gingerol and Colitis--Ulcerative

The clinical treatment of ulcerative colitis (UC) faces great challenges due to lifetime medication. In this study, Gingerol oil was extracted and purified by the process easily scale-up and cost effective, with productivity 2.72 ± 0.38% (w/w, versus crude drugs). The quality control of gingerol oil was fully established by HPLC fingerprint with 4 common peaks identified as 6-gingerol, 8-gingerol, 6-shogaol and 10-gingerol. The similarities of 6 batches of gingerol oil are within 0.931-0.999. The protective effects of gingerol oil are equivalent to or even stronger than that of 6-gingerol on inflammation and oxidative stress of HT-29 cells induced by lipopolysaccharide and H

Topics: Animals; Colitis; Colitis, Ulcerative; Colon; Dextran Sulfate; Disease Models, Animal; Hydrogen Peroxide; Mice; Mice, Inbred C57BL; Molecular Structure; Rats

The imbalance of Treg/Thl7 cells and inflammatory injury are believed to be involved in the development of ulcerative colitis (UC). Meanwhile, 6-gingerol has been reported to alleviate intestinal inflammatory damage in mice models, but the underlying mechanism remains elusive.. In this study, dextran sulfate sodium (DSS)-induced colitis mice models were established to examine the effects of 6-gingerol on IL-17 and IL-10 secretion, and the activation of NF-κB signaling was evaluated using enzyme-linked immunosorbent assay (ELISA), Western blotting, and immunohistochemistry.. 6-gingerol could significantly reduce the weight loss caused by DSS in mice models (P<0.05), which is similar to the therapeutic drug, mesalazine. Immunohistochemistry showed that 6-gingerol can repair the damaged glandular structure gradually caused by DSS, significantly decrease the IL-17 level, and increase IL-10 level in bowel tissue. ELISA revealed that 6-gingerol could significantly decrease the IL17 level and increase IL-10 level in both serum and bowel tissue, and the differences were all statistically significant (P<0.05). In addition, 6-gingerol could suppress the phosphorylation level of IκBα and p65, which was up-regulated by DSS. Further analysis with immunohistochemistry indicated p-p65 staining was mainly in the nucleus with some in the cytoplasm after DSS treatment, and the treatment with 6-gingerol could significantly weaken the density of p-p65 both in the cytoplasm and nucleus.. Our study suggests that 6-gingerol may alleviate inflammatory injury in UC mice by regulating NF-κB signaling pathway.

Topics: Animals; Catechols; Colitis, Ulcerative; Dextran Sulfate; Fatty Alcohols; Mice; NF-kappa B; Signal Transduction

The persistent inflammation and oxidative stress at the local site in ulcerative colitis reportedly extend to the testes via systemic circulation resulting in testicular dysfunction. The influence of 6-gingerol (6G), a phenolic compound isolated from Zingiber officinale, on colitis-mediated testicular dysfunction in mice was investigated in this study. Chronic ulcerative colitis was induced in mice using 2.5% dextran sulfate sodium (DSS) in drinking water for three cycles. Each cycle consisted of 7 consecutive days of exposure to DSS-treated water followed by 14 consecutive days of normal drinking water. 6G (100 mg/kg) or sulfasalazine (SZ; 100 mg/kg) was orally administered alone or in combination with DSS-treated water during the three cycles. SZ served as standard reference drug for colitis in this study. 6G significantly prevented the incidence of rectal bleeding, decrease in the body weight gain and colon mass index in DSS-exposed mice. 6G significantly prevented colitis-mediated decreases in luteinizing hormone, follicle-stimulating hormone and testosterone and decreases oxidative stress indices, pro-inflammatory cytokines and caspase-3 activity with concomitant augmentation of antioxidant enzymes activities, sperm characteristics, marker enzymes of testicular function and histoarchitecture in DSS-exposed mice. 6G exerted protective influence against ulcerative colitis-induced testicular damage via mechanisms involving its antioxidant and anti-inflammatory properties.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Caspase 3; Catechols; Colitis, Ulcerative; Colon; Dextran Sulfate; Disease Models, Animal; Fatty Alcohols; Follicle Stimulating Hormone; Inflammation Mediators; Luteinizing Hormone; Male; Mice, Inbred BALB C; Oxidative Stress; Spermatozoa; Testicular Diseases; Testis; Testosterone

Ulcerative colitis (UC) is a relapsing and remitting inflammatory disease of the colon, with an increasing incidence worldwide. 6-Gingerol (6G) is a bioactive constituent of Zingiber officinale, which has been reported to possess various biological activities. This study was designed to evaluate the role of 6G in chronic UC. Chronic UC was induced in mice by three cycles of 2.5% dextran sulfate sodium (DSS) in drinking water. Each cycle consisted of 7 days of 2.5% DSS followed by 14 days of normal drinking water. 6G (100 mg/kg) and a reference anti-colitis drug sulfasalazine (SZ) (100 mg/kg) were orally administered daily to the mice throughout exposure to three cycles of 2.5% DSS. Administration of 6G and SZ significantly prevented disease activity index and aberrant crypt foci formation in DSS-treated mice. Furthermore, 6G and SZ suppresses immunoexpression of tumor necrosis factor alpha, interleukin-1β, inducible nitric oxide synthase, Regulated on activation, normal T cell expressed and secreted (RANTES), and Monocyte chemoattractant protein-1 (MCP-1) in the DSS-treated mice. 6G effectively protected against colonic oxidative damage by augmenting the antioxidant status with marked decrease in lipid peroxidation levels in DSS-treated mice. Moreover, 6G significantly inhibited nuclear factor kappa B (P65), p38, cyclooxygenase-2, and β-catenin whereas it enhanced IL-10 and adenomatous polyposis coli expression in DSS-treated mice. In conclusion, 6G prevented DSS-induced chronic UC via anti-inflammatory and antioxidative mechanisms and preservation of the Wnt/β-catenin signaling pathway.

Topics: Animals; beta Catenin; Catechols; Chemokines; Chronic Disease; Colitis, Ulcerative; Cytokines; Dextran Sulfate; Fatty Alcohols; Gastrointestinal Agents; Genes, APC; Lipid Peroxidation; Male; Mice, Inbred BALB C; NF-kappa B; Nitric Oxide Synthase Type II; Oxidative Stress; Phenotype; Proto-Oncogene Proteins c-akt; Sulfasalazine; Wnt Signaling Pathway; Zingiber officinale

The deterioration of male reproductive health may represent an outcome of an active disease and environmental factors. The present study investigated the modulatory role of [6]-gingerol in spermatotoxicity resulting from colitis and benzo[a]pyrene (B[a]P), an environmental and food-borne pollutant.. Group I (control) mice received corn oil alone, while group II ([6]-gingerol alone) mice orally received [6]-gingerol alone at 100 mg/kg body weight. Group III [benzo[a]pyrene+dextran sulfate sodium (BDS) alone] mice were orally exposed to B[a]P at 125 mg/kg for 7 days followed by three cycles of 4% dextran sulfate sodium (DSS) in drinking water. A cycle consisted of seven consecutive days of exposure to DSS-treated water followed by 14 consecutive days of normal drinking water. Group IV (BDS+[6]-gingerol) mice were orally treated daily with 100 mg/kg of [6]-gingerol during exposure to B[a]P and DSS in the same manner as those of group III.. [6]-Gingerol significantly abrogated BDS-mediated increase in disease activity index and restored the colon wet weight, colon length and colon mass index to near normal when compared to BDS alone group. Moreover, [6]-gingerol significantly prevented BDS-induced decreases in the daily sperm production (DSP), testicular sperm number (TSN), epididymal sperm number, sperm progressive motility and sperm membrane integrity when compared with the control. [6]-Gingerol markedly increased the sperm antioxidant enzymes activities and decreased the sperm head, mid-piece and tail abnormalities as well as suppressed oxidative stress and inflammatory biomarkers in BDS-exposed mice.. [6]-Gingerol protected against spermatotoxicity in experimental model of interaction of colitis with environmental pollutant B[a]P.

Topics: Animals; Benzo(a)pyrene; Catechols; Colitis, Ulcerative; Dextran Sulfate; Disease Models, Animal; Fatty Alcohols; Male; Mice; Mice, Inbred BALB C; Oxidative Stress; Sperm Motility; Spermatozoa

Ulcerative colitis is one of the most common types of inflammatory bowel disease and is multifactorial and relapsing. 6-Gingerol, a component of gingerols extracted from ginger (Zingiber officinale), has been reported to improve ulcerative colitis. The present study aims to investigate the therapeutic efficacy of two analogous forms of 6-gingerol, 8-gingerol, and 10-gingerol, on ulcerative colitis. Colitis was induced in rats through consumption of 5% (w/v) dextran sulfate sodium drinking water for 7 consecutive days. 6-Gingerol, 8-gingerol, and 10-gingerol were then given intraperitoneally at doses of 30 mg kg

Topics: Animals; Catechols; Colitis, Ulcerative; Colon; Dextran Sulfate; Disease Models, Animal; Fatty Alcohols; Interleukin-1beta; Intestinal Mucosa; Male; Malondialdehyde; Oxidative Stress; Peroxidase; Rats; Rats, Sprague-Dawley; Superoxide Dismutase; Tumor Necrosis Factor-alpha

There is a clinical need for new, more effective treatments for chronic and debilitating inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis. In this study, we characterized a specific population of nanoparticles derived from edible ginger (GDNPs 2) and demonstrated their efficient colon targeting following oral administration. GDNPs 2 had an average size of ∼230 nm and exhibited a negative zeta potential. These nanoparticles contained high levels of lipids, a few proteins, ∼125 microRNAs (miRNAs), and large amounts of ginger bioactive constituents (6-gingerol and 6-shogaol). We also demonstrated that GDNPs 2 were mainly taken up by intestinal epithelial cells (IECs) and macrophages, and were nontoxic. Using different mouse colitis models, we showed that GDNPs 2 reduced acute colitis, enhanced intestinal repair, and prevented chronic colitis and colitis-associated cancer (CAC). 2D-DIGE/MS analyses further identified molecular target candidates of GDNPs 2 involved in these mouse models. Oral administration of GDNPs 2 increased the survival and proliferation of IECs and reduced the pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β), and increased the anti-inflammatory cytokines (IL-10 and IL-22) in colitis models, suggesting that GDNPs 2 has the potential to attenuate damaging factors while promoting the healing effect. In conclusion, GDNPs 2, nanoparticles derived from edible ginger, represent a novel, natural delivery mechanism for improving IBD prevention and treatment with an added benefit of overcoming limitations such as potential toxicity and limited production scale that are common with synthetic nanoparticles.

Topics: Animals; Antineoplastic Agents, Phytogenic; Catechols; Cell Line; Cell Line, Tumor; Colitis, Ulcerative; Colonic Neoplasms; Fatty Alcohols; Female; Humans; Inflammatory Bowel Diseases; Mice; Mice, Inbred C57BL; Nanoparticles; Phytotherapy; Zingiber officinale

Gingerols are phenolic compounds in ginger (Zingiber officinale), which have been reported to exhibit antiinflammatory, antioxidant, and anticancer properties. The present study aimed at evaluating the possible pharmacologic activity of 6-gingerol in a mouse model of dextran sulphate sodium (DSS)-induced ulcerative colitis. Adult male mice were exposed to DSS in drinking water alone or co-treated with 6-gingerol orally at 50, 100, and 200 mg/kg for 7 days. Disease activity index, inflammatory mediators, oxidative stress indices, and histopathological examination of the colons were evaluated to monitor treatment-related effects of 6-gingerol in DSS-treated mice. Administration of 6-gingerol significantly reversed the DSS-mediated reduction in body weight, diarrhea, rectal bleeding, and colon shrinkage to near normal. Moreover, 6-gingerol significantly suppressed the circulating concentrations of interleukin-1β and tumor necrosis factor alpha and restored the colonic nitric oxide concentration and myeloperoxidase activity to normal in DSS-treated mice. 6-Gingerol efficiently prevented colonic oxidative damage by increasing the activities of antioxidant enzymes and glutathione content, decreasing the hydrogen peroxide and malondialdehyde levels, and ameliorated the colonic atrophy in DSS-treated mice. 6-Gingerol suppressed the induction of ulcerative colitis in mice via antioxidant and antiinflammatory activities, and may thus represent a potential anticolitis drug candidate.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Catechols; Colitis, Ulcerative; Colon; Dextran Sulfate; Disease Models, Animal; Fatty Alcohols; Glutathione; Interleukin-1beta; Male; Malondialdehyde; Mice; Mice, Inbred BALB C; Nitric Oxide; Oxidative Stress; Tumor Necrosis Factor-alpha