Displaying publications 1 - 20 of 115 in total

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  1. Unveiling synergism of polymyxin B with chloramphenicol derivatives against multidrug-resistant (MDR) Klebsiella pneumoniae
    Idris N, Leong KH, Wong EH, Abdul Rahim N
    J Antibiot (Tokyo), 2023 Dec;76(12):711-719.
    PMID: 37821539 DOI: 10.1038/s41429-023-00659-2
    Polymyxins are last-line antibiotics against multidrug-resistant Klebsiella pneumoniae but using polymyxins alone may not be effective due to emerging resistance. A previous study found that combining polymyxin B with chloramphenicol effectively kills MDR K. pneumoniae, although the bone marrow toxicity of chloramphenicol is concerning. The aim of this study is to assess the antibacterial efficacy and cytotoxicity of polymyxin B when combined with chloramphenicol and its derivatives, namely thiamphenicol and florfenicol (reported to have lesser toxicity compared to chloramphenicol). The antibacterial activity was evaluated with antimicrobial susceptibility testing using broth microdilution and time-kill assays, while the cytotoxic effect on normal bone marrow cell line, HS-5 was evaluated using the MTT assay. All bacterial isolates tested were found to be susceptible to polymyxin B, but resistant to chloramphenicol, thiamphenicol, and florfenicol when used alone. The use of polymyxin B alone showed bacterial regrowth for all isolates at 24 h. The combination of polymyxin B and florfenicol demonstrated additive and synergistic effects against all isolates (≥ 2 log10 cfu ml-1 reduction) at 4 and 24 h, respectively, while the combination of polymyxin B and thiamphenicol resulted in synergistic killing at 24 h against ATCC BAA-2146. Furthermore, the combination of polymyxin B with florfenicol had the lowest cytotoxic effect on the HS-5 cells compared to polymyxin B combination with chloramphenicol and thiamphenicol. Overall, the combination of polymyxin B with florfenicol enhanced bacterial killing against MDR K. pneumoniae and exerted minimal cytotoxic effect on HS-5 cell line.
    Matched MeSH terms: Drug Synergism
  2. Multi-constituent synergism is responsible for anti-inflammatory effect of Azadirachta indica leaf extract
    Umar MI, Asmawi MZ, Sadikun A, Abdul Majid AM, Atangwho IJ, Khadeer Ahamed MB, et al.
    Pharm Biol, 2014 Nov;52(11):1411-22.
    PMID: 25026347 DOI: 10.3109/13880209.2014.895017
    Azadirachta indica A. Juss. (Meliaceaes) leaves have been used traditionally to treat swelling and rheumatism in Indian cultures.
    Matched MeSH terms: Drug Synergism
  3. Enhancement of anti-proliferative activities of Metformin, when combined with Celecoxib, without increasing DNA damage
    Ullah A, Ashraf M, Javeed A, Anjum AA, Attiq A, Ali S
    Environ Toxicol Pharmacol, 2016 Jul;45:227-34.
    PMID: 27327526 DOI: 10.1016/j.etap.2016.05.017
    Pathophysiological changes in diabetes like hyperglycemia, oxidative stress, insulin resistance and compensatory hyperinsulinemia predispose cells to malignant transformation and damage DNA repair mechanism. This study was designed to explore the potential synergistic toxic effects of anti-diabetic drug (Metformin), and an analgesic drug (Celecoxib) at cellular level. MTT assay run on Vero cell line revealed that the combinations of Metformin and Celecoxib augment the anti-proliferative effects, whereas Single cell gel electrophoresis spotlighted that Metformin produce non-significant DNA damage with the threshold concentration of 400μg/ml in peripheral blood mononuclear cells (lymphocytes and monocytes), while Celecoxib produced significant (P<0.05) DNA damage (class III comets) above the concentration of 75μg/ml, however the DNA damage or DNA tail protrusions by combinations of both drugs were less than what was observed with Celecoxib alone. Metformin or Celecoxib did not appear mutagenic against any mutant strains (TA 100 and TA 98) but their combination exhibited slight mutagenicity at much higher concentration. The results obtained at concentrations higher than the therapeutic level of drugs and reflect that Metformin in combination with Celecoxib synergistically inhibits the cell proliferation in a concentration dependent pattern. Since, this increase in cytotoxicity did not confer an increase in DNA damage; this combination could be adopted to inhibit the growth of malignant cell without producing any genotoxic or mutagenic effects at cellular level.
    Matched MeSH terms: Drug Synergism
  4. Fulltext Synergistic antibacterial activity of Curcumin with antibiotics against Staphylococcus aureus
    Teow SY, Ali SA
    Pak J Pharm Sci, 2015 Nov;28(6):2109-14.
    PMID: 26639480
    This study evaluated the synergistic antibacterial activity of Curcumin with 8 different antibiotic groups. Two reference, one clinical and ten environmental strains of Staphylococcus aureus (S. aureus) were tested. Disc diffusion assay with 25 μg/mL Curcumin demonstrated synergism in combination with a majority of tested antibiotics against S. aureus. However, checkerboard micro dilution assay only showed synergism, fractional inhibitory concentration index (FICI) <0.5 in three antibiotics i.e. Gentamicin, Amikacin, and Ciprofloxacin. Other antibiotics showed indifferent interactions but no antagonism was observed. In time-kill curve, appreciable reduction of bacterial cells was also observed in combination therapy (Curcumin + antibiotics) compared to monotherapy (Curcumin or antibiotic(s) alone). The antibiotics with higher synergistic interaction with Curcumin are arranged in a decreasing order: Amikacin > Gentamicin > Ciprofloxacin.
    Matched MeSH terms: Drug Synergism
  5. Altered antibacterial activity of Curcumin in the presence of serum albumin, plasma and whole blood
    Teow SY, Ali SA
    Pak J Pharm Sci, 2017 Mar;30(2):449-457.
    PMID: 28649069
    Antibacterial effect is one of the major therapeutic activities of plant-derived Curcumin. This work evaluated the effect of serum albumin, human plasma, and whole blood on the in vitro activity of Curcumin against eight clinical bacterial isolates by standard broth microdilution and plate-counting methods. Toxicological effects of Curcumin towards human red blood cells (RBCs) and peripheral blood mononuclear cells (PBMCs) were also investigated. Curcumin exhibited weak activity against gram-negative bacteria, except Escherichia coli and Shigella flexneri were susceptible and was most active against gram-positive bacteria: Staphylococcus aureus, Streptococcus pyogenes and Enterococcus faecalis. The antibacterial activity was impaired in the presence of bovine serum albumin (BSA), human plasma and whole blood. Curcumin was not toxic to PBMCs and RBCs at 200μg/mL. Furthermore, Curcumin showed synergistic activity in combination with antibiotics: Ciprofloxacin, Gentamicin, Vancomycin and Amikacin against Staphylococcus aureus. This study demonstrated that the interaction of Curcumin with plasma proteins diminishes its in vitro antibacterial activity. Curcumin derivatives with reduced affinity for plasma protein may improve the bioavailability and antibacterial activities.
    Matched MeSH terms: Drug Synergism
  6. Fulltext Antibiotic resistance modifying ability of phytoextracts in anthrax biological agent Bacillus anthracis and emerging superbugs: a review of synergistic mechanisms
    Dassanayake MK, Khoo TJ, An J
    Ann Clin Microbiol Antimicrob, 2021 Dec 02;20(1):79.
    PMID: 34856999 DOI: 10.1186/s12941-021-00485-0
    BACKGROUND AND OBJECTIVES: The chemotherapeutic management of infections has become challenging due to the global emergence of antibiotic resistant pathogenic bacteria. The recent expansion of studies on plant-derived natural products has lead to the discovery of a plethora of phytochemicals with the potential to combat bacterial drug resistance via various mechanisms of action. This review paper summarizes the primary antibiotic resistance mechanisms of bacteria and also discusses the antibiotic-potentiating ability of phytoextracts and various classes of isolated phytochemicals in reversing antibiotic resistance in anthrax agent Bacillus anthracis and emerging superbug bacteria.

    METHODS: Growth inhibitory indices and fractional inhibitory concentration index were applied to evaluate the in vitro synergistic activity of phytoextract-antibiotic combinations in general.

    FINDINGS: A number of studies have indicated that plant-derived natural compounds are capable of significantly reducing the minimum inhibitory concentration of standard antibiotics by altering drug-resistance mechanisms of B. anthracis and other superbug infection causing bacteria. Phytochemical compounds allicin, oleanolic acid, epigallocatechin gallate and curcumin and Jatropha curcas extracts were exceptional synergistic potentiators of various standard antibiotics.

    CONCLUSION: Considering these facts, phytochemicals represents a valuable and novel source of bioactive compounds with potent antibiotic synergism to modulate bacterial drug-resistance.

    Matched MeSH terms: Drug Synergism*
  7. Toxicity of tetramethylammonium hydroxide to aquatic organisms and its synergistic action with potassium iodide
    Mori IC, Arias-Barreiro CR, Koutsaftis A, Ogo A, Kawano T, Yoshizuka K, et al.
    Chemosphere, 2015 Feb;120:299-304.
    PMID: 25151133 DOI: 10.1016/j.chemosphere.2014.07.011
    The aquatic ecotoxicity of chemicals involved in the manufacturing process of thin film transistor liquid crystal displays was assessed with a battery of four selected acute toxicity bioassays. We focused on tetramethylammonium hydroxide (TMAH, CAS No. 75-59-2), a widely utilized etchant. The toxicity of TMAH was low when tested in the 72 h-algal growth inhibition test (Pseudokirchneriellia subcapitata, EC50=360 mg L(-1)) and the Microtox® test (Vibrio fischeri, IC50=6.4 g L(-1)). In contrast, the 24h-microcrustacean immobilization and the 96 h-fish mortality tests showed relatively higher toxicity (Daphnia magna, EC50=32 mg L(-1) and Oryzias latipes, LC50=154 mg L(-1)). Isobologram and mixture toxicity index analyses revealed apparent synergism of the mixture of TMAH and potassium iodide when examined with the D. magna immobilization test. The synergistic action was unique to iodide over other halide salts i.e. fluoride, chloride and bromide. Quaternary ammonium ions with longer alkyl chains such as tetraethylammonium and tetrabutylammonium were more toxic than TMAH in the D. magna immobilization test.
    Matched MeSH terms: Drug Synergism
  8. Pharmacological mechanisms underlying the vascular activities of Loranthus ferrugineus Roxb. in rat thoracic aorta
    Ameer OZ, Salman IM, Siddiqui MJ, Yam MF, Sriramaneni RN, Mohamed AJ, et al.
    J Ethnopharmacol, 2010 Jan 8;127(1):19-25.
    PMID: 19808083 DOI: 10.1016/j.jep.2009.09.057
    The present study was aimed to investigate the pharmacological basis for the use of Loranthus ferrugineus in hypertension.
    Matched MeSH terms: Drug Synergism
  9. Fulltext In vitro evaluation of the synergistic antioxidant and anti-inflammatory activities of the combined extracts from Malaysian Ganoderma lucidum and Egyptian Chlorella vulgaris
    Abu-Serie MM, Habashy NH, Attia WE
    BMC Complement Altern Med, 2018 May 10;18(1):154.
    PMID: 29747629 DOI: 10.1186/s12906-018-2218-5
    BACKGROUND: Since oxidative stress and inflammation are two linked factors in the pathogenesis of several human diseases. Thus identification of effective treatment is of great importance. Edible mushroom and microalgae are rich in the effective antioxidant phytochemicals. Hence, their beneficial effects on oxidative stress-associated inflammation are extremely required to be investigated.

    METHODS: This study evaluated the functional constituents, antioxidant and anti-inflammatory activities of Malaysian Ganoderma lucidum aqueous extract (GLE) and Egyptian Chlorella vulgaris ethanolic extract (CVE). Also, the synergistic, addictive or antagonistic activities of the combination between the two extracts (GLE-CVE) were studied. Expression of inducible nitric oxide synthase, cyclooxygenase-2, and nuclear factor-kappa B, as well as levels of nitric oxide, tumor necrosis factor (TNF)-α, lipid peroxidation, reduced glutathione and antioxidant enzymes were determined using in vitro model of lipopolysaccharide-stimulated white blood cells.

    Matched MeSH terms: Drug Synergism
  10. Effect of ribavirin on zidovudine efficacy and toxicity in vitro: a concentration-dependent interaction
    Sim SM, Hoggard PG, Sales SD, Phiboonbanakit D, Hart CA, Back DJ
    AIDS Res Hum Retroviruses, 1998 Dec 20;14(18):1661-7.
    PMID: 9870320
    Zidovudine (ZDV) is converted to its active triphosphate (ZDVTP) by intracellular kinases. The intermediate ZDV monophosphate (ZDVMP) is believed to play a major role in ZDV toxicity. Manipulation of ZDV phosphorylation is a possible therapeutic strategy for altering the risk-benefit ratio. Here we investigate whether combining RBV with ZDV is able to modulate efficacy and toxicity of ZDV. We have measured the intracellular activation of ZDV (0.3 microM) in the absence and presence of ribavirin (RBV; 2 and 20 microM) in Molt 4 and U937 cells. MTT cytotoxicity of ZDV (10-1000 microM) was also measured with and without RBV (2 microM) in Molt 4 and U937 cells. Measurement of endogenous deoxythymidine triphosphate (dTTP) allowed investigation of the dTTP/ZDVTP ratio. The antiviral efficacy of ZDV in combination with RBV (2 microM) was assessed by HIV p24 antigen measurements. In the presence of RBV (2 and 20 microM) a decrease in total ZDV phosphates was observed, owing mainly to an effect primarily on ZDVMP rather than the active ZDVTP. RBV also increased endogenous dTTP pools in both cell types, resulting in an increase in the dTTP/ZDVTP ratio. ZDV alone significantly reduced p24 antigen production, with an IC50 of 0.34 microM. Addition of RBV increased the IC50 approximately fivefold (1.52 microM). However, at higher concentrations of ZDV (10 and 100 microM) the antagonistic effect of RBV (2 microM) on ZDV was lost. The RBV-mediated decrease in ZDVMP may explain the reduction in ZDV toxicity when combined with RBV (2 microM). Cytotoxicity of ZDV was reduced in the presence of RBV (2 microM) at all concentrations in both cell lines, probably owing to saturation of ZDVTP formation. The interaction of ZDV and RBV is concentration dependent.
    Matched MeSH terms: Drug Synergism
  11. Anti-plaque effect of a synergistic combination of green tea and Salvadora persica L. against primary colonizers of dental plaque
    Abdulbaqi HR, Himratul-Aznita WH, Baharuddin NA
    Arch Oral Biol, 2016 Oct;70:117-124.
    PMID: 27343694 DOI: 10.1016/j.archoralbio.2016.06.011
    OBJECTIVE: Green tea (Gt), leafs of Camellia sinensis var. assamica, is widely consumed as healthy beverage since thousands of years in Asian countries. Chewing sticks (miswak) of Salvadora persica L. (Sp) are traditionally used as natural brush to ensure oral health in developing countries. Both Gt and Sp extracts were reported to have anti-bacterial activity against many dental plaque bacteria. However, their combination has never been tested to have anti-bacterial and anti-adherence effect against primary dental plaque colonizers, playing an initial role in the dental plaque development, which was investigated in this study.

    METHODS: Two-fold serial micro-dilution method was used to measure minimal inhibitory concentration (MIC) of aqueous extracts of Gt, Sp and their combinations. Adsorption to hexadecane was used to determine the cell surface hydrophobicity (CSH) of bacterial cells. Glass beads were used to mimic the hard tissue surfaces, and were coated with saliva to develop experimental pellicles for the adhesion of the primary colonizing bacteria.

    RESULTS: Gt aqueous extracts exhibited better anti-plaque effect than Sp aqueous extracts. Their combination, equivalent to 1/4 and 1/2 of MIC values of Gt and Sp extracts respectively, showed synergistic anti-plaque properties with fractional inhibitory concentration (FIC) equal to 0.75. This combination was found to significantly reduce CSH (p<0.05) and lower the adherence ability (p<0.003) towards experimental pellicles.

    CONCLUSION: Combination between Gt and Sp aqueous extracts exhibited synergistic anti-plaque activity, and could be used as a useful active agent to produce oral health care products.

    Matched MeSH terms: Drug Synergism
  12. Synergy of flavone with vancomycin and oxacillin against vancomycin-intermediate Staphyloccus aureus
    Bakar NS, Zin NM, Basri DF
    Pak J Pharm Sci, 2012 Jul;25(3):633-8.
    PMID: 22713953
    This study evaluated in vitro activity of 9 flavonoids in combination with vancomycin or oxacillin against vancomycin-intermediate Staphylococcus aureus (VISA) ATCC 700699 by employing the checkerboard method to obtain Minimal inhibitory concentration (MIC) and fractional inhibitory concentration (FIC) index. Six flavonoids namely hesperitin, rutin, naringenin, flavones, naringin and 3, 7-dihyroxyflavone which exhibited notable inhibitory activity (MIC values < 3200 μg/ml) were further evaluated for combination assay with antibiotics. The combinations of vancomycin+flavone and oxacillin+flavone were found synergistic with the FIC index value 0.094 and 0.126, respectively. Other combinations showed an additive interaction (FIC index = 1.063) but no antagonistic reaction (FIC index > 4) were observed. In time kill studies, oxacillin-flavone combination at synergistic concentration demonstrated bactericidal effect at 24 h period with concentration-dependent manner on the VISA strain. Following 1 h exposure, the combination also produced persistent effect on the bacteria growth for 2.9 hrs at 1x sub-MIC and more than 24 h at 5x of sub-MIC and there was a significant difference between both concentrations (p<0.05). Vancomycin-flavone combination, however, showed no concentration-dependent effect and lower PAE values (1.159 h and 2.322 h at 1x and 5x sub-MIC, respectively) on the VISA strain. In conclusion, flavone markedly intensifies the susceptibility of oxacillin against VISA and the combination can be implicated for further interaction studies at molecular level.
    Matched MeSH terms: Drug Synergism
  13. Fulltext Hippuric acid nanocomposite enhances doxorubicin and oxaliplatin-induced cytotoxicity in MDA-MB231, MCF-7 and Caco2 cell lines
    Hussein Al Ali SH, Al-Qubaisi M, Hussein MZ, Ismail M, Bullo S
    Drug Des Devel Ther, 2013;7:25-31.
    PMID: 23345969 DOI: 10.2147/DDDT.S37070
    The aim of the current study is to design a new nanocomposite for inducing cytotoxicity of doxorubicin and oxaliplatin toward MDA-MB231, MCF-7, and Caco2 cell lines. A hippuric acid (HA) zinc layered hydroxide (ZLH) nanocomposite was synthesized under an aqueous environment using HA and zinc oxide (ZnO) as the precursors.
    Matched MeSH terms: Drug Synergism
  14. Synergistic Antibacterial Activity Between 1,4-Naphthoquinone and β-Lactam Antibiotics Against Methicillin-Resistant Staphylococcus aureus
    Yap JKY, Tan SYY, Tang SQ, Thien VK, Chan EWL
    Microb Drug Resist, 2021 Feb;27(2):234-240.
    PMID: 32589487 DOI: 10.1089/mdr.2020.0178
    Aims: Currently, limited antibiotics are available to treat methicillin-resistant Staphylococcus aureus (MRSA) infections. One approach is the use of adjuvants in antibiotic therapy. 1,4-Naphthoquinones are naturally occurring alkaloids shown to have antibacterial properties. The objective of this study is to investigate the synergy between 1,4-naphthoquinone and selected β-lactam antibiotics and to evaluate the potential use of 1,4-naphthoquinone as an adjuvant in antibiotic treatment against MRSA infections. Methods: The antibacterial activity of 1,4-naphthoquinone and plumbagin was tested against nine pathogenic bacterial strains using the microdilution broth method. The interactions between 1,4-naphthoquinone and three antibiotics (cefuroxime, cefotaxime, and imipenem) were estimated by calculating the fractional inhibitory concentration of the combination. Results: The compounds 1,4-naphthoquinone and plumbagin exhibited a broad range of bacteriostatic and bactericidal effects against both Gram-positive and Gram-negative bacteria. The interaction between 1,4-naphthoquinone and imipenem, cefuroxime, and cefotaxime was synergistic against methicillin-sensitive Staphylococcus aureus and MRSA clinical strains. Against ATCC-cultured MRSA, a synergistic effect was observed between 1,4-naphthoquinone and cefotaxime. However, combination with imipenem only produced an additive effect, and an antagonistic action was observed between 1,4-naphthoquinone and cefuroxime. Conclusions: Although individually less potent than common antibiotics, 1,4-naphthoquinone acts synergistically with imipenem, cefuroxime, and cefotaxime against MRSA clinical strains and could potentially be used in adjuvant-antibiotic therapy against multidrug resistant bacteria.
    Matched MeSH terms: Drug Synergism
  15. Mechanisms of antihyperuricemic effect of Phyllanthus niruri and its lignan constituents
    Murugaiyah V, Chan KL
    J Ethnopharmacol, 2009 Jul 15;124(2):233-9.
    PMID: 19397979 DOI: 10.1016/j.jep.2009.04.026
    ETHNOPHARMACOLOGICAL RELEVANCE: Phyllanthus niruri Linn. (Euphorbiaceae) is used as folk medicine in South America to treat excess uric acid. Our initial study showed that the methanol extract of Phyllanthus niruri and its lignans were able to reverse the plasma uric acid of hyperuricemic animals.
    AIM OF THE STUDY: The study was undertaken to investigate the mechanisms of antihyperuricemic effect of Phyllanthus niruri and its lignan constituents.
    MATERIAL AND METHODS: The mechanisms were investigated using xanthine oxidase assay and uricosuric studies in potassium oxonate- and uric acid-induced hyperuricemic rats.
    RESULTS: Phyllanthus niruri methanol extract exhibited in vitro xanthine oxidase inhibition with an IC50 of 39.39 microg/mL and a moderate in vivo xanthine oxidase inhibitory activity. However, the lignans display poor xanthine oxidase inhibition in vitro and a relatively weak in vivo inhibitory activity at 10mg/kg. On the other hand, intraperitoneal treatment with Phyllanthus niruri methanol extract showed 1.69 folds increase in urinary uric acid excretion when compared to the hyperuricemic control animals. Likewise, the lignans, phyllanthin, hypophyllanthin and phyltetralin exhibited up to 2.51 and 11.0 folds higher in urinary uric acid excretion and clearance, respectively. The co-administration of pyrazinamide with phyllanthin exhibited a significant suppression of phyllanthin's uricosuric activity resembling that of pyrazinamide with benzbromarone.
    CONCLUSIONS: The present study showed that the antihyperuricemic effect of Phyllanthus niruri methanol extract may be mainly due to its uricosuric action and partly through xanthine oxidase inhibition, whereas the antihyperuricemic effect of the lignans was attributed to their uricosuric action.
    Matched MeSH terms: Drug Synergism
  16. Olanzapine-induced and Risperidone-induced Leukopenia: A Case of Synergistic Adverse Reaction?
    Woon LS, Tee CK, Gan LLY, Deang KT, Chan LF
    J Psychiatr Pract, 2018 Mar;24(2):121-124.
    PMID: 29509183 DOI: 10.1097/PRA.0000000000000292
    Leukopenia is a known hematological side effect of atypical antipsychotics. We report a case of an antipsychotic-naive patient with schizophrenia who developed leukopenia after a single dose of olanzapine, which worsened during subsequent treatment with risperidone. Normalization of the white blood cell counts occurred within 24 hours of risperidone discontinuation. Possible synergistic mechanisms underlying olanzapine-induced and risperidone-induced leukopenia are discussed. This case highlights the challenges in identifying and managing nonclozapine antipsychotic-induced leukopenia in a susceptible patient.
    Matched MeSH terms: Drug Synergism
  17. Synergistic Growth Inhibition by Afatinib and Trametinib in Preclinical Oral Squamous Cell Carcinoma Models
    Yee PS, Zainal NS, Gan CP, Lee BKB, Mun KS, Abraham MT, et al.
    Target Oncol, 2019 04;14(2):223-235.
    PMID: 30806895 DOI: 10.1007/s11523-019-00626-8
    BACKGROUND: Given that aberrant activation of epidermal growth factor receptor family receptors (ErbB) is a common event in oral squamous cell carcinoma, and that high expression of these receptor proteins is often associated with poor prognosis, this rationalizes the approach of targeting ErbB signaling pathways to improve the survival of patients with oral squamous cell carcinoma. However, monotherapy with the ErbB blocker afatinib has shown limited survival benefits.

    OBJECTIVES: This study was performed to identify mechanisms of afatinib resistance and to explore potential afatinib-based combination treatments with other targeted inhibitors in oral squamous cell carcinoma.

    METHODS: We determined the anti-proliferative effects of afatinib on a panel of oral squamous cell carcinoma cell lines using a crystal violet-growth inhibition assay, click-iT 5-ethynyl-2'-deoxyuridine staining, and cell-cycle analysis. Biochemical assays were performed to study the underlying mechanism of drug treatment as a single agent or in combination with the MEK inhibitor trametinib. We further evaluated and compared the anti-tumor effects of single agent and combined treatment by using oral squamous cell carcinoma xenograft models.

    RESULTS: In this study, we showed that afatinib inhibited oral squamous cell carcinoma cell proliferation via cell-cycle arrest at the G0/G1 phase, and inhibited tumor growth in xenograft mouse models. Interestingly, we demonstrated reactivation of the mitogen-activated protein kinase (ERK1/2) pathway in vitro, which possibly reduced the effects of ErbB inhibition. Concomitant treatment of oral squamous cell carcinoma cells with afatinib and trametinib synergized the anti-tumor effects in oral squamous cell carcinoma-bearing mouse models.

    CONCLUSIONS: Our findings provide insight into the molecular mechanism of resistance to afatinib and support further clinical evaluation into the combination of afatinib and MEK inhibition in the treatment of oral squamous cell carcinoma.

    Matched MeSH terms: Drug Synergism*
  18. Fulltext Estrogenicity of glabridin in Ishikawa cells
    Su Wei Poh M, Voon Chen Yong P, Viseswaran N, Chia YY
    PLoS One, 2015;10(3):e0121382.
    PMID: 25816349 DOI: 10.1371/journal.pone.0121382
    Glabridin is an isoflavan from licorice root, which is a common component of herbal remedies used for treatment of menopausal symptoms. Past studies have shown that glabridin resulted in favorable outcome similar to 17β-estradiol (17β-E2), suggesting a possible role as an estrogen replacement therapy (ERT). This study aims to evaluate the estrogenic effect of glabridin in an in-vitro endometrial cell line -Ishikawa cells via alkaline phosphatase (ALP) assay and ER-α-SRC-1-co-activator assay. Its effect on cell proliferation was also evaluated using Thiazoyl blue tetrazolium bromide (MTT) assay. The results showed that glabridin activated the ER-α-SRC-1-co-activator complex and displayed a dose-dependent increase in estrogenic activity supporting its use as an ERT. However, glabridin also induced an increase in cell proliferation. When glabridin was treated together with 17β-E2, synergistic estrogenic effect was observed with a slight decrease in cell proliferation as compared to treatment by 17β-E2 alone. This suggest that the combination might be better suited for providing high estrogenic effects with lower incidences of endometrial cancer that is associated with 17β-E2.
    Matched MeSH terms: Drug Synergism
  19. In vitro investigation of antifungal activity of allicin alone and in combination with azoles against Candida species
    Khodavandi A, Alizadeh F, Aala F, Sekawi Z, Chong PP
    Mycopathologia, 2010 Apr;169(4):287-95.
    PMID: 19924565 DOI: 10.1007/s11046-009-9251-3
    Candidiasis is a term describing infections by yeasts from the genus Candida, and the type of infection encompassed by candidiasis ranges from superficial to systemic. Treatment of such infections often requires antifungals such as the azoles, but increased use of these drugs has led to selection of yeasts with increased resistance to these drugs. In this study, we used allicin, an allyl sulfur derivative of garlic, to demonstrate both its intrinsic antifungal activity and its synergy with the azoles, in the treatment of these yeasts in vitro. In this study, the MIC(50) and MIC(90) of allicin alone against six Candida spp. ranged from 0.05 to 25 microg/ml. However, when allicin was used in combination with fluconazole or ketoconazole, the MICs were decreased in some isolates. Our results demonstrated the existing synergistic effect between allicin and azoles in some of the Candida spp. such as C. albicans, C. glabrata and C. tropicalis, but synergy was not demonstrated in the majority of Candida spp. tested. Nonetheless, In vivo testing needs to be performed to support these findings.
    Matched MeSH terms: Drug Synergism
  20. Review: antimicrobial properties of allicin used alone or in combination with other medications
    Choo S, Chin VK, Wong EH, Madhavan P, Tay ST, Yong PVC, et al.
    Folia Microbiol (Praha), 2020 Jun;65(3):451-465.
    PMID: 32207097 DOI: 10.1007/s12223-020-00786-5
    Garlic (Allium sativum L.) is a well-known spice widely utilised for its medicinal properties. There is an extensive record of the many beneficial health effects of garlic which can be traced back to as early as the ancient Egyptian era. One of the most studied properties of garlic is its ability to cure certain ailments caused by infections. In the 1940s, the antimicrobial activities exhibited by garlic were first reported to be due to allicin, a volatile compound extracted from raw garlic. Since then, allicin has been widely investigated for its putative inhibitory activities against a wide range of microorganisms. Allicin has demonstrated a preference for targeting the thiol-containing proteins and/or enzymes in microorganisms. It has also demonstrated the ability to regulate several genes essential for the virulence of microorganisms. Recently, it was reported that allicin may function better in combination with other antimicrobials compared to when used alone. When used in combination with antibiotics or antifungals, allicin enhanced the antimicrobial activities of these substances and improved the antimicrobial efficacy. Hence, it is likely that combination therapy of allicin with additional antimicrobial drug(s) could serve as a viable alternative for combating rising antimicrobial resistance. This review focuses on the antimicrobial activities exhibited by allicin alone as well as in combination with other substances. The mechanisms of action of allicin elucidated by some of the studies are also highlighted in the present review in order to provide a comprehensive overview of this versatile bioactive compound and the mechanistic evidence supporting its potential use in antimicrobial therapy.
    Matched MeSH terms: Drug Synergism
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