Anti-oxidant and anti-inflammatory activities of macelignan in murine hippocampal cell line and primary culture of rat microglial cells

Jin, Da Qing; Lim, Chol Seung; Hwang, Jae Kwan; Ha, Ilho; Han, Jung‐Soo

doi:10.1016/j.bbrc.2005.04.036

Cited by 99 publications

(61 citation statements)

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“…Previously, macelignan was found to possess therapeutic potential against neurodegenerative diseases as it was known to display antioxidant and antiinflammatory activities (20). Here, we have shown that macelignan functions as a PPAR ␣/␥ dual agonist, but the potency was less than WY14643, a full PPAR␣ agonist, and troglitazone, a PPAR␥ agonist, in in vitro transactivation and transient transfection.…”

Section: Discussionmentioning

confidence: 74%

Therapeutic Potential of Peroxisome Proliferators–Activated Receptor-α/γ Dual Agonist With Alleviation of Endoplasmic Reticulum Stress for the Treatment of Diabetes

et al. 2008

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OBJECTIVE-Peroxisome proliferator-activated receptor (PPAR)␣/␥ dual agonists have the potential to be used as therapeutic agents for the treatment of type 2 diabetes. This study evaluated the function of macelignan, a natural compound isolated from Myristica fragrans, as a dual agonist for PPAR␣/␥ and investigated its antidiabetes effects in animal models.RESEARCH DESIGN AND METHODS-GAL4/PPAR chimera transactivation was performed and the expression of PPAR␣/␥ target genes was monitored to examine the ability of macelignan to activate PPAR␣/␥. Additionally, macelignan was administrated to obese diabetic (db/db) mice to investigate antidiabetes effects and elucidate its molecular mechanisms.RESULTS-Macelignan reduced serum glucose, insulin, triglycerides, free fatty acid levels, and triglycerides levels in the skeletal muscle and liver of db/db mice. Furthermore, macelignan significantly improved glucose and insulin tolerance in these mice, and without altering food intake, their body weights were slightly reduced while weights of troglitazone-treated mice increased. Macelignan increased adiponectin expression in adipose tissue and serum, whereas the expression and serum levels of tumor necrosis factor-␣ and interleukin-6 decreased. Macelignan downregulated inflammatory gene expression in the liver and increased AMP-activated protein kinase activation in the skeletal muscle of db/db mice. Strikingly, macelignan reduced endoplasmic reticulum (ER) stress and c-Jun NH 2 -terminal kinase activation in the liver and adipose tissue of db/db mice and subsequently increased insulin signaling. T he worldwide prevalence of type 2 diabetes is steadily rising; therefore, in addition to a more aggressive approach in managing diabetes through diet and exercise, antidiabetes agents that ameliorate insulin resistance and hyperlipidemia are also needed. CONCLUSIONS-MacelignanAs members of the nuclear hormone receptor superfamily, peroxisome proliferator-activated receptors (PPARs) bind to specific DNA response elements as heterodimers with the retinoid-X receptor to control glucose and lipid metabolism, which offers a promising therapeutic approach for treating the metabolic syndrome (1). There are several PPAR isoforms, including PPAR ␣, ␥, and ␦ that share 60 -80% homology in the ligand-and DNA-binding domains (2). Widely expressed in the liver, PPAR␣ functions in the catabolism of fatty acids responsible for decreasing serum triglyceride levels and increasing HDL cholesterol levels in dyslipidemia (3). Therefore, PPAR␣ agonists have the potential to be used to ameliorate insulin resistance and hyperlipidemia. Moreover, PPAR␥ is highly expressed in adipocytes and is involved in adipocyte differentiation, lipid storage, glucose homeostasis, and adipocytokine regulation, which can improve insulin sensitivity and glucose tolerance (4). The primary issue with the utility of classic full PPAR␥ agonists is that they exert a variety of side effects, chiefly weight gain due to edema and increased fat mass (5). However, the side effects ...

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Section: Discussionmentioning

confidence: 74%

Therapeutic Potential of Peroxisome Proliferators–Activated Receptor-α/γ Dual Agonist With Alleviation of Endoplasmic Reticulum Stress for the Treatment of Diabetes

et al. 2008

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“…Therefore, the effects of macelignan on this signaling pathway were examined to attempt to pinpoint the mechanism of action based on the results reported earlier. 8) As demonstrated in the aforementioned report, 8) macelignan suppressed the expression of COX-2 in LPS-stimulated primary microglial cells and reduced the generation of intracellular ROS in glutamate-stimulated neuronal hippocampal cells. The present study demonstrated that macelignan suppresses the degradation of IkBa and increases nuclear NFkB in LPS-stimulated BV-2 microglia cells.…”

Section: Discussionmentioning

confidence: 76%

“…Macelignan in LPS-stimulated BV-2 cells significantly suppressed the abundance of p38 phosphorylation (F (3,8)ϭ5.14, pϽ0.05) but did not affect the abundance of p38. Post hoc analyses revealed that treatment with 1 mM of macelignan decreased the abundance of p38 phosphorylation in LPS-stimulated BV-2 cells, whereas the amounts of 2.5 mM and 5 mM did not (Fig.…”

Section: Effects Of Macelignan On Activities Of Mapks In Lpsstimulatementioning

confidence: 96%

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Macelignan Attenuates Activations of Mitogen-Activated Protein Kinases and Nuclear Factor kappa B Induced by Lipopolysaccharide in Microglial Cells

Hwang

Cho

et al. 2009

Biological & Pharmaceutical Bulletin

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Chronic inflammatory processes play an important role in the pathogenesis of Alzheimer's disease (AD) and other neurodegenerative diseases. 1) In particular, AD is characterized by neuroinflammatory changes and increased free radicals, as well classic neuropathological features such as amyloid plaques, neuronal loss, and neurofibrillary tangles.2) For example, clumps of activated microglias and reactive astrocytes appear in the vicinity of senile plaques. 2)Microglial cells play major roles in host defense and tissue repair in the central nervous system (CNS).3) Microglial cells are activated in response to brain injury and exposure to lipopolysaccharide (LPS), interferon (IFN)-g, or b-amyloid. 4,5) Once chronically activated, microglial cells produce a variety of proinflammatory mediators and potentially neurotoxic compounds such as interleukin (IL)-1b, IL-6, tumor necrosis factor (TNF)-a, reactive oxygen species (ROS) and nitric oxide (NO). These have the deleterious effects on brain injuries and neurodegenerative diseases. 6,7) Macelignan, isolated from Myristica fragrans HOUTT, has been reported to exhibit free-radical scavenging and prostaglandin inhibitory properties. 7) Studies using neuronal cells and primary microglial cells have demonstrated that macelignan suppresses NO production by inhibiting inducible nitric oxide (iNOS) expression at the transcriptional level; it also significantly suppresses the production of proinflammatory cytokine TNF-a and IL-6.8) The anti-inflammatory effects of macelignan were also evaluated using animal model with a chronic infusion of LPS, one of wellcharacterized animal models incorporating important neuropathological features seen in AD. Oral administration of macelignan reduces hippocampal microglial activation and the impairments of spatial memory that are induced by chronic infusions of LPS into the fourth ventricle in rat brains.9) These results indicate that macelignan possesses therapeutic potential against neurodegenerative diseases that involve neuroinflammation. 8,9) However, the protecting molecular mechanisms of its actions have not yet been studied.It has recently been suggested that mitogen-activated protein kinases (MAPKs) play a role in the inflammation associated with the formation of plaques, eventually leading to AD.10) The present study investigates whether macelignan has anti-inflammatory effects through the suppression of the LPS-induced activation of nuclear factor kappa B (NF-kB) by blocking the degradation of inhibitory-kappa B (IkBa) and the phosphorylations of MAPK. To determine the involvement of the MAPK signal pathway and NF-kB in mediating the anti-inflammatory effects of macelignan, the activities of MAPKs such as p38, extracellular-signal-regulated kinase1/2 (ERK1/2), and c-Jun NH 2 -terminal kinase (JNK) were measured in response to treatments of macelignan in LPS-stimulated BV-2 microglial cells. IBST, Konkuk University; Seoul 143-729, South Korea: and c Department of Biotechnology, Yonsei University; Seoul 120-752, South Korea. Re...

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“…1 Nutmeg has been shown to possess various biological and pharmacological activities including anti-carcinogenic, 2 anti-inflammatory, 3 protein tyrosine phosphatase 1B (PTP1B), 4 and hepatoprotective activities. 5 Previous phytochemical investigation on nutmeg have resulted in the isolation and identification of essential oils, 6 lignans, 7 and phenylpropanoids.…”

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confidence: 99%

Lipoxygenase Inhibitory Effects of Dibenzylbutane Lignans from the Seeds of Myristica fragrans (Nutmeg)

Kwon¹,

Cho²,

Ha³

et al. 2014

Bulletin of the Korean Chemical Society

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Anti-oxidant and anti-inflammatory activities of macelignan in murine hippocampal cell line and primary culture of rat microglial cells

Cited by 99 publications

References 28 publications

Therapeutic Potential of Peroxisome Proliferators–Activated Receptor-α/γ Dual Agonist With Alleviation of Endoplasmic Reticulum Stress for the Treatment of Diabetes

Therapeutic Potential of Peroxisome Proliferators–Activated Receptor-α/γ Dual Agonist With Alleviation of Endoplasmic Reticulum Stress for the Treatment of Diabetes

Macelignan Attenuates Activations of Mitogen-Activated Protein Kinases and Nuclear Factor kappa B Induced by Lipopolysaccharide in Microglial Cells

Lipoxygenase Inhibitory Effects of Dibenzylbutane Lignans from the Seeds of Myristica fragrans (Nutmeg)

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