Imperatorin Attenuates LPS-Induced Inflammation by Suppressing NF-κB and MAPKs Activation in RAW 264.7 Macrophages

Guo, Wei; Sun, Jingjing; Jiang, Lanxiang; Duan, Lingxin; Huo, Meixia; Chen, Na; Zhong, Weiying; Wassy, Lanan; Yang, Zhen-Guo; Feng, Hailan

doi:10.1007/s10753-012-9495-9

Cited by 73 publications

(41 citation statements)

References 29 publications

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“…It has been reported that three flavonoids (naringin, neoponcirin and poncirin) and three coumarins (umbelliferone, imperatorin and auraptene) isolated from the 70% ethanolic extract of Ponciri fructus have various pharmacological actions including antioxidant [27], anxiolytic-like [28], anticancer [29], and anti-inflammatory effects [30][31][32]. Therefore, we propose that PFE can have antiproliferative and antioxidant effects based on the various pharmacological activities of the chemical-chemical interactions on the development and progression of lesions in a TP-induced model of BPH.…”

Section: Discussionmentioning

confidence: 99%

Inhibitory effects of Ponciri Fructus on testosterone-induced benign prostatic hyperplasia in rats

Jeon

Ohn

Seo

et al. 2017

65th International Congress and Annual Meeting of the Society for Medicinal Plant and Natural Product Research (GA 2017)

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Background: Benign prostatic hyperplasia (BPH) is non-cancerous condition of enlargement of the prostate, a common occurrence in older men. The immature fruits of Poncirus trifoliata (L.) Rafinesque (Rutaceae), Ponciri Fructus are widely used in traditional oriental medicine for the therapy of various diseases. However, little is known about the mechanism underlying the pathogenesis of BPH. In the present study, we investigated the protective effects of a Ponciri Fructus extract (PFE) on the development of BPH in a in a rat model of BPH induced by testosterone propionate (TP). Methods: Male Sprague Dawley rats were used as a model of BPH after its induction by daily subcutaneous injections of TP/corn oil, for a period of four weeks. PFE was administrated daily 1 h before TP/corn oil injection by oral gavage at a dose level of 200 mg/kg during the 4 weeks of TP/corn oil injections. All rats were sacrificed at the end of the experiment, we measured the relative prostate weight, the levels of testosterone and dihydrotestosterone (DHT), histological changes, activities of antioxidant enzymes (catalase, glutathione peroxidase, glutathione reductase, and superoxide dismutase), and expression of proliferating cell nuclear antigen (PCNA). In addition, we also measured the inhibition (%) of 5α-reductase in the prostatic tissue.

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Section: Discussionmentioning

confidence: 99%

Inhibitory effects of Ponciri Fructus on testosterone-induced benign prostatic hyperplasia in rats

Jeon

Ohn

Seo

et al. 2017

65th International Congress and Annual Meeting of the Society for Medicinal Plant and Natural Product Research (GA 2017)

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“…This was in line with results published about the substances imperatorin and roxatidine, which inhibit LPS-induced p38 but not Erk activity in RAW 264.7 macrophages. These substances were shown to downregulate TNF-α and IL-6 production in LPS-stimulated macrophages, implying dispensability for the Erk pathway in this respect [42, 43]. Interestingly, TACE-mediated processing of pre-TNF was demonstrated to be dependent on Erk signaling in LPS-stimulated macrophages [44], indicating cell type-specific regulation of TNF-α production.…”

Section: Discussionmentioning

confidence: 99%

LPS-induced production of TNF-α and IL-6 in mast cells is dependent on p38 but independent of TTP

Hochdörfer

Tiedje

Stumpo

et al. 2013

Cellular Signalling

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The production of the proinflammatory cytokines TNF-α and IL-6 is regulated by various mRNA-binding proteins, influencing stability and translation of the respective transcripts. Research in macrophages has shown the importance of the p38-MK2-tristetraprolin (TTP) axis for regulation of TNF-α mRNA stability and translation. In the current study we examined a possible involvement of p38 and TTP in LPS-induced cytokine production in bone marrow-derived mast cells (BMMCs). Using pharmacological inhibitors we initially found a strong dependence of LPS-induced TNF-α and IL-6 production on p38 activation, whereas activation of the Erk pathway appeared dispensable. LPS treatment also induced p38-dependent expression of the TTP gene. This prompted us to analyze the proinflammatory cytokine response in BMMCs generated from TTP-deficient mice. Unexpectedly, there were no significant differences in cytokine production between TTP-deficient and WT BMMCs in response to LPS. Gene expression and cytokine production of TNF-α and IL-6 as well as stability of the TNF-α transcript were comparable between TTP-deficient and WT BMMCs. In contrast to TTP mRNA expression, TTP protein expression could not be detected in BMMCs. While we successfully precipitated and detected TTP from lysates of LPS-stimulated RAW 264.7 macrophages, this was not accomplished from BMMC lysates. In contrast, we found mRNA and protein expression of the other TIS11 family members connected to regulation of mRNA stability, BRF1 and BRF2, and detected their interaction with 14-3-3 proteins. These data suggest that control of cytokine mRNA stability and translation in MCs is exerted by proteins different from TTP.

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“…After adding LPS, the amount of NO was increased in peritoneal macrophages, yet it was decreased in ethanolstimulated GES-1 cells. It is, therefore, suggested that LPS can bind to the cell membrane receptor of the monocytes/macrophages and endothelial cells so as to activate the signal-transduction system, thus resulting in the synthesis and release of cytokines and inflammatory mediators such as the over expression of iNOS (Guo et al 2012). On the contrary, the expression of cNOS in gastric mucosa cells was reduced significantly after ethanol injury, showing that endogenous NO played an important role in acute gastric injury caused by ethanol.…”

Section: Discussionmentioning

confidence: 99%

The anti-inflammatory activity of several flavonoids isolated fromMurraya paniculataon murine macrophage cell line and gastric epithelial cell (GES-1)

Liu

Shi

2015

Pharmaceutical Biology

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ORIGINAL ARTICLEThe anti-inflammatory activity of several flavonoids isolated from Murraya paniculata on murine macrophage cell line and gastric epithelial cell (GES-1) Context Murraya paniculata (L.) Jack (Rutaceae), Qianlixiang in Chinese, is distributed in China. As an important traditional Chinese medicine (TCM), it demonstrates many bioactivities, such as febrifuge, astringent, anti-dysenteric, and tonic. Objective: The objective of this study is to evaluate the anti-inflammatory effect of three flavonoids isolated from M. paniculata in lipopolysaccharide (LPS)-activated murine macrophage cell line and ethanol-induced gastric damage on gastric epithelial cell (GES-1). Materials and methods Three identified flavonoids were isolated from stems and leaves of M. paniculata using ultra performance liquid chromatography (UPLC). Cell viability was measured with MTT, mouse peritoneal macrophages and GES-1 cells were incubated with 0, 0.01, 0.1, 1, 10, and 100 mM P1, P3 and P8 for 24, 48, and 72 h. The inhibitory effect of pretreatment with various concentrations of 5,7,3 0 ,4 0 ,5 0 -pentamethoxyflavone (P1), 5,7,3 0 ,4 0 -tetramethoxyflavone (P3), or 5-desmethylnobiletin 5-hydroxy-6,7,8,30 ,4 0 -pentameth-oxyflavone (P8) ranging from 0.03 to 30 mM on nitric oxide (NO) secretion was quantified by the Griess assay for 24 and 48 h, while interleukin-6 (IL-6) was measured by ELISA for 24 and 48 h. Results The effects of P1, P3, and P8 on mouse peritoneal macrophages and GES-1 cells were not attributable to cytotoxic effects at the doses of 0-10 mM. The IC 50 value of P1 is 53.40 mM, P3 is 120.98 mM, and P8 is 10.73 mM. The concentration of the three flavonoids had the best effects of anti-inflammation upon NO inhibition at the dose of 3 mM. P3 had the highest inhibition on IL-6 production. The GES-1 cells pretreated with three flavonoids showed a significant increase in the level of NO (P1: 7.94 ± 0.0635 mM, P3: 8.81 ± 0.0159 mM, and P8: 8.51 ± 0.0522 mM) at 24 h and a more significant increase at 48 h (P1: 9.34 ± 0.0975 mM, P3: 11.9 ± 0.0672 mM, and P8: 9.34 ± 0.0454 mM). Discussion and conclusion The current results suggested that the anti-inflammatory activity of three flavonoids was mainly manifested in the reduction of production of NO and IL-6 production. Analysis of the structure-activity relationship indicated that the double bond at C 2 -C 3 and the position of the B ring at C 2 /C 3 seemed to be indispensable for the anti-inflammatory activity.ARTICLE HISTORY

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Imperatorin Attenuates LPS-Induced Inflammation by Suppressing NF-κB and MAPKs Activation in RAW 264.7 Macrophages

Cited by 73 publications

References 29 publications

Inhibitory effects of Ponciri Fructus on testosterone-induced benign prostatic hyperplasia in rats

Inhibitory effects of Ponciri Fructus on testosterone-induced benign prostatic hyperplasia in rats

LPS-induced production of TNF-α and IL-6 in mast cells is dependent on p38 but independent of TTP

The anti-inflammatory activity of several flavonoids isolated fromMurraya paniculataon murine macrophage cell line and gastric epithelial cell (GES-1)

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