gingerol and Colitis

A nanolipidcarrier (NLC) loaded homogalacturonan enriched pectin (citrus modified pectin, MCP4) hydrogel was designed as a novel colon inflammation site-specific oral delivery system for 6-gingerol (6G) (6G-NLC/MCP4 hydrogel) administration, and its colitis alleviation effect were investigated. 6G-NLC/MCP4 exhibited typical "cage-like" ultrastructure with 6G-NLC embedded in the hydrogel matrix as observed by cryoscanning electron microscope. And due to the homogalacturonan (HG) domain in MCP4 specifically combined with Galectin-3, which is overexpressed in the inflammatory region, the 6G-NLC/MCP4 hydrogel targeted to severe inflammatory region. Meanwhile, the prolonged-release characteristics of 6G-NLC provided sustained release of 6G in severe inflammatory regions. The matrix of hydrogel MCP4 and 6G achieved synergistic alleviation effects for colitis through NF-κB/NLRP3 axis. Specifically, 6G mainly regulated the NF-κB inflammatory pathway and inhibited the activity of NLRP3 protein, while MCP4 regulated the expression of Galectin-3 and peripheral clock gene Rev-Erbα/β to prevent the activation of inflammasome NLRP3.

Topics: Colitis; Galectin 3; Humans; Hydrogels; Inflammasomes; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; Pectins

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 emerging concept that "the maximized therapeutic efficacy of encapsulates would be achieved by inducing appropriate absorption site and pharmacological signal pathways through smart intervention of targeted delivery systems" is quite intriguing in the field of drug delivery. Herein, we developed 6-gingerol (6G) loaded delivery system in the form of nanostructured lipid carriers (6G-NLC) or NLC imbedded microcapsule (6G-MC). The modulation effects of the constructed formulations on the digestive fate and functioning mechanisms of 6-gingerol on colitis were investigated. The small intestine dominant absorption of 6G-NLC differed significantly with the colorectal dominated accumulation of 6G-MC in terms of the site-specific release behavior, biodistribution and transit time. Moreover, 6G-NLC alleviated DSS-induced colitis primarily through interfering with the antioxidant/anti-inflammatory pathways and Firmicutes/Bacteroidetes ratio. Whereas, better therapeutic efficacy was achieved in 6G-MC via sustained release at site close to the colonic lesion, and triggering multiple mitigation mechanisms including enhancing the mucus barrier and immune homeostasis, maintaining the structure and diversity of gut microbiota and promoting the intestinal barrier function. This work confirmed that rational design of oral delivery system can flexibly interfere with the pharmacological function pathways of encapsulated cargos, guided by which the maximized and precise therapeutic efficacy could be achieved.

Topics: Anti-Inflammatory Agents; Antioxidants; Capsules; Catechols; Colitis; Delayed-Action Preparations; Drug Carriers; Excipients; Fatty Alcohols; Humans; Nanostructures; Tissue Distribution

6-gingerol has been reported to have anti-inflammatory effects in different experimental settings. The present study aimed at evaluating the effect of 6-gingerol on dextran sodium sulfate (DSS)-induced barrier impairment and inflammation in vitro and in vivo.. a differentiated Caco-2 monolayer was exposed to DSS and treated with different concentrations of 6-gingerol (0, 1, 5, 10, 50, and 100 μM). Changes in intestinal barrier function were determined using transepithelial electrical resistance (TEER). The anti-inflammatory activity of 6-gingerol was examined as changes in the expression of proinflammatory cytokine using quantitative real-time PCR. Western blotting was employed to determine the activation of adenosine monophosphate-activated protein kinase (AMPK). Mice with DSS-induced colitis were given different oral dosages of 6-gingerol daily for 14 days. Body weight and colon inflammation were evaluated, and level of proinflammatory cytokines in colon tissues was measured.. 6-gingerol treatment was shown to restore impaired intestinal barrier function and to suppress proinflammatory responses in DSS-treated Caco-2 monolayers. We found that AMPK was activated on 6-gingerol treatment in vitro. In animal studies, 6-gingerol significantly ameliorated DSS-induced colitis by restoration of body weight loss, reduction in intestinal bleeding, and prevention of colon length shortening. In addition, 6-gingerol suppressed DSS-elevated production of proinflammatory cytokines (IL-1β, TNFα, and IL-12).. our findings highlight the protective effects of 6-gingerol against DSS-induced colitis. We concluded that 6-gingerol exerts anti-inflammatory effects through AMPK activation. It is suggested that 6-gingerol has a promising role in treatment of IBD.

Topics: AMP-Activated Protein Kinases; Animals; Caco-2 Cells; Catechols; Cell Line, Tumor; Cell Survival; Colitis; Colon; Dextran Sulfate; Disease Models, Animal; Fatty Alcohols; Female; Humans; Inflammation; Interleukin-12; Interleukin-1beta; Mice; Mice, Inbred C57BL; Phosphorylation; Tumor Necrosis Factor-alpha