Kamel Ghedira

University of Monastir, Al Munastīr, Al Munastīr, Tunisia

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Publications (206)263.07 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The lack of an efficient agent that does not have the disadvantage of low activity (kojic acid), high cytotoxicity, and mutagenicity (hydroquinone), poor skin penetration (arbutin), or low stability in formulation (glabridin) led us to continue our research on new antipigmentation/skin-lightening agents. Therefore, research of natural products that can modulate the metabolism of pigmentation is of great interest. Otherwise, malignant melanoma is one of the most aggressive forms of skin cancer, with high metastatic potential, and currently, there is no effective chemotherapy against invasive melanoma. Therefore, it is necessary to develop new drugs with potent activity and weak side effects against melanoma. The in-vitro anticancer effect of hawthorn was analyzed against B16F10 melanoma cells using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The effect of isolated compounds from hawthorn on melanogenesis in B16F10 melanoma cells was investigated by measuring the amounts of melanin and tyrosinase spectrophotometrically at 475 nm. Balb/c mice models inoculated with B16F10 mouse tumor cells were used to evaluate the in-vivo antitumoral potential of hawthorn by assessing its effect on the growth of transplanted tumors. The antioxidant potential of tested samples was evaluated in B16F10 and primary human keratinocyte cells using a cellular antioxidant activity assay. Hawthorn tested samples inhibited effectively the growth of melanoma cells in vitro. Furthermore, it appears that tested samples from hawthorn reduced melanogenesis by inhibiting the tyrosinase activity of B16F10 cells in a dose-dependent manner. In-vivo studies showed that hawthorn total oligomer flavonoids extract treatment at a dose of 150 mg/kg body weight for 21 days in implanted tumor mice resulted in significant inhibition of the tumor growth volume and weight. In addition, tested samples showed significant cellular antioxidant capacity against the reactive oxygen species in B16F10 and primary human keratinocyte cells. Our results indicate that hawthorn could be considered as a promising agent for the treatment of melanoma as it shows antitumor activity in vitro and in vivo. Moreover, hawthorn constituents are shown to be highly effective at inhibiting tyrosinase-mediated melanogenesis in vitro on melanoma cells by preventing oxidation in these cells and without affecting the viability of normal human keratinocyte cells. Then, hawthorn might also be used as a new candidate of natural skin depigmenting agents in skin care products. Copyright
    No preview · Article · Jan 2016 · Melanoma Research
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    ABSTRACT: The search of natural immunomodulatory agents has become an area of great interest in order to reduce damage to the human body. In this study, the immunomodulatory potential of Crataegus azarolus and its isolated hyperoside on mouse lymphocytes and macrophages in vitro was assessed. The effect of C. azarolus natural compounds on splenocytes proliferation, natural killer (NK) and cytotoxic T lymphocytes (CTL) activities, and on macrophage-mediated cytotoxicity were assessed by MTT test. Phagocytic activity and inhibition of nitric oxide (NO) release by macrophages were also evaluated. The antioxidant capacity of these products was evaluated by determining their cellular antioxidant activity (CAA) in splenocytes and macrophages. Depending on the concentrations, both ethyl acetate (EA) extract and hyperoside (Hyp) from C. azarolus affect macrophage functions by modulating their lysosomal enzyme activity and nitric oxide release. Whereas, the above-mentioned products significantly promote LPS and lectin-stimulated splenocyte proliferation, implying a potential activation of lymphocytes B and T enhancing humoral and cellular immune responses. Moreover, EA extract and Hyp could enhance the activity of NK and T lymphocytes cells, as well as the macrophages-mediated cytotoxicity against B16F10 cells. The anti-inflammatory activity was concomitant with the cellular antioxidant effect of the tested compounds against macrophages and splenocytes. Collectively, C. azarolus and its isolated hyperoside exhibited an immunomodulatory effect through their antioxidant activity. These findings suggest that C. azarolus should be explored as a novel potential immunomodulatory agent for the treatment of inflammatory diseases.
    No preview · Article · Dec 2015 · Tumor Biology
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    ABSTRACT: Evaluation of the immunomodulatory activity of plant compounds is an interesting and growing area of research. Teucrium ramosissimum Desf. is a native and endemic medicinal plant from the South of Tunisia traditionally used for the treatment of many diseases. The anti-inflammatory activity of apigenin-7-glucoside, genkwanin, and naringenin isolated from T. ramosissimum were assayed. The phagocytic activities of macrophage and lymphocyte proliferation were investigated in the absence and presence of mitogens (lipopolysaccharide [LPS] or lectin). Depending on the concentrations, the compounds affect macrophage functions by modulating their lysosomal enzyme activity and nitric oxide (NO) release. The tested compounds enhance significantly splenocyte proliferation, either with or without mitogen stimulation. In studies to assess any potential effects of apigenin-7-glucoside, genkwanin, and naringenin on innate immunity, the results showed that these compounds significantly enhanced the killing activity of natural killer (NK) cells and cytotoxic activity of the T lymphocyte (CTL) isolated from splenocytes. These results suggest that T. ramosissimum compounds such as apigenin-7-glucoside, genkwanin, and naringenin may be potentially useful for modulating immune cell functions in physiological and pathological conditions.
    Full-text · Article · Dec 2015 · Tumor Biology
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    ABSTRACT: Flavonoids impart a variety of biological activities, including anti-oxidant, anti-inflammatory, and anti-genotoxic effects. This study investigated the effects of flavone luteolin and apigenin on immune cell functions, including proliferation, natural killer (NK) cell activity, and cytotoxic T lymphocyte (CTL) activity of isolated murine splenocytes. We report for the first time that flavones enhance lymphocyte proliferation at 10 μM. Luteolin and apigenin significantly promote lipopolysaccharide (LPS)-stimulated splenocyte proliferation and enhance humoral immune responses. Luteolin induces a weak cell proliferation of lectin-stimulated splenic T cells, when compared to apigenin. In addition, both flavones significantly enhance NK cell and CTL activities. Furthermore, our study demonstrated that both flavones could inhibit lysosomal enzyme activity, suggesting a potential anti-inflammatory effect. The anti-inflammatory activity was concomitant with the cellular anti-oxidant effect detected in macrophages, red blood cells, and splenocytes. We conclude from this study that flavones exhibited an immunomodulatory effect which could be ascribed, in part, to its cytoprotective capacity via its anti-oxidant activity.
    No preview · Article · Dec 2015 · Tumor Biology
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    ABSTRACT: The purpose of this study was to assess the antitumor and immunomodulatory effects of the aqueous extract from Daphne gnidium in mice-bearing melanoma tumor. Balb/C mice were subcutaneously implanted with B16-F10 cells and treated intraperitoneally with the aqueous extract at 200 mg/Kg b.w for 21 days. After euthanization on day 22, the tumors were weighed; lymphocyte proliferation, cytotoxic T lymphocyte (CTL), and natural killer (NK) cell activities were evaluated using the MTT assay. Macrophage phagocytosis was studied by measuring the lysosomal activity. In addition to its potential to inhibit the growth of the transplantable tumor, the aqueous extract remarkably induced splenocyte proliferation and both NK and CTL activities in tumor-bearing mice. The aqueous extract was also seen to have promoted lysosomal activity of host macrophages.
    No preview · Article · Dec 2015 · Tumor Biology
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    ABSTRACT: Methanol extract of Daphne gnidium leaves was assessed for its antigenotoxic and neuroprotective effects through antioxidant and antibutyrylcholinesterase activities. Antigenotoxic activity was evaluated against methyl methanesulfonate injected intraperitoneally to mice, using the comet assay. The protective effect of D. gnidium reached 99.12%, at the lowest tested dose (44 mg/kg b.w.) in kidney cells, and 92.16% at the dose of 88 mg/kg b.w. in blood cells. The extract was dissolved in water and administrated to mice by intraperitoneal injection. Antioxidant activity was tested against DPPH radicals. It reached a maximum of 74.52% with an IC50 value of 45 µg/ml. Anticholinesterase activity was determined against butyrylcholinesterase, an enzyme linked to Alzheimer disease. The extract exhibited antibutyrylcholinestrase effect with an inhibition percentage of 35.82% at the lowest tested dose (44 mg/kg b.w.).
    No preview · Article · Nov 2015 · Drug and Chemical Toxicology
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    ABSTRACT: Aims: In this study, we have investigated the effects of apigenin-7-glucoside, genkwanin and naringenin, on mouse melanoma B16F10 cell proliferation. Influence of these natural products on percentage cell distribution in cycle phases and melanogenesis was also studied. Main methods: Cell viability was determined at various periods using the MTT assay, whereas effects of tested compounds on progression through the cell cycle were analyzed by flow cytometry. In addition, amounts of melanin and tyrosinase were measured spectrophotometrically at 475nm. Besides, the mechanism involved on the death route induced by the tested molecules was evaluated using the bis-benzimide trihydrochloride coloration method (Hoechst 33258). Key findings: Apigenin-7-glucoside, genkwanin and naringenin exhibited significant anti-proliferative activity against B16F10 melanoma cells after 24 and 48h of incubation. Furthermore, apigenin-7-glucoside, genkwanin and naringenin provoked an increase of subG0/G1, S and G2/M phase cell proportion with a significant decrease of cell proportion in G0/G1 phases. The results evaluated using Hoechst 33,258, confirm that the percentage of B16F10 cells observed in the sub G0/G1 phase were undergoing apoptosis. Moreover, apigenin-7-glucoside and naringenin revealed an ability to enhance melanogenesis synthesis and tyrosinase activity of B16F10 melanoma cells. Whereas genkwanin induces a decrease of melanin synthesis by inhibiting tyrosinase activity. Significance: Our results promote the introduction of genkwanin in cosmetic preparations, as skin whitening agent, whereas apigenin-7-glucoside and naringenin should be introduced into cosmetic products as natural tanning agents.
    Full-text · Article · Nov 2015 · Life sciences
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    ABSTRACT: Limited success has been achieved in extending the survival of patients with metastatic colorectal cancer (CRC). There is a strong need for novel agents in the treatment and prevention of CRC. Therefore, in the present study we evaluated the antiproliferative and pro-apoptotic potential of Crataegus azarolus ethyl acetate extract in HCT-116 and HT-29 human colorectal cancer cell lines. Moreover, we attempted to investigate the signaling pathways that should be involved in its cytotoxic effect. The Crataegus azarolus ethyl acetate extract-induced growth inhibitory effect was associated with DNA fragmentation, sub-G1 peak, loss of mitochondrial potential and poly (ADP-ribose) polymerase (PARP) cleavage. In addition, ethyl acetate extract of Crataegus azarolus induced the cleavage of caspase-8. It has no effect on steady-state levels of total Bcl-2 protein. Whereas Bax levels decreased significantly in a dose-dependent manner in both tested cell lines. Taken together, these findings confirm the involvement of the extrinsic pathway of apoptosis. The apoptotic cell death induced by ethyl acetate extract of Crataegus azarolus was accompanied by an enhancement of the p21 expression but not through p53 activation in human colorectal cancer cells. The above-mentioned data provide insight into the molecular mechanisms of Crataegus azarolus ethyl acetate extract-induced apoptosis in CRC. Therefore, this compound should be a potential anticancer agent for the treatment of CRC. This article is protected by copyright. All rights reserved.
    No preview · Article · Oct 2015 · Journal of Cellular Biochemistry
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    ABSTRACT: Cancer metastasis is the major cause of cancer-related death. Chemoprevention is defined as the use of natural or synthetic substances to prevent cancer formation or cancer progress. In the present study, we investigate the antitumor activity of esculin and its oligomer fractions in U87 glioblastoma cells. We showed that esculin and its oligomers reduced U87 cell growth in a dose dependent manner. They also inhibited cell adhesion to collagen IV and vitronectin by interfering with the function of their respective receptors α2β1 and αvβ5 integrins. Furthermore, the tested samples were able to reduce migration of U87 cells towards another extracellular matrix fibronectin. Moreover, esculin and its oligomer fractions inhibited in vitro angiogenesis of endothelial cells (HMEC-1). In summary, our data provide the first evidence that esculin and its oligomer fractions are able to reduce adhesion, migration of glioblastoma cells and in vitro angiogenesis. Esculin and its oligomers may thus exert multi-target functions against cancer cells.
    No preview · Article · Oct 2015 · Tumor Biology
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    ABSTRACT: Background: Here, phytochemical profile of Nitraria retusa (N. Retusa) leaf extracts was identified and their ability to induce apoptosis and inhibiting growth of melanoma cells and enhancing melanogenesis of B16F10 melanoma was evaluated. Methods: The Apoptosis was evidenced by investigating DNA fragmentation, and Acridine orange/ethidium bromide staining. Amounts of melanin and tyrosinase were measured spectrophotometrically at 475 nm. Results: Extracts from Nitraria retusa exhibited significant anti-proliferative activity after 48 h of incubation. Our result was confirmed by ladder DNA fragmentation profile. All extracts showed also the ability to enhance melanogenesis and tyrosinase activity of B16F10 melanoma cells. Conclusion: The tested extracts have a significant biological effect which may be due to their bioactive compounds.
    Full-text · Article · Sep 2015 · BMC Complementary and Alternative Medicine
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    ABSTRACT: Reactive oxygen species are well-known mediators of various biological responses. In this study, we examined the effect of three phenolic acids, caffeic, coumaric and ferulic acids, on superoxide anion production, adhesion and migration of human lung (A549) and colon adenocarcinoma (HT29-D4) cancer cell lines. Proliferation of both tumor cells was inhibited by phenolic acids. Caffeic, coumaric and ferulic acids also significantly inhibited superoxide production in A549 and HT29-D4 cells. Superoxide anion production decreased by 92% and 77% at the highest tested concentration (200µM) of caffeic acid in A549 and HT29-D4 cell lines respectively. Furthermore, A549 and HT29-D4 cell adhesion was reduced by 77.9% and 79.8% respectively at the higher tested concentration of ferulic acid (200µM). Migration assay performed towards A549 cell line, revealed that tested compounds reduced significantly cell migration. At the highest concentration tested (200µM), the covered surface was 7.7%, 9.5% and 35% for caffeic, coumaric or ferulic acids, respectively. These results demonstrate that caffeic, coumaric and ferulic acids may participate as active ingredients in anticancer agents against lung and colon cancer development, at adhesion and migration steps of tumor progression.
    Full-text · Article · Sep 2015 · European journal of pharmacology
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    ABSTRACT: The purpose of this study was to assess the antitumoral effect of the methanol extract (MeOH) from Nitraria retusa leaves and to investigate its immunomodulatory activity that mediated the prevention of tumor progression in tumor-bearing mice. Balb/c mice weighing 18-20 g were subcutaneously implanted with B16-F10 cells then injected intra-peritoneally, 7 days later with (200 mg/kg bw) of MeOH extract, for 21 days. After euthanization on day 21, the tumors were weighed. Lymphocyte proliferation, cytotoxic T lymphocyte (CTL) and NK activity were evaluated using the MTT assay. Macrophage phagocytosis was studied by measuring their lysosomal activity and nitric oxide production. The methanol extract inhibited significantly the growth of the implanted tumor, and increased remarkably splenocyte proliferation as well as NK and CTL activities, in tumor-bearing mice. It also promoted lysosomal activity of treated animal macrophages. Our findings suggest that antitumoral effect of MeOH extract is related with to immunomodulatory activity.
    Full-text · Article · Aug 2015 · Cancer Cell International
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    ABSTRACT: Textile industry is considered as one of the important factors of the economic growth in Tunisia. However, this prominent role has certainly some drawbacks mainly represented by the huge amounts of textile wastewaters generated that become a real menace to nature. Many previous studies showed the purifying potential of some activated sludge and bacteria (Pseudomonas putida) to decolourize textile effluents. However, in many cases, decolourization of wastewaters is not necessary associated with detoxification, generating a real risk for the ecosystem in general. We evaluated in this work the induced toxicity of a textile effluent before and after its treatment with activated sludge followed by P. putida, using a battery of biotests. This study proved the detoxifying power of the activated sludge according to most of ecotoxicity tests. The treatment with P. putida did not improve the quality of the effluent; on the contrary, it could increase its toxicity. Daphnia magna and Raphidocelis subcapitata appear to be the most sensitive organisms in assessing eventual toxicity caused by this kind of wastewaters.
    No preview · Article · Jun 2015 · Environmental Science and Pollution Research
  • K. Ghedira · P. Goetz

    No preview · Article · Jun 2015 · Phytotherapie
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    ABSTRACT: The leaves of Eriobotrya japonica (Thunb.) Lindl. (Rosaceae) are used in traditional medicine to treat inflammatory diseases. However, information about the antigenotoxic and antioxidant properties of its leaves remains to be elucidated. The objective of this work was to evaluate the mutagenic/antimutagenic, genotoxic/antigenotoxic, and antioxidant potentials of aqueous and total oligomers flavonoid (TOF) extracts from E. japonica. The mutagenic/antimutagenic and genotoxic/antigenotoxic potentials of extracts (50, 250, and 500 µg/plate) were evaluated, respectively, by the Ames test with 48 h incubation and the SOS chromotest test with 2 h incubation. The antioxidant capacity of these extracts (ranging from 50 to 700 µg/mL) was tested using xanthine/xanthine oxidase and the deoxyribose assays. Eriobotrya japonica extracts showed neither mutagenic nor genotoxic effect. The highest protective effect against methyl methanesulfonate and 2-aminoanthracene was obtained in the presence of aqueous extract, with IC50 values of 80 and 140 µg/plate, respectively, against S. typhimurium TA104. Moreover, this extract (500 µg/plate) was also able to reduce significantly the genotoxicity induced by nitrofurantoin and aflatoxin B1 with IC50 values of 140 and 240 µg/assay, respectively. Likewise, aqueous and TOF extracts inhibited xanthine oxidase and superoxide anion formation with IC50 values ranging from 45 to 95 and from 70 to 90 µg/mL, respectively. However, TOF extract is more efficient in inhibiting hydroxyl radical and chelating iron ion with IC50 values of 140 and 400 µg/mL, respectively, when compared with the aqueous extract. Eriobotrya japonica prevents the genotoxicity of some carcinogenic substances probably thanks to its antioxidant capacities.
    No preview · Article · Apr 2015 · Pharmaceutical Biology
  • K. Ghedira · P. Goetz

    No preview · Article · Apr 2015 · Phytotherapie
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    ABSTRACT: Many studies have been performed to assess potential utility of natural products as immunomodulants to enhance antitumor activity in situ. In this study, an essential oil (EO) from the aerial parts of Pituranthos tortuosus was prepared using hydrodistillation, its composition was characterized, and its immunomodulatory potential was assessed. The results indicated that the EO contained sabinene, α-pinene, limonene, and terpinen-4-ol as major constituents. EO was also found to be able to significantly promote lipopolysaccharide (LPS)-stimulated splenocyte proliferation, suggestive of a potential for activation of B cells and enhanced humoral immune responses in hosts given this product. Effects of EO on cell proliferation and apoptosis were also investigated in B16F10 melanoma cells. EO-induced tumor cell growth inhibition was associated with characteristic apoptotic changes in the cells, including nuclear condensation. In conclusion, these data suggested to us that an EO of P. tortuosus could evolve to be a potential medicinal resource for use in the treatment of cancers.
    Full-text · Article · Feb 2015 · Tumor Biology
  • K. Ghedira · P. Goetz

    No preview · Article · Feb 2015 · Phytotherapie
  • K. Ghedira · P. Goetz

    No preview · Article · Feb 2015 · Phytotherapie
  • K. Ghedira · P. Goetz

    No preview · Article · Feb 2015 · Phytotherapie

Publication Stats

2k Citations
263.07 Total Impact Points

Institutions

  • 2009-2015
    • University of Monastir
      Al Munastīr, Al Munastīr, Tunisia
    • Université de Caen Basse-Normandie
      • Equipe de Recherche en Physico-Chimie et Biotechnologies (ERPCB)
      Caen, Lower Normandy, France
  • 2012
    • Faculty of Medecine of Tunis
      Tunis-Ville, Tūnis, Tunisia
  • 2011
    • Institut de Génétique et de Biologie Moléculaire et Cellulaire
      Strasburg, Alsace, France
  • 2007-2011
    • Faculté de Médecine Dentaire de Monastir
      Al Munastīr, Al Munastīr, Tunisia
  • 2003
    • Institut Supérieur de Biotechnologie de Monastir
      Al Munastīr, Al Munastīr, Tunisia
    • Université de Reims Champagne-Ardenne
      Rheims, Champagne-Ardenne, France