Abietic acid

J Clin Biochem Nutr. 2010 Mar;46(2):119-25.

Tetrahydroabietic Acid, a Reduced Abietic Acid, Inhibits the Production of Inflammatory Mediators in RAW264.7 Macrophages Activated with Lipopolysaccharide.[Pubmed: 20216944 ]

Abietic acid (AA), the main component of the rosin fraction of oleoresin synthesized by conifer species, has been reported to have anti-inflammatory effects. AA is a weak contact allergen; however, compounds resulting from its oxidation by air elicit stronger allergic response. Hydrogenation of the conjugated double bonds of AA, as in tetrahydroAbietic acid (THAA), decreases its susceptibility to air oxidation and would thus reduce the allergenicity of AA. The aim of this study was to investigate whether THAA could exert anti-inflammatory effects to the same extent as AA in RAW264.7 macrophages activated with the endotoxin lipopolysaccharide (LPS).
METHODS AND RESULTS:
THAA and AA inhibited the production of nitric oxide (NO) and prostaglandin E(2) by suppressing the expression of inducible NO synthase and cyclooxygenase-2, respectively, in LPS-activated RAW264.7 macrophages. They also inhibited the LPS-induced production of interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha.
CONCLUSIONS:
Both THAA and AA prevented the LPS-induced nuclear translocation of the nuclear factor-kappaB/p65 subunit, suggesting that THAA may inhibit the production of pro-inflammatory mediators through the same mechanism as AA. In comparison, the anti-inflammatory effects of THAA and AA were almost identical, indicating that THAA retains the anti-inflammatory activity of AA at least in LPS-activated RAW264.7 macrophages.

J Med Food. 2011 Sep;14(9):1052-6.

Abietic acid has an anti-obesity effect in mice fed a high-fat diet.[Pubmed: 21812648]

We investigated the anti-obesity effect of Abietic acid in mice fed a high-fat diet with emphasis on changes in adipogenesis in epididymal adipose tissues.
METHODS AND RESULTS:
Male C57BL/6J mice were divided into four groups and fed a normal diet, a high-fat diet (HFD), or HFD plus oral administration of Abietic acid (20 mg/kg of body weight/day [LA] or 40 mg/kg of body weight/day [HA]) for 8 weeks. Compared with the HFD group, mice orally administered 40 mg of Abietic acid/kg of body weight/day exhibited significantly decreased body weight and adipose tissue weights. Serum triglyceride concentrations in the HA group were significantly lower than those in the HFD group, as were the levels of serum insulin and leptin. Hematoxylin and eosin staining revealed that epididymal adipose tissue mass was decreased by Abietic acid administration. Abietic acid also inhibited the protein expression of sterol regulatory element-binding protein-1c, CCAAT/enhancer-binding protein α, and CD36 in epididymal adipose tissues, which are up-regulated by HFDs.
CONCLUSIONS:
These data demonstrate that Abietic acid has an anti-obesity effect in mice mediated by the regulation of adipogenesis.

Exp Dermatol. 2015 Feb;24(2):140-5.

Abietic acid inhibits UVB-induced MMP-1 expression in human dermal fibroblast cells through PPARα/γ dual activation.[Pubmed: 25496486]

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of ligand-activated transcription factors and consist of three isotypes: PPARα, PPARβ/δ and PPARγ. PPARs are expressed in various cell types in the skin, including keratinocytes, fibroblasts and infiltrating immune cells. Thus, these receptors are highly studied in dermato-endocrine research, and their ligands are targets for the treatment of various skin disorders, such as photoageing and chronological ageing of skin.
METHODS AND RESULTS:
Intensive studies have revealed that PPARα/γ functions in photoageing and age-related inflammation by regulating matrix metalloproteinases (MMPs) via nuclear factor-kappa B (NF-κB) and activator protein-1 (AP-1). However, the detailed mechanism of PPARα/γ's role in photoageing has not yet been elucidated. In this study, we confirmed that Abietic acid (AA) is a PPARα/γ dual ligand and significantly decreased UVB-induced MMP-1 expression by downregulating UVB-induced MAPK signalling and downstream transcription factors, subsequently reducing IκBα degradation and blocking NF-κB p65 nuclear translocation in Hs68 human dermal fibroblast cells. Treatment of cells with AA and GW6471 or bisphenol A diglycidyl ether (BADGE), PPARα or PPARγ antagonists, respectively, reversed the effect on UVB-induced MMP-1 expression and inflammatory signalling pathway activation.
CONCLUSIONS:
Taken together, our data suggest that AA acts as a PPARα/γ dual activator to inhibit UVB-induced MMP-1 expression and age-related inflammation by suppressing NF-κB and the MAPK/AP-1 pathway and can be a useful agent for improving skin photoageing.

FEBS Lett. 2003 Aug 28;550(1-3):190-4.

Abietic acid activates peroxisome proliferator-activated receptor-gamma (PPARgamma) in RAW264.7 macrophages and 3T3-L1 adipocytes to regulate gene expression involved in inflammation and lipid metabolism.[Pubmed: 12935909]

Abietic acid is one of the terpenoids, which are multifunctional natural compounds. It has been reported that Abietic acid suppresses effects on inflammation. However, the mechanism underlying the anti-inflammatory effects remains unclear.
METHODS AND RESULTS:
The present work indicates that Abietic acid suppresses the protein expression of tumor necrosis factor-alpha and cyclooxygenase 2, which are involved in inflammation, in lipopolysaccharide-stimulated macrophages. Moreover, this effect resembles that of thiazolidinedione, a synthetic peroxisome proliferator-activated receptor-gamma (PPARgamma) ligand. Indeed, Abietic acid activates PPARgamma in luciferase reporter assays. The activity of Abietic acid induces PPARgamma target gene expression in RAW264.7 macrophages and 3T3-L1 adipocytes. These data indicate that Abietic acid is a PPARgamma ligand and that its anti-inflammatory effect is partly due to the activation of PPARgamma in stimulated macrophages.
CONCLUSIONS:
The present work suggests a novel possibility that Abietic acid, a naturally occurring compound, can be used not only for anti-inflammation but also for regulating lipid metabolism and atherosclerosis.