Mechanistic insights into ginsenoside Rd nanoparticles-mediated protection against memory impairment: From preparation and physicochemical characterization to in vivo efficacy.
📄 Abstract
Ginsenoside Rd, a protopanaxadiol abundant in Panax ginseng and Panax notoginseng, possesses well-documented neuroprotective properties but suffers from low bioavailability. Here, we engineered nanoparticles from zein, chitosan-α-lipoic acid copolymer, and sodium alginate for the delivery of ginsenoside Rd (Rd) and evaluated their efficacy in alleviating scopolamine-induced memory impairment in a mouse model. The results demonstrated that the nanoparticles successfully encapsulated Rd, with an encapsulation efficiency of approximately 73.23 %, and exhibited a hollow spherical morphology. Additionally, the carrier exhibited exceptional stability under varying temperature and salt ion conditions, along with the ability to be readily redispersed. The incorporation of Rd into nanoparticles significantly improved its antioxidant efficacy, as well as its stability and sustained release profile in the gastrointestinal environment. In vivo experiments demonstrated that Rd-loaded nanoparticles significantly improved scopolamine-induced memory deficits, oxidative stress, cholinergic system dysfunction, and neuronal damage in the hippocampal region of mice, outperforming the effects of ginsenoside Rd alone. Western blot results indicated that Rd-loaded nanoparticles improved memory-impaired mice by upregulating p-CaMKII, p-CREB, and BDNF protein expression through modulating the long-term potentiation pathway. We further found that Rd-loaded nanoparticles treatment increased the richness and diversity of gut microbiota. This study provides a promising strategy for the effective treatment of improving learning memory.