Colitis Is Effectively Ameliorated by (±)-8-Acetonyl-dihydrocoptisine via the XBP1-NF-κB Pathway
| العنوان: | Colitis Is Effectively Ameliorated by (±)-8-Acetonyl-dihydrocoptisine via the XBP1-NF-κB Pathway |
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| المؤلفون: | Song Huachen, Zhi-Hui Zhang, Wen-Jie Wang, Hai-Jing Zhang, GuangMing Song, An-Jun Deng, Lian-Qiu Wu, Tang Xiaonan, Hai-Lin Qin |
| المصدر: | Frontiers in Pharmacology, Vol 8 (2017) Frontiers in Pharmacology |
| بيانات النشر: | Frontiers Media SA, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, XBP1, X-box binding protein 1, Pharmacology, NF-κB, Proinflammatory cytokine, 03 medical and health sciences, chemistry.chemical_compound, Downregulation and upregulation, medicine, Pharmacology (medical), Colitis, Original Research, ulcerative colitis, biology, business.industry, lcsh:RM1-950, coptisine, medicine.disease, Ulcerative colitis, cytokines, lcsh:Therapeutics. Pharmacology, 030104 developmental biology, chemistry, Myeloperoxidase, biology.protein, Cancer research, Tumor necrosis factor alpha, business |
| الوصف: | Ulcerative colitis (UC) is a recurrent, chronic intestinal disease. Available treatments for UC are poor effective and/or cause severe adverse events. X-box binding protein 1 (XBP1) and nuclear factor-κB (NF-κB) have been reported to play important roles in UC. Specifically, deletion or downregulation of XBP1 leads to spontaneous enteritis and results in imbalanced secretion of NF-κB and other proinflammatory cytokines. (±)-8-acetonyl-dihydrocoptisine, i.e., (±)-8-ADC, is a monomer semi-synthesized from coptisine. In vitro, (±)-8-ADC activated the transcriptional activity of XBP1, inhibited expression of NF-κB, and reduced production of proinflammatory cytokines, such as tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β), in lipopolysaccharide-stimulated IEC6 cells. Therefore, silencing XBP1 would reduce the inhibition effect of (±)-8-ADC on NF-κB expression and the cytokines secretion in vitro. In a dextran sulfate sodium-induced colitis mouse model, oral administration of (±)-8-ADC ameliorated weight loss and colon contracture, and decreased the average disease activity index score and pathological damage. Simultaneously, (±)-8-ADC also increased XBP1 expression, and decreased NF-κB expression and secretion of myeloperoxidase, TNF-α, IL-6 and IL-1β in the colon. Therefore, (±)-8-ADC may ameliorate UC via the XBP1-NF-κB pathway and should be considered as a therapeutic candidate for UC. |
| تدمد: | 1663-9812 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::efb980b4a902d98a113a62eec2c1ea85Test https://doi.org/10.3389/fphar.2017.00619Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....efb980b4a902d98a113a62eec2c1ea85 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 16639812 |
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