41 research outputs found
Potent Antioxidant and Genoprotective Effects of Boeravinone G, a Rotenoid Isolated from Boerhaavia diffusa
Background and Aims: Free radicals are implicated in the aetiology of some gastrointestinal disorders such as gastric ulcer, colorectal cancer and inflammatory bowel disease. In the present study we investigated the antioxidant and genoprotective activity of some rotenoids (i.e. boeravinones) isolated from the roots of Boerhaavia diffusa, a plant used in the Ayurvedic medicine for the treatment of diseases affecting the gastrointestinal tract. Methods/Principal Findings: Antioxidant activity has been evaluated using both chemical (Electron Spin Resonance spectroscopy, ESR) and Caco-2 cells-based (TBARS and ROS) assays. DNA damage was evaluated by Comet assay, while pERK 1/2 and phospho-NF-kB p65 levels were estimated by western blot. Boeravinones G, D and H significantly reduced the signal intensity of ESR induced by hydroxyl radicals, suggesting a scavenging activity. Among rotenoids tested, boeravinone G exerted the most potent effect. Boeravinone G inhibited both TBARS and ROS formation induced by Fenton's reagent, increased SOD activity and reduced H 2O 2-induced DNA damage. Finally, boeravinone G reduced the levels of pERK 1 and phospho-NF-kB p65 (but not of pERK 2) increased by Fenton's reagent. Conclusions: It is concluded that boeravinone G exhibits an extraordinary potent antioxidant activity (significant effect in the nanomolar range). The MAP kinase and NF-kB pathways seem to be involved in the antioxidant effect of boeravinone G. Boeravinone G might be considered as lead compound for the development of drugs potentially useful against those pathologies whose aetiology is related to ROS-mediated injuries
Plant-derived compounds in experimental inflammatory bowel disease and colon carcinogenesis
Abstract
Background Inflammatory bowel disease (IBD) and colorectal cancer (CRC) are widespread intestinal diseases. The link between these two diseases is highlighted by the observation that patients with IBD are at increased risk for CRC. Plants have been traditionally used in folk medicine and are actually practiced in industrialized countries where their use is often integrated into conventional medicine. Most survey agree that digestive tract ailments cure/prevention, including IBD and CRC, is one of the most frequent reasons for trying plant medicines. Aim To evaluate the effect of a number of plant-derived compounds [i.e. cannabigerol (CBG), a non-psychotropic cannabinoid from Cannabis sativa, diallyl sulfide (DAS) and diallyl disulfide (DADS), two organosulfur compounds from Allium sativum, bromelain, a cysteine protease from Ananas comosus and boeravinone G, a rotenoid isolated from the Ayurvedic plant Boerhaavia diffusa) in experimental models of IBD and colon cancer.
Methods. Experimental colitis was induced in mice by intracolonic administration of dinitrobenzene sulfonic acid (DNBS). Inflammation was assessed by evaluating inflammatory markers/parameters (e.g. colon weight/colon length ratio and myeloperoxidase activity), by histological analysis and by immunohistochemistry; interleukin-1β, interleukin-10, interferon-γ (IFN-γ), interferon-γ-induced protein 10 (IP-10) levels were measured by ELISA, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) by western blot and RT-PCR; CuZn-superoxide dismutase (SOD) activity were evaluated by a colorimetric assay. Murine macrophages and intestinal epithelial cells were used to evaluate the in vitro antinflammatory action (nitric oxide production, oxidative stress, interferon-γ, interleukin-6 (IL-6) and IP-10 levels or mRNA expression). Motility changes were investigated in vivo in the model of intestinal inflammation induced by croton oil.
Colon carcinogenesis was induced by the administration of the carcinogenic agent azoxymethane (AOM) in mice, which induces the formation of preneoplastic lesions (aberrant crypt foci), polyps and tumours. In colorectal carcinoma (Caco-2) cells, proliferation was evaluated using the 3H-thymidine incorporation assay; ERK, Akt and phospho-NF-kB p65 expression was evaluated by western blot analysis, ROS production by fluorescent probe, DNA damage by Comet assay.
Results Main results indicate that 1) CBG exerts therapeutic actions in the DNBS model of colitis in mice. The effect of CBG was associated to modulation of intestinal cytokine levels and down-regulation of intestinal iNOS expression. In macrophages, CBG inhibited iNOS-derived nitric oxide production. Also, CBG protected intestinal epithelial cells exposed to oxidative stress. 2) DAS and DADS exert beneficial actions in the DNBS model of IBD. Both compounds reduced intestinal inflammation and damage, as revealed by gross evaluation, histology and immunohistochemistry. In intestinal epithelial cells, DADS reduced IP-10 and IL-6 levels, while DAS inhibited IFN-γ-stimulated nitrite production. 3) Bromelain normalises intestinal inflammation-induced hypermotility and exerts chemopreventive actions in the AOM model of colon carcinogenesis. In Caco-2 cells, bromelain stimulated apoptotic processes via blockade of MAP kinase and (PI3K)/Akt signalling. 4). Boeravinone G exerts potent antioxidant and genoprotective actions in Caco-2 cells. The genoprotective effect of boeravinone G was associated to up-regulation of pERK1 and NF-kB expression.
Conclusions. The plant ingredients CBG, DAS, DADS, bromelain and boeravinone G exerts promising intestinal antiinflammatory and antitumoural actions. In view of their safety records, these plant-derived compounds might be worthy of consideration in future clinical trials for the evaluation of new therapeutics in IBD and CRC prevention/treatmen
PALMITOYLETHANOLAMIDE COUNTERACTS IRRITABLE BOWEL SYNDROME (IBS)-LIKE ACCELERATED UPPER GASTROINTESTINAL TRANSIT IN MICE
Orally administered allyl sulfides from garlic ameliorate murine colitis
Inflammatory bowel disease (IBD) is an incurable disease which affects millions of people. Garlic (Allium sativum) preparations have been traditionally employed for the treatment of diseases affecting the digestive tract. Here, we have investigated the effect of diallyl sulfide (DAS) and diallyl disulfide (DADS), two garlic-derived sulfur compounds, on intestinal inflammation in vivo as well as in intestinal isolated cells
Orally-administered allyl sulphides from garlic ameliorate murine colitis induced by dinitrobenzene sulphonic acid
Cannabichromene reduces nitrite production in macrophages and ameliorates experimental colitis in mice
In-Situ Synthesis and Characterization of Chitosan/Hydroxyapatite Nanocomposite Coatings to Improve the Bioactive Properties of Ti6Al4V Substrates
Ti6Al4V alloy is still attracting great interest because of its application as an implant material for hard tissue repair. This research aims to produce and investigate in-situ chitosan/hydroxyapatite (CS/HA) nanocomposite coatings based on different amounts of HA (10, 50 and 60 wt.%) on alkali-treated Ti6Al4V substrate through the sol-gel process to enhance in vitro bioactivity. The influence of different contents of HA on the morphology, contact angle, roughness, adhesion strength, and in vitro bioactivity of the CS/HA coatings was studied. Results confirmed that, with increasing the HA content, the surface morphology of crack-free CS/HA coatings changed for nucleation modification and HA nanocrystals growth, and consequently, the surface roughness of the coatings increased. Furthermore, the bioactivity of the CS/HA nanocomposite coatings enhanced bone-like apatite layer formation on the material surface with increasing HA content. Moreover, CS/HA nanocomposite coatings were biocompatible and, in particular, CS/10 wt.% HA composition significantly promoted human mesenchymal stem cells (hMSCs) proliferation. In particular, these results demonstrate that the treatment strategy used during the bioprocess was able to improve in vitro properties enough to meet the clinical performance. Indeed, it is predicted that the dense and crack-free CS/HA nanocomposite coatings suggest good potential application as dental implants