Objective:To evaluate the neutralizing effects of flavonoids on snake venom toxicity by stand-alone and combinatorial approaches.Methods:Synthetic flavonoids were assessed,either individually or in combination with an...Objective:To evaluate the neutralizing effects of flavonoids on snake venom toxicity by stand-alone and combinatorial approaches.Methods:Synthetic flavonoids were assessed,either individually or in combination with antivenom,for their neutralization of phospholipase A_(2)(PLA_(2)),protease,antioxidant(DPPH)assay and hemotoxic activity.Molecular docking studies were performed to understand possible binding of flavonoids with Naja naja venom PLA_(2).In vivo studies were carried out to confirm the neutralisation effects using a mouse model.Moreover,inhibition of PLA_(2) was monitored using combinatorial approaches.Results:Among the flavonoids used,quercetin and naringenin inhibited PLA_(2)(56%and 45%),protease(71%and 64%),DPPH scavenging(69.0%and 77.5%)and hemotoxic(70%)activities.Molecular docking studies indicated that the flavonoids bind to the substrate-binding site of PLA_(2)(Cys44 and Tyr63).In vivo studies showed a reduction in the venom toxicity level in the presence of naringenin.Additionally,combinatorial studies using the mixture of flavonoid and anti-venom revealed the possibility of synergistic effect(up to 32%enhancement)in neutralising the venom enzymes.Conclusions:These flavonoids can be used as additives for the treatment of snake bites,which may exert synergistic effects in combination with antivenom and decrease the post-therapeutic effects caused by excessive use of antivenom.展开更多
Chronic inflammation induced hyper-proliferation, and migration of keratinocytes are pathological hallmarks of psoriasis. Extracts from Sphaeranthus spp. demonstrate pharmacological activity in-vitro and in-vivo. Howe...Chronic inflammation induced hyper-proliferation, and migration of keratinocytes are pathological hallmarks of psoriasis. Extracts from Sphaeranthus spp. demonstrate pharmacological activity in-vitro and in-vivo. However, the activity in modulating disease relevant pathways in psoriasis has not been reported. In the current study, a standardized herbal extract from Sphaeranthus indicus (NPS31807) was used to study the mechanistic activity under conditions of inflammation, keratinocyte proliferation and migration using cell based and gene expression assays. NPS31807 treatment reduced levels of pro-inflammatory cytokines from human macrophages and activated epidermal keratinocytes in a dose dependent manner. Treatment with NPS31807 diminished NFκB and AP-1 transcription activity in human macrophages. Lowered nuclear translocation of p65 sub-unit in macrophages by treatment confirmed reduced activity of NFκB. Gene expression profiling showed attenuated expression of genes involved with inflammation such as TNF signaling, and angiogenesis by NPS31807. Inhibition of angiogenesis and matrix metalloproteinase production in keratinocytes was confirmed using RTq-PCR assays. Pretreatment with NPS31807 led to significant reduction of STAT3 phosphorylation and mitogen induced cellular migration. NPS31807 induced inhibition of proliferative genes and BrdU uptake in epidermal keratinocytes. In summary, our study provides novel molecular insights into the anti-inflammatory, anti-migratory and anti-proliferative properties of NPS31807. In summary, NPS31807, an extract from Sphaeranthus indicus can be used as therapeutic option in inflammatory and auto-immune conditions such as psoriasis.展开更多
文摘Objective:To evaluate the neutralizing effects of flavonoids on snake venom toxicity by stand-alone and combinatorial approaches.Methods:Synthetic flavonoids were assessed,either individually or in combination with antivenom,for their neutralization of phospholipase A_(2)(PLA_(2)),protease,antioxidant(DPPH)assay and hemotoxic activity.Molecular docking studies were performed to understand possible binding of flavonoids with Naja naja venom PLA_(2).In vivo studies were carried out to confirm the neutralisation effects using a mouse model.Moreover,inhibition of PLA_(2) was monitored using combinatorial approaches.Results:Among the flavonoids used,quercetin and naringenin inhibited PLA_(2)(56%and 45%),protease(71%and 64%),DPPH scavenging(69.0%and 77.5%)and hemotoxic(70%)activities.Molecular docking studies indicated that the flavonoids bind to the substrate-binding site of PLA_(2)(Cys44 and Tyr63).In vivo studies showed a reduction in the venom toxicity level in the presence of naringenin.Additionally,combinatorial studies using the mixture of flavonoid and anti-venom revealed the possibility of synergistic effect(up to 32%enhancement)in neutralising the venom enzymes.Conclusions:These flavonoids can be used as additives for the treatment of snake bites,which may exert synergistic effects in combination with antivenom and decrease the post-therapeutic effects caused by excessive use of antivenom.
文摘Chronic inflammation induced hyper-proliferation, and migration of keratinocytes are pathological hallmarks of psoriasis. Extracts from Sphaeranthus spp. demonstrate pharmacological activity in-vitro and in-vivo. However, the activity in modulating disease relevant pathways in psoriasis has not been reported. In the current study, a standardized herbal extract from Sphaeranthus indicus (NPS31807) was used to study the mechanistic activity under conditions of inflammation, keratinocyte proliferation and migration using cell based and gene expression assays. NPS31807 treatment reduced levels of pro-inflammatory cytokines from human macrophages and activated epidermal keratinocytes in a dose dependent manner. Treatment with NPS31807 diminished NFκB and AP-1 transcription activity in human macrophages. Lowered nuclear translocation of p65 sub-unit in macrophages by treatment confirmed reduced activity of NFκB. Gene expression profiling showed attenuated expression of genes involved with inflammation such as TNF signaling, and angiogenesis by NPS31807. Inhibition of angiogenesis and matrix metalloproteinase production in keratinocytes was confirmed using RTq-PCR assays. Pretreatment with NPS31807 led to significant reduction of STAT3 phosphorylation and mitogen induced cellular migration. NPS31807 induced inhibition of proliferative genes and BrdU uptake in epidermal keratinocytes. In summary, our study provides novel molecular insights into the anti-inflammatory, anti-migratory and anti-proliferative properties of NPS31807. In summary, NPS31807, an extract from Sphaeranthus indicus can be used as therapeutic option in inflammatory and auto-immune conditions such as psoriasis.
