Effects and mechanisms of harmine on ameliorating ethanol-induced memory impairment

Peganum harmala L., a traditional Uyghur ethnic medicine widely used in China, is commonly used in the treatment of conditions such as hemiplegia, forgetfulness, cough, and asthma. Harmine and other β-carboline alkaloids, one of the main active ingredients in P. harmala, have exhibited various pharmacological activities, including anti-Alzheimer's, antidepressant, anti-inflammatory, and antioxidant effects. However, the effects and underlying mechanisms of harmine on improving ethanol-induced memory impairment remain unclear.

This study aimed to investigate the effects of harmine on ameliorating ethanol-induced memory impairment, and to explore potential mechanisms.

Ethanol (30%, i. g.) was used to induce memory impairment model. The effect of harmine on memory impairment was evaluated by Morris water maze (MWM). The histopathological analysis, immunofluorescence staining, RT-qPCR and UHPLC-MS/MS methods were performed to further investigate the underlying mechanisms.

MWM experiments showed that harmine significantly improved ethanol-induced spatial learning memory deficit. Harmine exhibited anti-inflammatory effect by downregulating inflammatory factors such as IL-6, IL-1β and tumor necrosis factor-α (TNF-α) induced by ethanol. Harmine also upregulated brain-derived neurotrophic factor (BDNF) levels to exert neuroprotective effect. Moreover, harmine protected neuronal cells and increased the protein expression of myelin basic protein (MBP). The cellular results indicated that harmine protected SH-SY5Y cells from ethanol-induced cytotoxicity and upregulated the relative mRNA expression of synaptosome associated protein 25 (SNAP25), syntaxin 1 A (STX1A), vesicle associated membrane protein 2 (VAMP2), synaptotagmin 1 (SYT1) and synaptophysin (SYP).

Harmine improved ethanol-induced memory impairment by ameliorating inflammation, increasing BDNF levels, promoting synaptic vesicle fusion, protecting myelin sheath, and modulating neurotransmitter levels. These findings provided a scientific basis for development of therapeutic drugs for alcohol-induced memory impairments and other related disorders.