Phellinus linteus inhibits inflammatory mediators by suppressing redox-based NF-κB and MAPKs activation in lipopolysaccharide-induced RAW 264.7 macrophage

Kim, Ho Gyoung; Yoon, Deok Hyo; Lee, Won Ho; Han, Sang Kuk; Shrestha, Bhushan; Kim, Chun Hoi; Lim, Mi Hee; Chang, Won Hyuk; Lim, Soyeon; Choi, Sunga; Song, Won O.; Sung, Jae Mo; Hwang, Ki Chul; Kim, Tae‐Woong

doi:10.1016/j.jep.2007.08.011

Cited by 127 publications

(72 citation statements)

References 39 publications

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“…Several studies have shown that MAPKs are involved in the activation of NF-κB (28)(29)(30). The effects of TFHDW on the LPS-induced phosphorylation of p38, JNK and ERK1/2 were examined in the present study in order to further elucidate its anti-inflammatory mechanism.…”

Section: Discussionmentioning

confidence: 98%

Total flavonoids of Hedyotis diffusa Willd inhibit inflammatory responses in LPS-activated macrophages via suppression of the NF-κB and MAPK signaling pathways

Yunlong

Lin

et al. 2015

Experimental and Therapeutic Medicine

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Abstract. Nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways play a central role in inflammatory responses. Total flavonoids of Hedyotis diffusa Willd (TFHDW) are active compounds derived from Hedyotis diffusa Willd, which has been long used in Chinese traditional medicine for the treatment of various inflammatory diseases, including ulcerative colitis and bronchitis; however, the precise mechanisms underlying the effects of TFHDW are largely unknown. In the present study, the anti-inflammatory effect of TFHDW was evaluated and the underlying molecular mechanisms were investigated in an in vitro inflammatory model comprising lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. The results indicated that TFHDW inhibited the inflammatory response as it significantly reduced the LPS-induced expression of pro-inflammatory nitric oxide, tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β in a concentration-dependent manner, without causing cytotoxicity. In addition, the mRNA expression of inducible nitric oxide synthase, TNF-α, IL-6 and IL-1β was suppressed by treatment with TFHDW in LPS-stimulated RAW 264.7 cells. Moreover, TFHDW treatment significantly inhibited the LPS-induced activation of NF-κB via the suppression of inhibitor of κB (IκB) phosphorylation, and reduced the phosphorylation of MAPK signaling molecules (p38, c-Jun N-terminal protein kinase and extracellular signal-regulated kinase 1/2), which resulted in the inhibition of cytokine expression. These findings suggest that TFHDW exerted anti-inflammatory activity via suppression of the NF-κB and MAPK signaling pathways. IntroductionInflammation is an orchestrated biological process, induced by tissue injury or microbial infection, which protects the body from these inflammatory stimuli. However, persistent or excessive inflammation is associated with a variety of pathological conditions, including rheumatoid arthritis, bacterial sepsis and skin inflammation (1,2). Macrophages play a key role in the host defense against noxious substances and are involved in numerous inflammatory diseases (3). The activation of macrophages by inflammatory stimuli can generate reactive oxygen species, such as H 2 O 2 and superoxide, and induce the expression of various genes such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α, in addition to other inflammatory mediators, including nitric oxide (NO) and prostaglandin E2 (PGE2), which are synthesized by inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, respectively. Inflammatory cytokines and mediators contribute to the pathogenesis of numerous inflammation-associated human diseases (4). Lipopolysaccharide (LPS) from gram-negative bacteria induces inflammation and is frequently used to stimulate macrophages in order to study inflammation and the mechanisms of action of potential anti-inflammatory agents.The anti-inflammatory actions of various phytochemicals have been found to be mediated through suppression of the NF-κB pathway (5). NF-κB is a key regu...

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Section: Discussionmentioning

confidence: 98%

Total flavonoids of Hedyotis diffusa Willd inhibit inflammatory responses in LPS-activated macrophages via suppression of the NF-κB and MAPK signaling pathways

Yunlong

Lin

et al. 2015

Experimental and Therapeutic Medicine

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“…Similarly, other mushroom extracts, such as Phellinus linteus, were reported to modulate iNOS expression in LPS-induced macrophage, mediated by NF-κB and MAPK pathways (43,44).…”

Section: Discussionmentioning

confidence: 96%

Daedalea gibbosa substances inhibit LPS-induced expression of iNOS by suppression of NF-κB and MAPK activities in RAW 264.7 macrophage cells

Ruimi

Rwashdeh²,

Wasser³

et al. 2010

Int J Mol Med

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Abstract. Nitric oxide (NO) is a radical molecule produced by iNOS and plays a role in various physiological and pathophysiological conditions including inflammatory diseases and cancer. In the present study, organic extract of Daedalea gibbosa was effective in inhibiting NO and PGE 2 production in RAW 264.7 cells. The extract of D. gibbosa was chemically fractionated leading to the isolation of three active fractions (F5-F7) that were effective in inhibiting NO and iNOS production. In addition, F6 and F7 significantly inhibited the iNOS transcript, while F5 did not cause a reduction in the iNOS transcript. Furthermore, the active fractions showed a differential effect on levels of phospho-p38, phospho-JNK, and phospho-IKB·. Phopsho-p38 was moderately inhibited by F5 and only F7 was significantly active in inhibiting phospho-IKB·. Interestingly, all active fractions significantly enhanced levels of phospho-JNK. In addition, the three active fractions also showed differential inhibitory effects on NF-κB DNA binding activity.

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“…A voucher specimen (GFRI-NS-01) was deposited in the entomopathogenic fungal culture collection of the GFRI. The fruiting bodies were dried at 50˚C, crushed in a blender, and the crude powder was extracted with ethanol at 70˚C for 3 h according to a previous report, producing a 14.6% yield (10). The extract was evaporated at 60˚C under pressure and resuspended in distilled water.…”

Section: Methodsmentioning

confidence: 99%

“…For example, popular and edible mushrooms have been traditionally used to maintain health, and their components have been used in the prevention and treatment of diseases in many countries, including Korea. The n-butanol fraction of Phellinus linteus was effective in eliciting anti-inflammatory activity in RAW264.7 macrophages, inhibiting the production of NO and PGE 2 (10). Cordyceps spp., whose main chemical constituent is cordycepin, have also been demonstrated to confer anti-inflammatory effects.…”

Section: Introductionmentioning

confidence: 97%

The n-butanol fraction of Naematoloma sublateritium suppresses the inflammatory response through downregulation of NF-κB in human endothelial cells

et al. 2012

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Abstract. Naematoloma sublateritium (Fr.) P. Karst is a chestnut mushroom that is currently a popular edible fungus in the USA, Japan, China and Korea. Although its therapeutic potential in the treatment of diseases has been demonstrated, the pharmacological effect of N. sublateritium (NS) has been poorly studied. In the present study, we demonstrate for the first time that NS suppresses TNF-α-induced inflammatory response in human umbilical vein endothelial cells. The n-butanol fraction of NS (BFNS) inhibited TNF-α-induced monocyte adhesion to endothelial cells in a dose-dependent manner. The anti-adhesive activity of BFNS correlated with suppressed expression of vascular cell adhesion molecule-1, intercellular adhesion molecule-1, monocyte chemoattractant protein-1 and interleukin-8 at both the mRNA and protein levels. In addition, BFNS dose-dependently decreased the expression of inducible nitrogen oxygen synthase (iNOS) and cyclooxygenase-2 (COX-2). Notably, BFNS significantly regulated the nuclear factor (NF)-κB transcriptional activity that was activated by TNF-α stimulation. When considered together, these results suggest that BFNS inhibits the expression of TNF-α-induced adhesion molecules in addition to regulating the iNOS/COX-2 pathways through the modulation of NF-κB in endothelial cells. In conclusion, we propose that BFNS may be a potential therapeutic agent against vascular inflammation, such as atherosclerosis. IntroductionAtherosclerosis, a cardiovascular disease, is a leading cause of death worldwide and is the result of a complicated inflammatory processes on the inner wall of large blood vessels. Immune responses can cause vascular endothelial dysfunctions that eventually disturb blood flow (1). In the early pathogenesis of atherosclerosis, the endothelium is activated by a variety of relevant stimuli, including oxidized lipids, cytokines, or signaling molecules such as endotoxins, and viruses, subsequently expressing specific adhesion receptors that enhance mononuclear cell recruitment into the vessel wall (2,3).The immune reactions in atherosclerotic lesions are mediated by nitric oxide (NO) and cyclooxygenase-2 (COX-2) (4). In the physiological function of the endothelium, NO production is required to inhibit monocyte adhesion and smooth muscle cell chemotaxis and proliferation (5). However, high levels of NO, which are produced by inducible NO synthase (iNOS) in response to stimuli, induce subsequent inflammatory reactions, thus contributing to the progression of atherosclerosis (6). COX-2 has also been associated with pro-atherogenic reactions, generating lipid mediators of inflammation, such as prostaglandin E 2 (PGE 2 ) (7).Epidemiological data continue to support the premise that dietary intake of natural products may improve vascular endothelial dysfunction in both in vivo and in vitro atherosclerotic models (8,9). For example, popular and edible mushrooms have been traditionally used to maintain health, and their components have been used in the prevention and treatment of diseases i...

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Phellinus linteus inhibits inflammatory mediators by suppressing redox-based NF-κB and MAPKs activation in lipopolysaccharide-induced RAW 264.7 macrophage

Cited by 127 publications

References 39 publications

Total flavonoids of Hedyotis diffusa Willd inhibit inflammatory responses in LPS-activated macrophages via suppression of the NF-κB and MAPK signaling pathways

Total flavonoids of Hedyotis diffusa Willd inhibit inflammatory responses in LPS-activated macrophages via suppression of the NF-κB and MAPK signaling pathways

Daedalea gibbosa substances inhibit LPS-induced expression of iNOS by suppression of NF-κB and MAPK activities in RAW 264.7 macrophage cells

The n-butanol fraction of Naematoloma sublateritium suppresses the inflammatory response through downregulation of NF-κB in human endothelial cells

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