crocin and Colitis--Ulcerative

The immune system when acts against selfmolecules results in an imbalance in immunologic tolerance leading to the development of several autoimmune diseases (ADs) such as rheumatoid arthritis, asthma, ulcerative colitis, type 1 diabetes, and multiple sclerosis. Improved recognition of the mechanisms of ADs has led to the advancement of the management of these diseases. The principal mediators of ADs are inflammatory molecules. The herbal medicines due to their antioxidant and antiinflammatory properties have an important role in the management of ADs. Crocin is the principal chemical component extracted from saffron, which is a medicinal plant. This review focuses on the therapeutic effects of Crocin in various ADs.

Topics: Anti-Inflammatory Agents; Antioxidants; Arthritis, Rheumatoid; Autoimmune Diseases; Carotenoids; Colitis, Ulcerative; Crocus; Diabetes Mellitus, Type 1; Humans; Multiple Sclerosis; Plant Extracts

Ulcerative colitis (UC) is an inflammatory bowel disease with characteristic inflammation to mucosal cells in rectum and colon leading to lesions in mucosa and submucosa. Moreover, crocin is a carotenoid compound among active constituents of saffron with many pharmacological effects as antioxidant, anti-inflammatory and anticancer activities. Therefore, we aimed to investigate therapeutic effects of crocin against UC through affecting the inflammatory and apoptotic pathways. For induction of UC in rats, intracolonic 2 ml of 4% acetic acid was used. After induction of UC, part of rats was treated with 20 mg/kg crocin. cAMP was measured using ELISA. Moreover, we measured gene and protein expression of B-cell lymphoma 2 (BCL2), BCL2-associated X (BAX), caspase-3/8/9, NF-κB, tumor necrosis factor (TNF)-α and IL-1β/4/6/10. Colon sections were stained with hematoxylin-eosin and Alcian blue or immune-stained with anti-TNF-α antibodies. Microscopic images of colon sections in UC group revealed destruction of intestinal glands associated with infiltration of inflammatory cell and severe hemorrhage. While images stained with Alcian blue showed damaged and almost absent intestinal glands. Crocin treatment ameliorated morphological changes. Finally, crocin significantly reduced expression levels of BAX, caspase-3/8/9, NF-κB, TNF-α, IL-1β and IL-6, associated with increased levels of cAMP and expression of BCL2, IL-4 and IL-10. In conclusion, protective of action of crocin in UC is proved by restoration of normal weight and length of colon as well as improvement of morphological structure of colon cells. The mechanism of action of crocin in UC is indicated by activation of anti-apoptotic and anti-inflammatory effects.

Topics: Alcian Blue; Animals; Anti-Inflammatory Agents; Apoptosis; bcl-2-Associated X Protein; Carotenoids; Caspase 3; Colitis, Ulcerative; Colon; Disease Models, Animal; Inflammation; NF-kappa B; Rats; Tumor Necrosis Factor Inhibitors; Tumor Necrosis Factor-alpha

Ulcerative colitis is a chronic inflammatory bowel disease with high incidence and prevalence worldwide. To investigate the therapeutic potency of crocin, as a pharmacologically active component of saffron, in dextran sodium sulfate (DSS)-induced colitis mice model. Experimental colitis was induced by 7-day administration of DSS dissolved in water at a concentration of 1.5% (w/v). The animals were randomly divided into four groups (n¼6 for each group). (1) Control group received regular drinking water for four weeks, (2) the second group of mice received regular drinking water for three weeks and then received DSS for one week, (3) and (4) the other two groups received 50-ppm or 200-ppm crocin for three weeks, respectively, and then treated with DSS for one week. Our results showed that Crocin attenuates colitis disease activity index including body weight loss, diarrhea, rectal bleeding, and colon shortening in crocin pre-tread mice. Comparison of histology of colon tissues between groups showed that crocin significantly decreases colon histopathological score, at least partially, by eliciting anti-inflammatory responses in DSS-induced colitis mice. These results clearly showed that crocin is a novel therapeutic agent with low toxicity as well as great clinical significance in treatment of colitis.

Topics: Animals; Carotenoids; Colitis, Ulcerative; Colon; Dextran Sulfate; Disease Models, Animal; Male; Mice; Mice, Inbred C57BL

Ulcerative colitis (UC) is usually a mildly active disease; however, it can be associated with serious systemic complications. The current study was undertaken to evaluate the anti-ulcerogenic and coloprotective properties of crocin; the major biologically active ingredient of saffron against experimentally-induced UC, by intracolonic instillation of AA (AA). Rats received either felodipine (3 mg/kg) or crocin (20 mg/kg) orally for 8 successive days as protective and curative therapies. Either as a protective or as a curative remedy, crocin significantly reversed AA-induced colonic damage. Intracolonic AA-induced a significant functional, biochemical and inflammatory colon injury. On the other hand, crocin significantly attenuated AA-induced oxidative, inflammatory and apoptotic activity. Crocin significantly enhanced colon anti-oxidant defenses and reduced colon tumor necrosis factor-α (TNF-α) and Ca+2 contents with down-regulation of the inflammatory response and oxidative load. The anti-ulcerogenic effect of crocin appears to be Ca+2 dependent. Most importantly, crocin enhanced colon Nuclear Factor, Erythroid-Derived 2 like Protein 2 (Nrf2) content and Heme Oxygenase-1 (HO-1) activity and attenuated caspase-3 activity. In conclusion; crocin demonstrated anti-ulcerogenic and coloprotective effect mediated primarily by its antioxidant, anti-inflammatory and anti-apoptotic properties. The therapeutic impact is mediated primarily via enhancement of colon Nrf2 content by 211% in protective protocol and by 350% in curative and HO-1 signaling by 49% in protective protocol and, 288% in the curative protocol. Enhancement of Nrf2 and HO-1 signaling and down-regulation of caspase-3 activity are believed to underly the observed therapeutic effect.

Topics: Animals; Carotenoids; Colitis, Ulcerative; Drug Delivery Systems; Free Radical Scavengers; Heme Oxygenase (Decyclizing); Male; NF-E2-Related Factor 2; Rats; Rats, Sprague-Dawley; Signal Transduction