Costunolide inhibits production of tumor necrosis factor-α and interleukin-6 by inducing heme oxygenase-1 in RAW264.7 macrophages

Pae, Hyun‐Ock; Jeong, Gil‐Saeng; Kim, H.-S.; Woo, Won-Hong; Rhew, Hyun Yul; Kim, H. S.; Sohn, Dong Hwan; Kim, Y.-C.; Chung, Hun‐Taeg

doi:10.1007/s00011-007-7015-4

Cited by 41 publications

(28 citation statements)

References 43 publications

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“…Rana et al reported downregulation of RANKL by Nrf2 activation [36]. Furthermore, another famous osteoclastogenic cytokine TNF-α is downregulated by Nrf2 activation [37]. Therefore, further investigations, especially of potential indirect effects of 7R-ETGE peptide on osteoclastogenesis -i.e.…”

Section: Discussionmentioning

confidence: 96%

Nuclear Nrf2 Induction by Protein Transduction Attenuates Osteoclastogenesis

Kanzaki

Shinohara

Kajiya

et al. 2014

Free Radical Biology and Medicine

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It has been reported that reactive oxygen species (ROS) play a role as intracellular signaling molecules in RANKL stimulation. Previously we demonstrated that induction of cytoprotective enzyme expression by Nrf2-gene transfer successfully ameliorated RANKL-dependent osteoclastogenesis. In the present study, we hypothesized that Nrf2 activation by inhibiting ubiquitination and degradation of Nrf2 by ETGE-peptide would induce Nrf2-dependent cytoprotective enzyme expression, attenuate ROS signaling, and thereby inhibit RANKL-dependent osteoclastogenesis. ETGE-peptide containing a cell-permeable sequence (seven consecutive arginine; 7R-ETGE) was applied to a mouse macrophage cell-line RAW 264.7 cell or a primary macrophage culture. ETGE-peptide prevents Keap1 from binding to Nrf2. Nrf2 nuclear translocation and Nrf2-dependent cytoprotective enzyme induction was observed. The effects of 7R-ETGE on RANKL-dependent induction of intracellular ROS levels and osteoclastogenesis were examined. Finally, the protective effect of 7R-ETGE on RANKL-mediated bone destruction was investigated in mice. 7R-ETGE dose-dependently induced nuclear Nrf2, followed by the induction of cytoprotective enzyme expression at both the gene and protein level. 7R-ETGE inhibited upregulation of intracellular ROS levels by RANKL stimulation, and osteoclastogenesis was attenuated. Of particular interest was that local injection of 7R-ETGE ameliorated RANKL-mediated bone destruction. Local induction of nuclear Nrf2 by protein transduction is a potential novel therapeutic target for bone destruction diseases such as periodontitis and rheumatoid arthritis.

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Section: Discussionmentioning

confidence: 96%

Nuclear Nrf2 Induction by Protein Transduction Attenuates Osteoclastogenesis

Kanzaki

Shinohara

Kajiya

et al. 2014

Free Radical Biology and Medicine

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“…As a medicine, costunolide is a famous sesquiterpene lactone, which is used as popular herbal remedies, with anti-ulcer (Matsuda et al, 2002;Pandey et al, 2007), anti -inflammatory (Kassuya et al, 2009;Macias et al, 1999;Mondranondra et al, 1990;Pae et al, 2007;Park et al, 1996;Song et al, 2001;Stefani et al, 2006), anti-fungal (Barrero et al, 2000;Kang et al, 2004;Wedge et al, 2000), anti-viral properties (Chen et al, 1995), Antipyretic (Kassuya et al, 2009), antimycobacterial activities (Fischer et al, 1998;Luna-Herrera et al, 2007), and inhibition of the cellular production of melanin (Choi et al, 2008), human lamin-B by farnesyl-protein transferase (FPTase) (Park et al, 2001b), and protein tyrosine phosphatase 1B (hPTP1B) (Li et al, 2006). Costunolide exhibited strong larvicidal activity against A. albopictus (Liu et al, 2011b).…”

Section: Biological Functionsmentioning

confidence: 99%

Costunolide: A novel anti-cancer sesquiterpene lactone

Rasul

Parveen

2012

Bangladesh J Pharmacol

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Costunolide: A novel anti Costunolide: A novel anti Costunolide: A novel anti---cancer cancer cancer sesquiterpene lactone sesquiterpene lactone sesquiterpene lactone BJP IntroductionCancer is the leading cause of death and represents one of the most threatening diseases worldwide. In the recent report, it has been estimated that 12.7 million new cancer cases and 7.6 million cancer deaths occur in 2008, with 56% of new cancer cases and 63% of the cancer deaths occurring in the less developed regions of the world (Ferlay et al., 2010). Throughout the history of civilization, the human have relied on natural products as a primary source of medicine. Herbal medicines have been proven to be an important source of novel agents with a pharmaceutical potential. Many anti-cancer drugs in current use are either natural products or are derived from natural products. Herbal medicines, such as paclitaxel, camptothecin, vinca alkaloids, and etoposide hold great potential as promising agents for the treatment of cancer (Cragg and Newman, 2005). Natural products have tradition-ally provided a rich source of drugs for many diseases, including cancer and plants are an important source of novel natural products (Amin et al., 2009). In 2008, of the 225 drugs being developed, 164 were of natural origin, with 108 being derived from plants, 25 from bacterial sources, 7 from fungal and 24 from animal sources. And, to throw some more numbers around, of the 108 plant-based drugs, 46 were in preclinical development, 14 in phase I, 41 in phase II, 5 in phase III and two had already reached pre-registration stage (Harvey, 2008). David Newman and Gordon Cragg (Newman and Cragg, 2007) found that of 155 FDA-approved small molecule anti-cancer drugs, 47% were either natural products or directly derived there from.C o s t u n o l i d e ( 6 E , 1 0 E , 1 1 a R ) -6 , 1 0 -d i m e t h y l -3 -methylidene-3a, 4,5,8,9,11a-hexahydrocyclodeca [b] furan-2-one) is a sesquiterpene lactone. It is a colorless crystalline powder with molecular formula of C15H20O2 and molecular weight of 232.318 g/mol (Figure 1). This review is aimed to summarize the recent researches on costunolide focusing on anti-cancer activity and to lay emphasis on molecular mechanisms which suggests a promising for such pursuits in oncology. Literature was searched through Pub Med, Scopus and Elsevier Science Direct Journal. Access to the Elsevier Science Direct Journal was made possible through library of AbstractCurrently an ample interest is found among oncologists to explore anti-cancer compounds from herbs. Sesquiterpene lactones have accredited significant attention in pharmacological research. Costunolide is a well-known sesquiterpene lactone present in plants used as popular herbal remedy. Several plantderived compounds are currently successfully employed in cancer treatment. Growing evidences demonstrated that costunolide possesses anti-cancer activities by inhibiting cell proliferation, tumor invasion, angiogenesis, metastasis and inducing apoptosis of a variety of tumor...

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“…3). Actually, HO-1 reduces the production of tumor necrosis factor (TNF)-a, interleukin (IL)-1b, and IL-6, whereas it enhances IL-10 expression in vitro (183,197). In addition, HO-1 upregulation blocks IL-18 signaling and reduces IL-18-dependent vascular injury and inflammation (297).…”

Section: A Cytokines Chemokines and Mediatorsmentioning

confidence: 99%

Heme Oxygenase in the Regulation of Vascular Biology: From Molecular Mechanisms to Therapeutic Opportunities

Kim

Pae

Park

et al. 2011

Antioxidants & Redox Signaling

185

171

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Heme oxygenases (HOs) are the rate-limiting enzymes in the catabolism of heme into biliverdin, free iron, and carbon monoxide. Two genetically distinct isoforms of HO have been characterized: an inducible form, HO-1, and a constitutively expressed form, HO-2. HO-1 is a kind of stress protein, and thus regarded as a sensitive and reliable indicator of cellular oxidative stress. The HO system acts as potent antioxidants, protects endothelial cells from apoptosis, is involved in regulating vascular tone, attenuates inflammatory response in the vessel wall, and participates in angiogenesis and vasculogenesis. Endothelial integrity and activity are thought to occupy the central position in the pathogenesis of cardiovascular diseases. Cardiovascular disease risk conditions converge in the contribution to oxidative stress. The oxidative stress leads to endothelial and vascular smooth muscle cell dysfunction with increases in vessel tone, cell growth, and gene expression that create a pro-thrombotic= pro-inflammatory environment. Subsequent formation, progression, and obstruction of atherosclerotic plaque may result in myocardial infarction, stroke, and cardiovascular death. This background provides the rationale for exploring the potential therapeutic role for HO system in the amelioration of vascular inflammation and prevention of adverse cardiovascular outcomes. Antioxid. Redox Signal. 14, 137-167.

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Costunolide inhibits production of tumor necrosis factor-α and interleukin-6 by inducing heme oxygenase-1 in RAW264.7 macrophages

Abstract: Costunolide is an effective HO-1 inducer capable of inhibiting macrophage-derived pro-inflammatory cytokines. CH2-BL moiety of costunolide is essential for Nrf2 activation leading to HO-1 expression.

Cited by 41 publications

References 43 publications

Nuclear Nrf2 Induction by Protein Transduction Attenuates Osteoclastogenesis

Nuclear Nrf2 Induction by Protein Transduction Attenuates Osteoclastogenesis

Costunolide: A novel anti-cancer sesquiterpene lactone

Heme Oxygenase in the Regulation of Vascular Biology: From Molecular Mechanisms to Therapeutic Opportunities

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