Osthole Regulates Inflammatory Mediator Expression through Modulating NF-κB, Mitogen-Activated Protein Kinases, Protein Kinase C, and Reactive Oxygen Species

Liao, Pei‐Chun; Chien, Shih‐Chang; Ho, Chyi-Chen; Wang, Eugene I-Chen; Lee, Shu-Ching; Kuo, Yueh‐Hsiung; Jeyashoke, Narumon; Chen, Jie; Dong, Wei-Chih; Chao, Louis Kuoping; Hua, Kuo-Feng

doi:10.1021/jf102812t

Cited by 98 publications

(106 citation statements)

References 30 publications

(55 reference statements)

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“…In contrast, p38 MAPK inhibitors attenuate renal damage by reducing inflammatory mediator production [23]. Osthole is reported to abrogate p38 MAPK activation in LPS-stimulated macrophages [24]. Consistent with that report, the present data showed that osthole treatment attenuates p38 MAPK activation, contributing to ameliorating the inflammatory response in injured kidneys.…”

Section: Discussionsupporting

confidence: 81%

Osthole Ameliorates Renal Ischemia-Reperfusion Injury by Inhibiting Inflammatory Response

Zheng

Lü²,

Ma³

et al. 2013

Urol Int

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Introduction: Renal ischemia-reperfusion (I/R) injury is a primary cause of acute renal failure that results in high mortality. This study aimed to investigate the effect of osthole, a natural coumarin derivative, on renal I/R injury in a rat model. Materials and Methods: Rats were randomly allocated to the sham operation + vehicle, I/R + vehicle, and I/R + osthole groups. Renal I/R injury was induced by clamping the left renal artery for 45 min followed by 12 h of reperfusion and a contralateral nephrectomy. Osthole (40 mg/kg) was intraperitoneally injected 30 min before inducing I/R. Renal function and histological damage were determined subsequently. Myeloperoxidase activity, monocyte/macrophage infiltration, as well as tumor necrosis factor-α, IL-1β, and activated p38 mitogen-activated protein kinase expression in kidneys were also assessed. Results: Osthole treatment significantly ameliorated I/R-induced renal functional and morphological injuries. Moreover, osthole treatment attenuated myeloperoxidase activity, monocyte/macrophage infiltration, and tumor necrosis factor-α, IL-1β, and activated p38 mitogen-activated protein kinase expression in kidneys. Conclusions: Osthole treatment ameliorates renal I/R injury by inhibiting inflammatory responses in kidneys. Thus, osthole may represent a novel practical strategy to prevent renal I/R injury.

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Section: Discussionsupporting

confidence: 81%

Osthole Ameliorates Renal Ischemia-Reperfusion Injury by Inhibiting Inflammatory Response

Zheng

Lü²,

Ma³

et al. 2013

Urol Int

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“…Another natural coumarin, osthole, which has immunomodulatory activities, also inhibits COX-2 expression in LPS-stimulated macrophages. 26) Our observation that 4-methylcoumarin derivatives reduce COX-2 and iNOS expression is in line with the above mentioned investigation that show the target of these compounds is at the protein expression level.…”

Section: Discussionsupporting

confidence: 78%

“…Previous studies have shown that various coumarin derivatives are able to inhibit LPS-induced NO 10,25,26) and PGE 2 production 10) in macrophages and other investigators have reported the ability of coumarin related compounds in lowering the protein expression of inflammatory enzymes. It has been observed that 7,8-diacetoxy-4-methylcoumarin reduces COX-2 expression in A549 human lung adenocarcinoma cells 27) and other authors, studying the effect of 63 natural oxycoumarin derivatives on LPS-induced inflammation in RAW264.7 cells, showed that many of these compounds inhibited the protein expressions of iNOS and COX-2.…”

Section: Discussionmentioning

confidence: 99%

“…23,26) 4-Methylcoumarin derivatives bearing 7,8-dihydroxy and 7,8-diacetoxy moieties have been reported to be potent antioxidant compounds. [12][13][14] Most of these reports have suggested that 7,8-dihydroxy confers higher activity compared to 7,8-diacetoxy, 13,14) probably due the important contribution of catechol moiety to the antioxidant activity.…”

Section: Discussionmentioning

confidence: 99%

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4-Methylcoumarin Derivatives with Anti-inflammatory Effects in Activated Microglial Cells

Togna

Firuzi

Latina

et al. 2014

Biological & Pharmaceutical Bulletin

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Inflammation contributes to the pathogenesis of neurodegenerative diseases and anti-inflammatory compounds may have a role in prevention or treatment of these pathologies. 4-Methylcoumarins are effective antioxidants with anti-inflammatory properties. In this study, the inhibitory effects of two 4-methylcoumarin derivatives, 7,8-dihydroxy-3-ethoxycarbonylmethyl-4-methylcoumarin (DHEMC) and 7,8-diacetoxy-3-ethoxycarbonylmethyl-4-methylcoumarin (DAEMC) were examined on the inflammatory processes induced by lipopolysaccharide (LPS) in activated primary rat microglial cultures. LPS-induced production of nitric oxide (NO, measured by Griess method) and other pro-inflammatory mediators, thromboxane (TX) B 2 and prostaglandin (PG) E 2 (both determined by radioimmunoassay (RIA)), as well as tumor necrosis factor (TNF)-α (determined by enzyme-linked immunosorbent assay (ELISA)) were inhibited in the presence of 100 µM DHEMC and DAEMC. DAEMC was able to significantly inhibit NO, TXB 2 and TNF-α production also at 50 µM. Both compounds at 100 µM significantly lowered cyclooxygenase-2 (COX-2) protein expression in LPS-stimulated microglial cells measured by Western blot, but only DAEMC showed an inhibitory effect on inducible nitric oxide synthase (iNOS) protein expression at 100 µM. In conclusion, our findings show that 4-methylcoumarin derivatives can modulate inflammatory pathways in microglial cells, probably by acting at the protein expression level.

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“…We previously isolated osthol from C. monnieri fruits and reported antifibrotic activity (Shin et al, 2011). Diverse biological activity of osthol including antitumor, anti-inflammatory, and neuroprotective activities have been also reported (Chao et al, 2014;Chou et al, 2007;Liao et al, 2010;Liu et al, 2010). In the present study, we investigated the melanogenesis inhibitory activity of osthol in B16F10 melanoma cells.…”

Section: Introductionmentioning

confidence: 99%

Optimization of extraction conditions for osthol, a melanogenesis inhibitor fromCnidium monnierifruits

Kim

Liu

et al. 2016

Pharmaceutical Biology

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Context: Coumarin derivatives have been reported to inhibit melanin biosynthesis. Objective: The melanogenesis inhibitory activity of osthol, a major coumarin of the fruits of Cnidium monnieri Cusson (Umbelliferae), and optimized extraction conditions for the maximum yield from the isolation of osthol from C. monnieri fruits were investigated. Materials and methods: B16F10 melanomas were treated with osthol at concentration of 1, 3, and 10 mM for 72 h. The expression of melanogenesis genes, such as tyrosinase, TRP-1, and TRP-2 was also assessed. For optimization, extraction factors such as extraction solvent, extraction time, and sample/solvent ratio were tested and optimized for maximum yield of osthol using response surface methodology with the Box-Behnken design (BBD). Results: Osthol inhibits melanin content in B16F10 melanoma cells with an IC 50 value of 4.9 mM. The melanogenesis inhibitory activity of osthol was achieved not by direct inhibition of tyrosinase activity but by inhibiting melanogenic enzyme expressions, such as tyrosinase, TRP-1, and TRP-2. The optimal condition was obtained as a sample/solvent ratio, 1500 mg/10 ml; an extraction time 30.3 min; and a methanol concentration of 97.7%. The osthol yield under optimal conditions was found to be 15.0 mg/g dried samples, which were well matched with the predicted value of 14.9 mg/g dried samples. Conclusion: These results will provide useful information about optimized extraction conditions for the development of osthol as cosmetic therapeutics to reduce skin hyperpigmentation. ARTICLE HISTORY

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Osthole Regulates Inflammatory Mediator Expression through Modulating NF-κB, Mitogen-Activated Protein Kinases, Protein Kinase C, and Reactive Oxygen Species

Cited by 98 publications

References 30 publications

Osthole Ameliorates Renal Ischemia-Reperfusion Injury by Inhibiting Inflammatory Response

Osthole Ameliorates Renal Ischemia-Reperfusion Injury by Inhibiting Inflammatory Response

4-Methylcoumarin Derivatives with Anti-inflammatory Effects in Activated Microglial Cells

Optimization of extraction conditions for osthol, a melanogenesis inhibitor fromCnidium monnierifruits

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