research showed the potent anticancer effect of tetrandrine against different cancers.

Objective

Present study is aimed at determining the synergistic cytotoxic effect of tetrandrine and cisplatin against breast cancer under in vitro.

Methods

Cytotoxic effect of tetrandrine and cisplatin on MDA-MB-231 cells was performed using MTT - (3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide). Synergistic, antagonistic and additive effects of tetrandrine and cisplatin were calculated using Compusyn software. Clonogenic assay was performed in 12 wells plate. The generation of Reactive Oxygen Species (ROS) was measured using H₂DCF-DA. Cell cycle assay was carried out using flow cytometry. The caspase-3, -8 and -9 activities in the cells were measured based on the hydrolysis of peptide substrates by their respective enzymes to release p-nitroaniline (pNA).

Results

The study demonstrated synergistic cytotoxic effect on MDA-MB-231 cells in a dose dependent manner. The cells undergoing apoptosis and necrosis were evidenced by microscopic observation and colony formation and cell cycle assays. The study also revealed elevated levels of ROS and, increased activities of caspase-3 and -8 which also indicate the apoptosis of cells.

Conclusion

The study showed a promising synergistic cytotoxic effect of tetrandrine and cisplatin against MDA-MB-231 cells with cell cycle arrest and intracellular ROS mediated apoptosis. Hence, the study suggests the possible synergistic use of tetrandrine and cisplatin to treat triple negative breast cancer.

T cell acute lymphoblastic leukaemia is a type of cancer that develops from lymphoid progenitors, and chemotherapy is corner stone of the treatment. Thiopurine drugs, consisting of 6-mercaptopurine, 6-thioguanine, and azathioprine (Aza), can effectively treat this disease. To be activated, Aza must first be biotransformed to 6-mercaptopurine by thiol groups in glutathione. However, glutathione is decreased in cancer cells due to high levels of reactive oxygen species (ROS). N-acetylcysteine could provide thiol groups for glutathione synthesis to biotransform Aza. Using flow cytometry, the ability of N-acetylcysteine to increase the antiproliferative and apoptotic effects of Aza without increasing ROS was tested in Jurkat cells. Individually, Aza 1.0 and 2.0 μM, as well as N- acetylcysteine 3.0 mM, induced apoptosis and cell cycle arrest. Together, Aza + N-acetylcysteine significantly reduced proliferation compared to that obtained with the individual drugs. Combination of N-acetylcysteine 3.0 mM with Aza 1.0 μM was as effective at inducing apoptosis as Aza 2.0 μM alone. The combination of N-acetylcysteine 3.0 mM + Aza 1.0 μM increased cell cycle arrest at the G₂/M phase. We found that Aza 1.0 or 2.0 μM induced a significant increase in ROS compared to that in untreated cells, while N-acetylcysteine 3.0 mM and N-acetylcysteine 3.0 mM  + Aza 1.0 μM kept ROS at control levels; the latter drugpairing represents a favourable combination to reduce oxidative stress in the presence of Aza. In conclusion, N-acetylcysteine augments antiproliferative and apoptotic effects of Aza without increasing ROS in vitro.

Purpose

The antibacterial effects of three essential oils were tested against three bacterial strains (ATCC: Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa) commonly known for their implication on wound healing infections.

Methods

The disc diffusion method and the determination of the Minimal Inhibitory Concentration (MIC) and Minimal Bactericidal Concentration (MBC) were carried out to evaluate their antibacterial activity. The combined effect of essential oils against the tested bacteria was assessed by the checkerboard method and the Fractional Inhibitory Concentration Index (FICI) calculation.

Results

The results of the dissemination method demonstrated that the three EOs have antibacterial activity against the three tested bacteria at 20 μl.

Concerning the MIC, Lavender, Rosemary and Wormwood essential oils inhibited the bacterial growth at 1.33, 3.33 and 42.67 μl/ml; 1.33 1.67 and 42.67 μl/ml ; and 4.00, 6.67 and 42.67 μl/ml for S. aureus, E. coli and P. aeruginosa, respectively. The evaluation of the essential oils in combination revealed that the maximum of required concentration were 0.5 μl/ml for Artemisia herba alba and 1 μl/ml for Lavandula angustifolia and Rosmarinus officinalis.

Conclusions

These results indicate a synergism for the combination of lavender, wormwood and rosemary essential oils at very low concentrations compared to MICs.

Objective

Resveratrol (RES) is a well known cardioprotective phytoconstituent, but the poor bioavailability provides further scope for research to improve its therapeutic efficacy. The present study was designed to address this challenge by combining with bio-enhancer like Naringin (NAR) in the prevention of ischemia reperfusion injury (IRI) induced myocardial toxicity in rats.

Methods

Rats (n = 8) were treated with RES (20 mg/kg, p.o.) alone and combination of NAR (15 mg/kg, p.o.) and RES (20 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 a histopathological examination. The Influence of NAR on the pharmacokinetics of RES was studied by HPLC. Results were assessed by one‑way analysis of variance followed by Tukey–Karmer multiple comparison test.

Results

Combination of RES and NAR demonstrated significant (P < 0.01) restoration of biomarker, antioxidant, tension and heart rate compared to RES alone treated group. Significant (P < 0.01) increase in bioavailability and half life, along with significant (P < 0.001) decrease in clearance was observed for RES in combination group compared to RES alone treated group.

Conclusion

The combination of RES and NAR exhibited profound protection compared to RES alone treated group against IRI induced myocardial toxicity. Findings of pharmacokinetic interaction support the results of a pharmacodynamic interaction.

The median-effect equation (MEE) derived from the mass-action law (MAL) is the unified theory of dose-effect pharmacodynamics (PD) and biodynamics (BD). MEE enables the linearization of a dose-effect curve into a straight linedefined by two data points. Thus any two data points can represent an entire dose-effect curve. For dose-effect curves using MAL, dose-zero can serve as 3^rd point, and the universal reference point, the median-effect dose (D_m) serves as 4^th point. This functionality has tremendous significance for in vivo studies. Fewer data points are required for a dose-effect curve, facilitating economical and ethically sustainable PD analyses. The extension of MEE from a single drug to multiple drugs establishes the general combination index equation (CIE), which quantitatively defines synergism (CI < 1), additive effect (CI = 1) and antagonism [CI > 1]. Although the CI method is often (>6000 citations) applied in in vitro studies, it is rarely used in animal studies or clinical trials. In vivo drug combination studies that use only single dose or statistical p value analyses do not allow quantitative synergy claims. This article presents two examples for drug combinations in vivo: (i) in animals (anticancer drug combination against human HCT-116 colon carcinoma xenografts in nude mice, Taxotere + T607) and (ii) in a clinical trial (anti-retroviral drug combinations against HIV/AIDS, AZT + INF). Only 36 patients respectively only 66 nude mice were required. Both examples require only ten data points (D₁, D₂ and [D₁+D₂], each with 3 doses plus one control) to quantitatively determine synergism or antagonism with the CompuSyn software.