iridoids and verminoside

Breast cancer is one of the most common cancers in women and is associated with a high mortality rate. The majority of deaths resulting from breast cancer are attributable to metastatic growth; in addition, chemoresistance is a major concern in the treatment of patients with breast cancer. However, limited drugs are available for the treatment of metastatic breast cancer. In this study, the chemoadjuvant effects of a methanolic extract from the leaves of Pseudolysimachion rotundum var. subintegrum (NC13) and an active component isolated from the plant, verminoside (Vms), were evaluated. Furthermore, their potent anti-metastatic activities were validated in vitro and in vivo in animal models. The anti-metastatic and chemosensitizing activities of NC13 and Vms on cisplatin treatment were found to be partly mediated by suppression of the epithelial-mesenchymal transition of cancer cells. Collectively, our results implied that NC13 and its bioactive component Vms could be developed as effective chemoadjuvants in combination with conventional therapeutics.

Topics: Adjuvants, Pharmaceutic; Allografts; Animals; Antineoplastic Agents; Breast Neoplasms; Cell Survival; Cisplatin; Diet; Disease Models, Animal; Drug Resistance, Neoplasm; Epithelial-Mesenchymal Transition; Female; Humans; Iridoids; Male; MCF-7 Cells; Mice; Mice, Inbred BALB C; Neoplasm Metastasis; Phytotherapy; Plant Extracts; Plant Leaves; Veronica

A simple and reliable high-performance liquid chromatographic method was successfully developed for the study of fingerprint chromatograms of extract and fractions from the leaves of Spathodea campanulata (SC) using verminoside (1) and 1-O-(E)-caffeoyl-β-gentiobiose (2) as marker compounds. Antioxidant activity of SC was determined by using free radical of 2,2-diphenyl-1-picryl-hydrazyl-hydrate as an experimental model. The docking study of selected target, tyrosinase and ligands (ascorbic acid, compounds 1 and 2) was performed through Autodock Vina v0.8. Fingerprints of methanol, chloroform, ethylacetate, n-butanol and water extracts could resolve 13, 11, 22, 16 and 5 peaks, respectively. Extract, fractions and compounds 1 and 2 previously isolated from SC displayed remarkable antioxidant activity with radical-scavenging activity ranging from 2.5 to 6.7 μg/mL. In silico study identified compounds 1 and 2 as potential inhibitors of tyrosinase correlating with the observed antioxidant activity in vitro.

Topics: Antioxidants; Bignoniaceae; Chromatography, High Pressure Liquid; Disaccharides; Iridoids; Molecular Structure; Plant Extracts; Plant Leaves

The discovery of bioactive molecules modulating aging in living organism promotes development of natural therapeutics for curing age-related afflictions. The progression in age-related disorders can be attributed to increment in intracellular reactive oxygen species (ROS) and oxidative stress level. To this end, we isolated an iridoid verminoside (VMS) from Stereospermum suaveolens (Roxb.) DC. and evaluated its effect on Caenorhabditis elegans. The present study delineates VMS-mediated alteration of intracellular ROS, oxidative stress, and life span in C. elegans. The different tested doses of VMS (5 μM, 25 μM, and 50 μM) were able to enhance ROS scavenging and extend mean life span in C. elegans. The maximal life span extension was observed in 25 μM VMS, that is, 20.79% (P < 0.0001) followed by 9.84% (P < 0.0001) in 5 μM VMS and 8.54% (P < 0.0001) in 50 μM VMS. VMS was able to alleviate juglone-induced oxidative stress and enhanced thermotolerance in worms. The stress-modulating and ROS-scavenging potential of VMS was validated by increment in mean survival by 29.54% (P < 0.0001) in VMS-treated oxidative stress hypersensitive mev-1 mutant strain. Furthermore, VMS modulates expression of DAF-16 (a FoxO transcription factor) promoting stress resistance and longevity. Altogether, our results suggest that VMS attenuates intracellular ROS and stress (oxidative and thermal) level promoting longevity. The longevity and stress modulation can be attributed to VMS-mediated alterations in daf-16 expression which regulates insulin signaling pathway. This study opens doors for development of phytomolecule-based therapeutics for prolonging life span and managing age-related severe disorders.

Topics: Aging; Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Iridoids; Longevity; Oxidative Stress

This study was undertaken to evaluate the efficiency of extract, fractions and pure molecules from Spathodea campanulata (SC) towards inflammation. Polarity-based extracts of SC were found active in stabilising red blood cell (RBC) membrane indicating anti-inflammatory potential. Bioactivity-guided isolation of SC produced 1-O-(E)-caffeoyl-β-gentiobiose and (2S)-1,2-di-O-[(9Z,12Z,15Z)-octadeca-9,12,15-trienoyl]-3-O-[α-d-galctopyranosyl-(1″ → 6')-O-β-d-galactopyranosyl] glycerol as the active constituents with 65.91% and 67.41% of membrane stability, respectively. Activity of the third compound (verminoside) could not be ascertained owing to extremely low recoverability. Furthermore, the isolated compounds were subjected to in silico studies. The compounds showed good binding affinity towards cyclooxygenase-2. Absorption, distribution, metabolism & excretion (ADME)-toxicity studies illustrated that the isolated compounds are free of toxicity. These observations help us to conclude that SC might exert its anti-inflammatory activity by soothing the RBC membrane as it is the case for non-steroidal anti-inflammatory drugs towards lysozomal membranes. Therefore, SC might be considered as a potential candidate for development of anti-inflammatory drugs.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Bignoniaceae; Cell Membrane; Cyclooxygenase 2; Disaccharides; Iridoids

Extracts from Veronica officinalis L. are traditionally used for the treatment of lung diseases; however, the effective compounds and the mode of action are still unknown.. Here we analyzed the effects of a standardized Veronica extract on genes expression and signalling protein production associated with the development of inflammatory lung diseases.. The degranulation capacity of primary mast cells, as well as gene expression and release of inflammatory mediators from human lung epithelial cells (A549 cells) were analyzed in relation to the synthetic drugs azelastine and dexamethasone. Gene and protein expression of cyclooxygenase-2 were investigated by semi-quantitative RT-PCR and western blotting, respectively. The involvement of phosphorylated mitogen-activated protein kinases and NF-κB signaling in regulation of these molecules were characterized by western blotting and electrophoretic mobility shift assays. Characteristic extract components were identified by LC-MS and verminoside was quantified by HPLC analysis.. We demonstrated that Veronica officinalis has a small influence on the degranulation capacity of mast cells but rather inhibits gene and protein expression of the chemokine eotaxin in A549 lung epithelial cells, which is essential for recruitment of inflammatory-associated cells in lung diseases. Furthermore, release of the inflammatory mediator PGE(2) was diminished through inhibition of COX-2 expression via the NF-κB signaling pathway in TNF-α-activated A549 cells. Phytochemical analysis identified verproside and verminoside as the most abundant iridoid glycosides.. Our results are a contribution to explaining the observed anti-inflammatory effects of Veronica offcinalis extract on a molecular level. However, its clinical potency has at first to be proven in animals and subsequently in clinical trials.

Topics: Animals; Bone Marrow Cells; Cell Line; Cell Survival; Cyclooxygenase 2; Dexamethasone; Epithelial Cells; Gene Expression; Humans; Inflammation Mediators; Iridoid Glucosides; Iridoids; Lung; Mast Cells; Medicine, Traditional; Mice; Mitogen-Activated Protein Kinases; NF-kappa B; Phosphorylation; Phthalazines; Plant Extracts; Signal Transduction; Veronica

The antioxidant principles isolated from the various parts of the plant are verminoside (leaf, stem bark and flowers; EC(50) = 2.04 µg/ml), Specioside (flowers; EC(50) = 17.44 µg/ml), Kampeferol diglucoside (leaf; EC(50) = 8.87 µg/ml) and Caffeic acid (leaf and fruits). The non anti-oxidant components isolated in the study include ajugol (stem bark and fruits) and phytol (leaf).

Topics: Antioxidants; Bignoniaceae; Caffeic Acids; Flowers; Fruit; Glycosides; Iridoid Glucosides; Iridoid Glycosides; Iridoids; Kaempferols; Phytol; Plant Extracts; Plant Leaves; Plant Stems; Pyrans

Verminoside and verbascoside are natural compounds present in plants used in traditional medicine. They exhibit several biological activities including anti-inflammatory, anti-bacterial and anti-tumor properties. The potential applications of these compounds as ingredients in pharmaceutical formulations and cosmetics prompted us to investigate on cytotoxic and genotoxic activity of verminoside and verbascoside on human lymphocytes using genetic toxicity assays recommended in preclinical studies by the US Food and Drug Administration (FDA). We analyzed chromosome aberrations (CAs) and sister chromatid exchanges (SCEs) as well as the mitotic index (MI) and cell viability after the treatments with verminoside and verbascoside. This report is the first to clearly demonstrate a significant increase of structural CAs and SCEs on normal human lymphocytes associated with a reduction of the MI in both verminoside- and verbascoside-treated cells. Moreover, we observed enhanced protein expression levels of PARP-1 and p53 that are key regulatory proteins involved in cell proliferation and DNA repair. Interestingly, mass spectrometric analysis of the compounds in the culture supernatants also showed that verminoside remained unchanged during the culture period while verbascoside was hydrolyzed to its derivative, caffeic acid and the last one seems to be responsible for the observed biological activity.

Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents, Phytogenic; Blotting, Western; Cell Line; Cell Survival; Chromosome Aberrations; Chromosomes; DNA Repair; Dose-Response Relationship, Drug; Glucosides; Humans; Iridoids; Lymphocytes; Male; Mitotic Index; Mutagens; Phenols; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerases; Sister Chromatid Exchange; Spectrometry, Mass, Electrospray Ionization; Tumor Suppressor Protein p53

Kigelia africana is a plant used in Africa for anti-inflammatory, anti-microbial, and anti-skin-aging effects. Various papers have reported on the composition and biological activities of its CH2Cl2 extracts and dermal formulations. Chemical analysis of a polar extract of fruit from K. africana indicated the presence of verminoside (1), an iridoid, as a major constituent, and of a series of polyphenols such as verbascoside (2). In vitro assays showed that 1 had significant anti-inflammatory effects, inhibiting both iNOS expression and NO release in the LPS-induced J774.A1 macrophage cell line. Cytotoxicity and cutaneous irritation of the extract and of compounds 1 and 2 were investigated. The crude extract and 1 did not affect cell viability in vitro either in cells grown in monolayers (ML) or in the reconstituted human epidermis (RHE, 3D) model; neither caused release of pro-inflammatory mediators or histomorphological modification of RHE.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Bignoniaceae; Cells, Cultured; Epidermis; Fruit; Glucosides; Humans; Iridoids; Macrophages; Mali; Mice; Models, Biological; Molecular Structure; Monocytes; Nitric Oxide; Nitric Oxide Synthase Type II; Phenols; Plants, Medicinal