Role Of Nerolidol, An Aliphatic Sesquiterpene, In Colon Inflammation

الموضوعات

طب

الملخص

Inflammatory bowel diseases, which comprise Crohn’s disease (CD) and ulcerative colitis (UC), are chronic and progressive immune-mediated inflammatory conditions of the gastrointestinal (GI) tract. Both genetic and environmental factors influence this condition. Conventional therapy to suppress aberrant immune responses seen in IBD with corticosteroid or with biological agents has a high relapse rate that limits their use. Therefore, approximately 40% of IBD patients switch to alternative therapies that include dietary supplements rich in phytochemicals. Nerolidol (NED) is a naturally occurring sesquiterpene alcohol present in various plants and has potent anti-inflammatory properties. Therefore, in the current study, the role of NED in preclinical models of colon inflammation were investigated. Initial experiments were carried out to investigate the anti-inflammatory properties of NED in lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophage cells. NED significantly decreased proinflammatory cytokine such as TNF-α, IL-1β, and IL-6 both at protein and mRNA level in LPS-stimulated RAW macrophages. In addition, NED also significantly decreased expression of proinflammatory mediators such as COX-2 and iNOS. Based on these results NED was further investigated as a putative anti-inflammatory compound in in vivo and in vitro models of colon inflammation. C57BL/6J male black mice administered with 3% dextran sodium sulfate (DSS) used as in vivo model of colon inflammation. DSS-induced colitis groups received either vehicle or NED (50, 100, and 150 mg/kg body weight/per day) by oral gavage. NED significantly decreased the DAI, colon length and preserved microscopic architecture of the colon to near control level. NED significantly decreased tissue MPO concentrations, CXCL-2, CCL2 mRNA expression and proinflammatory cytokines (IL-1β, IL-6, and TNF-α) and mediators (COX-2 and iNOS) level both at the protein and at mRNA level in DSS administered mice. NED promoted Nrf-2 nuclear translocation and increased antioxidant enzyme (SOD and CAT) activity, HO-1 and SOD-3 mRNA levels. In vitro model of colon inflammation was established by challenging HT-29 cells with TNF-α (1ng/ml concentration) and treated with NED (25μM and 50μM). NED treatment significantly decreased proinflammatory chemokines (CXCL-1, IL-8, CCL2, and COX-2) mRNA levels. NED significantly decreased phosphorylation of MAPK (p38, JNK, and ERK 1/2 ) and NF-κB in the DSS-induced colitis and in LPS-stimulated RAW macrophages. Intestinal epithelial barrier dysfunction leading to enhanced intestine permeability is associated with IBD pathogenesis. Therefore, the effect of NED on intestine tight junction integrity using DSS-induced colitis and in LPS challenged Caco-2 monolayers was investigated. NED significantly decreased FITC-dextran permeability in DSS group and decreased transepithelial electrical resistance (TEER) in LPS-treated Caco-2 monolayers. NED significantly increased expression of tight junction proteins such as claudin-1, -3, -7, and occludin in in vitro and in vivo models. Collectively, results from the present study indicates that NED supplementation attenuates colon inflammation through its potent antioxidant and anti-inflammatory activity and enhances intestine tight junction integrity.

روابط وملفات

التعريف والنوع

رقم الوثيقة

0a1874ab-5f45-40e9-92c9-82b205d09034

رقم العقد

0

نوع الوسائط

Crawler

نوع المحتوى

الرسائل العلمية

صيغة المصدر

رسائل دكتوراة

نوع الملف

pdf text

أسماء الملفات

2325626_2.pdf

بيانات النشر

ألقاب المؤلفين

[{"name_ar":"Sandeep B Subramanya","title_ar":"اشراف","title_en":"Supervision"},{"name_ar":"Vishnu Raj","title_ar":"اعداد","title_en":"Preparation"}]

اللغة

English

المصدر والدورية

اسم المصدر

Role Of Nerolidol, An Aliphatic Sesquiterpene, In Colon Inflammation

المحتوى والصفحات

عدد الصفحات

0

إشراف وإعداد

الإشراف

Sandeep B Subramanya

الإعداد

Vishnu Raj

الاقتباسات الببليوغرافية