Yamada Bee Farm Corp.

Fermented royal jelly (fRJ) is generated via the complete bioconversion of the fatty acid 10-hydroxy-2-decenoic acid (10H2DA) into 10-hydroxydecanoic acid (10HDAA). This process occurs through fermentation with the lactic acid bacterium (LAB) Lactobacillus panisapium M1, which was isolated from honeybee queens (Apis mellifera L.). The resultant fRJ contains approximately fivefold higher levels of 10HDAA than RJ and demonstrated enhanced immunostimulatory activity. To further assess the immunological efficacy of fRJ, we performed in vitro assays using Flt3L-induced murine bone marrow-derived plasmacytoid dendritic cells (pDCs). fRJ treatment significantly upregulated activation markers MHC-II, CD86, CD80, and CD40 compared to RJ, with over two-fold higher expression levels. This effect was attributed, in part, to the activity of L. panisapium M1, whereas 10HDAA alone did not reproduce the same response. A pilot open-label clinical trial was conducted in healthy volunteers to evaluate the effect of fRJ on human pDC activation. After four weeks of daily fRJ intake, CD80 expression on peripheral blood pDCs increased by 1.1-fold compared to baseline. These findings suggest that fRJ has the potential to modulate host immune defense through pDC activation.

Royal jelly (RJ), secreted by honeybees, contains major fatty acids such as 10-hydroxy-2-decenoic acid and 10-hydroxydecanoic acid, which are considered to contribute to bone metabolism. However, these fatty acids are rapidly metabolized in the liver following ingestion, resulting in 2-decenoic acid (2DA) and sebacic acid (SA), respectively. Therefore, elucidating the roles of these metabolites in bone metabolism is of considerable importance. In this study, we focused and investigated the effects of 2DA and SA on osteoblast differentiation using osteoblast-lineage cells. SA treatment significantly upregulated the expression of osteoblast marker genes whereas 2DA had no apparent effect. In addition, SA enhanced alkaline phosphatase activity, a typical marker of osteoblast differentiation and mineralization.

Brazilian green propolis (BGP), produced by honey bees, induces beige adipocyte formation and accelerates whole-body energy metabolism. Artepillin C (ArtC), the major cinnamic acid derivative of BGP, induces beige adipocyte formation and increases thermogenesis in inguinal white adipose tissue. However, the effects of BGP on beige adipocyte formation and energy metabolism remain unclear. Therefore, we aimed to examine the effects of BGP on beige adipocyte formation and thermogenesis. We used in vitro and in vivo approaches, such as cell culture and differentiation, component testing, thermogenesis measurement, and calcium influx assay. First, ArtC was confirmed to be a major BGP component contributing to beige adipocyte formation in vitro and in vivo. BGP-induced interscapular brown adipose tissue (iBAT) thermogenesis was not observed upon ArtC stimulation. Thereafter, inhibitory studies revealed that iBAT thermogenesis could be related to the transient receptor potential vanilloid 1 (TRPV1)-sympathetic nervous system channel. Finally, we identified culifolin, a cinnamic acid derivative of BGP, as an active component of this response, which activates calcium signaling in TRPV1-expressing cells. In addition, culifolin administration significantly increased the mouse iBAT temperature to the same extent as increased by BGP. Thus, BGP has a unique biological function in activating the two distinct pathways of brown-adipocyte and beige-adipocyte thermogenesis, contributing to increased energy expenditure.