Telomerase activators derived from Astragalus sapogenins via biotransformation with the recently discovered endophytic fungus Camarosporium laburnicola
Bildiriler > Tam Metin Bildiri · 2019
Yazarlar: MELİS KÜÇÜKSOLAK, GÜNER EKİZ, seda duman, Sinem YILMAZ, Petek BALLAR KIRMIZIBAYRAK, ERDAL BEDİR
Planta Medica, Innsbruck, Uluslararası, Poster, Tam Metin Bildiri, 2019-2019, Wos, cilt 85, ss 1451-1451
Özet
Telomeres are nucleotide sequences that are located at the end of chromosomes shortening with each cell division. Telomerase is a reverse transcriptase enzyme, and it helps to replenish telomere ends that are truncated by aging and stress factors [ 1 ]. Telomere shortening is considered not only a result of the biological aging process but also a risk factor for many disorders such as neurodegeneration, macular degeneration, coronary artery diseases, hypertension, diabetes, pulmonary fibrosis. Thus, activation of telomerase enzyme introduces a great promise for the treatment of many chronic and degenerative diseases. Cycloastragenol, isolated from Astragalus species, is the only natural product as a telomerase activator in the dietary supplement market. The initiation of clinical studies with Cycloastragenol derivatives in Alzheimer’s disease and metabolic syndrome is a sign of their potential [ 2 ],[ 3 ],[ 4 ]. Aims of this study were: i) to carry out microbial transformation studies on Astragalus sapogenins using endophytic fungi ( Alternaria eureka, Neosartorya hiratsukae, Penicillum roseopurpureum, Camarosporium laburnicola ) isolated from the tissues of Astragalus species ii) to expand our chemical library with new/novel metabolites; iii) to investigate effects of the metabolites on telomerase activation. As a result, 42 metabolites were identified [ 5 ] and screened in Telomerase PCR ELISA Assay using HEKn cell line. Sixteen compounds increased telomerase activation ranging from 1.2 to 11.3-fold between doses of 0.5 to 300 nM compared to the control (DMSO). The most potent molecules were found to be A-ring modified cycloastragenol derivatives obtained with the fungus Camarosporium laburnicola .