Red Ginseng Aqueous Extract Superior to White Ginseng Exhibited Anti‐Aging Property Through IIS Signaling Pathway in <i>Caenorhabditis elegans</i>

The traditional Chinese herbal medicine Panax ginseng can optimize physical health and is anticipated to be a valuable resource for investigating anti-aging therapies. This study investigated the anti-aging effects of red ginseng aqueous extract (RG) and white ginseng aqueous extract (WG). Network pharmacology forecasted that the key mechanisms of anti-aging in white and red ginsengs were the PI3K-Akt and IIS signaling pathways. Experiments conducted on Caenorhabditis elegans (C. elegans) showed that 5 mg/mL WG and RG notably prolonged lifespan and improved stress resistance. The qPCR analysis revealed that changes in upstream genes activated downstream genes in the IIS pathway. Furthermore, forward and reverse validation indicated that WG and RG acted through the IIS pathway in promoting longevity. RG exhibited superior anti-aging effects compared to WG at the same concentration. This might be attributed to the fact that RG contained more reducing sugars, polyphenols, melanoidins, total saponin content, and especially the conversion of ginsenosides. Molecular docking showed that ginsenosides interacted with the key protein DAF-2, with ginsenosides Rg3, Rg5, Rh4, Rf, and Rc binding more strongly than ginsenosides Rb1, Rb2, and Rd. Overall, RG possessed different active ingredients compared to WG and showed superior results in improving aging in C. elegans.