Mechanism of Fufang Congrong Yizhi Capsules in treatment of mild cognitive impairment based on network pharmacology

Aim To predict the mechanism of Fufang Congrong Yizhi Capsules (FCYC) in the treatment of mild cognitive impairment (MCI) by network pharmacology method, and further validate it in combination with cellular experiments. Methods TCMSP, GeneCards, OMIM and TTD databases, Chinese Pharmacopoeia and related literature were used to screen the active ingredients of FCYC and the targets of MCI treatment. The TCM-compound-target-disease network and PPI of intersection targets were constructed, and the GO and KEGG analysis were performed by the Ehamb bioinformation platform. GO and KEGG analysis were performed through Yihanbo biological information platform. Cell model of MCI was established by PC-12 injury induced by Aβ25-35, and its efficacy and mechanism were explored by pretreatment of compound FCYC. Cell viability was detected by CCK-8 and LDH kit. The mitochondrial membrane potential was detected by JC-1. The expressions of IL-1β, IL-6 and TNF-α were detected by ELISA. The expressions of Bcl2, Bax and PI3K/AKT signaling pathways were detected by immunofluorescence and WB. Results A total of 57 active components of FCYC could be used to treat MCI through 66 potential targets. GO enrichment analysis showed that these targets were involved in 339 biological processes (BP), 39 cell compositions (CC) and 65 molecular functions (MF). KEGG enrichment pathways were mainly involved in PI3K-Akt signaling pathway and TNF signaling pathway. The results of experiments showed that FCYC could significantly increase the activity of injured PC-12 cells induced by Aβ25-35, reduce the secretion of IL-1β, IL-6 and TNF-α in PC-12 cells, up-regulate the ratio of Bcl2/Bax, and increase the expression of p-PI3K/PI3K and p-Akt /AKT. Conclusions This study preliminarily shows that FCYC can treat MCI through multi-component, multi-target, and multi-pathway. In vitro experiments demonstrate that FCYC can significantly inhibit neuro-inflammation and neuronal apoptosis, and the possible mechanism may be the regulation of PI3K/Akt signaling for MCI.