Isoquinoline alkaloids in Coptis chinensis to treat Alzheimer’s disease through promoting growth of Bifidobacterium breve inhibiting abnormal autophagy using a novel AI high-content intelligent imaging system

Coptis chinensis (Huanglian in Chinese) has been shown to increase beneficial intestinal bacteria and treat Alzheimer’s disease (AD). Bifidobacterium breve can effectively treat AD through gut-brain axis. Therefore, this study aimed to study the joint effects of C. chinensis and B. breve in the treatment of AD. 16S rRNA was used to test the abundance of bacterial flora in APP swe /PS1ΔE9 mice after C. chinensis administration. To determine the efficacy of C. chinensis combined with B. breve on AD, pathological section staining, Barnes maze, Western blotting and ELISA were utilized to confirm the improvement of cognitive dysfunction in AD mice after administration. In order to elucidate the pharmacodynamic components of monomers in C. chinensis , network pharmacology was used to screen the component related to autophagy and confirm the pharmacodynamic effects by artificial intelligence (AI) high-content intelligent imaging. The results of 16S rRNA sequencing indicated that C. chinensis could modulate the abundance of B. breve in AD mice. Pathological assessments, Barnes maze testing, and additional experiments have shown that C. chinensis combined with B. breve can improve the memory and learning ability of AD mice by reducing neuronal apoptosis and amyloid- β (A β ) peptide deposition. Network pharmacology combined with AI high-content intelligent imaging technology and Western blotting experiments demonstrated that magnoflorine, 13-methylberberine and palmatrubine in C. chinensis could exert neuroprotective effects in AD mice by up-regulating p62 protein expression while down-regulating Beclin-1 and microtubule-associated protein 1 light 3 II (LC3II) protein levels, thereby modulating autophagy-related pathways. Conclusion: C. chinensis. can enhance the abundance of beneficial bacteria in the gut and ameliorate cognitive dysfunction in AD mice by interacting with B. breve . Moreover, magnnoflorine, 13-methylberberine, and palmatrubine within C. chinensis can also mitigate excessive autophagy and oxidative stress in nerve cells.