ABSTRACT
Sepsis is characterized by a dysregulated immune response to infection characterized by an early hyperinflammatory and oxidative response followed by a subsequent immunosuppression phase. Although there have been some advances in the treatment of sepsis, mortality rates remain high, urging for the search of new therapies. ß-Lapachone (ß-Lap) is a natural compound obtained from Tabebuia avellanedae Lorentz ex Griseb. with several pharmacological properties including bactericidal, anti-inflammatory, and antioxidant activity. Thus, the aim of this study was to evaluate the effects of ß-Lap in a mouse sepsis model. To this, we tested two therapeutic protocols in mice submitted to cecal ligation and puncture- (CLP-) induced sepsis. First, we found that in pretreated animals, ß-Lap reduced the systemic inflammatory response and improved bacterial clearance and mouse survival. Moreover, ß-Lap also decreased lipid peroxidation and increased the total antioxidant capacity in the serum and peritoneal cavity of septic animals. In the model of severe sepsis, the posttreatment with ß-Lap was able to increase the survival of animals and maintain the antioxidant defense function. In conclusion, the ß-Lap was able to increase the survival of septic animals by a mechanism involving immunomodulatory and antioxidant protective effects.
Subject(s)
Naphthoquinones/therapeutic use , Sepsis/drug therapy , Sepsis/mortality , Animals , Anti-Inflammatory Agents/therapeutic use , Chemoprevention/methods , Cytokines/metabolism , Disease Models, Animal , Immunosuppression Therapy/methods , Inflammation/drug therapy , Inflammation/metabolism , Inflammation/mortality , Inflammation Mediators/metabolism , Male , Mice , Oxidative Stress/drug effects , Sepsis/metabolism , Sepsis/pathology , Survival RateABSTRACT
Chemical transformations of eremantholide C (1), a sesquiterpene lactone that was isolated from Lychnophora trichocarpha Spreng. led to five new derivatives: 1',2'- epoxyeremantholide C (2), 5-n-propylamine-4,5-dihydro-1',2'-epoxyeremantholide C (3), 5-n-propylammonium-4,5-dihydro-1',2'-epoxyeremantholide C chloride (4), 5-n-propylammonium-4,5-dihydroeremantolide C chloride (5) and 16-O-ethyleremantholide C (6). The structures of all these derivatives were assigned on the basis of IR, MS, 1H and 13C NMR data by 1D and 2D techniques. Eremantholide C and the derivatives 2, 4 and 5 were evaluated against trypomastigotes Y and CL strains of Trypanosoma cruzi. Eremantholide C completely inhibited the growth of both the parasites strains while all derivatives were partially active against the CL strain and inactive against the Y strain.
Subject(s)
Asteraceae/chemistry , Plant Extracts/pharmacology , Sesquiterpenes/pharmacology , Trypanosoma cruzi/drug effects , Magnetic Resonance Spectroscopy , Parasitic Sensitivity Tests , Sesquiterpenes/chemistry , Sesquiterpenes/isolation & purificationABSTRACT
This paper reports on the syntheses and spectrometric characterisation of eleven novel ent-kaurane diterpenoids, including a complete set of (1)H, (13)C NMR and crystallographic data for two novel ent-kaurane diepoxides. Moreover, the antineoplastic cytotoxicity for kaurenoic acid and the majority of ent-kaurane derivatives were assessed in vitro against a panel of fourteen cancer cell lines, of which allylic alcohols were shown to be the most active compounds. The good in vitro antimalarial activity and the higher selectivity index values observed for some ent-kaurane epoxides against the chloroquine-resistant W2 clone of Plasmodium falciparum indicate that this class of natural products may provide new hits for the development of antimalarial drugs.
Subject(s)
Antimalarials/pharmacology , Antineoplastic Agents/pharmacology , Diterpenes, Kaurane/pharmacology , Plasmodium falciparum/drug effects , Antimalarials/chemical synthesis , Antimalarials/chemistry , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Death/drug effects , Cell Proliferation/drug effects , Diterpenes, Kaurane/chemical synthesis , Diterpenes, Kaurane/chemistry , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Models, Molecular , Molecular Structure , Parasitic Sensitivity Tests , Structure-Activity RelationshipABSTRACT
A recent reinvestigation of aerial parts of Wedelia paludosa D.C. is described and reports, for the first time, the isolation of iso-kaurenoic acid from this species.
