Chemical Composition, Antioxidant Activity, and the Predicted Anti-Aging Mechanisms of Lotus Seed Coat: Evidence From the Caenorhabditis elegans Model and Network Pharmacology

Background: Aging is a critical global public health challenge, and natural products represent a key area in anti-aging research. Therefore, this study aimed to explore the chemical composition and anti-aging efficacy of the lotus seed coat. Methods: Ultra-high-performance liquid chromatography-Orbitrap mass spectrometry (UHPLC/Orbitrap-MS) was used to analyze chemical components. The lifespan of Caenorhabditis elegans (C. elegans) treated with lotus seed coat extract was measured, along with oxidative stress markers and antioxidant enzyme activity. Network pharmacology and molecular dynamics simulations were employed to predict any associated anti-aging mechanisms. Results: A total of 67 compounds were tentatively identified in the lotus seed coat, including 14 alkaloids, 19 flavonoids, and 6 phenolic acids. Lotus seed coat extract prolonged the lifespan of C. elegans (p < 0.05), reduced lipofuscin and reactive oxygen species (ROS) levels (p < 0.001), increased superoxide dismutase (SOD) and catalase (CAT) activity, and decreased malondialdehyde (MDA) content. Network pharmacology linked the anti-aging effects of the lotus seed coat extract to the regulation of SRC, PIK3R1, AKT1, IL6, and TNF genes expression and implicated the phosphatidylinositol 3-kinase/protein kinase B pathway (PI3K–Akt), mitogen-activated protein kinase (MAPK), hypoxia-inducible factor 1 (HIF-1), forkhead box O (FOXO), tumor necrosis factor (TNF), and mammalian target of rapamycin (mTOR) signaling pathways. Molecular simulations confirmed that neferine strongly binds to phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), histone acetyltransferase p300 (EP300), and RAC-alpha serine/threonine-protein kinase (AKT1). Conclusion: Lotus seed coat is rich in bioactive compounds and exhibits significant anti-aging potential.