Abstract
Dehydroabietic acid (DAA) is a naturally occurring diterpene resin acid derived from coniferous plants such as Pinus and Picea. Various bioactive effects of DAA have been studied including antibacterial, antifungal, and anticancer activities. However, the anti-inflammatory mechanism of DAA remains unclear. We evaluated the anti-inflammatory effect of DAA in macrophage cell lines. Dehydroabietic acid clearly reduced nitric oxide (NO) production and inflammatory gene expression decreased according to RT-PCR results. Dehydroabietic acid displayed anti-inflammatory activity at the transcriptional level in results from NF-κB- or AP-1-mediated luciferase assays. To identify the DAA target protein, we investigated NF-κB and AP-1 pathways by Western blotting analysis. Dehydroabietic acid suppressed the activity of proto-oncogene tyrosine protein kinase (Src) and spleen tyrosine kinase (Syk) in the NF-κB cascade and transforming growth factor beta-activated kinase 1 (TAK1) in the AP-1 cascade. Using overexpression strategies, we confirmed that DAA targeted these kinases. Our findings demonstrate the anti-inflammatory effects and molecular mechanism of DAA. This suggests that DAA has potential as a drug or supplement to ameliorate inflammation.
Highlights
Inflammation is an innate defense system of the mammalian body against pathogens. This first line of defense is activated to remove invading pathogens accompanying fever, swelling, pain, and redness [1–3]. Immune cells such as monocytes, macrophages, and neutrophils are rapidly recruited to inflamed sites, recognize foreign invaders, and release chemical mediators [4,5]
In the process of recognition, pathogen recognition receptors (PRRs) of cells need to form a complex with the pathogens’ conserved structure called pathogen-associated molecular patterns (PAMPs) [2,6]
The phosphory7laotfio1n4 of MAPKs was ascertained in a time-dependent manner using LPS-exposed RAW264.7 cells with
Summary
Inflammation is an innate defense system of the mammalian body against pathogens This first line of defense is activated to remove invading pathogens accompanying fever, swelling, pain, and redness [1–3]. Each TLR detects different types of activators including lipids, lipoproteins, glycans, and nucleic acids and initiates the inflammatory signal activation [6,7]. M10ol.tyScpi.e2s0.1E9,a2c0h, 15T9L3R detects different types of activators including lipids, lipoproteins, gly2coafn1s4, and nucleic acids and initiates the inflammatory signal activation [6,7]. TThhee EEffffeecctt ooff DDAAAA oonn NNiittrriicc OOxxiiddee PPrroodduuccttiioonn. TTooeexxaammiinneewwhheetthheerrDDAAAA hhaass aann aannttii--iinnflflaammmmaattoorryy eeffffeecctt,, wwee fifirrsstt iinnvveessttiiggaatteedd tthhee pprroodduuccttiioonn ooff nniittrriicc ooxxiiddee ((NNOO)) uunnddeerr lliippooppoollyyssaacccchhaarriiddee ((LLPPSS)) iinndduuccttiioonn ccoonnddiittiioonnss iinn RRAAWW226644..77 cceellllss. EEffffeeccttss ooff DDAAAA oonn NNOO pprroodduuccttiioonn aanndd ccyyttoottooxxiicciittyy.. CCeellll ssuuppeerrnnaattaannttss wweerree ccoolllleecctteedd,, aanndd tthhee pprroodduuccttiioonn ooff NNOO wwaass mmeeaassuurreedd bbyy GGrriieessss aassssaayy.. ((bb)) CCyyttoottooxxiicciittyy ooff DDAAAA iinn RRAAWW226644..77 cceellllss aanndd HHEEKK229933TT cceellllss.
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