Quansanqi (derived from Panax notoginseng (Burk.) F. H. Chen) tablets extend the lifespan and ameliorate cellular inflammaging via regulating CD38 and senescence-associated secretory phenotype

ETHNOPHARMACOLOGICAL RELEVANCE: Quansanqi (PSQ) is derived from the whole plant of Panax notoginseng, including the flowers, stems, leaves, and roots. Its principal active ingredients include saponins, flavonoids, and polysaccharides. Unlike traditional P. notoginseng preparations, PSQ features a more diverse chemical composition. Aging is marked by systemic chronic inflammation, termed "inflamm-aging". Notably, PSQ exhibits significant anti-inflammatory properties. However, its anti-aging mechanism is unelucidated. AIM OF THE STUDY: This study aimed to determine the active ingredients of PSQ and the potential targets and mechanisms of PSQ against aging. MATERIALS AND METHODS: Anti-aging activity of PSQ was evaluated using yeast, Caenorhabditis elegans, zebrafish, and mice models. LPS-induced BMDMs were used to examine the anti-inflamm-aging mechanism of PSQ through molecular docking, molecular dynamics simulation, network pharmacology and experimental validation. RESULTS: PSQ increased yeast survival rates and average lifespan of C. elegans under natural conditions and exposure to H₂O₂. PSQ also extended the median and maximum lifespans of mice upon doxorubicin-induced aging. Furthermore, PSQ reduced the expression levels of p16, p21, and p53 mRNAs and β-gal contents in zebrafish with H₂O₂-induced aging. PSQ improved the survival rates of LPS-induced BMDMs and reduced the positive staining rates of β-gal and p53 protein expression. PSQ inhibited CD38 protein and mRNA expression while increasing intracellular NAD⁺ levels, and reduced the expression of several intracellular SASP molecules, including IL-1β, IL-6, TNF-α, and NO. Akt/MAPK/NF-κB were indicated to be key signaling pathways for inflamm-aging action of PSQ, and it inhibited CD38 and SASP expression. The main chemical components of PSQ exhibited good binding energy with the CD38 protein, and three of them were suggested to be specific to the flowers, stems, and leaves of P. notoginseng. CONCLUSION: PSQ exhibits significant anti-aging effects, extending lifespan in various aging models. CD38 and SASP may be the key targets of PSQ, with its regulatory effects mediated by Akt/MAPK/NF-κB pathway suppression. Flavonoids and saponins are the active anti-aging components of PSQ. Furthermore, the holistic utilization of the entire P. notoginseng plant aims to minimize resource wastage while enhancing its clinical value.