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Phytochemical, Pharmacological and Therapeutic Profile of Bacopa monnieri
Published in Dilip Ghosh, Pulok K. Mukherjee, Natural Medicines, 2019
Muhammad Shahid, Fazal Subhan, Nazar Ul Islam, Ihsan Ullah, Javaid Alam, Nisar Ahmad, Gowhar Ali
Bacopa monnieri has strong anti-inflammatory activity (Vidya et al. 2011) that is mediated through decreased release of tumour necrosis factor-α and interleukin-6 from mononuclear cells (Viji and Helen 2011), inhibition of activities of cyclooxygenase-2, lipooxygenase-5 and lipooxygenase-15 (Viji and Helen 2008), inhibition of prostaglandin-E2 production (Channa et al. 2006), and stabilisation of lysosomal membranes (Jain et al. 1994) and mast cells (Samiulla et al. 2001). The presence of bacoside A in Bacopa monnieri inhibits bacteria-derived proteases and is responsible for its wound-healing effect (Sharath et al. 2010). Bacopa monnieri reduces airway inflammation and inhibits the activities of leukotriene-C4-synthase, leukotriene-A4-hydrolase and/or cyclooxygenase-2. Moreover, it also downregulates the expression of mRNA of leukotriene-C4-synthase (Soni et al. 2014)]. Additionally, Bacopa monnieri and its active constituent, bacoside A, inhibit the release of inflammatory cytokines (TNF-α and IL-6) from microglial cells and inhibit enzymes (caspase 1 and 3, and matrix metalloproteinase-3) associated with inflammation in the brain (Nemetchek et al. 2017).
Reproductive System and Mammary Gland
Published in Pritam S. Sahota, James A. Popp, Jerry F. Hardisty, Chirukandath Gopinath, Page R. Bouchard, Toxicologic Pathology, 2018
Justin D. Vidal, Charles E. Wood, Karyn Colman, Katharine M. Whitney, Dianne M. Creasy
There are a number of mechanisms through which efferent duct blockage can occur. A 5-hydroxytryptamine agonist has been shown to cause vasoconstriction of the blood vessels overlying the rete testis and efferent ducts, resulting in inhibition of fluid resorption and dilation of the seminiferous tubules, rete testis and efferent ducts (Piner et al. 2002). La et al. (2012) demonstrated a close correlation between efferent duct inflammation and seminiferous tubule dilation and atrophy (which was largely unilateral) due to a leukotriene A4 hydrolase inhibitor. Similarly, Tani et al. (2005) described predominantly unilateral testicular atrophy associated with sperm granulomas in the efferent ducts and initial segment of the epididymis in mice in a 2-year bioassay with 2-methylimidazole. One of the best characterized examples of efferent duct toxicants with testicular atrophy secondary to impaired fluid reabsorption is the fungicide Benomyl and its metabolite, carbendazim (Nakai et al. 1992; Gotoh et al. 1999; Hess and Nakai 2000). Efferent duct dilation and seminiferous tubule dilation occurred in mice administered an estrogen antagonist and a similar effect was reported in the Estrogen Receptor Knockout (ERKO) mouse (Hess et al. 2002; Hess 2014).
Tuberculosis of the Central Nervous System
Published in Peter D O Davies, Stephen B Gordon, Geraint Davies, Clinical Tuberculosis, 2014
How corticosteroids exert their beneficial effect is an important question, for it may suggest novel, more targeted therapies. However, until very recently, the mechanism by which corticosteroids improved survival from TBM remained elusive. Subsets of patients enrolled into the Vietnamese trial were carefully studied to determine whether corticosteroids reduced intra cerebral inflammation, but no effect was found other than a possible reduction in CSF matrix metalloproteinase-9 in those given corticosteroids [16,80,81]. However, a possible explanation for this puzzling lack of anti-inflammatory effect has recently been uncovered. Using the zebra fish model of mycobacterial infection, Tobin and others screened a large number of genetic mutants for resistance or susceptibility to mycobacterial infection [82]. They found a polymorphism in the gene encoding the leukotriene A4 hydrolase enzyme influenced tuberculosis susceptibility in zebra fish and humans by causing either excessive or inadequate TNF-α expression. Zebra fish at both poles of the inflammatory response (minor and major allele homozygotes) were unable to control mycobacterial replication within granulomas, whereas those fish with an intermediate TNF-α response (the heterozygotes) controlled the infection.
New and emerging drugs for the treatment of acne vulgaris in adolescents
Published in Expert Opinion on Pharmacotherapy, 2019
Isabel Cristina Valente Duarte De Sousa
Leukotrienes, which are products of arachidonic acid metabolism, are major players in the development of tissue inflammation [182]. Acebilustat, (formerly CTX-4430) [183], is a new once-daily oral anti-inflammatory drug that inhibits leukotriene A4 hydrolase and thus reduces leukotriene B4 (LTB4) production [184]. LTB4 stimulates sebocyte and follicular keratinocyte differentiation, increasing sebum production and comedogenesis as well as the migration of neutrophils to the sebaceous follicles [82,185,186]. Inhibition of leukotriene A4 hydrolase could thus play a role in acne management through LTB4 reduction. The efficacy and safety of acebilustat for the treatment of moderate to severe facial acne vulgaris in patients 16 years of age and older, was assessed in a phase II multicenter, double-blind, randomized, placebo-controlled study completed in 2016. However, official results are not available [187].
Use of omic technologies in early life gastrointestinal health and disease: from bench to bedside
Published in Expert Review of Proteomics, 2021
Lauren C Beck, Claire L Granger, Andrea C Masi, Christopher J Stewart
While noninvasive urine/stool and blood are convenient samples and ideal targets for biomarkers, they cannot provide specific information relating to the site of disease, which is more likely to provide mechanistic insight. Mottawea et al. (2016) characterized the microbiome and proteome of MLI aspirates, showing that CD patients had increased bacteria producing hydrogen sulfide (H2S) and downregulation in mitochondrial proteins necessary for H2S detoxification [93]. However, the presence of butyrate-producing bacteria was associated with an increase in mitochondrial proteins, suggesting host-microbial cross-talk is altered in CD patients. In a separate study, the same group reported an increase in proteins associated with defense mechanisms from the microbiome and higher levels of L-cysteine desulfidase involved in the production of H2S, further suggesting an altered host-microbiome cross-talk [98]. A proteome profile enriched in anti-bacterial and general inflammatory immune response has also been reported in a separate study utilizing MLI aspirates [105]. This latter study identified a panel of four proteins able to correctly classify >95% pIBD and healthy children. Alteration of two of the panel proteins was also confirmed in stool through enzyme-linked immunosorbent assay (ELISA), demonstrating clear potential for diagnosis using this noninvasive sample. Moreover, a different panel of four proteins (one in common with the other panel) could classify UC severity with 100% accuracy. These panels included leukotriene A4 hydrolase, which added to a panel of 11 other proteins separated CD and UC in patient biopsies [106]. However, in both studies, the proteome levels were analyzed starting from invasive samples (MLI aspirates and biopsies), and analysis using more accessible noninvasive samples would improve prospective diagnostic. Nonetheless, when patients undergo biopsy for pIBD diagnosis, protein panels are valuable to guide disease stratification and identification of the best treatment.