Network Pharmacology On Triterpenoid From Rosa Laevigata Michx.for The Treatment Of Alzheimer’s Disease

Rosa laevigata Michx.is a plant belonging the genus Rosa of Rosaceae,also known as Ci Li Zi,thorn head,pheasant head,sugar orange,apple ball,lantern fruit,rattan hooks,etc.The part used as medicine is the dried and mature fruit of the plant.It is a traditional folk medicine widely used in China."Compendium of Materia Medica"has a record:"Rosa laevigata Michx,taste sour,astringent,flat in nature,non-toxic,mainly treat splenic diarrhea and diarrhea,relieve small and convenient,astringent essence;long-term use,cold resistance,light body,nourishing blood,nourishing essence,and has a miraculous effect".The fruit contains a variety of effective ingredients,including triterpenoids,polysaccharides,flavonoids,organic acids and other ingredients.Triterpenoids are one of the main active components of R.laevigata,which have the functions of anti-oxidation,anti-inflammation,improving body immunity,improving kidney health and treating neurasthenia.Alzheimer’s disease（AD）is a complex neurodegenerative disorder characterized by impaired cognitive function.Some studies have shown that triterpenes have strong pharmacological activities against AD.However,its“multi-components”and“multi-targets”characteristics make it difficult to systematically interpret the molecular mechanism of AD if using only routine methods.Therefore,in this paper,the research method of network pharmacology was used to preliminarily predict the anti-AD mechanism of triterpenoids from R.laevigata.Through literature review and database screening,a total of 66 potential target proteins in human AD and 69 triterpenoids extracted from R.laevigata were obtained.Screening through molecular docking,a total of 69 active compounds and 55 selected target proteins were obtained.The compound-target（C-T）,protein–protein interaction（PPI）network,gene ontology（GO）analysis,Kyoto encyclopedia of genes and genomes（KEGG）pathway enrichment analysis and compound-target-pathway（C-T-P）were established to identify the key compounds,key target proteins and key signaling pathways.The results showed that 13 compounds,12 target proteins and 7 signaling pathways played an important role in the mechanism of triterpenoids from R.laevigata in the treatment of AD.The direct target experiment,neuronal protection models and molecular dynamics（MD）simulation were imported to verify the above results.Direct target experiments showed that compounds（8,9,11,23,18,20,24,28,50 and 51）exhibited inhibitory activity,especially,compound 8 showed the obvious inhibitory activity on ACHE and compound 23 showed the obvious inhibitory activity on BCHE.In the H₂O₂-induced SH-SY5Y cell injury model experiment,compound 11 showed the significant protective activity,closed to the positive control Trolox.Furthermore,MD simulation was carried out to explore the binding interactions between the compounds（8,23 and 28）and their receptors（ACHE,BCHE,BACE1 and BACE2）.The above results indicated that triterpenoids from R.laevigata might play a role in the treatment of AD through the modulation of these relevant proteins.