Alzheimer's disease, a progressive neurodegenerative disease, affects learning and memory resulting from cholinergic dysfunction. Scopolamine has been employed to induce Alzheimer's disease-like pathology in vivo an...Alzheimer's disease, a progressive neurodegenerative disease, affects learning and memory resulting from cholinergic dysfunction. Scopolamine has been employed to induce Alzheimer's disease-like pathology in vivo and in vitro through alteration of cholinergic system. N-benzylcinnamide (PT-3), purified from Piper submultinerve, has been shown to exhibit neuroprotective properties against amyloid-β-induced neuronal toxicity in rat cortical primary cell culture and to improve spatial learning and memory of aged rats through alleviating oxidative stress. We proposed a hypothesis that PT3 has a neuroprotective effect against scopolamine-induced cholinergic dysfunction. PT-3 (125-200 nM) pretreatment was performed in human neuroblastoma SH-SY5Y cell line following scopolamine induction. PT-3 (125-200 nM) inhibited scopolamine (2 mM)-induced generation of reactive oxygen species, cellular apoptosis, upregutation of ace- tylcholinesterase activity, downregulation of choline acetyltransferase level, and activation of p38 and JNK signalling pathways. These findings revealed the underlying mechanisms of scopolamine-induced Alzheimer's disease-like cellular dysfunctions, which provide evidence for developing drugs for the treatment of this de- bilitating disease.展开更多
Objecive: To explore the effect of gibberellic acid(GA_3) and its inhibitor paclobutrazol(PBZ)on chemical composition and their pharmacological effects on Andrographis paniculata(Burm.f.) Wall. ex Nees, and to clarify...Objecive: To explore the effect of gibberellic acid(GA_3) and its inhibitor paclobutrazol(PBZ)on chemical composition and their pharmacological effects on Andrographis paniculata(Burm.f.) Wall. ex Nees, and to clarify action mode of andrographolide.Methods: The chemical composition was extracted by sequential extraction with hexane, dichloromethane, ethyl acetate and methanol, respectively. Andrographolide and its derivatives were evaluated by HPLC. Moreover, the metabolic profiling was analyzed by GC-MS. Inhibitory effect of crude extracts was tested against Staphylococcus aureus using agar well diffusion method. Mode of action was tested against mutant yeast by spotting assay. Andrographolide were tested for their mode of action against eukaryotes. Rsults: Among different solvents, dichloromethane gave the highest yield of crude(3.58% DW), with the highest andrographolide content(8.3 mg/g DW). The effect of plant hormone(10 mg/L GA_3 or PBZ) on phytochemical variations and bioactivity of Andrographis paniculata was demonstrated. It was found that PBZ promoted sesquiterpene compounds about 3.5 times over than GA_3 treatment. But inhibitory effect of extracts against Staphylococcus aureus was highest in GA_3 treated plants; andrographolide and 14-deoxy-11,12-didehydroandrographolide contents were significantly higher than those of water or PBZ. It was found that there were 11 strains involving in ergosterol biosynthesis, V-ATPase activity and homeostasis, and superoxide detoxification process. In this regard, andrographolide might cause the damage on the lipid bilayer of yeast cell and plasma membrane by interfering ergosterol biosynthesis.Conclusions: It is found that GA_3 promotes andrographolide and 14-deoxy-11,12-didehydroandrographolide content while PBZ promotes sesquiterpene content. Andrographolide might cause the damage on the lipid bilayer of yeast cell and plasma membrane by interfering ergosterol biosynthesis. It might also affect mitochondria electron transport chain, leading to the occurrence of ROS, which can further harm cell organelles. However, the library screening is the first step to investigate mode of action of andrographolide.展开更多
基金supported by a joint Mahidol University and The Thailand Research Fund(TRF)grant(IRG5780009)TRF Royal Golden Jubilee Ph.D.Program(grant No.PHD/0175/2552)the Office of the Higher Education Commission,Ministry of Education,Thailand
文摘Alzheimer's disease, a progressive neurodegenerative disease, affects learning and memory resulting from cholinergic dysfunction. Scopolamine has been employed to induce Alzheimer's disease-like pathology in vivo and in vitro through alteration of cholinergic system. N-benzylcinnamide (PT-3), purified from Piper submultinerve, has been shown to exhibit neuroprotective properties against amyloid-β-induced neuronal toxicity in rat cortical primary cell culture and to improve spatial learning and memory of aged rats through alleviating oxidative stress. We proposed a hypothesis that PT3 has a neuroprotective effect against scopolamine-induced cholinergic dysfunction. PT-3 (125-200 nM) pretreatment was performed in human neuroblastoma SH-SY5Y cell line following scopolamine induction. PT-3 (125-200 nM) inhibited scopolamine (2 mM)-induced generation of reactive oxygen species, cellular apoptosis, upregutation of ace- tylcholinesterase activity, downregulation of choline acetyltransferase level, and activation of p38 and JNK signalling pathways. These findings revealed the underlying mechanisms of scopolamine-induced Alzheimer's disease-like cellular dysfunctions, which provide evidence for developing drugs for the treatment of this de- bilitating disease.
基金financially supported by Agricultural Research Development Agency(Public Organization)or"ARDA"(Grant No.CRP6005020350)
文摘Objecive: To explore the effect of gibberellic acid(GA_3) and its inhibitor paclobutrazol(PBZ)on chemical composition and their pharmacological effects on Andrographis paniculata(Burm.f.) Wall. ex Nees, and to clarify action mode of andrographolide.Methods: The chemical composition was extracted by sequential extraction with hexane, dichloromethane, ethyl acetate and methanol, respectively. Andrographolide and its derivatives were evaluated by HPLC. Moreover, the metabolic profiling was analyzed by GC-MS. Inhibitory effect of crude extracts was tested against Staphylococcus aureus using agar well diffusion method. Mode of action was tested against mutant yeast by spotting assay. Andrographolide were tested for their mode of action against eukaryotes. Rsults: Among different solvents, dichloromethane gave the highest yield of crude(3.58% DW), with the highest andrographolide content(8.3 mg/g DW). The effect of plant hormone(10 mg/L GA_3 or PBZ) on phytochemical variations and bioactivity of Andrographis paniculata was demonstrated. It was found that PBZ promoted sesquiterpene compounds about 3.5 times over than GA_3 treatment. But inhibitory effect of extracts against Staphylococcus aureus was highest in GA_3 treated plants; andrographolide and 14-deoxy-11,12-didehydroandrographolide contents were significantly higher than those of water or PBZ. It was found that there were 11 strains involving in ergosterol biosynthesis, V-ATPase activity and homeostasis, and superoxide detoxification process. In this regard, andrographolide might cause the damage on the lipid bilayer of yeast cell and plasma membrane by interfering ergosterol biosynthesis.Conclusions: It is found that GA_3 promotes andrographolide and 14-deoxy-11,12-didehydroandrographolide content while PBZ promotes sesquiterpene content. Andrographolide might cause the damage on the lipid bilayer of yeast cell and plasma membrane by interfering ergosterol biosynthesis. It might also affect mitochondria electron transport chain, leading to the occurrence of ROS, which can further harm cell organelles. However, the library screening is the first step to investigate mode of action of andrographolide.