ROLE OF NEROLIDOL, AN ALIPHATIC SESQUITERPENE, IN COLON INFLAMMATION

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 ERK1/2) 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

Evidence for the involvement of the monoaminergic system in the antidepressant-like activity of methanolic extract of Bacopa monnieri in albino mice

Background: Depression is a common illness worldwide, with an estimated 121 million people affected. The efficacy of currently available drugs for treating depression often lack consistency and many of them exert undesirable side effects. This emphasises on the need for newer drugs for the treatment of major depression.Methods: The present study evaluated the antidepressant-like activity of methanolic extract of Bacopa monnieri in mouse forced swimming test (FST) and tail suspension test (TST), which are predictive models of antidepressant activity. An attempt was also made to understand the involvement of the monoaminergic system and the opioid system in Bacopas’ antidepressant activity. Albino mice were treated with vehicle, fluoxetine (20 mg/kg), or Bacopa monnieri (20, 40, 80, and 120 mg/kg) orally and evaluated in FST and TST. The actophotometer performance was also examined after different treatments. For understanding the mechanisms, different receptor antagonists were used.Results: Bacopa monnieri produced a significant reduction in the duration of immobility, with better activity at 80 mg/kg dose. Furthermore, the antidepressant-like action produced by Bacopa monnieri was abolished by the pre-treatment of mice with p-chlorophenylalanine (100 mg/kg, i.p., a serotonin synthesis inhibitor), pindolol (10 mg/kg, i.p., a β-adrenoceptor blocker/5HT1A/1B receptor antagonist, ketanserin (5 mg/kg, i.p., a 5HT2A/2B receptor antagonist), prazosin (1 mg/kg, i.p., an α1-adrenoceptor antagonist), and yohimbine (1 mg/kg, i.p., an α2-adrenoceptor antagonist), but not with ondansetron (1 mg/kg, i.p., a 5HT3 receptor antagonist) and naloxone (1 mg/kg, i.p., an opioid receptor antagonist).Conclusions: These findings suggest that the antidepressant-like effect produced by Bacopa monnieri may be mediated through an interaction with the serotonergic and noradrenergic nervous system. The antidepressant doses of Bacopa monnieri had no effect on the locomotor activity of mice

Assessment of the Apparent Contact Dimension and Co-Variates in Untreated and Orthodontically Treated Dentitions

This study assessed the existence of the Apparent Contact Dimension, a determinant of dental esthetics, using casts of orthodontically treated (n=40) and non-treated (n=27) subjects deemed to possess excellent occlusion. Co-variates studied included tooth size, tooth shape, tip and torque. The average ACD proportions in this study, relative to the height of an ipsilateral central incisor, were found to be 49, 38 and 27 % between the central incisors, central and lateral incisor, and the lateral incisor and canine, respectively. The ACD exhibited a positive correlation (p<0.05) with the height of the clinical crown and a negative correlation (p<0.05) with W/H ratios of the corresponding teeth. No statistically significant correlations were evident between the ACD with the shape of the clinical crown, the tip, and torque. This study is the first to validate the existence and proportions of the ACD