Systemic Analyses of Anti-Cell-Senescence Active Compounds in Camellia Sect. Chrysantha Chang and Their Mechanisms

Aging is an irreversible pathophysiological process for all organisms. The accumulation of senescent cells in pathological sites or tissues is recognized as the major cause of diseases and disorders during the aging process. Small molecules that reduce senescent cell burdens have gained increasing attention as promising intervention therapeutics against aging, but effective anti-senescence agents remain rare. Camellia Sect. Chrysantha Chang is documented as a traditional Chinese herbal medicine used by ethnic groups for many medical and health benefits, but its effect on aging is unclear. Here, we investigated the anti-senescence potential of eight C. Sect. Chrysantha Chang species. The results show that ethyl acetate fractions from these C. Sect. Chrysantha Chang species were able to delay the senescence of H9c2 cardiomyocytes except for C. pingguoensis (CPg). N-butanol fractions of C. multipetala (CM), C. petelotii var. grandiflora (CPt), and C. longzhouensis (CL) showed a senescent cell clearance effect by altering the expression levels of senescent-associated marker genes in the DNA-damage response (DDR) pathway and the senescent cell anti-apoptotic pathway (SCAPs). By using UPLC-QTOF-MS-based non-targeted metabolomics analyses, 27 metabolites from Sect. Chrysantha species were putatively identified. Among them, high levels of sanchakasaponin C and D in CM, CPt, and CL were recognized as the key bioactive compounds responsible for senescent cell clearance. This study is the first to disclose and compare the anti-cell-senescence effect of a group of C. Sect. Chrysantha Chang, including some rare species. The combination of senescent markers and metabolomics analyses helped us to reveal the differences in chemical constituents that target senescent cells. Significantly, contrary to the C. chrysantha var. longistyla (CCL), which is widely cultivated and commercialized for tea drinks, CM, CPt, and CL contain unique chemicals for managing aging and aging-related diseases. The results from this study provide a foundation for species selection in developing small-molecule-based drugs to alleviate diseases and age-related dysfunctions and may potentially be useful for advancing geroscience research.