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Fulltext 1'-Acetoxychavicol acetate inhibits growth of human oral carcinoma xenograft in mice and potentiates cisplatin effect via proinflammatory microenvironment alterations

In LL, Arshad NM, Ibrahim H, Azmi MN, Awang K, Nagoor NH

BMC Complement Altern Med, 2012;12:179.
PMID: 23043547 DOI: 10.1186/1472-6882-12-179

Oral cancers although preventable, possess a low five-year survival rate which has remained unchanged over the past three decades. In an attempt to find a more safe, affordable and effective treatment option, we describe here the use of 1'S-1'-acetoxychavicol acetate (ACA), a component of Malaysian ginger traditionally used for various medicinal purposes.

Matched MeSH terms: Inflammation Mediators/metabolism*
Fulltext A Synthetic Curcuminoid Analogue, 2,6-Bis-4-(Hydroxyl-3-Methoxybenzylidine)-Cyclohexanone (BHMC) Ameliorates Acute Airway Inflammation of Allergic Asthma in Ovalbumin-Sensitized Mice

Tham CL, Yeoh SY, Ong CH, Harith HH, Israf DA

Mediators Inflamm, 2021;2021:9725903.
PMID: 33883974 DOI: 10.1155/2021/9725903

2,6-Bis-(4-hydroxyl-3-methoxybenzylidine) cyclohexanone (BHMC), a synthetic curcuminoid analogue, has been shown to exhibit anti-inflammatory properties in cellular models of inflammation and improve the survival of mice from lethal sepsis. We further evaluated the therapeutic effect of BHMC on acute airway inflammation in a mouse model of allergic asthma. Mice were sensitized and challenged with ovalbumin (OVA), followed by intraperitoneal administration of 0.1, 1, and 10 mg/kg of BHMC. Bronchoalveolar lavage fluid, blood, and lung samples were collected, and the respiratory function was measured. OVA sensitization and challenge increased airway hyperresponsiveness (AHR) and pulmonary inflammation. All three doses of BHMC (0.1-10 mg/kg) significantly reduced the number of eosinophils, lymphocytes, macrophages, and neutrophils, as well as the levels of Th2 cytokines (IL-4, IL-5 and IL-13) in bronchoalveolar lavage fluid (BALF) as compared to OVA-challenged mice. However, serum level of IgE was not affected. All three doses of BHMC (0.1-10 mg/kg) were effective in suppressing the infiltration of inflammatory cells at the peribronchial and perivascular regions, with the greatest effect observed at 1 mg/kg which was comparable to dexamethasone. Goblet cell hyperplasia was inhibited by 1 and 10 mg/kg of BHMC, while the lowest dose (0.1 mg/kg) had no significant inhibitory effect. These findings demonstrate that BHMC, a synthetic nonsteroidal small molecule, ameliorates acute airway inflammation associated with allergic asthma, primarily by suppressing the release of inflammatory mediators and goblet cell hyperplasia to a lesser extent in acute airway inflammation of allergic asthma.

Matched MeSH terms: Inflammation Mediators
Fulltext A pathogenic role for tumor necrosis factor-related apoptosis-inducing ligand in chronic obstructive pulmonary disease

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
Fulltext Adipocyte-Specific Fatty Acid-Binding Protein (AFABP) and Chemerin in Association with Gestational Diabetes: A Case-Control Study

Mosavat M, Mirsanjari M, Lwaleed BA, Kamarudin M, Omar SZ

J Diabetes Res, 2021;2021:5533802.
PMID: 34007846 DOI: 10.1155/2021/5533802

BACKGROUND: Adipocytokines participate in regulating the inflammatory response in glucose homeostasis and type 2 diabetes. However, among these peptides, the role of adipocyte-specific fatty-acid-binding protein (AFABP), chemerin, and secreted protein acidic and rich in cysteine (SPARC) in gestational diabetes (GDM) has not been fully investigated.
METHOD: The maternal fasting level of adipocytokines of 53 subjects with GDM and 43 normal pregnant (NGDM) was measured using multiplex immunoassay at 24-28 weeks, before delivery, immediate postpartum, and 2-6 months postpuerperium.
RESULTS: Higher levels of AFABP were associated with a 3.7-fold higher risk of GDM. Low chemerin levels were associated with a 3.6-fold higher risk of GDM. Interleukin-10 (IL-10) was inversely associated with the risk of GDM. SPARC had no association with GDM. AFABP was directly correlated to interleukin-6 (r = 0.50), insulin resistance index (r = 0.26), and body mass index (r = 0.28) and inversely correlated to C-reactive protein (r = -0.27). Chemerin levels were directly and strongly correlated with IL-10 (r = 0.41) and interleukin-4 (r = 0.50) and inversely correlated to insulin resistance index (r = -0.23) in GDM but not NGDM. In the longitudinal assessment, there were no significant differences in AFABP and chemerin concentrations of both studied groups.
CONCLUSION: AFABP and chemerin were associated with a higher risk of GDM. These adipocytokines were related to insulin resistance, body mass index, and inflammation in pregnant women diagnosed with GDM.

Matched MeSH terms: Inflammation Mediators/blood
Ameliorative effect of Albizia chinensis synthesized ZnO-NPs on Mycoplasma pneumoniae infected pneumonia mice model

Yu L, Lu M, Zhang W, Alarfaj AA, Hirad AH, Zhang H

Microb Pathog, 2020 Apr;141:103960.
PMID: 31953224 DOI: 10.1016/j.micpath.2019.103960

BACKGROUND: Mycoplasma pneumoniae (MP) is a common cause of community-acquired pneumonia (CAP) among the children and adults that results upper and lower respiratory tract infections.
OBJECTIVE: This study was aimed to inspect the ameliorative action of A. chinensis synthesized ZnONPs against M. pneumoniae infected pneumonia mice model.
MATERIALS AND METHODS: ZnO NPs was synthesized from Albizia chinensis bark extract and characterized by UV-Vis spectroscopy, Fourier Transform Infrared (FTIR), Transmission Electron Microscopy (TEM), energy dispersive X-ray (EDX) and atomic force microscope (AFM) analyses. The antibacterial effectual of synthesized ZnONPs were examined against clinical pathogens. The pneumonia was induced to BALB/c mice via injecting the M. pneumoniae and treated with synthesized ZnONPs, followed by the total protein content, total cell counts and inflammatory mediators level was assessed in the BALF of experimental animals. The Histopathological investigation was done in the lung tissues of test animals.
RESULTS: The outcomes of this work revealed that the formulated ZnONPs was quasi-spherical, radial and cylindrical; the size was identified as 116.5 ± 27.45 nm in diameter. The in vitro antimicrobial potential of formulated ZnO-NPs displayed noticeable inhibitory capacity against the tested fungal and bacterial strains. The administration of synthesized ZnO-NPs in MP infected mice model has significantly reduced the levels of total protein, inflammatory cells, inflammatory cytokines such as IL-1, IL-6, IL-8, tumour necrosis factor-alpha (TNF-a) and transforming growth factor (TGF). Besides, the histopathological examination of MP infected mice lung tissue showed the cellular arrangements were effectively retained after administration of synthesized ZnO-NPs.
CONCLUSION: In conclusion, synthesized ZnO-NPs alleviate pneumonia progression via reducing the level of inflammatory cytokines and inflammatory cells in MP infected mice model.

Matched MeSH terms: Inflammation Mediators
Andrographolide and its analogues: versatile bioactive molecules for combating inflammation and cancer

Lim JC, Chan TK, Ng DS, Sagineedu SR, Stanslas J, Wong WS

Clin Exp Pharmacol Physiol, 2012 Mar;39(3):300-10.
PMID: 22017767 DOI: 10.1111/j.1440-1681.2011.05633.x

1. Andrographis paniculata (Burm. f) Nees, commonly known as 'king of bitters', is a herbaceous plant belonging to the Family Acanthaceae. It has been widely used for centuries in Asian countries like China, India, Thailand and Malaysia for the treatment of sore throat, flu and upper respiratory tract infections. 2. Andrographolide, 14-deoxy-11,12-didehydroandrographolide and neoandrographolide are examples of the major labdane diterpenoids isolated from A. paniculata. These bioactive molecules have exhibited varying degrees of anti-inflammatory and anticancer activities in both in vitro and in vivo experimental models of inflammation and cancer. 3. Extensive libraries of andrographolide analogues have been synthesised mainly by modifying the α,β-unsaturated γ-butyrolactone moiety, the two double bonds Δ(8,(17)) and Δ(12,(13)) and the three hydroxyls at C-3 (secondary), C-14 (allylic) and C-19 (primary). Many of these synthetic analogues exhibit superior anticancer activity over the naturally occurring andrographolides. 4. Andrographolide and its derivatives have been shown to have anti-inflammatory effects in experimental models of asthma, stroke and arthritis, as well as in patients with upper respiratory tract infections. Andrographolide reduces the production of cytokines, chemokines, adhesion molecules, nitric oxide and lipid mediators, probably via inhibition of the nuclear factor (NF)-κB signalling pathway. 5. The anticancer mechanisms for andrographolide include inhibition of Janus tyrosine kinases-signal transducers and activators of transcription, phosphatidylinositol 3-kinase and NF-κB signalling pathways, suppression of heat shock protein 90, cyclins and cyclin-dependent kinases, metalloproteinases and growth factors, and the induction of tumour suppressor proteins p53 and p21, leading to inhibition of cancer cell proliferation, survival, metastasis and angiogenesis. 6. Andrographolide drug discovery is a promising strategy for the development of a novel class of anti-inflammatory and anticancer drugs.

Matched MeSH terms: Inflammation Mediators/physiology*; Inflammation Mediators/therapeutic use*; Inflammation Mediators/chemistry
Andrographolide attenuates complete freund's adjuvant induced arthritis via suppression of inflammatory mediators and pro-inflammatory cytokines

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/antagonists & inhibitors*; Inflammation Mediators/metabolism
Fulltext Anti-inflammatory and antinociceptive activities of untreated, germinated, and fermented mung bean aqueous extract

Ali NM, Mohd Yusof H, Yeap SK, Ho WY, Beh BK, Long K, et al.

Evid Based Complement Alternat Med, 2014;2014:350507.
PMID: 25045389 DOI: 10.1155/2014/350507

Evaluation of anti-inflammatory and antinociceptive activities of untreated mung bean (MB), germinated mung bean (GMB), and fermented mung bean (FMB) was performed on both in vitro (inhibition of inflammatory mediator, nitric oxide(NO)) and in vivo (inhibition of ear oedema and reduction of response to pain stimulus) studies. Results showed that both GMB and FMB aqueous extract exhibited potent anti-inflammatory and antinociceptive activities in a dose-dependent manner. In vitro results showed that GMB and FMB were potent inflammatory mediator (NO) inhibitors at both 2.5 and 5 mg/mL. Further in vivo studies showed that GMB and FMB aqueous extract at 1000 mg/kg can significantly reduce ear oedema in mice caused by arachidonic acid. Besides, both 200 mg/kg and 1000 mg/kg concentrations of GMB and FMB were found to exhibit potent antinociceptive effects towards hotplate induced pain. With these, it can be concluded that GMB and FMB aqueous extract exhibited potential anti-inflammatory and antinociceptive effects.

Matched MeSH terms: Inflammation Mediators
Anti-inflammatory and renal protective effect of gingerol in high-fat diet/streptozotocin-induced diabetic rats via inflammatory mechanism

Song S, Dang M, Kumar M

Inflammopharmacology, 2019 Dec;27(6):1243-1254.
PMID: 30826930 DOI: 10.1007/s10787-019-00569-6

P38 mitogen-activated protein kinase (p38 MAPK), a tissue inflammatory factor can be activated under oxidative stress and in conditions associated with hyperglycemia. Gingerol containing various natural herbs has been extensively studied for its pharmacological actions both in reducing the inflammation and as immunity booster. The aim of the current investigation was to examine the renal protective effect of gingerol in high-fat diet/streptozotocin-induced type II diabetes mellitus in a rat model.NRK 52E cells were divided into normal and high glucose group treated with gingerol. The methylthiazotetrazolium assay was used to establish the cell proliferation progress. Streptozotocin-inducted diabetes in rats was treated with gingerol for 16 weeks. The blood glucose, serum creatinine, body weight, food intake, biochemical, antioxidant and haematological parameters were assayed to establish the correlation. Pro-inflammatory cytokines including Il-1β, IL-6, TNF-α; inflammatory mediator COX-2, PGE2, NF-kB, p38MAPK, and TGF-β, were also determined to assess the molecular mechanism. Gingerol exhibited the protective effect on the high glucose level induced NRK 52E cells and did not show any effect on the normal cells. Gingerol significantly (P

Matched MeSH terms: Inflammation Mediators/analysis
Fulltext Antinociceptive activity of a synthetic curcuminoid analogue, 2,6-bis-(4-hydroxy-3-methoxybenzylidene)cyclohexanone, on nociception-induced models in mice

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
Fulltext Antioxidative and anti-inflammatory activities of Polygonum minus: a review of literature

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/antagonists & inhibitors*; Inflammation Mediators/metabolism
Fulltext Are Oxidative Stress and Inflammation Mediators of Bone Loss Due to Estrogen Deficiency? A Review of Current Evidence

Mohamad NV, Ima-Nirwana S, Chin KY

Endocr Metab Immune Disord Drug Targets, 2020;20(9):1478-1487.
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*
Arterial stiffness, inflammatory and pro-atherogenic markers in gestational diabetes mellitus

Salmi AA, Zaki NM, Zakaria R, Nor Aliza AG, Rasool AH

VASA, 2012 Mar;41(2):96-104.
PMID: 22403127 DOI: 10.1024/0301-1526/a000171

This study aims to determine whether gestational diabetes mellitus (GDM) is associated with increased arterial stiffness, inflammatory and pro-atherogenic markers compared to age matched controls.

Matched MeSH terms: Inflammation Mediators/blood*
Fulltext Association between hypertension and periodontitis: possible mechanisms

Leong XF, Ng CY, Badiah B, Das S

ScientificWorldJournal, 2014;2014:768237.
PMID: 24526921 DOI: 10.1155/2014/768237

This review is to examine the current literatures on the relationship between periodontitis and hypertension as well as to explore the possible biological pathways underlying the linkage between these health conditions. Hypertension is one of the major risk factors for cardiovascular diseases. Oxidative stress and endothelial dysfunction are among the critical components in the development of hypertension. Inflammation has received much attention recently and may contribute to a pivotal role in hypertension. Periodontitis, a chronic low-grade inflammation of gingival tissue, has been linked to endothelial dysfunction, with blood pressure elevation and increased mortality risk in hypertensive patients. Inflammatory biomarkers are increased in hypertensive patients with periodontitis. Over the years, various researches have been performed to evaluate the involvement of periodontitis in the initiation and progression of hypertension. Many cross-sectional studies documented an association between hypertension and periodontitis. However, more well-designed prospective population trials need to be carried out to ascertain the role of periodontitis in hypertension.

Matched MeSH terms: Inflammation Mediators/metabolism*
Atrovirinone inhibits proinflammatory mediator synthesis through disruption of NF-kappaB nuclear translocation and MAPK phosphorylation in the murine monocytic macrophage RAW 264.7

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/antagonists & inhibitors*; Inflammation Mediators/metabolism
Fulltext Attenuation of Inflammatory Mediators (TNF-α and Nitric Oxide) and Up-Regulation of IL-10 by Wild and Domesticated Basidiocarps of Amauroderma rugosum (Blume & T. Nees) Torrend in LPS-Stimulated RAW264.7 Cells

Chan PM, Tan YS, Chua KH, Sabaratnam V, Kuppusamy UR

PLoS One, 2015;10(10):e0139593.
PMID: 26427053 DOI: 10.1371/journal.pone.0139593

Amauroderma rugosum, commonly known as "Jiǎzī" in China, is a wild mushroom traditionally used by the Chinese to reduce inflammation, to treat diuretic and upset stomach, and to prevent cancer. It is also used by the indigenous communities in Malaysia to prevent epileptic episodes and incessant crying by babies. The aim of this study was to compare the wild and domesticated basidiocarps of A. rugosum for antioxidant and in vitro anti-inflammatory effects in LPS-stimulated RAW264.7 cells. The wild basidiocarps of A. rugosum were collected from the Belum Forest, Perak, Malaysia and the domesticated basidiocarps of A. rugosum were cultivated in the mushroom house located in the University of Malaya, Kuala Lumpur, Malaysia. Both the wild and domesticated basidiocarps were subjected to ethanolic extraction and the extracts were tested for antioxidant and anti-inflammatory activities. In this study, the crude ethanolic extract of wild (WB) and domesticated (DB) basidiocarps of A. rugosum had comparable total phenolic content and DPPH scavenging activity. However, WB (EC50 = 222.90 μg/mL) displayed a better ABTS cation radical scavenging activity than DB (EC50 = 469.60 μg/mL). Both WB and DB were able to scavenge nitric oxide (NO) radical and suppress the NO production in LPS-stimulated RAW264.7 cells and this effect was mediated through the down-regulation of inducible nitric oxide synthase (iNOS) gene. In addition, both WB and DB caused down-regulation of the inflammatory gene TNF-α and the up-regulation of the anti-inflammatory gene IL-10. There was no inhibitory effect of WB and DB on nuclear translocation of NF-κB p65. In conclusion, the wild and domesticated basidiocarps of A. rugosum possessed antioxidant and in vitro anti-inflammatory properties. WB and DB inhibited downstream inflammatory mediators (TNF-α and NO) and induced anti-inflammatory cytokine IL-10 production. No inhibitory effects shown on upstream nuclear translocation of NF-κB p65. WB and DB exhibited antioxidant activity and attenuation of proinflammatory mediators and therefore, A. rugosum may serve as a potential therapeutic agent in the management of inflammation.

Matched MeSH terms: Inflammation Mediators/metabolism*
Fulltext BDMC33, A curcumin derivative suppresses inflammatory responses in macrophage-like cellular system: role of inhibition in NF-κB and MAPK signaling pathways

Lee KH, Chow YL, Sharmili V, Abas F, Alitheen NB, Shaari K, et al.

Int J Mol Sci, 2012;13(3):2985-3008.
PMID: 22489138 DOI: 10.3390/ijms13032985

Our preliminary screening has shown that curcumin derivative BDMC33 [2,6-bis(2,5-dimethoxybenzylidene)cyclohexanone] exerted promising nitric oxide inhibitory activity in activated macrophages. However, the molecular basis and mechanism for its pharmacological action is yet to be elucidated. The aim of this study was to investigate the anti-inflammatory properties of BDMC33 and elucidate its underlying mechanism action in macrophage cells. Our current study demonstrated that BDMC33 inhibits the secretion of major pro-inflammatory mediators in stimulated macrophages, and includes NO, TNF-α and IL-1β through interference in both nuclear factor kappaB (NF-κB) and mitogen activator protein kinase (MAPK) signaling cascade in IFN-γ/LPS-stimulated macrophages. Moreover, BDMC33 also interrupted LPS signaling through inhibiting the surface expression of CD-14 accessory molecules. In addition, the inhibitory action of BDMC33 not only restricted the macrophages cell (RAW264.7), but also inhibited the secretion of NO and TNF-α in IFN-γ/LPS-challenged microglial cells (BV-2). The experimental data suggests the inflammatory action of BDMC33 on activated macrophage-like cellular systems, which could be used as a future therapeutic agent in the management of chronic inflammatory diseases.

Matched MeSH terms: Inflammation Mediators/metabolism
Barrier protective effects of 2,4,6-trihydroxy-3-geranyl acetophenone on lipopolysaccharides-stimulated inflammatory responses in human umbilical vein endothelial cells

Chong YJ, Musa NF, Ng CH, Shaari K, Israf DA, Tham CL

J Ethnopharmacol, 2016 Nov 04;192:248-255.
PMID: 27404229 DOI: 10.1016/j.jep.2016.07.032

PHARMOCOLOGICAL RELEVANCE: 2,4,6-trihydroxy-3-geranyl acetophenone (tHGA), is a phloroglucinol compound found naturally in Melicope ptelefolia. Melicope ptelefolia has been used traditionally for centuries as natural remedy for wound infections and inflammatory diseases.
AIM OF THE STUDY: Endothelial barrier dysfunction is a pathological hallmark of many diseases and can be caused by lipopolysaccharides (LPS) stimulation. Therefore, this study aims to investigate the possible barrier protective effects of tHGA upon LPS-stimulated inflammatory responses in human umbilical vein endothelial cells (HUVECs).
MATERIALS AND METHODS: HUVECs were pretreated with tHGA prior to LPS stimulation, where inflammatory parameters including permeability, monocyte adhesion and migration, and release of pro-inflammatory mediators were examined. Additionally, the effect of tHGA on F-actin rearrangement and adhesion protein expression of LPS-stimulated HUVECs was evaluated.
RESULTS: It was found that pretreatment with tHGA inhibited monocyte adhesion and transendothelial migration, reduced endothelial hyperpermeability and secretion of prostaglandin E2 (PGE2). Additionally, tHGA inhibited cytoskeletal rearrangement and adhesion protein expression on LPS-stimulated HUVECs.
CONCLUSION: As the regulation of endothelial barrier dysfunction can be one of the therapeutic strategies to improve the outcome of inflammation, tHGA may be able to preserve vascular barrier integrity of endothelial cells following LPS-stimulated dysfunction, thereby endorsing its potential usefulness in vascular inflammatory diseases.

Matched MeSH terms: Inflammation Mediators/metabolism
Beneficial effect of Amorphophallus paeoniifolius tuber on experimental ulcerative colitis in rats

Dey YN, Sharma G, Wanjari MM, Kumar D, Lomash V, Jadhav AD

Pharm Biol, 2017 Dec;55(1):53-62.
PMID: 27600166

CONTEXT: The tuber of Amorphophallus paeoniifolius (Dennst.) Nicolson (Araceae), commonly called Suran or Jimmikand, has high medicinal value and is used ethnomedicinally for the treatment of different gastrointestinal and inflammatory disorders.
OBJECTIVE: The present study evaluated the effects of extracts of Amorphophallus paeoniifolius tubers on acetic acid-induced ulcerative colitis (UC) in rats.
MATERIALS AND METHODS: Wistar rats were orally administered methanol extract (APME) or aqueous extract (APAE) (250 and 500 mg/kg) or standard drug, prednisolone (PRDS) (4 mg/kg) for 7 days. On 6th day of treatment, UC was induced by transrectal instillation of 4% acetic acid (AA) and after 48 h colitis was assessed by measuring colitis parameters, biochemical estimations and histology of colon.
RESULTS: APME or APAE pretreatment significantly (p

Matched MeSH terms: Inflammation Mediators/metabolism
Boldine suppresses dextran sulfate sodium-induced mouse experimental colitis: NF-κB and IL-6/STAT3 as potential targets

Pandurangan AK, Mohebali N, Hasanpourghadi M, Looi CY, Mustafa MR, Mohd Esa N

Biofactors, 2016 May;42(3):247-58.
PMID: 26891685 DOI: 10.1002/biof.1267

Ulcerative colitis (UC) is a nonspecific inflammatory disorder characterized by oxidative and nitrosative stress, leucocyte infiltration, and upregulation of inflammatory mediators. Boldine is an alkaloid compound found in Boldo tree, with multiple pharmacological actions, mainly anti-inflammatory, antioxidant, antitumor, and immunomodulatory activities. Hence, the effect of boldine for its anti-inflammatory properties against dextran sulfate sodium (DSS)-induced UC in BALB/c mice was studied. Administration of boldine to DSS-induced mice protects colon damage by reduced disease activity index, spleen weight, and increased colon length. Also administration of boldine showed a reduction in the activity of myeloperoxidase (MPO) and CD 68+ expression. Boldine reduced the colon damage, with significant reductions in both the extent and the severity of the inflammation as well as in crypt damage and leukocyte infiltration in the mucosa. Analysis in vivo showed clear decrease in the production of tumor necrosis factor (TNF)-α, Interleukin (IL)-6, IL-17, and signal transducer and activator of transcription-(p-STAT3)(Y705) with nuclear factor (p65-NF-κB) production being reduced significantly. Moreover, p65-NF-κB activation was reduced in mouse macrophage RAW 264.7 cells in vitro. The data demonstrated that boldine may be beneficial in colitis through selective immunomodulatory effects, which may be mediated, at least in part, by inhibition of p65-NF-κB and STAT3 signaling pathways. © 2016 BioFactors, 42(3):247-258, 2016.

Matched MeSH terms: Inflammation Mediators/administration & dosage

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