Chemical Constituents Of Sinomenii Caulis And Their Biological Activities

Sinomenii Caulis(SC),the dried stems and rhizomes of Sinomenium acutum(Thunb.)Rehd.et Wils.or Sinomenium acutum(Thunb.)Rehd.et Wils.var.cinereum Rehd.et Wils.,is a commonly used herbal medicine for the treatment of rheumatoid arthritis,widely distributed in China.Pharmacological investigations show that SC has a broad range of bioactivities such as sedation,analgesia,anti-inflammation,anticancer,immunosuppression,and anti-arrhythmia.In order to promote a better understanding of this ancient anti-rheumatic herb,as well as to search for more bioactive natural products,recently,a detailed chemical research on SC has been conducted.Herein,the rapid profiling,isolation,structural elucidation,biological activity,and quantitative analysis has been described.In our study,an integrated characterization strategy by combing mass defect filtering-based structure classification and diagnostic fragment-ion-based extension was proposed for rapid profiling of alkaloids in SC via ultra-perfoemance liquid chromatography/quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS).The total ion chromatograms of SC were obtained by electrospray ionization(ESI)in positive ion modes,and data analysis was conducted by combing UNIFI software with manual work,and 55 chemical constituents were identified.According to the cracking rules,the SC alkaloids could be classified into five groups including morphiinans,aporphines,protoberberines,benzylisoquinolines and other type.Four novel compounds(1,2,3,4),and 24 know chemical components were isolated from95%aqueous Et OH extract of the SC.The structures and absolute configurations of the isolates were elucidated on the basis of comprehensive analysis of 1D and 2D NMR,HRMS,and by comparison of the experimental and circulae dichroism(CD)data.Four new compounds were named as dehydrodauricumidine(1),8-demethoxycephatonine-2-O-β-D-glucopyranoside(2),5,5’-bis-N,N-dimethylsinomenine(3),9-ethyl ester-rhemaneolignan A(4),and 24 know isolated compounds were identified as bianfugenine(5),acutumine(6),menisperine(7),stepharanine(8),magnoflorine(9),acutumidine(10),(S)-disinomenine(11),sinomenine(12),sinomenine N-oxide(13),dauricumidine(14),8-demethoxyrunanine(15),sinoracutine(16),cepharatine A(17),8-oxoepiberberine(18),14-episinomenine(19),eleutheroside E(20),syringaresinol-4’-O-β-D-glucopyroside(21),glucosyringic acid(22),equoyitol(23),salvadoraside(24),viburnitol(25),saccharose(26),syringing(27),and corchoionoside C(28).Among them,compounds 1-4 were first isolated from this plants,which were new compounds.SC can be used in the treatment of rheumatoid arthritis and other diseases,showing anti-inflammatory analgesia,immune suppression,immune regulation and other effects.The NO inhibitory activity of the compounds was determined by measuring the production of NO in the macrophages of mice RAW 264.7 cells.The results showed that compound 4,5 had strong NO inhibitory activity.In addition,UPLC and QE methods were used to determine the contents of 15 alkaloids in SC,and the contents of different alkaloids in roots,stems,leaves and seeds of Sinomenium acutum were analyzed and compared.The results showed that the established method could achieve good separation of the components in the sample.The concentrations showed quite goodlinear relationship within the peak area(R~2≥0.999).The average recoveries were 92.4%-102.5%,and the RSD%of the recoveries were all less than 5%.The results of different tissue of Sinomenium acutum content determination showed that the amount of alkaloids contained in roots,stems,leaves,and seeds varies greatly.