Chemical Structures And Mechanism Research Of Anti-aging Leading Compounds From Natural Products

Aging is an inevitable process of functional impairment, which increases the susceptibility of an organism to a variety of age-dependent diseases. The precise molecular mechanisms that link aging to age-related diseases have not been clearly understood, but some small molecules, such as resveratrol, were found not only to possess an activity that extended the lifespan of animals, but also to produce positive effects in models of diabetes and neurodegenerative diseases. Therefore, the research on anti-aging substances can contribute to the development of preventive and therapeutic drugs for the treatment of age-related diseases.The traditional yeast bioassay is an effective method to screen samples with anti-aging activity with a complex process. K6001, a Saccharomyces cerevisiae mutant, has been used to establish a more convenient bioassay system for evaluating the anti-aging activity of natural products'extracts. After a screening of a larger number extracts of traditional Chinese medicines, the extract of spores of G. lucidum was found to have significant activity. Furthermore, guided by this bioassay, the extracts of spores of G. lucidum were subjected to partitioning, separation through silica and ODS open column, and HPLC purification (two times) in order to obtained six pure active compounds. Their chemical structures were determined as sterol compounds based on the spectroscopic analysis and comparison spectroscopic data with those reported. It is found that the four of them possess novel chemical structures and named as ganodermasides A-D (1-4), which have a 4,6,8(14),22-tetraene-3-one unit with a unique hydroxylation at C-15 [ganodermasides A(1)-B(2)] or C-9 [ganodermasides D(3)-C(4)]. The results of structure-activity relationships study revealed that the steroids skeleton plays an important role in their anti-aging activity, whereas the attachment groups worked as regulatory roles. Finally, the mechanism investigation of the active compounds showed that they regulated UTH1 expression in order to extend the replicative life span of yeast.