Gerardo Mora

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.

Study of sesquiterpene lactones from Milleria quinqueflora on their anti-inflammatory activity using the transcription factor NF-κB as molecular target.

In Central America aerial parts of the Asteraceae Milleria quinqueflora are used in traditional medicine as a remedy for skin infections. Reinvestigation of this plant afforded thirteen sesquiterpene lactones (Sls), three of them are new. All isolated Sls were studied for their anti-inflammatory activity using the transcription factor NF-kappa B as molecular target. NF-kappa B is involved in the synthesis of inflammatory mediators, such as cytokines and chemokines. NF-kappa B DNA binding was inhibited at micromolar concentrations by all Sls.

Antifeedant activity of Quassia amara (Simaroubaceae) extracts on Hypsipyla grandella (Lepidoptera: Pyralidae) larvae.

Abstract The inhibitory effect of methanolic wood and leaf extracts of bitterwood tree (Quassia amara) on mahogany shootborer (Hypsipyla grandella) larval feeding and growth was studied. A randomized complete block design, with four replications, was used. H. grandella third instar larvae were exposed for 24 h to Cedrela odorata leaf discs dipped in several treatment dissolutions of each extract (0.1, 0.316, 1.0, 3.162, and 10%); afterwards, each larva was transferred to a flask containing artificial diet, where it was allowed to complete its development. Variables measured included food consumption (foliar area eaten in 24 h), mortality, and developmental effects (developmental time for each larval instar and the pupa, and pupal weight). Both Q. amara extracts showed a clear antifeedant activity against H. grandella larvae, but it was higher for the wood extract; it was detected at a concentration as low as 0.32% for the wood extract and as high as 3.16% for the leaf extract.

Anti-inflammatory and antinociceptive activities of Loasa speciosa in rats and mice

In the range of doses of 250-500 mg/kg (given i.p.) the aqueous extract of Loasa speciosa leaves showed an inhibitory effect on leukocyte migration, and a reduction on the pleural exudate, as well as dose-dependent anti-inflammatory and peripheral antinociceptive activities.

Anti‐HIV activity of dibenzylbutyrolactone‐type lignans from Phenax species endemic in Costa Rica

Previously, we isolated two new dibenzylbutyrolactone‐type lignans, named phenaxolactones 1 and 2, from the leaves of Phenax angustifolius Wedd. (Urticaceae). In this investigation three new dibenzylbutyrolactone lignans (phenaxolactones 3–5), together with phenaxolactone 1, and flavones vitexin (6), isovitexin (7), were isolated from Phenax rugosus Wedd. leaves collected in Santa Ana, Costa Rica. The structures were elucidated using 1D and 2D NMR spectroscopy as well as mass spectrometry. Phenaxolactones 1–5 and flavones 6 and 7 were evaluated for their inhibitory activity against HIV‐1MN in infected C8166 cells. The most promising compound was phenaxolactone 1 with an EC50 value of 3.0μM, no cytotoxicity at 112μM and a therapeutic index value of 37.3.

Systemic activity of plant extracts in Cedrela odorata (Meliaceae) seedlings and their biological activity on Hypsipyla grandella (Lepidoptera: Pyralidae) larvae

1 Deterrent and toxic substances known to affect Hypsipyla grandella larvae were bioassayed to determine their possible systemic activity under laboratory conditions in Turrialba, Costa Rica.

Chapter 15 Promissory botanical repellents/deterrents for managing two key tropical insect pests, the whitefly Bemisia tabaci and the mahogany shootborer Hypsipyla grandella

Publisher Summary The acceptance and spread of integrated pest management (IPM) as a sound strategy to deal with pest problems has made a growing number of agrichemical companies to develop commercial bioinsecticides. Thus, there is a need to revisit ethnobotanical knowledge to formally pursue screening of crude extracts for biological activity. But, unfortunately, the discovery, characterization, and exploitation of natural products against insects have proceeded in a biased trend toward bioinsecticides, disregarding repellent, and deterrent substances. Perhaps this is because their production process is as complex as that for an insecticide, whereas their effects under field conditions do not eliminate a pest problem but rather could transfer it to neighboring farmers. Nevertheless, for key insect pests showing a very low damage threshold, semiochemicals (repellents and deterrents) could play an important role as a component of IPM programs based upon a preventive approach. This is the case of the whitefly Bemisia tabaci and the mahogany shootborer Hypsipyla grandella on which the authors have conducted research in recent years.