Anti-aging effects of rare prosaikogenin F from microbial biotransformation of saikosaponin A

Oxidative damage is an important cause of aging. Saikosaponin A (SSA) is a major triterpenoid naturally occurring in Radix Bupleuri (RB), a well-recognized superior-grade Chinese herb. Additionally, a rare secondary glycoside, namely prosaikogenin F (PSF) can be obtained after removal of one glucose from SSA. This study aimed to efficiently prepare PSF from SSA, and further investigate and compare their anti-aging activities in Caenorhabditis elegans. Evaluation of antioxidant capacity, heat stress resistance, and aging-related physiological change were conducted, and potential mechanisms were revealed as well. The results showed that Aspergillus niger demonstrated the highest conversion efficiency, achieving a relative PSF yield of 83.9%. Average lifespan of nematodes was extended by 9.32% after treatment with 120 μM SSA, which was further increased to 11.41% while PSF being applied. Under thermal stress stimulation, 120 μM PSF prolonged survival time of nematodes by 35.76% compared to SSA by 33.59%. In addition, they increased the activity of antioxidant enzymes, reduced lipid peroxidation, enhanced the body's resistance to stress damage, and effectively prolonged the lifespan of nematodes. The expression of daf-16, hsp-16.2 and sir-2.1 in the nematodes treated with SSA or PSF were significantly up-regulated, whereas that of the daf-2 gene was significantly down-regulated (p < 0.05). In conclusion, the rare secondary triterpenoid saponin PSF was conveniently obtained from abundant SSA by microbial biotransformation. It showed stronger anti-aging activity than its primary form SSA and acted via regulation of insulin/insulin-like growth factor signaling (IIS) pathway, demonstrating its greater potential for applications in anti-aging and antioxidant.