| This dissertation investigated anti-inflammatory and analgesic activities of crude extract and various fractions from Curcuma kwangsiensis,Neolamarckia cadamba,and Hypecoum erectum in vivo and in vitro,and this studies validate their traditional application.the forementioned three medicinal plants were phytochemically studied,and a total of 84 compounds were isolated,which contains 15 new ones(3 novel skeleton ones),by various chromatography techniques.The structures of all the isolates were established based on extensive spectroscopic data,quantum computational chemistry methods and X-ray diffraction analysis.Moreover,some major compounds and trace compounds isolated from the three plants were evaluated for antiinflammatory and analgesic activities in vivo and in vitro.The aforementioned studies further certify traditional use and effective fraction of the three medicinal plants,which not only would account for scientific knowledge for their traditional use,but also provide credible theoretical foundation for the further development of antiinflammatory and antinociceptive agents.The dissertation consists of three chapters,which detailedly demonstrates the chemical constituents and anti-inflammatory and antinociceptive effects of C.kwangsiensis,N.cadamba,and H.erectum by more comprehensively phytochemical and pharmacological studies,respectively.The structural type of the isolates involved in terpenoids,alkaloids(monoterpenoid indole and isoduinoline),phenylpropanoids,Phenolic glycosides and so on.Moreover,the pharmacological results exhibited partial isolates with anti-inflammatory and antinociceptive effects.Compounds isolated from the aforementioned three medicinal plants are listed below,and their chemical structures are exhibited in the following figures.1 Anti-inflammatory and Antinociceptive effects of C.kwangsiensis and Its Chemical Constituents “Curcumae Radix”,the dried rhizomes of C.kwangsiensis(Zingiberaceae)documented in Chinese pharmacopoeia,which have been recorded in Chinese pharmacopoeia(2020 edition)and used to treat jaundice and red urine,the heart-fire and depression,arthralgia,and dysmenorrhea.According to its traditional use,various fractions from C.kwangsiensis were investigated with anti-inflammatory and antinociceptive actions in vivo,and the results indicates the EA fraction exhibited better activity.Subsequent phytochemical investigation on EA fraction of C.kwangsiensis led to the isolates of 36 compounds,including 34 terpenoids(three new ones)and two curcumin consitituents.Four major sesquiterpenoids(4,6,14,and 15)were achieved for their anti-inflammatory and antinociceptive assays models in vivo.some compounds were evaluated for their anti-inflammatory effects via detecting inflammatory mediator releases(COX-2,IL-1β,and TNF-α)in RAW 264.7 macrophage cells induced by LPS.the majority of sesqui-and diterpenoids isolated(3,4,6,17,18,and 21)could inhibited the secretion of inflammatory mediators(COX-2,IL-1β,and TNF-α)in LPS-stimulated RAW 264.7 macrophages cells.2 Anti-inflammatory and Antinociceptive effects of N.cadamba and Its Chemical ConstituentsN.cadamba,belonging to Rubiaceae family,which has been used traditionally to treat inflammation,fever,dysentery,and pruritus in the Dai ethnopharmacy in Yunnan province,P.R.China.However,according to literature survey,the action basis of antiinflammatory and analgesic activities of this plant were rarely reported and majority of reports focused on the crude extrcts.Based on its traditional use,we firstly investigated the anti-inflammatory and analgesic actions of methanolic extract(ME),ethyl acetate(EA)and aqueous(AQS)fractions of N.cadamba,and further explored the accurate compounds responsible for the activities of EA fraction(Enrichment of alkaloids).Subsequent phytochemical investigation of EA fraction led to the characterization of16 compounds,including 13 monoterpenoid indole alkaloids,two phenylpropanoids compounds,1 Phenolic glycosides compound.Moreover,in four new monoterpenoid indole alkaloids,neocadambines A–D(1–4),Neocadambine A possesses a novel 14-nor-MIA skeleton that could be derived from the corynantheine-type MIAs via oxidative cleavage of C3-C14 bond and subsequently degradation of C14.Moreover,the structure of a bioactive known MIA,cadambine acid(6),was reassigned by analysis of its NMR spectroscopic data.Further biological assays revealed that the major constituent 3β-dihydrocadambine(7)relieved the paw edema and decreased the number of writhing in vivo.In addition,most of the isolates displayed in vitro anti-inflammatory effects by inhibiting the secretion of aforementioned inflammatory mediators(COX-2,IL-1β,and TNF-α),and compounds 4,7,and 9 showed anti-inflammatory effects.3 Anti-inflammatory and Antinociceptive effects of H.erectum and Its Chemical ConstituentsH.erectum is an herbaceous plant in the Papaveraceae family that mainly distributes in northeast,southwest,and north of China,also known as throat grass,mountain coptis or wild fennel,etc.It is used as antipyretic,analgesic and anti-inflammatory agents in traditional medicines.Previous research found that isoquinoline alkaloids are the main components of H.erectum.according to literature survey,there are few reports on the chemical constituents and analgesic and anti-inflammatory actions of H.erectum.Based on the aforementioned data,this study firstly investigated the anti-inflammatory and analgesic actions of methanolic extract(ME),total alkaloids(AL)and nonalkaloids(Non-AL)fractions of H.erectum,and further explored the accurate compounds responsible for the activities of AL fraction(Enrichment of alkaloids).Subsequent phytochemical investigation of AL fraction led to the characterization of32 alkaloids,including 8 new ones.Further biological assays revealed that the major constituent(10,21,22,23,and 28)relieved the paw edema and decreased the number of writhing in vivo.In addition,most of the isolates displayed in vitro anti-inflammatory effects by inhibiting the secretion of aforementioned inflammatory mediators(COX-2,IL-1β,and TNF-α)and compounds 19,21,28,and 29 showed better anti-inflammatory effects. |
PDF Full Text Request