Cardamonin inhibits COX and iNOS expression via inhibition of p65NF-κB nuclear translocation and Iκ-B phosphorylation in RAW 264.7 macrophage cells

Israf, Daud Ahmad; Khaizurin, TA; Ahmad, Sadeem; Lajis, Nordin Hj; Khozirah, S.

doi:10.1016/j.molimm.2006.04.025

Cited by 175 publications

(113 citation statements)

References 27 publications

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“…NF-κB is present as a complex with IκB located in the cytoplasm in unstimulated cells. When stimulated, IκB is phosphorylated, ubiquitinated and rapidly degraded, which releases the p65 subunit of NF-κB from IκB, resulting in p65 translocation into the nucleus where it regulates gene transcription (26,27). To explore the mechanism of NF-κB inactivation by TFHDW, the effects of the extract on the LPS-induced phosphorylation of p65 and IκB were examined by western blotting.…”

Section: Discussionmentioning

confidence: 99%

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: 99%

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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“…Under normal physiological conditions, NF-kB forms a cytoplasmic complex with its inhibitors, the IkBs. Once the IkBs become phosphorylated, NF-kB is released and translocates to the nucleus where its target genes are then activated (Israf et al, 2007). Our study results indicated that sophocarpine not only decreased MMP-2 and MMP-9 levels but also inhibited p-IKBa expression in AC rats.…”

Section: Discussionmentioning

confidence: 50%

Oral sophocarpine protects rat heart against pressure overload-induced cardiac fibrosis

Zhao

Chu

et al. 2014

Pharmaceutical Biology

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Context: Sophocarpine, a tetracyclic quinolizidine alkaloid, is one of the most abundant active ingredients in Sophora alopecuroides Linn. (Kudouzi). Sophocarpine injection was found to have significant antiviral effects against coxsackievirus B3 and therapeutic effects for viral myocarditis in the clinic. Objective: This study assessed the effects of sophocapine on overload-induced cardiac fibrosis and investigated potential mechanisms. Materials and methods: Adult male Sprague-Dawley rats were subjected to a suprarenal abdominal aorta constriction (AC) or sham to induce sustained pressure overload. Six weeks later, rats were randomly assigned to receive sophocapine (10, 20, and 40 mg/kg, gavage) or vehicle treatment for an additional 6 weeks. Six weeks after treatment, cardiac dysfunction, cardiac coefficient, cardiac fibrosis, hydroxyproline concentration, and inflammation mediators were examined. Results: When compared with the model group, the left ventricular weight/body weight decreased by 25.4% and 39.0% in 20 and 40 mg/kg sophocarpine groups, respectively. The beneficial effects were associated with amelioration of left ventricular systolic pressure (LVSP) and left ventricular enddiastolic pressure (LVEDP). Moreover, pressure overload-induced cardiac fibrosis was attenuated in sophocarpine treated groups. Importantly, sophocarpine (20 and 40 mg/kg) decreased pro-inflammatory cytokine levels (IL-6, 14.6% and 18.5%; IL-1b, 23.1% and 32.6%), collagen content (27.7% and 50.1%), as well as matrix metalloproteinases-2, 9 (MMP-2, 9) expression (MMP-2, 11.8% and 18.5%; MMP-9, 16.2% and 21.1%). Sophocarpine (40 mg/kg) inhibited IkB-a phosphorylation (19.0%). Conclusion: These findings indicated that sophocarpine potentially had antifibrotic effects. The mechanism might be due to modulation of the balance between pro-inflammatory cytokine expression and collagen content level as well as MMPs expression via the NF-kB signaling pathway.

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“…3 Cardamonin's name comes from the fact that it can be found in cardamom spice (Fig. 4), but since the first article where it was described, 22 it has been found in many other (some of them edible) plant species, such as Alpinia blepharocalyx, 23,24 Alpinia gagnepainii, 25 Alpinia conchigera, 26,27 Alpinia hainanensis, [28][29][30][31][32][33][34][35][36][37][38][39][40] Alpinia malaccensis, 41 Alpinia mutica, 42,43 Alpinia pricei, 44 Alpinia rafflesiana, [45][46][47][48] Alpinia speciosa, 22,49,50 Amomum subulatum, 51 Artemisia absinthium, 52 Boesenbergia pandurata, [53][54][55][56][57][58][59][60] Boesenbergia rotunda, 61,62 Carya cathayensis, 63 Cedrelopsis grevei, 64 Combretum apiculatum, 65 Comptonia pere...…”

Section: Sources Of Cardamoninmentioning

confidence: 99%

“…83 Its interference over the NF-jB pathway and subsequently, the p65NF-jB protein cellular distribution inhibits cyclooxygenase-2 and inducible nitric oxide synthase. 47 It also appears to end up inhibiting prostaglandin E2, tumor necrosis factor a (TNF-a) release, thromboxane B2 production, and intracellular reactive oxygen species generation, all in a dose-dependent manner. 48,54 In most of these studies, RAW264.7 cells were used and analyzed by enzyme-linked immunosorbent assays, western blotting, and interestingly, luciferase gene reporter assays.…”

Section: Health Applicationsmentioning

confidence: 99%

An Overview on Cardamonin

Gonçalves

Valente

Rodrigues

2014

Journal of Medicinal Food

109

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Cardamonin, as shown by the increasing number of publications, has received growing attention from the scientific community due to the expectations toward its benefits to human health. In this study, research on cardamonin is reviewed, including its natural sources, health promoting aspects, and analytical methods for its determination. Therefore, this article hopes to aid current and future researchers on the search for reliable answers concerning cardamonin's value in medicine.

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Cardamonin inhibits COX and iNOS expression via inhibition of p65NF-κB nuclear translocation and Iκ-B phosphorylation in RAW 264.7 macrophage cells

Cited by 175 publications

References 27 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

Oral sophocarpine protects rat heart against pressure overload-induced cardiac fibrosis

An Overview on Cardamonin

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