Objective: To determine the cytotoxicity, reduction in nitric oxide production and antioxidative activity of the aqueous leaf extract from Tithonia diversifolia(T. diversifolia) in an in vitro model.Methods: Leaves of...Objective: To determine the cytotoxicity, reduction in nitric oxide production and antioxidative activity of the aqueous leaf extract from Tithonia diversifolia(T. diversifolia) in an in vitro model.Methods: Leaves of T. diversifolia were collected from natural habitats and extracted with distilled water using the decoction method. The cytotoxic effect of the extract in terms of cell viability was determined using RAW264.7 cells and human peripheral blood mononuclear cells(PBMCs) via the mitochondrial respiration method using the MTT reagent. The effect of the extract on lipopolysaccharide(LPS)-induced nitric oxide production in RAW264.7 cells was measured using the Griess reagent. The chemical antioxidant was evaluated by ABTS- and DPPH-radical scavenging assays.Results: The half-maximal cytotoxic concentration values were 145.87 mg/m L and73.67 mg/m L for human PBMCs and RAW264.7 cells, respectively. In the presence of phytohemagglutinin-M, the IC_(50) on PBMCs proliferation was 4.42 mg/m L. The noncytotoxic range of the extracts inhibited LPS-induced nitrite production in RAW264.7 cells with an IC_(50) value of 11.63 mg/m L. To determine the anti-oxidative properties, the N-acetyl cysteine equivalent antioxidant capacity of the extract was(32.62 ± 1.87) and(20.99 ± 2.79)mg N-acetyl cysteine/g extract, respectively determined by the ABTS-radical and DPPHradical assay. However, the extract did not confer death protection in a hydrogen peroxideinduced RAW264.7 co-culturing model.Conclusions: Our study demonstrated the immunomodulation caused by the aqueous leaf extract of T. diversifolia, resulting from the inhibition of phytohemagglutinin-Minduced PBMCs proliferation and LPS-induced nitric oxide production in RAW264.7macrophages. Although the anti-oxidative activity was presented in the chemical-based anti-oxidant assay, the extract cannot protect cell death from stress conditions.展开更多
Glioblastoma multiforme is a highly aggressive primary brain malignancy that resists most conventional chemoand radiotherapeutic interventions.Nitric oxide(NO),a short lived free radical molecule produced by inducible...Glioblastoma multiforme is a highly aggressive primary brain malignancy that resists most conventional chemoand radiotherapeutic interventions.Nitric oxide(NO),a short lived free radical molecule produced by inducible NO synthase(iNOS)in glioblastomas and other tumors,is known to play a key role in tumor persistence,progression,and chemo/radiotherapy resistance.Site-specific and minimally invasive photodynamic therapy(PDT),based on oxidative damage resulting from non-ionizing photoactivation of a sensitizing agent,is highly effective against glioblastoma,but resistance also exists in this case.Studies in the authors’laboratory have shown that much of the latter is mediated by iNOS/NO.For example,when glioblastoma U87 or U251 cells sensitized in mitochondria with 5-aminolevulinic acid-induced protoporphyrin IX were exposed to a moderate dose of visible light,the observed apoptosis was strongly enhanced by an iNOS activity inhibitor or NO scavenger,indicating that iNOS/NO had increased cell resistance to photokilling.Moreover,cells that survived the photochallenge proliferated,migrated,and invaded more aggressively than controls,and these responses were also driven predominantly by iNOS/NO.Photostress-upregulated iNOS rather than basal enzyme was found to be responsible for all the negative effects described.Recognition of NO-mediated hyper-resistance/hyper-aggression in PDT-stressed glioblastoma has stimulated interest in how these responses can be prevented or at least minimized by pharmacologic adjuvants such as inhibitors of iNOS activity or transcription.Recent developments along these lines and their clinical potential for improving anti-glioblastoma PDT are discussed.展开更多
An efficient approach has been developed for the synthesis of naturally occurring prenylated chalcones viz. kanzonol C （1）, stipulin （2）, crotaorixin （3）, medicagenin （4）, licoagrochalcone A （5） and abyssino...An efficient approach has been developed for the synthesis of naturally occurring prenylated chalcones viz. kanzonol C （1）, stipulin （2）, crotaorixin （3）, medicagenin （4）, licoagrochalcone A （5） and abyssinone D （6） along with the pyranochalcones paratocarpin C （7）, anthyllisone （8） and 3-O-methylabyssinone A （9）. The key step of the synthesis is a Claisen-Schmidt condensation. Subsequently, their anti-inflammatory effects were investigated in lipopolysaccharides （LPSs）-induced RAW-264.7 macrophages. Of the synthesized chalcones, compounds 5 （IC50= 10.41 μmol[L）, 6 （IC50= 9.65 μmol/L） and 8 （IC50= 15.34 μmol/L） show remarkable activity with no cytotoxicity. Compound 9 （IC50 = 4.5 μmol/L） exhibits maximum （83.6%） nitric oxide （NO） inhibition, but shows slight cytotoxicity. The results reveal that the chalcones bearing the prenyl group at 3- and/or 5-position on ring A （acetophenone moiety）, i.e., 1-4 and 7 show weak, or no inhibition activity, whereas chalcones having the prenyl group only on ring B （aldehyde part）, i.e., 5, 6 and 8 show significant activity on the production of inflammatory mediated NO with no cytotoxicity.展开更多
基金Supported by the Institute of Research and Development,Walailak University,Thailand(Grant No.WU55304)
文摘Objective: To determine the cytotoxicity, reduction in nitric oxide production and antioxidative activity of the aqueous leaf extract from Tithonia diversifolia(T. diversifolia) in an in vitro model.Methods: Leaves of T. diversifolia were collected from natural habitats and extracted with distilled water using the decoction method. The cytotoxic effect of the extract in terms of cell viability was determined using RAW264.7 cells and human peripheral blood mononuclear cells(PBMCs) via the mitochondrial respiration method using the MTT reagent. The effect of the extract on lipopolysaccharide(LPS)-induced nitric oxide production in RAW264.7 cells was measured using the Griess reagent. The chemical antioxidant was evaluated by ABTS- and DPPH-radical scavenging assays.Results: The half-maximal cytotoxic concentration values were 145.87 mg/m L and73.67 mg/m L for human PBMCs and RAW264.7 cells, respectively. In the presence of phytohemagglutinin-M, the IC_(50) on PBMCs proliferation was 4.42 mg/m L. The noncytotoxic range of the extracts inhibited LPS-induced nitrite production in RAW264.7 cells with an IC_(50) value of 11.63 mg/m L. To determine the anti-oxidative properties, the N-acetyl cysteine equivalent antioxidant capacity of the extract was(32.62 ± 1.87) and(20.99 ± 2.79)mg N-acetyl cysteine/g extract, respectively determined by the ABTS-radical and DPPHradical assay. However, the extract did not confer death protection in a hydrogen peroxideinduced RAW264.7 co-culturing model.Conclusions: Our study demonstrated the immunomodulation caused by the aqueous leaf extract of T. diversifolia, resulting from the inhibition of phytohemagglutinin-Minduced PBMCs proliferation and LPS-induced nitric oxide production in RAW264.7macrophages. Although the anti-oxidative activity was presented in the chemical-based anti-oxidant assay, the extract cannot protect cell death from stress conditions.
基金USPHS Grant(CA70823)the National Cancer Institute,BSC Grant(FP12605)+2 种基金Rock River Grant(FP14869)the MCW Cancer Center(to Girotti AW)NCN Grant 2017/27/B/NZ5/02620(to Korytowski W).
文摘Glioblastoma multiforme is a highly aggressive primary brain malignancy that resists most conventional chemoand radiotherapeutic interventions.Nitric oxide(NO),a short lived free radical molecule produced by inducible NO synthase(iNOS)in glioblastomas and other tumors,is known to play a key role in tumor persistence,progression,and chemo/radiotherapy resistance.Site-specific and minimally invasive photodynamic therapy(PDT),based on oxidative damage resulting from non-ionizing photoactivation of a sensitizing agent,is highly effective against glioblastoma,but resistance also exists in this case.Studies in the authors’laboratory have shown that much of the latter is mediated by iNOS/NO.For example,when glioblastoma U87 or U251 cells sensitized in mitochondria with 5-aminolevulinic acid-induced protoporphyrin IX were exposed to a moderate dose of visible light,the observed apoptosis was strongly enhanced by an iNOS activity inhibitor or NO scavenger,indicating that iNOS/NO had increased cell resistance to photokilling.Moreover,cells that survived the photochallenge proliferated,migrated,and invaded more aggressively than controls,and these responses were also driven predominantly by iNOS/NO.Photostress-upregulated iNOS rather than basal enzyme was found to be responsible for all the negative effects described.Recognition of NO-mediated hyper-resistance/hyper-aggression in PDT-stressed glioblastoma has stimulated interest in how these responses can be prevented or at least minimized by pharmacologic adjuvants such as inhibitors of iNOS activity or transcription.Recent developments along these lines and their clinical potential for improving anti-glioblastoma PDT are discussed.
基金financially supported by Priority Research Centers Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (No. NRF-2009-0094071), South Korea
文摘An efficient approach has been developed for the synthesis of naturally occurring prenylated chalcones viz. kanzonol C （1）, stipulin （2）, crotaorixin （3）, medicagenin （4）, licoagrochalcone A （5） and abyssinone D （6） along with the pyranochalcones paratocarpin C （7）, anthyllisone （8） and 3-O-methylabyssinone A （9）. The key step of the synthesis is a Claisen-Schmidt condensation. Subsequently, their anti-inflammatory effects were investigated in lipopolysaccharides （LPSs）-induced RAW-264.7 macrophages. Of the synthesized chalcones, compounds 5 （IC50= 10.41 μmol[L）, 6 （IC50= 9.65 μmol/L） and 8 （IC50= 15.34 μmol/L） show remarkable activity with no cytotoxicity. Compound 9 （IC50 = 4.5 μmol/L） exhibits maximum （83.6%） nitric oxide （NO） inhibition, but shows slight cytotoxicity. The results reveal that the chalcones bearing the prenyl group at 3- and/or 5-position on ring A （acetophenone moiety）, i.e., 1-4 and 7 show weak, or no inhibition activity, whereas chalcones having the prenyl group only on ring B （aldehyde part）, i.e., 5, 6 and 8 show significant activity on the production of inflammatory mediated NO with no cytotoxicity.
