Studies On Chemical Constituents And Neuroprotective Activities Of Pyrola Incarnata And Talaromyces Aculeatus

Pyrola incarnata is a traditional medicinal plant in China,which has good effects in strengthening the muscles and bones,tonifying the kidney and filling the essence,strengthening the immunity and so on.The AD model of C57BL/6 mice induced by A?_25-35 was established.The 95%ethanol extract of P.incarnata was administered to the memory impairment model mice induced by A?_25-35.The experimental results showed that P.incarnata extract could protect the spatial memory impairment of mice induced by A?_25-35 and reduce the A?_25-35 level in the hippocampus.Nine compounds,including seven triterpenoids,one iridoid glycoside and one flavonoid,were isolated from P.incarnata.The behavioral memory performance of ursolic acid group in Barnes maze and water maze was better than that of model group.It was found that ursolic acid could improve the learning and memory impairment induced by A?_25-35 and the deposition of A?_25-35 in hippocampus by activating microglia and up regulating the level of Iba1 in a dose-dependent manner.This result also revealed that ursolic acid may be one of the neuroprotective chemical entities in P.incarnata.Meanwhile,the chemical constituents of ethyl acetate extract from Talaromyces aculeatus were isolated and identified.Fourteen compounds were isolated by silica gel column chromatography,C18 reversed phase silica gel column chromatography,dextran gel Sephadex LH-20 and semi preparative high performance liquid chromatography.The structures of these compounds were identified by NMR,MS,IR and CD spectroscopy,including a new compound:schizosteroids?10?,which has a novel 6/6/5 cyclosteroidal skeleton,and 13 known compounds:ergone?11?,dankasterone a?12?Two polyketide compounds:rigenolide D?13?,blapsin e?14?;seven small molecules:5-hydroxymethylfurfural?15?,dimer 5-hydroxymethylfurfural?16?,3,4-dimethylfuran?17?;monoethyl malonate?18?,trichodimerol?19?,lignoren?20?,alcohol?21?;two penicillide compounds:penicillide?22?,isopenicillide?23?.Polyketones and penicillides are secondary metabolites of Talaromyces sp.The molecular docking of AD pathology related proteins was carried out.Compound 10 showed potential inhibitory activities on?secretase BACE1,tau protein phosphorylation key enzyme GSK3?and ache,a cholinesterase inhibitor.