• Fisheries and Aquatic Sciences
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• 제17권2호
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• pp.209-214
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• 2014

With the continuing demand for new solutions in the development of effective and safe candidiasis therapies, we investigated the efficacy of an antifungal agent from the marine brown alga Eisenia bicyclis. The methanolic extract of E. bicyclis evinced potential antifungal activity against Candida species. The ethyl acetate (EtOAc)-soluble extract from E. bicyclis demonstrated the strongest antifungal activity against Candida species among five solvent-soluble extracts. Indeed, the EtOAc-soluble extract showed minimum inhibitory concentrations (MICs) ranging from 4 to 8 mg/mL. Furthermore, the EtOAc-soluble extract considerably reversed high-level fluconazole resistance of Candida species. The MIC values of fluconazole against Candida species decreased substantially (from 64 to $4{\mu}g/mL$) in combination with the MIC of the EtOAc-soluble extract (4 mg/mL). The fractional inhibitory concentration indices of fluconazole ranged from 0.531 to 0.625 in combination with 4, 2, or 1 mg/mL of the EtOAc-soluble extract against Candida isolates, indicating that these combinations exert a marked synergistic effect against Candida isolates. These findings imply that compounds derived from E. bicyclis can be a potential source of natural antifungal agents against Candida species.

• 약학회지
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• 제23권1호
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• pp.11-16
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• 1979

Benorylate and ethoxybenzamide have been used alone or in combination as an analgesic, antipyretic and antiinflammatory agent. We investigated the significance of the differences of analgesic activities between single and concurrent administration of benorylate and ethoxybenzamide and lorazepam in mice and also antipyretic activity between single and concurrent administration of benorylate and ethoxybenzamide in rats. 1). Concurrent administration of each half dose of benorylate and ethoxybenamide showed much inhibiting effect on the acetic acid-induced writhing syndrome of mice than the above drug alone, and the some increased analgesic response by hot plate method. 2). The synergistic and analgesic effect of combined administration of benorylate and lorazepam was found to be significant. 3). Antipyretic effect of half-dose combined administration of benorylate and ethoxybenzamide on the rat pyrexia induced by yeast(s.c.) and T.T.G. (i.v.) was shown to be similar to the effect of each drug.

• 대한미생물학회지
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• 제21권3호
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• pp.375-380
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• 1986

Thirty-one strains of Pseudomonas aeruginosa were submitted to the synergistic activity test of amikacin(AK) and gentamicin(GM) combined with moxalactam(MX), ceftizoxime(CTZ) or cefoperazone(CFZ). The minimal inhibitory concentrations(MICs) of each drug and drugs combined in various ratios were measured by checkerboard dilution method. The synergism was determined through analysing the MIC distribution curve on isobologram and calculating the fractional inhibitory concentration index(FICI). MICs of GM, AK, MX, CFZ and CTZ against the 31 tested strains were distributed from $12.5{\mu}g/ml$ to $800{\mu}g/ml$, from $0.8{\mu}g/ml$ to $25{\mu}g/ml$, from $3.1{\mu}g/ml$ to $50{\mu}g/ml$, from $3.1{\mu}g/ml$ to $400{\mu}g/ml$, and from $12.5{\mu}g/ml$ to $100{\mu}g/ml$, respectively. The rate synergism of each drug combination by means of FICl was 45.5% in GM-MX, 36.4% in GM-CFZ, 63.6% in GM-CTZ, 48.6% in AK-MX, 35.3% in AK-CFZ, and 35.7% in AK-CTZ combination. Thus, it is suggested that Pseudomonas aeruginosa may effectively be inhibited by various aminoglycoside and cephalosporin combinations.

• Journal of Microbiology and Biotechnology
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• 제33권7호
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• pp.849-856
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• 2023

Short-chain fatty acids (SCFAs), such as butyrate, propionate, and acetate produced by the gut microbiota have been implicated in physiological responses (defense mechanisms, immune responses, and cell metabolism) in the human body. In several types of cancers, SCFAs, especially butyrate, suppress tumor growth and cancer cell metastasis via the regulation of the cell cycle, autophagy, cancer-related signaling pathways, and cancer cell metabolism. In addition, combination treatment with SCFAs and anticancer drugs exhibits synergistic effects, increasing anticancer treatment efficiency and attenuating anticancer drug resistance. Therefore, in this review, we point out the importance of SCFAs and the mechanisms underlying their effects in cancer treatment and suggest using SCFA-producing microbes and SCFAs to increase therapeutic efficacy in several types of cancers.

• Biomolecules & Therapeutics
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• 제19권4호
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• pp.371-389
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• 2011

A new strategy for cancer therapy has emerged during the past decade based on molecular targets that are less likely to be essential in all cells in the body, therefore confer a wider therapeutic window than traditional cytotoxic drugs which mechanism of action is to inhibit essential cellular functions. Exceptional heterogeneity and adaptability of cancer impose significant challenges in oncology drug discovery, and the concept of complex tumor biology has led the framework of developing many anticancer therapeutics. Protein kinases are the most pursued targets in oncology drug discovery. To date, 12 small molecule kinase inhibitors have been approved by US Food and Drug Administration, and many more are in clinical development. With demonstrated clinical efficacy of bortezomib, ubiquitin proteasome and ubiquitin-like protein conjugation systems are also emerging as new therapeutic targets in cancer therapy. In this review, strategies of targeted cancer therapies with inhibitors of kinases and proteasome systems are discussed. Combinational cancer therapy to overcome drug resistance and to achieve greater treatment benefit through the additive or synergistic effects of each individual agent is also discussed. Finally, the opportunities in the future cancer therapy with molecularly targeted anticancer therapeutics are addressed.

• The Korean Journal of Physiology and Pharmacology
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• 제24권4호
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• pp.299-310
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• 2020

Alzheimer's disease (AD) is a multi-faceted neurodegenerative disease. Thus, current therapeutic strategies require multitarget-drug combinations to treat or prevent the disease. At the present time, single drugs have proven to be inadequate in terms of addressing the multifactorial pathology of AD, and multitarget-directed drug design has not been successful. Based on these points of views, it is judged that combinatorial drug therapies that target several pathogenic factors may offer more attractive therapeutic options. Thus, we explored that the combination therapy with lower doses of cilostazol and aripiprazole with add-on donepezil (CAD) might have potential in the pathogenesis of AD. In the present study, we found the superior efficacies of donepezil add-on with combinatorial mixture of cilostazol plus aripiprazole in modulation of expression of AD-relevant genes: Aβ accumulation, GSK-3β, P300, acetylated tau, phosphorylated-tau levels, and activation of α-secretase/ADAM 10 through SIRT1 activation in the N2a Swe cells expressing human APP Swedish mutation (N2a Swe cells). We also assessed that CAD synergistically raised acetylcholine release and choline acetyltransferase (CHAT) expression that were declined by increased β-amyloid level in the activated N2a Swe cells. Consequently, CAD treatment synergistically increased neurite elongation and improved cell viability through activations of PI3K, BDNF, β-catenin and α7-nicotinic cholinergic receptors in neuronal cells in the presence of Aβ_1-42. This work endorses the possibility for efficient treatment of AD by supporting the synergistic therapeutic potential of donepezil add-on therapy in combination with lower doses of cilostazol and aripiprazole.

• The Korean Journal of Pain
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• 제18권1호
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• pp.10-14
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• 2005

Background: Previous studies have suggested synergistic analgesic drug interactions between NSAIDs and opioids in neuropathic and inflammatory pain models. The aim of this study was to investigate the analgesic drug interaction between intraperitoneal (IP) ketorolac and morphine in radiant thermal stimulation rat. Methods: Initially, we assessed the withdrawal latency time of the hindpaw to radiant thermal stimulation every 15 min for 1 hour and every 30 min for next 1 hour after IP normal saline 5 ml (control group). The latency time was changed into percent maximal possible effect (%MPE). Next, IP dose response curves were established for the %MPE of morphine (0.3, 1, 3, 10 mg/kg) and ketorolac (3, 10, 30 mg/kg) to obtain the $ED_{50}$ for each agent. And we confirmed that the IP morphine effect was induced by opioid receptor through IP morphine followed by IP naloxone. At last, we injected three doses of IP ketorolac (3, 10, 30 mg/kg) mixed with one dose of morphine (2 mg/kg) for fixed dose analysis. Results: IP morphine delayed the paw withdrawal latency time dose dependently, but not ketorolac. $ED_{50}$ of IP morphine was 2.1 mg/kg. And the IP morphine effect was reversed to control level by IP naloxone. IP ketorolac + morphine combination showed no further additional effects on paw withdrawal latency time over morphine only group. Conclusions: IP ketorolac did not produce antinociceptive effect during radiant thermal stimulation. There was neither additional nor synergistic analgesic interaction between IP morphine and ketorolac in thermal stimulation rat.

• Journal of Microbiology and Biotechnology
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• 제27권4호
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• pp.685-693
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• 2017

Candidiasis involving the biofilms of Candida albicans is a threat to immunocompromised patients. Candida biofilms are intrinsically resistant to the antifungal drugs and hence novel treatment strategies are desired. The study intended to evaluate the anti-Candida activity of allyl isothiocyanate (AITC) alone and with fluconazole (FLC), particularly against the biofilms. Results revealed the concentration-dependent activity of AITC against the planktonic growth and virulence factors of C. albicans. Significant (p <0.05) inhibition of the biofilms was evident at ${\leq}1mg/ml$ concentrations of AITC. Notably, a combination of 0.004 mg/ml of FLC and 0.125 mg/ml of AITC prevented the biofilm formation. Similarly, the preformed biofilms were significantly (p <0.05) inhibited by the AITC-FLC combination. The fractional inhibitory concentration indices ranging from 0.132 to 0.312 indicated the synergistic activity of AITC and FLC against the biofilm formation and the preformed biofilms. No hemolytic activity at the biofilm inhibitory concentrations of AITC and the AITC-FLC combination suggested the absence of cytotoxic effects. The recognizable synergy between AITC and FLC offers a potential therapeutic strategy against biofilm-associated Candida infections.

• Asian Pacific Journal of Cancer Prevention
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• 제14권9호
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• pp.5243-5248
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• 2013

Background: Triptolide, extracted from the herb Tripteryglum wilfordii Hook.f that has long been used as a natural medicine in China, has attracted much interest for its anti-cancer effects against some kinds of tumours in recent years. Artesunate, extracted from the Chinese herb Artemisia annua, has proven to be effective and safe as an anti-malarial drug that possesses anticancer potential. The present study attempted to clarify if triptolide enhances artesunate-induced cytotoxicity in pancreatic cancer cell lines in vitro and in vivo. Methods: In vitro, to test synergic actions, cell viability and apoptosis were analyzed after treatment of pancreatic cancer cell lines with the two agents singly or in combination. The molecular mechanisms of apoptotic effects were also explored using qRT-PCR and Western blotting. In vivo, a tumor xenograft model was established in nude mice, for assessment of inhibitory effects of triptolide and artesunate. Results: We could show that the combination of triptolide and artesunate could inhibit pancreatic cancer cell line growth, and induce apoptosis, accompanied by expression of HSP 20 and HSP 27, indicating important roles in the synergic effects. Moreover, tumor growth was decreased with triptolide and artesunate synergy. Conclusion: Our result indicated that triptolide and artesunate in combination at low concentrations can exert synergistic anti-tumor effects in pancreatic cancer cells with potential clinical applications.

• Asian Pacific Journal of Cancer Prevention
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• 제14권4호
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• pp.2503-2508
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• 2013

Histone deacetylation mediated by histone deacetylases (HDACs) has been reported as one of the epigenetic mechanisms associated with tumorigenesis. The poor responsiveness of anticancer drugs found with cholangiocarcinoma (CCA) leads to short survival rate. We aimed to investigate mRNA expression of HDACs class I and II, and the effect of HDAC inhibitors, suberoylanilide hydroxamic acid (SAHA) and valproic acid (VPA), in CCA in vitro. Expression of HDACs was studied in CCA cell lines (M213, M214 and KKU-100) and an immortal cholangiocyte (MMNK1) by semi-quantitative reverse transcription-PCR. SAHA and VPA, as well as a classical chemotherapeutic drug 5 -fluorouacil (5-FU) were used in this study. Cell proliferation was determined by sulforhodamine assay. $IC_{50}$ and $IC_{20}$ were then analyzed for each agent and cell line. Moreover, synergistic potentional of VPA or SAHA in combination with 5-FU at sub toxic does ($IC_{20}$) of each agent was also evaluated. Statistic difference of HDACs expression or cell proliferation in each experimental condition was analyzed by Student's t-test. The result demonstrated that HDACs were expressed in all studied cell types. Both SAHA and VPA inhibited cell proliferation in a dose-dependent manner. Interestingly, KKU-100 which was less senstitive to classical chemotheraoeutic 5-FU was highly was sensitive to HDAC inhibitors. Simultaneous combination of subtoxic doses of HDAC inhibitors and 5-FU signiicantly inhibited cell proliferation in CCA cell lines compared to single sgent treatment($P{\leq}0.01$), while sequentially combined treatments were less effective. The present study showed inhibitory effects of HDACIs on cell proliferation in CCA cell lines, with synergistic antitumor potential demonstrated by simultaneous combination of VPA or SAHA with 5-FU, suggesting a novel alternative therapeutic strategy in effective treatment of CCA.