Potent telomerase activators from a novel sapogenin via biotransformation utilizing Camarosporium laburnicola, an endophytic fungus

Abstract

Background Cycloartane-type triterpenoids possess important biological activities, including immunostimulant, wound healing, and telomerase activation. Biotransformation is one of the derivatization strategies of natural products to improve their bioactivities. Endophytic fungi have attracted attention in biotransformation studies because of their ability to perform modifications in complex structures with a high degree of stereospecificity. Results This study focuses on biotransformation studies on cyclocephagenol (1), a novel cycloartane-type sapogenin from Astragalus species, and its 12-hydroxy derivatives (2 and 3) to obtain new telomerase activators. Since the hTERT protein levels of cyclocephagenol (1) and its 12-hydroxy derivatives (2 and 3) on HEKn cells were found to be notable, biotransformation studies were carried out on cyclocephagenol and its 12-hydroxy derivatives using Camarosporium laburnicola, an endophytic fungus isolated from Astragalus angustifolius. Later, immunoblotting and PCR-based ELISA assay were used to screen starting compounds and biotransformation products for their effects on hTERT protein levels and telomerase activation. All compounds showed improved telomerase activation compared to the control group. Conclusions As a result of biotransformation studies, seven new metabolites were obtained and characterized, verifying the potential of C. laburnicola as a biocatalyst. Additionally, the bioactivity results showed that this endophytic biocatalyst is unique in transforming the metabolites of its host to afford potent telomerase activators.

Genetically determined telomere length as a risk factor for hematological malignancies: evidence from Mendelian randomization analysis

“…In addition, certain drugs and compounds are being studied for their potential in intervening with telomere length. For example, some anti-aging compounds are speculated to have potential telomere protection effects, such as telomerase activators, antioxidants, and certain vitamins [46][47][48]. However, it should be noted that the relationship between telomere length and various diseases is complex.…”

Anti-Aging Activity and Modes of Action of Compounds from Natural Food Sources

“…Hence, telomerase activation in vivo has significant potential for delaying aging and alleviating aging-associated diseases [308][309][310][311]. For example, the terpenoid cycloastragenol (CA) and its biotransformation products showed anti-aging effects by improving telomerase activation [193,312,313]. Similarly, the polysaccharide extracted from Angelica sinensis polysaccharide (ASP) and Astragalus membranaceus polysaccharide (AMP) were shown to exert anti-aging activity by improving telomerase activity and regulating p53-p21 and p16-pRb pathways [44].…”