Alzheimer’s disease (AD) is a brain disease with a peculiarity of multiformity and an insidious onset. Multiple-target drugs, especially Chinese traditional medicine, have achieved a measure of success in AD treatment. Evodia rutaecarpa (Juss.) Benth. (Wuzhuyu, WZY, i.e., E. rutaecarpa), a traditional Chinese herb, has been identified as an effective drug to cure migraines. To our surprise, our in silico study showed that rather than migraines, Alzheimer’s disease was the primary disease to which the E. rutaecarpa active compounds were targeted. Correspondingly, a behavioral experiment showed that E. rutaecarpa extract could improve impairments in learning and memory in AD model mice. However, the mechanism underlying the way that E. rutaecarpa compounds target AD is still not clear. For this purpose, we employed methods of pharmacology networking and molecular docking to explore this mechanism. We found that E. rutaecarpa showed significant AD-targeting characteristics, and alkaloids of E. rutaecarpa played the main role in binding to the key nodes of AD. Our research detected that E. rutaecarpa affects the pathologic development of AD through the serotonergic synapse signaling pathway (SLC6A4), hormones (PTGS2, ESR1, AR), anti-neuroinflammation (SRC, TNF, NOS3), transcription regulation (NR3C1), and molecular chaperones (HSP90AA1), especially in the key nodes of PTGS2, AR, SLCA64, and SRC. Graveoline, 5-methoxy-N, N-dimethyltryptamine, dehydroevodiamine, and goshuyuamide II in E. rutaecarpa show stronger binding affinities to these key proteins than currently known preclinical and clinical drugs, showing a great potential to be developed as lead molecules for treating AD.

Background. Abdominal aortic aneurysm (AAA) is a fatal disease characterized by high morbidity and mortality in old population. Globally, effective drugs for AAA are still limited. Si-Miao-Yong-An decoction (SMYAD), a traditional Chinese medicine (TCM) formula with a high medical value, was reported to be successfully used in an old AAA patient. Thus, we reason that SMYAD may serve as a potential anti-AAA regime. Objective. The exact effects and detailed mechanisms of SMYAD on AAA were explored by using the experimental study and bioinformatics analysis. Methods. Firstly, C57BL/6N mice induced by Bap and Ang II were utilized to reproduce the AAA model, and the effects of SMYAD were systematically assessed according to histology, immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA). Then, network pharmacology was applied to identify the biological processes, pathways, and hub targets of SMYAD against AAA; moreover, molecular docking was utilized to identify the binding ability and action targets. Results. In an animal experiment, SMYAD was found to effectively alleviate the degree of pathological expansion of abdominal aorta and reduce the incidence of Bap/Ang II-induced AAA, along with reducing the damage to elastic lamella, attenuating infiltration of macrophage, and lowering the circulating IL-6 level corresponding to the animal study, and network pharmacology revealed the detailed mechanisms of SMYAD on AAA that were related to pathways of inflammatory response, defense response, apoptotic, cell migration and adhesion, and reactive oxygen species metabolic process. Then, seven targets, IL-6, TNF, HSP90AA1, RELA, PTGS2, ESR1, and MMP9, were identified as hub targets of SMYAD against AAA. Furthermore, molecular docking verification revealed that the active compounds of SMYAD had good binding ability and clear binding site with core targets related to AAA formation. Conclusion. SMYAD can suppress AAA development through multicompound, multitarget, and multipathway, which provides a research direction for further study.