Study On Terpenoids With Anti-cholinesterase Activies From Two Tibetan Medicinal Plants

Tibetan medicine has a long history more than 2000 years of medication,with complete theory and definite therapeutic effect.After long-term practice,Tibetan medicine has finally formed a unique medical system which widely absorbed the theoretical basis of Traditional Chinese Medicine and Indian Medicine.Tibetan herbs mainly distributed in the Qinghai Tibet Plateau with high altitude,large temperature difference,strong light,cold and hypoxia.So it may be rich in unique chemical structures and excellent bioactivites.Therefore,it is of great significance to find drug with good pharmacological activities and unique skeletons from Tibetan medicine plants.Alzheimer’s disease（AD）is a kind of neurodegenerative disease characterized by cognitive impairment,which mainly occurs in the elderly and seriously affects the quality of life.Classical pharmacology believes that the content of acetylcholine（ACh）is reduced in the brain of AD patients.Thus,the increase of ACh content can significantly improve the cognitive function of patients.Therefore,it is an important strategy for development of anti-Alzheimer drug by inhibiting the cholinesterase activity to improve the content of ACh in the brain.Terpenoids with various structure types have shown a good prospect in the research and development of anti-Alzheimer drugs.In order to further searching for novel terpenoids with significant anticholinesterase activity,this research systematically studied terpenoids from Salvia castanea and Pterocephalus hookeri.As a result,48 terpenoids,including 20 new compounds,were isolated and identified.Meanwhile,their anticholinesterase activities were tested in vitro.1.Chemical study on the diterpenoids from S.castanea26 compounds were isolated from S.castanea by positive or reverse phase silica gel column chromatography,Sephedex LH-20 and semi-preparative HPLC.All compounds ware respectively identified as salcastaniols A-J（SD-1～10）,6,7-dehydroferruginol（SD-11）,ferruginol（SD-12）,sahandinone（SD-13）,prionidipene A（SD-14）,prionidipene B（SD-15）,rosmariquinone（SD-16）,1-deoxyviroxocin（SD-17）,saprirearine（SD-18）,taxodione（SD-19）,sibiriqninone A（SD-20）,12-hydroxysapriparaquinone（SD-21）,12-methoxybarbatusol（SD-22）,（3-rac）-4,12-epoxy-3,11-cyclo-4,5-seco-20（10→5）-abeoabieta-5（10）,6,8,11,13-pentaene（SD-23）,12-deoxyroyleanone（SD-24）,microstegiol（SD-25）,7-dehydroabietanone（SD-26）by MS,NMR,UV,IR or ORD.All compounds are diterpenoids,including 8 abietanes,11 seco-abietanes,5 icetexanes and 2diterpene dimers.Among them,SD-1～10 are new compounds2.Chemical study on the terpenoids from P.hookeri22 compounds were isolated from P.hookeri by various chromatographic methods.All compounds were respectively identified as ptehoosides A-J（PH-1～10）,loganetin（PH-11）,loganin（PH-12）,sweroside（PH-13）,vogeloside（PH-14）,7-epi-vogeloside（PH-15）,secoxyloganin（PH-16）,laciniatosideⅡ（PH-17）,sylvestrosideⅣ（PH-18）,cantleyoside（PH-19）,sylvestrosideⅣdimethyl acetal（PH-20）,abelioside A methyl acetal（PH-21）,triplostoside A（PH-22）by MS,NMR,UV,IR or ECD.Among them,PH-1～10 are new compounds and all compounds are iridoids except PH-10.3.Study on the anticholinesterase activity of all compounds in vitroAll compounds were evaluated the anticholinesterase activity.The result showed that 9 compounds（SD-1,SD-9,SD-10,SD-12～14,SD-16,PH-1,PH-5）exhibited significant antiacetylcholinesterase activity in vitro.Among them,6 compounds（SD-9,SD-10,SD-12～14,SD-16）showed stronger inhibitory activity than that of positive control(IC₅₀1.58±0.13μM)with IC₅₀values of 0.15±0.01,0.41±0.04,0.58±0.08,0.46±0.01,0.74±0.06,0.43±0.03μM,respectively.And 4 diterpenoids exhibited moderate antibutyrylcholinesterase activity in vitro with IC₅₀values of 9.31±0.33、7.42±1.69、4.45±0.85、14.93±2.83μM,respectively.This research provides potential lead compounds for the development of new drugs against Alzheimer’s disease,and reference for the development of new clinical indications of S.castanea and P.hookeri.