Displaying publications 21 - 40 of 64 in total

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  1. Mohamad NV, Ima-Nirwana S, Chin KY
    PMID: 32496996 DOI: 10.2174/1871530320666200604160614
    Osteoporosis is one of the major health issues associated with menopause-related estrogen deficiency. Various reports suggest that the hormonal changes related to menopausal transition may lead to the derangement of redox homeostasis and ultimately oxidative stress. Estrogen deficiency and oxidative stress may enhance the expression of genes involved in inflammation. All these factors may contribute, in synergy, to the development of postmenopausal osteoporosis. Previous studies suggest that estrogen may act as an antioxidant to protect the bone against oxidative stress, and as an antiinflammatory agent in suppressing pro-inflammatory and pro-osteoclastic cytokines. Thus, the focus of the current review is to examine the relationship between estrogen deficiency, oxidative stress and inflammation, and the impacts of these phenomena on skeletal health in postmenopausal women.
    Matched MeSH terms: Inflammation Mediators/metabolism*
  2. Yong DOC, Saker SR, Chellappan DK, Madheswaran T, Panneerselvam J, Choudhury H, et al.
    PMID: 32359343 DOI: 10.2174/1871530320666200503053846
    The application of medicinal plants has captured the interest of researchers in recent times due to their potent therapeutic properties and a better safety profile. The prominent role of herbal products in treating and preventing multiple diseases dates back to ancient history and most of the modern drugs today originated from their significant sources owing to their ability to control multiple targets via different signalling pathways. Among them, flavonoids consist of a large group of polyphenols, which are well known for their various therapeutic benefits. Rutin is considered one of the attractive phytochemicals and important flavonoids in the pharmaceutical industry due to its diverse pharmacological activities via various underlying molecular mechanisms. It is usually prescribed for various disease conditions such as varicosities, haemorrhoids and internal haemorrhage. In this review, we have discussed and highlighted the different molecular mechanisms attributed to the various pharmacological activities of rutin, such as antioxidant, anti-inflammatory, anticancer, anti-allergic and antidiabetic. This review will be beneficial to herbal, biological and molecular scientists in understanding the pharmacological relevance of rutin at the molecular level.
    Matched MeSH terms: Inflammation Mediators/metabolism
  3. Mohamad Isa II, Abu Bakar S, Md Tohid SF, Mat Jais AM
    J Ethnopharmacol, 2016 Dec 24;194:469-474.
    PMID: 27732902 DOI: 10.1016/j.jep.2016.10.033
    ETHNOPHARMACOLOGICAL RELEVANCE: Haruan, Channa striatus, is a freshwater fish which has been well-known locally to accelerate wound healing during post-operative and post-partum periods. The fish extract also has potent anti-inflammatory and analgesic properties.

    AIM OF THE STUDY: To assess topical anti-inflammatory effect of Haruan cream on 12-0-tetradecanoylphorbol-13-acetate (TPA)-induced chronic-like dermatitis in mice.

    MATERIALS AND METHODS: Male ICR mice were randomized into six groups of five mice each: acetone (vehicle), TPA alone (negative control), three Haruan treatment groups (Haruan 1%, Haruan 5% and Haruan 10%) and hydrocortisone 1% (positive control). Briefly, both surfaces of mouse ears were applied with TPA (2.5μg/20μl acetone) for five times on alternate days and with Haruan or hydrocortisone 1% cream for the last three days. Mouse ear thickness was measured 24h after final treatment with the cream and the ears were harvested for further histological analysis and gene expression studies of TNF-α by real-time reverse transcriptase-polymerase chain reaction (RT-qPCR).

    RESULTS: Topical application of Haruan cream had reduced the mouse ear thickness 18.1-28%) with comparable effect to the positive control. In addition, histopathological comparison had shown evident reduction in various parameters of cutaneous inflammation including dermal oedema, inflammatory cells infiltration and proliferation of epidermal keratinocytes. Furthermore, TPA application had resulted in the up-regulation of TNF-α gene expression by 353-fold, which was subsequently down-regulated by the Haruan cream (34- to 112-fold).

    CONCLUSION: Haruan is an effective topical anti-inflammatory agent in this mouse model of chronic-like dermatitis, thus suggesting its potential as a non-steroidal treatment option for chronic inflammatory dermatoses.

    Matched MeSH terms: Inflammation Mediators/metabolism
  4. Tan HT, Hagner S, Ruchti F, Radzikowska U, Tan G, Altunbulakli C, et al.
    Allergy, 2019 02;74(2):294-307.
    PMID: 30267575 DOI: 10.1111/all.13619
    BACKGROUND: Asthma is a chronic respiratory disease with marked clinical and pathophysiological heterogeneity. Specific pathways are thought to be involved in the pathomechanisms of different inflammatory phenotypes of asthma; however, direct in vivo comparison has not been performed.

    METHODS: We developed mouse models representing three different phenotypes of allergic airway inflammation-eosinophilic, mixed, and neutrophilic asthma via different methods of house dust mite sensitization and challenge. Transcriptomic analysis of the lungs, followed by the RT-PCR, western blot, and confocal microscopy, was performed. Primary human bronchial epithelial cells cultured in air-liquid interface were used to study the mechanisms revealed in the in vivo models.

    RESULTS: By whole-genome transcriptome profiling of the lung, we found that airway tight junction (TJ), mucin, and inflammasome-related genes are differentially expressed in these distinct phenotypes. Further analysis of proteins from these families revealed that Zo-1 and Cldn18 were downregulated in all phenotypes, while increased Cldn4 expression was characteristic for neutrophilic airway inflammation. Mucins Clca1 (Gob5) and Muc5ac were upregulated in eosinophilic and even more in neutrophilic phenotype. Increased expression of inflammasome-related molecules such as Nlrp3, Nlrc4, Casp-1, and IL-1β was characteristic for neutrophilic asthma. In addition, we showed that inflammasome/Th17/neutrophilic axis cytokine-IL-1β-may transiently impair epithelial barrier function, while IL-1β and IL-17 increase mucin expressions in primary human bronchial epithelial cells.

    CONCLUSION: Our findings suggest that differential expression of TJ, mucin, and inflammasome-related molecules in distinct inflammatory phenotypes of asthma may be linked to pathophysiology and might reflect the differences observed in the clinic.

    Matched MeSH terms: Inflammation Mediators/metabolism
  5. Cheong HC, Lee CYQ, Cheok YY, Shankar EM, Sabet NS, Tan GMY, et al.
    Immunobiology, 2019 01;224(1):34-41.
    PMID: 30477893 DOI: 10.1016/j.imbio.2018.10.010
    BACKGROUND: Persistent inflammation caused by Chlamydia trachomatis in the female genital compartment represents one of the major causes of pelvic inflammatory disease (PID), ectopic pregnancy and infertility in females. Here, we examined the pro-inflammatory cytokine response following stimulation with three different types of C. trachomatis antigens, viz. chlamydial protease-like factor (CPAF), heat shock protein 60 (HSP60) and major outer membrane protein (MOMP).

    METHODS: A total of 19 patients with genital C. trachomatis infection and 10 age-matched healthy controls were recruited for the study. Peripheral blood mononuclear cells (PBMCs) isolated from genital C. trachomatis-infected females were cultured in the presence of CPAF, HSP60 and MOMP antigens, and cytokines were measured by ELISA assay.

    RESULTS: We reported that pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) were robustly secreted following antigenic exposure. Notably, CPAP and MOMP were more potent in triggering IL-1β, as compared to HSP60. Elevated levels of the proinflammatory cytokines were also noted in the samples infected with plasmid-bearing C. trachomatis as compared to those infected with plasmid-free strains.

    CONCLUSIONS: Our study highlights distinct ability of chlamydial antigens in triggering pro-inflammatory response in the host immune cells.

    Matched MeSH terms: Inflammation Mediators/metabolism
  6. Hudu SA, Niazlin MT, Nordin SA, Saeed MI, Tan SS, Sekawi Z
    Iran J Immunol, 2017 Dec;14(4):281-292.
    PMID: 29276181 DOI: IJIv14i4A3
    BACKGROUND: Hepatitis viruses are non-cytopathic viruses that lead to the infection and pathogenesis of liver diseases as a result of immunologically mediated events.

    OBJECTIVE: To investigate the expression of human inflammatory cytokines in chronic hepatitis B patients according to the severity of the infection.

    METHODS: We recruited a total of 120 patients, 40 of whom from cirrhotic, 40 non-cirrhotic, and 40 acute flare chronic hepatitis B and 40 healthy controls. For all groups total cellular RNA was extracted from whole blood samples, genomic DNA was eliminated, and cDNA was synthesized using the RT2 first strand kit, as instructed by the manufacturer. The real-time profiler PCR array was performed on a master cycler ep realplex and the data were analyzed using an online data analysis software.

    RESULTS: Non-cirrhotic chronic hepatitis B patients were found to significantly upregulate interleukin 10 receptors that regulate the balance between T helpers 1 and 2. On the other hand, patients with cirrhosis were found to have significant upregulated interleukin 3 gene expression.

    CONCLUSION: Our finding suggests that upregulation of anti-inflammatory and downregulation of pro-inflammatory cytokines may play a role in the progression of non-cirrhotic chronic hepatitis B patients to cirrhotic and acute flare. However, a multi-center study with a larger sample size is needed to confirm our findings.

    Matched MeSH terms: Inflammation Mediators/metabolism
  7. Singh JC, Kakalij RM, Kshirsagar RP, Kumar BH, Komakula SS, Diwan PV
    Pharm Biol, 2015 May;53(5):630-6.
    PMID: 25472801 DOI: 10.3109/13880209.2014.935866
    Vanillic acid (VA), a flavoring agent used in food and drug products, obtained naturally from the plant Angelica sinensis (Oliv.) Diels (Apiaceae), used in the traditional Chinese medicine. It is reported to possess strong antioxidant, anti-inflammatory, and neuroprotective effects. However, the pharmacological effects on oxidative stress-induced neurodegeneration are not well investigated.
    Matched MeSH terms: Inflammation Mediators/metabolism
  8. Lee KH, Abas F, Mohamed Alitheen NB, Shaari K, Lajis NH, Israf DA, et al.
    Int J Rheum Dis, 2015 Jul;18(6):616-27.
    PMID: 24832356 DOI: 10.1111/1756-185X.12341
    Synovial fibroblast has emerged as a potential cellular target in progressive joint destruction in rheumatoid arthritis development. In this study, BDMC33 (2,6-bis[2,5-dimethoxybenzylidene]cyclohexanone), a curcumin analogue with enhanced anti-inflammatory activity has been synthesized and the potency of BDMC33 on molecular and cellular basis of synovial fibroblasts (SF) were evaluated in vitro.
    Matched MeSH terms: Inflammation Mediators/metabolism
  9. Syam S, Bustamam A, Abdullah R, Sukari MA, Hashim NM, Mohan S, et al.
    J Ethnopharmacol, 2014 Apr 28;153(2):435-45.
    PMID: 24607509 DOI: 10.1016/j.jep.2014.02.051
    The fruit hull of Garcinia mangostana Linn. has been used in traditional medicine for treatment of various inflammatory diseases. Hence, this study aims to investigate the in vitro and in vivo anti-inflammatory effect of β mangostin (βM), a major compound present in Garcinia mangostana.
    Matched MeSH terms: Inflammation Mediators/metabolism
  10. Ming-Tatt L, Khalivulla SI, Akhtar MN, Mohamad AS, Perimal EK, Khalid MH, et al.
    Basic Clin Pharmacol Toxicol, 2012 Mar;110(3):275-82.
    PMID: 21967232 DOI: 10.1111/j.1742-7843.2011.00804.x
    This study investigated the potential antinociceptive efficacy of a novel synthetic curcuminoid analogue, 2,6-bis-(4-hydroxy-3-methoxybenzylidene)cyclohexanone (BHMC), using chemical- and thermal-induced nociception test models in mice. BHMC (0.03, 0.1, 0.3 and 1.0 mg/kg) administered via intraperitoneal route (i.p.) produced significant dose-related inhibition in the acetic acid-induced abdominal constriction test in mice with an ID(50) of 0.15 (0.13-0.18) mg/kg. It was also demonstrated that BHMC produced significant inhibition in both neurogenic (first phase) and inflammatory phases (second phase) of the formalin-induced paw licking test with an ID(50) of 0.35 (0.27-0.46) mg/kg and 0.07 (0.06-0.08) mg/kg, respectively. Similarly, BHMC also exerted significant increase in the response latency period in the hot-plate test. Moreover, the antinociceptive effect of the BHMC in the formalin-induced paw licking test and the hot-plate test was antagonized by pre-treatment with the non-selective opioid receptor antagonist, naloxone. Together, these results indicate that the compound acts both centrally and peripherally. In addition, administration of BHMC exhibited significant inhibition of the neurogenic nociception induced by intraplantar injections of glutamate and capsaicin with ID(50) of 0.66 (0.41-1.07) mg/kg and 0.42 (0.38-0.51) mg/kg, respectively. Finally, it was also shown that BHMC-induced antinociception was devoid of toxic effects and its antinociceptive effect was associated with neither muscle relaxant nor sedative action. In conclusion, BHMC at all doses investigated did not cause any toxic and sedative effects and produced pronounced central and peripheral antinociceptive activities. The central antinociceptive activity of BHMC was possibly mediated through activation of the opioid system as well as inhibition of the glutamatergic system and TRPV1 receptors, while the peripheral antinociceptive activity was perhaps mediated through inhibition of various inflammatory mediators.
    Matched MeSH terms: Inflammation Mediators/metabolism
  11. Israf DA, Tham CL, Syahida A, Lajis NH, Sulaiman MR, Mohamad AS, et al.
    Phytomedicine, 2010 Aug;17(10):732-9.
    PMID: 20378317 DOI: 10.1016/j.phymed.2010.02.006
    In a previous communication we showed that atrovirinone, a 1,4-benzoquinone isolated from the roots of Garcinia atroviridis, was able to inhibit several major proinflammatory mediators of inflammation. In this report we show that atrovirinone inhibits NO and PGE(2) synthesis through inhibition of iNOS and COX-2 expression. We also show that atrovirinone inhibits the secretion of IL-1beta and IL-6 in a dose dependent fashion whereas the secretion of IL-10, the anti-inflammatory cytokine, was enhanced. Subsequently we determined that the inhibition of proinflammatory cytokine synthesis and inducible enzyme expression was due to a dose-dependent inhibition of phosphorylation of p38 and ERK1/2. We also showed that atrovirinone prevented phosphorylation of I-kappaBalpha, which resulted in a reduction of p65NF-kappaB nuclear translocation as demonstrated by expression analysis. We conclude that atrovirinone is a potential anti-inflammatory drug lead that targets both the MAPK and NF-kappaB pathway.
    Matched MeSH terms: Inflammation Mediators/metabolism
  12. Gupta S, Mishra KP, Kumar B, Singh SB, Ganju L
    J Ethnopharmacol, 2020 Oct 28;261:113022.
    PMID: 32569719 DOI: 10.1016/j.jep.2020.113022
    ETHNOPHARMACOLOGICAL RELEVANCE: Traditional plant-derived medicines have enabled the mankind in curing the wide spectrum of diseases throughout the ages. Andrographis paniculata (Burm.f.) Nees, is one of the traditional plant used as a folk medicine for the management of inflammation, arthritis, viral-bacterial infections and other ailments in India, China, Malaysia and other South-East Asian countries. Its major bioactive compound; andrographolide, a diterpenoid, also exerts cytoprotective properties and is reported to be effective in neuroprotection, hepatoprotection, etc. AIM: The study is aimed to explore the role of andrographolide in treatment of complete freund's adjuvant (CFA) induced arthritis.

    MATERIALS AND METHODS: The influx of immune cells, release of pro-inflammatory cytokines and subsequent accumulation of synovial fluid (swelling) and pain manifest into the disease. The present study used CFA induced Balb/c mice model and treated them intraperitoneally with andrographolide and dexamethasone (used as a positive control) on alternate days for six days. After 6 days, blood and peritoneal macrophages were collected to evaluate the expression of various arthritic markers and paw edema was measured on all days.

    RESULTS: The in vitro and ex vivo experiments showed that andrographolide treated animal group had reduced paw edema, cell cytotoxicity and nitric oxide production than dexamethasone treated animal group. Further, the study revealed the mechanistic role of andrographolide in treatment of arthritis by suppressing battery of molecules like COX-2, NF-κB, p-p38, CD40, TNF-α, IL-1β and IL-6 involved in arthritis.

    CONCLUSION: The study showed the potent anti-arthritic effects of andrographolide and warrants further investigations on andrographolide for the development of safe and effective anti-arthritic drug.

    Matched MeSH terms: Inflammation Mediators/metabolism
  13. Hamid AA, Aminuddin A, Yunus MHM, Murthy JK, Hui CK, Ugusman A
    Rev Cardiovasc Med, 2020 Jun 30;21(2):275-287.
    PMID: 32706215 DOI: 10.31083/j.rcm.2020.02.50
    Inflammation and oxidative stress are involved in the pathogenesis of cardiovascular diseases such as atherosclerosis, hypertension and ischemic heart disease. Natural products play an important role as nutritional supplements with potential health benefits in cardiovascular diseases. Polygonum minus (PM) is an aromatic plant that is widely used as a flavoring agent in cooking and has been recognized as a plant with various medicinal properties including antioxidative and anti-inflammatory actions. Phytoconstituents found in PM such as phenolic and flavonoid compounds contribute to the plant's antioxidative and anti-inflammatory effects. We conducted this review to systematically identify articles related to the antioxidative and anti-inflammatory activities of PM. A computerized database search was conducted on Ovid MEDLINE, PubMed, Scopus, and ACS publication, from 1946 until May 2020, and the following keywords were used: 'Kesum OR Polygonum minus OR Persicaria minor' AND 'inflammat* OR oxida* OR antioxida*'. A total of 125 articles were obtained. Another eight additional articles were identified through Google Scholar and review articles. Altogether, 17 articles were used for data extraction, comprising 16 articles on antioxidant and one article on anti-inflammatory activity of PM. These studies consist of 14 in vitro studies, one in vivo animal study, one combined in vitro and in vivo study and one combined in vitro and ex vivo study. All the studies reported that PM exhibits antioxidative and anti-inflammatory activities which are most likely attributed to its high phenolic and flavonoid content.
    Matched MeSH terms: Inflammation Mediators/metabolism
  14. Haque MA, Jantan I, Harikrishnan H
    Int Immunopharmacol, 2018 Feb;55:312-322.
    PMID: 29310107 DOI: 10.1016/j.intimp.2018.01.001
    Zerumbone (ZER), isolated mainly from the Zingiber zerumbet (Z. zerumbet) rhizomes was found to be effective against numerous inflammatory and immune disorders, however, the molecular and biochemical mechanisms underlying its anti-inflammatory and immunosuppressive properties have not been well studied. This study was carried out to examine the profound effects of ZER on inflammatory mediated MyD88-dependent NF-κB/MAPK/PI3K-Akt signaling pathways in LPS-stimulated U937 human macrophages. ZER significantly suppressed the up-regulation pro-inflammatory mediators, TNF-α, IL-1β, PGE2, and COX-2 protein in LPS-induced human macrophages. Moreover, ZER significantly downregulated the phosphorylation of NF-κB (p65), IκBα, and IKKα/β as well as restored the degradation of IκBα. ZER correspondingly showed remarkable attenuation of the expression of Akt, JNK, ERK, and p38 MAPKs phosphorylation in a concentration-dependent manner. ZER also diminished the expression of upstream signaling molecules TLR4 and MyD88, which are prerequisite for the NF-κB, MAPK and PI3K-Akt activation. Additionally, quantification of relative gene expression of TNF-α, IL-1β, and COX-2 indicated that, at a higher dose (50μM), ZER significantly downregulated the elevated mRNA transcription levels of the stated pro-inflammatory markers in LPS-stimulated U937 macrophages. The strong suppressive effects of ZER on the activation of inflammatory markers in the macrophages via MyD88-dependent NF-κB/MAPK/PI3K-Akt signaling pathways suggest that ZER can be a preventive and potent therapeutic candidate for the management of various inflammatory-mediated immune disorders.
    Matched MeSH terms: Inflammation Mediators/metabolism
  15. Faghfouri AH, Zarezadeh M, Tavakoli-Rouzbehani OM, Radkhah N, Faghfuri E, Kord-Varkaneh H, et al.
    Eur J Pharmacol, 2020 Oct 05;884:173368.
    PMID: 32726657 DOI: 10.1016/j.ejphar.2020.173368
    Prolonged inflammation could be considered as the leading cause of chronic diseases such as cardiovascular disorders, type two diabetes, and obesity. N-acetylcysteine (NAC) is considered an antioxidant. The present meta-analysis aims to determine the efficacy of NAC in alleviating inflammation and oxidative stress. PubMed-Medline, SCOPUS, Web of Science and Embase databases and Google Scholar were searched up to Nov 2019. Random effect analysis was used to perform meta-analysis. Subgroup analyses were carried out to find heterogeneity sources. Meta-regression analysis was used to explore linear relationship between effect size and variables. Trim and fill analysis were performed in case of the presence of publication bias. Quality assessment was performed using Cochrane Collaboration's tool. A total of 28 studies were included in meta-analysis. NAC significantly decreased malondialdehyde (MDA) (SMD = -1.44 μmol/L; 95% CI: -2.05, -0.84; P 
    Matched MeSH terms: Inflammation Mediators/metabolism*
  16. Angelopoulou E, Paudel YN, Shaikh MF, Piperi C
    Pharmacol Res, 2020 08;158:104930.
    PMID: 32445958 DOI: 10.1016/j.phrs.2020.104930
    Neuroinflammation plays a crucial role in the pathogenesis of Parkinson's disease (PD) with the dysregulation of microglial activity being tightly linked to dopaminergic degeneration. Fractalkine (CX3CL1), a chemokine mainly expressed by neurons, can modulate microglial activity through binding to its sole G-protein-coupled receptor (CX3CR1), expressed by microglia. Fractalkine/CX3CR1 signaling is one of the most important mediators of the communication between neurons and microglia, and its emerging role in neurodegenerative disorders including PD has been increasingly recognized. Pre-clinical evidence has revealed that fractalkine signaling axis exerts dual effects on PD-related inflammation and degeneration, which greatly depend on the isoform type (soluble or membrane-bound), animal model (mice or rats, toxin- or proteinopathy-induced), route of toxin administration, time course and specific brain region (striatum, substantia nigra). Furthermore, although existing clinical evidence is scant, it has been indicated that fractalkine may be possibly associated with PD progression, paving the way for future studies investigating its biomarker potential. In this review, we discuss recent evidence on the role of fractalkine/CX3CR1 signaling axis in PD pathogenesis, aiming to shed more light on the molecular mechanisms underlying the neuroinflammation commonly associated with the disease, as well as potential clinical and therapeutic implications.
    Matched MeSH terms: Inflammation Mediators/metabolism*
  17. Abu Bakar MH, Azmi MN, Shariff KA, Tan JS
    Appl Biochem Biotechnol, 2019 May;188(1):241-259.
    PMID: 30417321 DOI: 10.1007/s12010-018-2920-2
    Withaferin A (WA), a bioactive constituent derived from Withania somnifera plant, has been shown to exhibit many qualifying properties in attenuating several metabolic diseases. The current investigation sought to elucidate the protective mechanisms of WA (1.25 mg/kg/day) on pre-existing obese mice mediated by high-fat diet (HFD) for 12 weeks. Following dietary administration of WA, significant metabolic improvements in hepatic insulin sensitivity, adipocytokines with enhanced glucose tolerance were observed. The hepatic oxidative functions of obese mice treated with WA were improved via augmented antioxidant enzyme activities. The levels of serum pro-inflammatory cytokines and hepatic mRNA expressions of toll-like receptor (TLR4), nuclear factor κB (NF-κB), tumor necrosis factor-α (TNF-α), chemokine (C-C motif) ligand-receptor, and cyclooxygenase 2 (COX2) in HFD-induced obese mice were reduced. Mechanistically, WA increased hepatic mRNA expression of peroxisome proliferator-activated receptors (PPARs), cluster of differentiation 36 (CD36), fatty acid synthase (FAS), carnitine palmitoyltransferase 1 (CPT1), glucokinase (GCK), phosphofructokinase (PFK), and phosphoenolpyruvate carboxykinase (PCK1) that were associated with enhanced lipid and glucose metabolism. Taken together, these results indicate that WA exhibits protective effects against HFD-induced obesity through attenuation of hepatic inflammation, oxidative stress, and insulin resistance in mice.
    Matched MeSH terms: Inflammation Mediators/metabolism
  18. Siddiqui A, Shah Z, Jahan RN, Othman I, Kumari Y
    Biomed Pharmacother, 2021 Dec;144:112250.
    PMID: 34607104 DOI: 10.1016/j.biopha.2021.112250
    The resin/gum of Boswellia species belonging to the family of Burseraceae is a naturally occurring mixture of bioactive compounds, which was traditionally used as a folk medicine to treat conditions like chronic inflammation. Several research studies have also explored its' therapeutic potential against multiple neurodegenerative diseases such as Alzheimer's disease (AD). The main chemical constituents of this gum include boswellic acids (BAs) like 3-O-acetyl-11-keto-β boswellic acid (AKBA) that possess potent anti-inflammatory and neuroprotective properties in AD. It is also involved in inhibiting the acetylcholinesterase (AChE) activity in the cholinergic pathway and improve choline levels as well as its binding with nicotinic receptors to produce anti-inflammatory effects. Multiple shreds of evidence have demonstrated that BAs modulate key molecular targets and signalling pathways like 5-lipoxygenase/cyclooxygenase, Nrf2, NF-kB, cholinergic, amyloid-beta (Aβ), and neurofibrillary tangles formation (NFTs) that are involved in AD progression. The present review focuses on the possible mechanistic therapeutic role of BAs in modulating the 5-LOX/COX pathway in arachidonic acid metabolism, activating Nrf2 through binding of ARE, inhibiting NF-kB and AChE activity. In addition, an inhibition of amyloid plaques (Aβ) and neurofibrillary tangles (NFTs) induced neurotoxicity and neuroinflammation in AD by BAs is also discussed in this review. We have also highlighted that BAs possess beneficial effects in AD by targeting multiple molecular pathways and makes it an emerging drug candidate for treating neurodegenerative diseases.
    Matched MeSH terms: Inflammation Mediators/metabolism*
  19. Ali SS, Noordin L, Bakar RA, Zainalabidin S, Jubri Z, Wan Ahmad WAN
    Cardiovasc Toxicol, 2021 08;21(8):605-618.
    PMID: 34114196 DOI: 10.1007/s12012-021-09666-x
    Clinically, timely reperfusion strategies to re-establish oxygenated blood flow in ischemic heart diseases seem to salvage viable myocardium effectively. Despite the remarkable improvement in cardiac function, reperfusion therapy could paradoxically trigger hypoxic cellular injury and dysfunction. Experimental laboratory models have been developed over the years to explain better the pathophysiology of cardiac ischemia-reperfusion injury, including the in vitro hypoxia-reoxygenation cardiac injury model. Furthermore, the use of nutritional myocardial conditioning techniques have been successful. The cardioprotective potential of flavonoids have been greatly linked to its anti-oxidant, anti-apoptotic and anti-inflammatory properties. While several studies have reviewed the cardioprotective properties of flavonoids, there is a scarce evidence of their function in the hypoxia-reoxygenation injury cell culture model. Hence, the aim of this review was to lay out and summarize our current understanding of flavonoids' function in mitigating hypoxia-reoxygenation cardiac injury based on evidence from the last five years. We also discussed the possible mechanisms of flavonoids in modulating the cardioprotective effects as such information would provide invaluable insight on future therapeutic application of flavonoids.
    Matched MeSH terms: Inflammation Mediators/metabolism
  20. Haw TJ, Starkey MR, Nair PM, Pavlidis S, Liu G, Nguyen DH, et al.
    Mucosal Immunol, 2016 Jul;9(4):859-72.
    PMID: 26555706 DOI: 10.1038/mi.2015.111
    Chronic obstructive pulmonary disease (COPD) is a life-threatening inflammatory respiratory disorder, often induced by cigarette smoke (CS) exposure. The development of effective therapies is impaired by a lack of understanding of the underlining mechanisms. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytokine with inflammatory and apoptotic properties. We interrogated a mouse model of CS-induced experimental COPD and human tissues to identify a novel role for TRAIL in COPD pathogenesis. CS exposure of wild-type mice increased TRAIL and its receptor messenger RNA (mRNA) expression and protein levels, as well as the number of TRAIL(+)CD11b(+) monocytes in the lung. TRAIL and its receptor mRNA were also increased in human COPD. CS-exposed TRAIL-deficient mice had decreased pulmonary inflammation, pro-inflammatory mediators, emphysema-like alveolar enlargement, and improved lung function. TRAIL-deficient mice also developed spontaneous small airway changes with increased epithelial cell thickness and collagen deposition, independent of CS exposure. Importantly, therapeutic neutralization of TRAIL, after the establishment of early-stage experimental COPD, reduced pulmonary inflammation, emphysema-like alveolar enlargement, and small airway changes. These data provide further evidence for TRAIL being a pivotal inflammatory factor in respiratory diseases, and the first preclinical evidence to suggest that therapeutic agents that target TRAIL may be effective in COPD therapy.
    Matched MeSH terms: Inflammation Mediators/metabolism
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