Network Pharmacology Combined With Experiments Reveal The Mechanism Of Action Of Traditional Chinese Medicine Compound Targeting Neuroinflammation And Metabolic Disorders To Intervene In A

Alzheimer’s disease(AD)is the most common neurodegenerative disease,characterized by progressive cognitive impairment and impairment of learning and memory.The incidence of AD increases with age,and with the aging of the world’s population,the number of AD patients is also increasing.But,the pathogenesis of AD is not clear,and there are no drugs that can cure or stop/delay the disease progression.In the long-term clinical practice,Traditional Chinese medicine(TCM)has accumulated numerous effective prescription drugs under the guidance of holistic view and syndrome differentiation,which contains the profound connotation of systematic treatment of complex diseases.AD involves many pathological lesions,and the current research model of "single target,single drug" has not achieved ideal results.This suggests that there should be more perspectives in the development of AD treatment drugs.With the rapid development of high-throughput omics technology and computational and analytical capabilities,the biomedical field has entered the era of "big data",ushering in new opportunities for the development of TCM.In the face of the complexity of diseases,TCM and their interactions,network pharmacology uses big data analysis to carry out systematic research on disease mechanism and drug mechanism from the perspective of complex biological network.This new model of drug research helps to explain the characteristics of TCM holistic treatment.In TCM,combination therapy has been advocated for thousands of years,and the "multiple components and multiple targets" characteristics of TCM may be advantageous over singletarget drugs in the treatment of complex diseases.Many herbal prescriptions have shown great progress toward neurodegenerative disease prevention and treatment,including improving the learning and memory ability,regulating metabolic dysfunction,inhibiting neuroinflammation,reducing oxidative stress,anti-aging effect.AD is recorded in the classics of TCM as"forgetfulness","unwisdom","dementia","stupor" and "ignorance".In the basic theory of TCM,"phlegm" is considered to be a key pathogenic factor in many diseases.Many TCM scholars believe that the accumulation of "phlegm" in the brain is the main TCM pathogenesis of AD.In our study.Nao Tan Qing(NTQ),consists of eight herbs,was designed to ameliorate the progress of AD based on the removal of " phlegm " pathological factors.In vivo experiments identified that NTQ significantly mitigated cognitive impairment,Aβburden and neuroinflammation in 5×FAD transgenic AD mouse model.Network pharmacology results revealed that the active components of NTQ could target inflammatory and metabolic pathways.In addition,hippocampal transcriptomics suggested that NTQ regulated signaling pathways related to inflammation and lipid metabolism.Consistently,serum metabolomics further indicated that NTQ could modulate both lipid and glucose metabolism.In summary,a combination of system pharmacology and animal studies demonstrates that NTQ could alleviate behavioral abnormality and pathological alterations of AD by targeting neuroinflammation and metabolism,and is accordingly a potential therapeutic agent for AD.