Telomerase activators derived from Astragalus sapogenins via biotransformation with the recently discovered endophytic fungus Camarosporium laburnicola

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.

Acknowledgement

This study was supported by TÜBİTAK (Project: 114Z958).

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