10-Hydroxy-2-decenoic acid

Therapeutic Properties of Bioactive Compounds from Different Honeybee Products.[Pubmed:28701955]

Front Pharmacol. 2017 Jun 28;8:412.

Honeybees produce honey, royal jelly, propolis, bee venom, bee pollen, and beeswax, which potentially benefit to humans due to the bioactives in them. Clinical standardization of these products is hindered by chemical variability depending on honeybee and botanical sources, but different molecules have been isolated and pharmacologically characterized. Major honey bioactives include phenolics, methylglyoxal, royal jelly proteins (MRJPs), and oligosaccharides. In royal jelly there are antimicrobial jelleins and royalisin peptides, MRJPs, and hydroxy-decenoic acid derivatives, notably 10-Hydroxy-2-decenoic acid (10-HDA), with antimicrobial, anti-inflammatory, immunomodulatory, neuromodulatory, metabolic syndrome preventing, and anti-aging activities. Propolis contains caffeic acid phenethyl ester and artepillin C, specific of Brazilian propolis, with antiviral, immunomodulatory, anti-inflammatory and anticancer effects. Bee venom consists of toxic peptides like pain-inducing melittin, SK channel blocking apamin, and allergenic phospholipase A2. Bee pollen is vitaminic, contains antioxidant and anti-inflammatory plant phenolics, as well as antiatherosclerotic, antidiabetic, and hypoglycemic flavonoids, unsaturated fatty acids, and sterols. Beeswax is widely used in cosmetics and makeup. Given the importance of drug discovery from natural sources, this review is aimed at providing an exhaustive screening of the bioactive compounds detected in honeybee products and of their curative or adverse biological effects.

Comparison of salting-out and sugaring-out liquid-liquid extraction methods for the partition of 10-hydroxy-2-decenoic acid in royal jelly and their co-extracted protein content.[Pubmed:29247927]

J Chromatogr B Analyt Technol Biomed Life Sci. 2018 Jan 15;1073:90-95.

Homogeneous liquid-liquid extraction (h-LLE) has been receiving considerable attention as a sample preparation method due to its simple and fast partition of compounds with a wide range of polarities. To better understand the differences between the two h-LLE extraction approaches, salting-out assisted liquid-liquid extraction (SALLE) and sugaring-out assisted liquid-liquid extraction (SULLE), have been compared for the partition of 10-Hydroxy-2-decenoic acid (10-HDA) from royal jelly, and for the co-extraction of proteins. Effects of the amount of phase partition agents and the concentration of acetonitrile (ACN) on the h-LLE were discussed. Results showed that partition efficiency of 10-HDA depends on the phase ratio in both SALLE and SULLE. Though the partition triggered by NaCl and glucose is less efficient than MgSO4 in the 50% (v/v) ACN-water mixture, their extraction yields can be improved to be similar with that in MgSO4 SALLE by increasing the initial concentration of ACN in the ACN-water mixture. The content of co-extracted protein was correlated with water concentration in the obtained upper phase. MgSO4 showed the largest protein co-extraction at the low concentration of salt. Glucose exhibited a large protein co-extraction in the high phase ratio condition. Furthermore, NaCl with high initial ACN concentration is recommended because it produced high extraction yield for 10-HDA and the lowest amount of co-extracted protein. These observations would be valuable for the sample preparation of royal jelly.

Long-Term Administration of Queen Bee Acid (QBA) to Rodents Reduces Anxiety-Like Behavior, Promotes Neuronal Health and Improves Body Composition.[Pubmed:29295499]

Nutrients. 2017 Dec 23;10(1). pii: nu10010013.

BACKGROUND: Queen bee acid (QBA; 10-Hydroxy-2-decenoic acid) is the predominant fatty acid in royal jelly (RJ) and has activity at estrogen receptors, which affect brain function and body composition. However, few, long-term studies have assessed QBA effects in brain health and body composition. METHODS: Primary hippocampal neurons were treated with QBA (0-30 microM) and challenged with glutamate or hypoxia. QBA was fed to aged, male Sprague-Dawley rats (12-24 mg/kg/day) and to adult male and female Balb/C mice (30-60 mg/kg/day) for >/=3.5 months. Rats were evaluated in a behavioral test battery of brain function. Mice were measured for fat and muscle composition, as well as bone density. RESULTS: QBA increased neuron growth and protected against glutamate challenge and hypoxia challenge. Rats receiving QBA had reduced anxiety-like behavior, increased body weight, and better maintenance of body weight with age. Mice receiving QBA exhibited increased body weight, muscle mass, and adiposity in males, and increased bone density, but decreased adiposity, in females. CONCLUSIONS: QBA is an active component of RJ that promotes the growth and protection of neurons, reduces anxiety-like phenotypes, and benefits bone, muscle and adipose tissues in a sex-dependent manner, which further implicates estrogen receptors in the effects of QBA.

In Vitro Anti-Inflammatory Effects of Three Fatty Acids from Royal Jelly.[Pubmed:27847405]

Mediators Inflamm. 2016;2016:3583684.

Trans-10-Hydroxy-2-decenoic acid (10-H2DA), 10-hydroxydecanoic acid (10-HDAA), and sebacic acid (SEA) are the three major fatty acids in royal jelly (RJ). Previous studies have revealed several pharmacological activities of 10-H2DA and 10-HDAA, although the anti-inflammatory effects and underlying mechanisms by which SEA acts are poorly understood. In the present study, we evaluated and compared the in vitro anti-inflammatory effects of these RJ fatty acids in lipopolysaccharide-stimulated RAW 264.7 macrophages. The results showed that 10-H2DA, 10-HDAA, and SEA had potent, dose-dependent inhibitory effects on the release of the major inflammatory-mediators, nitric oxide, and interleukin-10, and only SEA decreased TNF-alpha production. Several key inflammatory genes have also been modulated by these RJ fatty acids, with 10-H2DA showing distinct modulating effects as compared to the other two FAs. Furthermore, we found that these three FAs regulated several proteins involved in MAPK and NF-kappaB signaling pathways. Taken together, these findings provide additional references for using RJ against inflammatory diseases.

10-Hydroxy-2-decenoic acid prevents ultraviolet A-induced damage and matrix metalloproteinases expression in human dermal fibroblasts.[Pubmed:23030720]

J Eur Acad Dermatol Venereol. 2013 Oct;27(10):1269-77.

BACKGROUND: 10-Hydroxy-2-decenoic acid (10-HDA) is a major fatty acid component of royal jelly, which has been reported to have a variety of beneficial pharmacological characteristics. However, the effects of 10-HDA on skin photoageing and its potential mechanism of action are unclear. OBJECTIVE: We investigated the protective effects of 10-HDA on ultraviolet (UV) A-induced damage in human dermal fibroblasts (HDFs). We then explored the inhibitory effects of 10-HDA on UVA-induced matrix metalloproteinases (MMPs) expression and elucidated the signalling pathways controlling MMPs inhibition. METHODS: Primary human dermal fibroblasts were exposed to UVA. Cell proliferation, cellular senescent state and collagen content were analysed using CCK-8, senescence-associated beta-galactosidase staining and Sircol collagen assay, respectively. Fluorometric assays were performed to detect the formation of reactive oxygen species (ROS) in the cells. The mRNA levels of MMP-1, MMP-3 and type I (alpha1) collagen were determined by quantitative real-time PCR. Western blot was applied to detect the expression of MMP-1, MMP-3, JNK and p38 MAPK. RESULTS: HDFs treated with 10-HDA were significantly protected from UVA-induced cytotoxicity, ROS, cellular senescence and stimulated collagen production. Moreover, 10-HDA suppressed the UVA-induced expression of MMP-1 and MMP-3 at both the transcriptional and protein levels. Treatment with 10-HDA also reduced the UVA-induced activation of the JNK and p38 MAPK pathways. CONCLUSION: The data obtained in this study provide evidence that 10-HDA could prevent UVA-induced damage and inhibit MMP-1 and MMP-3 expressions. Therefore, 10-HDA may be a potential agent for the prevention and treatment of skin photoageing.

10-Hydroxy-2-decenoic acid, a unique medium-chain fatty acid, activates 5'-AMP-activated protein kinase in L6 myotubes and mice.[Pubmed:23754629]

Mol Nutr Food Res. 2013 Oct;57(10):1794-802.

SCOPE: 10-Hydroxy-2-decenoic acid (10H2DA) is one of the unique medium-chain fatty acids (MCFAs) specifically found in royal jelly. We hypothesize that 10H2DA has multiple biological functions and may aid in 5'-AMP-activated protein kinase (AMPK) activation and affect the glucose transport system in skeletal muscle. METHODS AND RESULTS: We examined whether various MCFAs present in royal jelly activated AMPKalpha. Treatment of L6 myotubes with various MCFAs showed that 10H2DA administration resulted in a significant increase in phosphorylated AMPKalpha. 10H2DA activates AMPK independently of insulin and significantly increased glucose uptake into L6 myotubes following translocation of glucose transporter 4 (Glut4) to the plasma membrane (PM). The activation was induced by the upstream kinase Ca(2)(+)/calmodulin-dependent kinase kinase beta, but was independent of changes in AMP:ATP ratio and the liver kinase B1 pathway. Oral administration of 10H2DA significantly stimulated phosphorylation of AMPK and Glut4 translocation to the PM in mouse skeletal muscle. CONCLUSION: These findings indicate that (i) 10H2DA activates AMPK, and insulin independently enhances glucose uptake following translocation of Glut4 to PM, (ii) activation of AMPKalpha by 10H2DA is mediated via extracellular Ca(2)(+)-dependent Ca(2)(+)/calmodulin-dependent kinase kinase beta, without alteration in the AMP:ATP ratio, and liver kinase B1 was not involved in the activation.

10-Hydroxy-2-decenoic acid inhibiting the proliferation of fibroblast-like synoviocytes by PI3K-AKT pathway.[Pubmed:26050632]

Int Immunopharmacol. 2015 Sep;28(1):97-104.

To reveal the mechanism of 10H2DA inhibiting the proliferation of fibroblast-like synoviocytes (FLSs) of RA patients. Cell proliferation, HDAC activity and histone acetylation level of FLS cells treated with 10H2DA were detected by MTT assay, Colorimetric HDAC Activity Assay and Western-blot. Different genes in FLS cells from RA patients were primary cultured and treated with 10H2DA. They were then screened by Human Transcriptome 1.0 ST microarrays and verified by real-time PCR. The results showed dose-dependent and time-dependent decreases in cell viability and HDAC activity in FLSs treated with 10H2DA, and time-dependent induction in the acetylation of H3 and H4 at the same time. 697 different genes were identified by HTA 1.0. The expressions of 7 target genes of the PI3K-AKT pathway were decreased and 4 target genes of cytokine-cytokine receptor interaction were increased verified by real-time PCR. These results imply that 10H2DA is a potential HDACI which inhibits the proliferation of FLS cells by PI3K-AKT pathway.

The functional property of royal jelly 10-hydroxy-2-decenoic acid as a melanogenesis inhibitor.[Pubmed:28793915]

BMC Complement Altern Med. 2017 Aug 9;17(1):392.

BACKGROUND: It has been reported that royal jelly would reduce melanin synthesis and inhibit the expression of melanogensis related proteins and genes. In this study, we evaluate the anti-melanogenic and depigmenting activity of 10-Hydroxy-2-decenoic acid (10-HDA) from royal jelly of Apis mellifera. METHODS: In this study, we assesses the 10-HDA whitening activity in comparison with the changes in the intracellular tyrosinase activity, melanin content and melanin production related protein levles in B16F1 melanoma cells after treating with 10-HDA. Furthermore, the skin whitening effect was evaluated by applying a cream product containing with 0.5%, 1% and 2% of 10-HDA onto the skin of mice (C57BL/6 J) for 3 week to observe the effect of DL*-values. RESULTS: The results showed that 10-HDA inhibited the MITF protein expression (IC50 0.86 mM) in B16F1 melanoma cells. Western blot analysis revealed that 10-HDA inhibited the activity of tyrosinase and the expression of tyrosinase-related protein 1 (TRP-1), TRP-2, and microphthalmia-associated transcription factor (MITF) in B16F1 melanoma cells. In addition, the 10-HDA was applied on the skin of mice show significantly increased the average skin-whitening index (L value). CONCLUSIONS: The validation data indicated the potential of 10-HDA for use in suppressing skin pigmentation. The 10-HDA is proposed as a candidate to inhibit melanogenesis, thus it could be developed as cosmetics skin care products.

10-Hydroxy-2-decenoic acid, a major fatty acid from royal jelly, inhibits VEGF-induced angiogenesis in human umbilical vein endothelial cells.[Pubmed:18955252]

Evid Based Complement Alternat Med. 2009 Dec;6(4):489-94.

Vascular endothelial growth factor (VEGF) is reported to be a potent pro-angiogenic factor that plays a pivotal role in both physiological and pathological angiogenesis. Royal jelly (RJ) is a honeybee product containing various proteins, sugars, lipids, vitamins and free amino acids. 10-Hydroxy-2-decenoic acid (10HDA), a major fatty acid component of RJ, is known to have various pharmacological effects; its antitumor activity being especially noteworthy. However, the mechanism underlying this effect is unclear. We examined the effect of 10HDA on VEGF-induced proliferation, migration and tube formation in human umbilical vein endothelial cells (HUVECs). Our findings showed that, 10HDA at 20 microM or more significantly inhibited such proliferation, migration and tube formation. Similarly, 10 microM GM6001, a matrix metalloprotease inhibitor, prevented VEGF-induced migration and tube formation. These findings indicate that 10HDA exerts an inhibitory effect on VEGF-induced angiogenesis, partly by inhibiting both cell proliferation and migration. Further experiments will be needed to clarify the detailed mechanism.