Walter Vichnewski

Inhibition of inflammatory cytokine production and lymphocyte proliferation by structurally different sesquiterpene lactones correlates with their effect on activation of NF-κB

Many sesquiterpene lactones (Sls) are known to possess anti-inflammatory activities. To gain further insight into their structure-activity relationships and the molecular mechanism of action, four germacranolide sesquiterpene lactones which differ in the skeleton and the number of reactive centers (4beta,15-epoxy-miller-9E-enolide (1), 15-acetoxy-eremantholide B (2), a mixture of 15-(isovaleroyl)/15-(2-methyl-butyryl)-2alpha-acetoxy-miguanin (3), and 15-(2-hydroxy)-isobutyryloxy-micrantholide (4)) were investigated for their effect on production of proinflammatory cytokines (interleukin-1beta [IL-1beta], IL-6, and tumor necrosis factor-alpha [TNF-alpha]) as well as proliferation of concanavalin A (Con A) and lipopolysaccharide (LPS)-stimulated mouse lymphocytes. Compounds 1 and 3 which possess an alpha-methylene-gamma-lactone function and a conjugated carbonyl group induced a half-maximal inhibition of cytokine synthesis in adherent mouse peritoneal exudate cells at micromolar concentrations (IC(50) 0.69-1.70 microM), while compound 4 which contains only an alpha-methylene-gamma-lactone residue was less active (IC(50) > or 38 microM). Interestingly, compound 2, which carries only a conjugated keto group, displayed a potency similar to those of the bifunctional compounds 1 and 3. All four Sls suppressed proliferation of murine lymphocyte at IC(50) concentrations between 0.22 and 5.03 microM. The rank order of potency was 1 = 2 > 3 > 4. Generally, the growth of LPS-stimulated cells was more strongly influenced than those of Con A-activated lymphocytes. This effect was particularly pronounced with 4. Inhibitory concentrations correlated well with those necessary for inhibition of the transcription factor nuclear factor kappaB (NF-kappaB) observed in a previous investigation. Therefore, it can be assumed that NF-kappaB may be involved in the suppressive effect of Sls on cytokine production and lymphocyte proliferation.

Diterpenoid furans from Pterodon species

Abstract Investigation of diterpenoids in four species of Pterodon show varying oxidation patterns on the vinhaticane or vouacapane skeletons.

Sesquiterpene lactones and other constituents from Eremanthus seidelii, E. Goyazensis and Vanillosmopsis erythropappa

Abstract Extraction of the aerial parts of Eremanthus seidelii and reinvestigation of E. goyazensis gave four new 4,5-dihydrofuranoheliangolides and two new 4,5-dihydroeremantholides as well as some known sesquiterpene lactones. X-Ray analysis of one of the 4,5-dihydroeremantholides showed that the new lactones from E. seidelii and E. goyazensis differ in C-4 stereochemistry from isomers previously isolated from Eremanthus and related species. Criteria based on NMR spectroscopy for distinguishing between the two series are given. The C-4 stereochemistry of zexbrevin is discussed and the tentative conclusion is reached that in the earlier correlation between tagitinin A and zexbrevin C-4 epimerization took place at the oxidation stage. Reinvestigation of Vanillosmopsis erythropappa wood resulted in isolation of several lactones not previously reported from this species.

A study of the trypanocidal and analgesic properties from Lychnophora granmongolense (Duarte) Semir & Leitão Filho.

Crude extracts from the aerial parts of Lychnophora granmongolense (Asteraceae) were bioassayed for trypanocidal (trypomastigote forms of Trypanosoma cruzi) and analgesic (writhing test) activities. The crude ethyl acetate extract from the leaves plus inflorescences exhibited trypanocidal activity but no analgesic activity in the writhing model of pain. The bioassay‐guided fractionation of this extract yielded three trypanocidal compounds: the sesquiterpene lactones centratherin (lychnophorolide A) and goyazensolide and the flavonoid eriodictyol. The flavonoids homoeriodictyol, eriodictyol 7,3′‐dimethyl ether, velutin, chrysoeriol, dihydroisorhamnetin, rhamnazin and the sesquiterpene lactone lychnophorolide B were also isolated from the ethyl acetate extract. Such flavonoids did not show any trypanocidal activity. The isolated amount of lychnophorolide B was not enough to account for the full activity against T. cruzi. Copyright

Sesquiterpene lactones from Brazilian Tithonia diversifolia

Abstract Aerial parts of Tithonia diversifolia collected in Sao Paulo State afforded two new heliangolides in addition to the heliangolides tagitinin F and 1,2-epoxytagitinin C, one known guaianolide and the flavone hispidulin. Structures were established by spectroscopic studies.

Polyhydroxyagarofuran derivatives from Austroplenckia populnea

Abstract The larvicidal extract of Austroplenckia populnea leaves gave two new polyesters of 8-oxo-1,2,3,4,9,14-hexahydroxydihydroagarofuran, a compound which is typical of Celastraceae species.

Sonication and liquid chromatography as a rapid technique for extraction and fractionation of plant material

A fast method of extraction and isolation of the major compounds of Lychnophora ericoides Mart. is described which uses only 100 g of dried, ground plant material and small amounts of solvent and solid phases. The method combines extraction by sonication with a mixture of non-miscible solvents, rapid pre-separation of the crude extract by vacuum-liquid chromatography (silica gel 60H), and separation by preparative, reversed-phase HPLC or classical liquid chromatography with polyvinylpyrrolidone. Eighteen compounds (flavonoids and sesquiterpene lactones) were isolated by this method and identified by spectrometric methods, namely 7,4′-dihydroxy-flavonol, 5,7-dihydroxy-3-methoxy-flavonol, galangine, 7,4′-dihydroxy-dihydroflavonol, 5,7,4′-trihydroxy-dihydroflavonol, 7-hydroxy-4′-methoxy-dihydroflavonol, pinobanksin, 5,7′-dihydroxy-4′-hydroxy-flavanone, 7-hydroxy-4′-methoxy-flavanone, 5,7-dihydroxy-flavone, acacetin, 7-hydroxy-3′,4′-dihydroxy-isoflavone, 15-desoxigoiazensolide, 2′,3′-dihydro-15-desoxygoyazensolide, eremantholides A and C, 4,5-dihydroeremantholide A and lychnopholide. Copyright

Cinnamoylgrandifloric acid from Mikania oblongifolia.

Abstract Isolation of the cinnamate of grandifloric acid from Mikania oblongifolia is reported.

Ent-kaurene diterpenes from Gochnatia polymorpha var. Polymorpha

Abstract Two diterpenes were isolated from the aerial parts of Gochnatia polymorpha var. polymorpha . Their structures were established as ent -3 β ,19-diacetoxy-12 β ,15 α -dihydroxy-kaur-16-ene and ent -17,19-diacetoxy-3 β ,16 β - dihydroxykaurane, respectively. In addition, the aerial parts afforded cycloart-25-ene-3β,22α-diol and the flavoids genkwanin and desmethoxycentaureidin while the roots furnished taraxerol and the eudesmanolide santamarin.

Drimane derivatives from Drimys brasiliensis

Abstract Drimys brasiliensis gave confertifolin and two new drimane derivatives identified as 1β-p-coumaroyloxypolygodial and 1β-p-coumaroyloxyvaldiviolide.