Dihuang Yinzi improves scopolamine-induced learning and memory impairment by regulating plasma exosome-derived BDNF

Dihuang Drink (DHD), formulated by Liu Hejian during the Yuan Dynasty, is listed as one of the first ancient classical prescriptions by the National Medical Products Administration of China. It is commonly used for the prevention and treatment of Alzheimer's disease (AD). This study further investigates the therapeutic effects and potential mechanisms of DHD in AD. This study aimed to evaluate the cognitive improvement effects of DHD on scopolamine (SCOP)-induced memory impairment in mice and to explore its anti-AD mechanisms mediated by exosomes. A cognitive impairment model was established in C57BL/6J mice via intraperitoneal injection of SCOP (1 mg/kg) for 21 consecutive days, followed by DHD intervention to assess its effects on learning, memory, hippocampal synaptic density, and the cholinergic system. SD rats were gavaged with DHD (22.00 g/kg) for 7 days, and plasma exosomes were extracted. These exosomes were injected into SCOP-treated mice (2 mg/kg, every other day for 14 days, 7 injections) to verify the role of exosomes in improving cognitive function. Behavioral performance and brain ChAT and BDNF levels were measured. DHD improved learning and memory in SCOP model mice, attenuated neuronal loss and decreases in dendritic spines induced by scopolamine, and modulated the expression of BDNF, SYN-1, PSD95, and M1 mAChR. DHD-derived plasma exosomes further enhanced learning and memory function and significantly increased brain ChAT activity and BDNF levels. DHD may alleviate cognitive impairment in SCOP model mice, potentially through exosome-mediated neuroprotection. [Display omitted] •This study hypothesizes that Dihuang Yinzi (Dihuang drink, DHD) may facilitate peripheral blood exosomes in crossing the blood-brain barrier (BBB) to exert its effects, offering a new perspective on improving cognitive function in Alzheimer’s disease (AD).•This study investigates the effects of DHD on a scopolamine-induced memory impairment model, emphasizing its potential to enhance cognitive function and providing novel insights into the application of traditional Chinese medicine (TCM) in neuroscience.•DHD has been shown to regulate neurotrophic factor levels in plasma-derived exosomes, potentially explaining its cognitive benefits and providing a scientific foundation for pharmacological research on TCM.