RESUMO
Aesculin, a coumarin compound, is one of the major active ingredients of traditional Chinese herbal medicine Qinpi (Cortex Fraxini), which has been reported to exhibit antioxidative, anti-inflammatory and neuroprotective properties against oxidative stress and cellular apoptosis. However, the regulatory mechanisms remain poorly characterized in vivo. This research was performed to explore the underlying molecular mechanisms behind aesculin response conferring oxidative stress resistance, and the protective effects on amyloid-ß (Aß)-mediated neurotoxicity in Caenorhabditis elegans. Study indicated that aesculin plays the protective roles for C. elegans against oxidative stress and Aß-mediated neurotoxicity and reduces the elevated ROS and MDA contents through enhancement of antioxidant defenses. The KEGG pathway analysis suggested that the differentially expressed genes are mainly involved in longevity regulating pathway, and the nuclear translocation of DAF-16 and the RNAi of daf-16 and hsf-1 indicated that DAF-16 and HSF-1 play critical roles in integrating upstream signals and inducing the expressions of stress resistance-related genes. Furthermore, the up-regulated expressions of their target genes such as sod-3 and hsp-16.2 were confirmed in transgenic GFP reporter strains CF1553 and CL2070, respectively. These results indicated that the regulators DAF-16 and HSF-1 elevate the stress resistance of C. elegans by modulating stress-responsive genes. Further experiments revealed that aesculin is capable of suppressing Aß-induced oxidative stress and apoptosis and improves chemosensory behavior dysfunction in Aß-transgenic nematodes. In summary, this study suggested that aesculin offers increased resistance against oxidative stress and protective effects against Aß-induced neurotoxicity through activation of stress regulators DAF-16 and HSF-1 in nematodes.
Assuntos
Caenorhabditis elegans , AnimaisRESUMO
Aging is a progressive process with degenerative changes of various tissues and organs. As a classic model organism in genetics and neurobiology, Caenorhabditis elegans is also a powerful system in aging and behavioral studies and can be used at both the molecular and organismal levels to evaluate potential therapeutics for age-related neurodegeneration, owing to its short life span, relative simplicity, and high degree of experimental tractability as well as significant conservation of disease genes and signaling pathways with humans. We attempt here to summarize the use of C. elegans models in exploring traditional Chinese medicine for potential remedies against aging and neurodegeneration.
Assuntos
Envelhecimento/fisiologia , Caenorhabditis elegans/fisiologia , Medicina Tradicional Chinesa , Degeneração Neural/tratamento farmacológico , Animais , Longevidade , Estresse OxidativoRESUMO
OBJECTIVE: To study the distribution frequency and characteristics of nucleotide repeat of 94 923 ESTs for developing microsatellite primers, providing a theoretical basis and technical support for appropriate conservation and application of sweet wormwood (Artemisia annua). METHOD: EST-SSR detection was performed using Perl program MISA. Gene Ontology (GO) annotations were formatted for input into the GOSlim program and the output was parsed to count the occurrence of each GO category. Primer 3 software was used to design 18 pairs primers, amplified products were separated on a 6% denaturing polyacrylamide gel using silver staining. RESULT: By searching with Active Perl, totally 2 110 SSRs were detected, accounting for 8.6%. The frequency of occurrence of dinucleotide and trinucleotide was 28% and 50.4%, respectively. The most common repeat motifs of trinucleotide were ACC/GGT, accounting for 9.8%. Three hundred and twelve SSR-ESTs were annotated using GO terms. The suitable PCR system of 15 pairs primers was established, and revealed microsatellite polymorphism in 36 individuals. CONCLUSION: There are a variety of motifs at EST-SSR locus in sweet wormwood, and more effective amplification and polymorphism in 18 pairs detected primers. Therefore, EST resource is an effective and feasible approach to develop SSR markers, and EST-SSRs will a powerful tool for studies of sweet wormwood genetic resources.