lignans and kobusin

The phytochemical investigation on the fruits of

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Benzodioxoles; Drug Evaluation, Preclinical; Eleutherococcus; Fruit; Glycosides; Lignans; Lipopolysaccharides; Magnetic Resonance Spectroscopy; Mice; Microglia; Molecular Structure; Monoterpenes; RAW 264.7 Cells

Piperaceae species are abundant in the tropics and are important components of secondary vegetation. Many of these plants have received considerable attention due to their wide range of biological activities. Here, the trypanocidal activity of extracts and fractions with different polarities obtained from Colombian Piper jericoense plant was evaluated. A furofuran lignan, (1S,3aS,4S,6aS)-1-(3',4'-dimethoxyphenyl)-4-(3″,4″-methylendioxyphenyl)hexahydrofuro[3,4-c]furan, (1), was isolated from Colombian Piper jericoense leaves ethyl acetate extract. Its relative configuration at the stereogenic centers was established on the basis of various spectroscopic analyses, including 1D- (1H, 13C, and DEPT) and 2D-NMR (COSY, NOESY, HMQC and HMBC) and a 2D INADEQUATE NMR experiment as well as by comparison of their spectral data with those of related compounds such as (+)-Kobusin (2). The activity against Trypanosoma cruzi indicated that compound 1 was active against all parasite forms (epimastigote, amastigote and trypomastigote) and presented lower toxicity than the reference drug, benznidazole (Bz), evidenced by a selective index of 18.4 compared to that of Bz, which was 6.7. Moreover, this compound inhibited the infectious process, and it was active in infected mice in the acute phase. This compound significantly inhibited the T. cruzi Fe-SOD enzyme, whereas Cu/Zn-SOD from human cells was not affected. Ultrastructural analyses, together with metabolism-excretion studies in the parasite, were also performed to identify the possible mechanism of action of the tested compound. Interestingly, the lignan affected the parasite structure, but it did not alter the energetic metabolism.

Topics: Animals; Benzodioxoles; Chagas Disease; Chlorocebus aethiops; Erythrocytes; Female; Humans; Inhibitory Concentration 50; Lignans; Magnetic Resonance Spectroscopy; Mice; Mice, Inbred BALB C; Piper; Plant Extracts; Plant Leaves; Trypanosoma cruzi; Vero Cells

Topics: Amides; Apigenin; Benzodioxoles; Catechin; Chromatography, High Pressure Liquid; Coumarins; Dioxoles; Flavonoids; Furans; Hesperidin; Hydroxybenzoates; Lignans; Limit of Detection; Plant Leaves; Powders; Reproducibility of Results; Seasons; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry; Zanthoxylum

Zanthoxylum rhetsa is an aromatic tree, known vernacularly as "Indian Prickly Ash". It has been predominantly used by Indian tribes for the treatment of many infirmities like diabetes, inflammation, rheumatism, toothache and diarrhea. In this study, we identified major volatile constituents present in different solvent fractions of Z. rhetsa bark using GC-MS analysis and isolated two tetrahydrofuran lignans (yangambin and kobusin), a berberine alkaloid (columbamine) and a triterpenoid (lupeol) from the bioactive chloroform fraction. The solvent fractions and purified compounds were tested for their cytotoxic potential against human dermal fibroblasts (HDF) and mouse melanoma (B16-F10) cells, using the MTT assay. All the solvent fractions and purified compounds were found to be non-cytotoxic to HDF cells. However, the chloroform fraction and kobusin exhibited cytotoxic effect against B16-F10 melanoma cells. The presence of bioactive lignans and alkaloids were suggested to be responsible for the cytotoxic property of Z. rhetsa bark against B16-F10 cells.

Topics: Alkaloids; Animals; Benzodioxoles; Cell Line, Tumor; Cell Survival; Fibroblasts; Furans; Humans; Lignans; Melanoma, Experimental; Mice; Plant Bark; Plant Extracts; Zanthoxylum

Activated microglia produces diverse neurotoxic factors such as nitric oxide (NO) and tumor necrosis factor-alpha that serve as apoptotic inducers resulting in various neurodegenerative diseases. The inhibition of microglia-derived NO production by inducible nitric oxide synthase (iNOS) has been reported to be beneficial in retarding neurodegenerative disorders. Three active lignans have been isolated from the flower buds of Magnolia fargesii by the bioassay-guided fractionation using lipopolysaccharide (LPS)-activated BV-2 microglial cell culture system. The structures of them were identified as kobusin (1), aschantin (2) and fargesin (3) by the analyses of spectroscopic data. They inhibited the production of NO by activated microglia. Their IC(50) values were 21.8 +/- 3.7, 14.8 +/- 2.5 and 10.4 +/- 2.8 microg/mL, respectively. They suppressed LPS-induced NF-kappaB activation and the expression of iNOS protein and mRNA. Furthermore, they showed scavenging activity of neurotoxic peroxynitrite that can be produced by NO and superoxide anion. These results imply that lignans from Magnolia fargesii might be beneficial for the treatment of neuro-inflammatory diseases through the inhibition of iNOS expression and peroxynitrite scavenging potential.

Topics: Animals; Benzodioxoles; Cell Line; Enzyme Inhibitors; Flowers; Free Radical Scavengers; Inhibitory Concentration 50; Lignans; Magnolia; Mice; Microglia; Molecular Structure; Nitric Oxide; Nitric Oxide Synthase Type II