Studies On Chemical Constituents And Bioactivities Of Piper Yunnanense And Rauvolfia Perakensis

In recent years,the world health organization?WHO?pointed out that due to the increasing number of elderly people over 60 years old,Age-related diseases such as cardiovascular and cerebrovascular diseases has increased.Cardiovascular and cerebrovascular diseases is a common disease in the old people,and has the characteristics of high morbidity,high disability rate and mortality in clinical practice,which seriously threaten the health of the elderly population.Therefore,there is an urgent need to develop more effective,safer and more economical drugs for cardiovascular and cerebrovascular diseases to meet the needs of demographic changes.The genus Piper and the genus Rauvolfia play an important role in the prevention and treatment of cardiovascular and cerebrovascular diseases in clinical application and traditional folk medicine,the activities of antihypertensive,antiplatelet,antithrombotic and sedation of the two genera have been found.Therefore,Piper yunnanense and Rauvolfia perakensis were selected for this study.The chemical constituents of the twigs and leaves of the two plants were studied,and screened for bioactivity,which provided reference for the development and utilization of the two genera.The main contents and results of this study are as follows:The total extractions of the two plants were obtained by solvent extraction and concentration.Extraction,chromatography column,ODS,sephadex LH-20,preparative thin layer chromatography and semi-preparative high performance liquid column were used to get compounds such as alkaloids,lignanoids,phenylpropanoids,terpenes,glycerides and steroids.There have been 27 compounds,including 16 new compounds,isolated from Piper yunnanense.The structures of these compounds were elucidated by extensive spectroscopic methods,including IR,UV,ECD,HRESIMS,ESIMS,NMR,and appropriate references,in addition,the absolute configuration of compounds 14-27 have been determined based on electronic circular dichroism spectra analysis.Piper yunnanense were identified as follow:4-allylbenzene-1,2-diol?1?,3,4-dihydroxypropiophenone?2?,3,4-dihydroxycinnamal-dehyde?3?,3,4-dihydroxybenzaldehyde?4?,chingchengenamide A?5?,retrofractamide A?6?,piperine?7?,1?,11-dihydroxy-5-eudesmene?8?,?±?-alloaromadendrane-4?,10?-diol?9?,4R-hydroxy-4-?9S-hydroxy-12-methylhexan-6-yl?-3-methyl-cyclopent-2-enone?10?,9-hydroxy-4-megastigmen-3-one?11?,piyundibenzofuranan 1?12?,piyundibenzofuranan 2?13?,piyunlignan A?14?,piyunlignan B?15?,piyunlignan C?16?,piyunlignan D?17?,piyunlignan E?18?,piyunlignan F?19?,piyunlignan G?20?,piyunlignan H?21?,piyunlignan I?22?,piyunlignan J?23?,piyunlignan K?24?,piyunlignan L?25?,piyunlignan M?26?,piyunlignan N?27?.Compounds 12 and 13 are new benzofuran lignins,compounds 14-27 with rare linkage between C₉ and other phenylpropanoid are dihydrobenzofuran neolignans.All of these compounds were isolated from Piper yunnanense for the first time.10 Alkaloid compounds from Rauvolfia perakensis were determined by NMR spectra,mass spectrometry,and the relevant literature data.Rauvolfia perakensis were identified as follow:?+?-yohimbine?28?,21?-hydroxyyohimbine?29?,16-R-E-sitsirikine?30?,11-methoxystrictamine?31?,norpurpeline?32?,21-deoxyvomilenine?33?,vomilenine?34?,perakine?35?,raucaffricin?36?,venoterpine?37?.Compounds 28-36 are indoles alkaloids,8compounds were isolated from Rauvolfia perakensis for the first time.The biological activities of 37 compounds were evaluated respectively.In this paper,antibacterial,antitumor and antagonistic activity of ion channels were studied.Other activity studies are still in progress.Compounds 1-6,8 and 11 were evaluated for their antifungal activities and antibacterial activities,and the antifungal activity of compound 14-19 was tested.These studies show that the minimum inhibitory concentration of compounds 16 and 17 to Alternaria alternata is 100?g/mL,other compounds showed no significant activity at the concentration of 100?g/mL.Compounds 1-11 and 28-37 were selected for the cytotoxic activities experiments of two types of cancer cells?MDA-MB-231 and A549?,and no cytotoxicity was found at the initial concentration of 10?mol/L.Ten alkaloid compounds obtained from R.perakensis were studied for acid-sensing ion channels?ASICs?activity.The study found that compound 31 showed strong antagonist ion channel activity at an initial concentration of 20?mol/L.ASICs are closely related to ischemic brain damage,migraine,angina and rheumatoid arthritis.Compound 31 is expected to be a candidate in the development of drugs for cardiovascular and cerebrovascular diseases.