Uncovering the Potential Mechanisms of Coptis chinensis Franch. for Serious Mental Illness by Network Pharmacology and Pharmacology-Based Analysis

Abstract

Yiyu Qi,1 Saijia Ni,2 Xia Heng,1 Shuyue Qu,1 Pingyuan Ge,1 Xin Zhao,1 Zengying Yao,2 Rui Guo,3 Nianyun Yang,1 Qichun Zhang,2 Huaxu Zhu1 1Department of Traditional Chinese Medicine Processing and Preparation, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 2Department of Pharmacology, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 3Department of Physiological, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of ChinaCorrespondence: Qichun Zhang; Huaxu Zhu, Email zhangqichun@njucm.edu.cn; zhuhx@njucm.edu.cnBackground: Serious mental illness is a disease with complex etiological factors that requires multiple interventions within a holistic disease system. With heat-clearing and detoxifying effects, Coptis chinensis Franch. is mainly used to treat serious mental illness.Aim of the Study: To explore the underlying mechanisms and therapeutic effect by which Coptis chinensis Franch. treats serious mental illnesses at a holistic level.Methods: A viable network pharmacology approach was adopted to obtain the potential active ingredients of Coptis chinensis Franch., and serious mental illnesses-related targets and signaling pathways. The interactions between crucial target HTR2A and constituents were verified by molecular docking, and the dynamic behaviors of binding were studied by molecular dynamics simulation. In addition, the anti-anxiety effect of Rhizoma Coptidis (the roots of Coptis chinensis Franch.) extract on lipopolysaccharide-stimulated mice was verified. The anxiety-like behavior was measured through the elevated plus-maze test, light–dark box test, and open field test. Radioimmunoassays detected the levels of interleukin-1β, tumor necrosis factor-α, interleukin-10, interleukin-4, 5-hydroxytryptamine, and dopamine in the serum, hippocampus, medial prefrontal cortex, and amygdala. Meanwhile, immunohistochemistry protocols for the assessment of neuronal loss (neuron-specific nuclear protein) and synaptic alterations (Synapsin I) were performed in the hippocampus.Results: Based on scientific analysis of the established networks, serious mental illnesses-related targets mostly participated in the calcium signaling pathway, cyclic adenosine monophosphate signaling pathway, mitogen-activated protein kinase signaling pathway, serotonergic and dopaminergic synapse. Molecular docking and molecular dynamics simulation studies illustrated that berberine, epiberberine, palmatine, and coptisine presented favorable binding patterns with HTR2A. The in vivo experiments confirmed that Rhizoma Coptidis extract ameliorated anxiety-like behaviors by improving the survival of neurons, regulating synaptic plasticity, and inhibiting neuroinflammation.Conclusion: These findings in the present study led to potential preventative and therapeutic strategies for serious mental illnesses with traditional Chinese medicine.Graphical Abstract: Keywords: Coptis chinensis Franch, serious mental illness, multitarget, network pharmacology, molecular mechanism