Chronological lifespan extension evaluation-driven comparative study of five Indian dietary spices for geroprotective action via phytochemical profiling, bioactivity screening and network pharmacology in Saccharomyces cerevisiae.

INTRODUCTION: Indian dietary spices are emerging to have nutraceutical potential; however, their role iFn modulating longevity remains largely unknown. This study investigated the geroprotective potential of aqueous extracts from 5 dietary spices-Trachyspermum ammi, Cuminum cyminum, Trigonella foenum-graecum, Foeniculum vulgare, and Nigella sativa-using yeast (Saccharomyces cerevisiae strain BY4741) as a eukaryotic model for chronological lifespan extension.
METHODS: In the Phase 1, assessment of anti-oxidant potential, anti-inflammatory activity, and yeast cell proliferation action was performed in a dose-response study (10-1000 μg/mL). The most efficacious dose (250 μg/mL) across all five extracts was further assessed (Phase 2) to identify the most efficacious spice extract that could extend the chronological lifespan in yeast. Metformin (25 mM) was used as a positive control for life-span extension assays. F. vulgare emerged as the most efficacious, and was additionally evaluated for oxidative/thermal stress tolerance. The said extract was characterized for metabolite profile via LC-MS/MS analysis and mechanistic action was predicted using network pharmacology.
RESULTS: F. vulgare extract characterisation indicated presence of diverse phytocompounds (40 compounds) and high phenolic and flavonoid content. The extract significantly enhanced survival percentage and survival integral in yeast up to 8th day post-stationary phase, conferred stress (oxidative/thermal) tolerance and reigned ROS accumulation. Network pharmacology based mechanistic prediction indicated action via MAPK pathway, peroxisome, and longevity regulating pathways.
DISCUSSION: FV's geroprotective effect, akin to metformin (positive control) is likely linked to its rich phytochemical makeup.
CONCLUSIONS: This study highlights F. vulgare as a potential natural geroprotector in yeast, necessitating validation in higher model organisms for translational relevance.