Identification of AMPN₁-Oxide in Royal Jelly as a Component Neurotrophic toward Cultured Rat Pheochromocytoma PC12 Cells

Royal jelly and its unique fatty acid, 10-hydroxy-trans-2-decenoic acid, promote neurogenesis by neural stem/progenitor cells in vitro

“…For instance, RJ exhibits immunomodulatory properties (3,22,24) and inhibits the development of atoptic dermatitis-like skin lesions (26). Earlier we found that RJ had the ability to induce neurites from cultured rat pheochromocytoma PC12 cells (10), which prompted us to test the effects of RJ and its components on NSCs cultured from the central nervous system (CNS). RJ consists of proteins, sugars, lipids, vitamins, and free amino acids (2,25), and includes various other components such as the unsaturated fatty acid 10-hydroxy-trans-2-decenoic acid (HDEA) (20).…”

Royal jelly-induced neurite outgrowth from rat pheochromocytoma PC12 cells requires integrin signal independent of activation of extracellular signalregulated kinases

“…In response to the binding of NGF to receptors p75 (6) and TrkA (4,19), PC12 cells stop dividing and extend neurites, differentiating into cholinergic cells similar to those found in the sympathetic neurons (10,16). However, the neurite growth-promoting activity of AMP N 1 -oxide was found to be mediated by adenylate cyclase-coupled adenosine A2a receptors (17), the activation of which leads to an increase in the cAMP level to stimulate neurite outgrowth in cultured PC12 cells perature for 2 h with hydrochloric solution (pH 3.0) containing 30 mg/mL collagen type IV (Nitta Gelatin, Osaka, Japan). Various reagents were added to the cells 1 day after plating, and morphological changes were then assessed under a phase-contrast microscope.…”

“…As the signal transduction pathways are mutually different among these molecules, the activity of AMP N 1 -oxide may be influenced and/or modified by endogenous or exogenous active substances. In fact, previous report showed a synergistic effect between AMP N 1 -oxide and NGF on the formation of neurites of longer length (17). The most important and plausible substances to interact with active components of RJ including AMP N 1 -oxide are thought to be extracellular matrix (ECM) components such as fibronectin, laminin or collagen, because they bind to integrin receptors on neurons and transduce signals to elicit neurite outgrowth (3,11).…”

“…We recently found that an extract of RJ induces outgrowth of neurites from cultured PC12 cells, a cell line obtained from rat pheochromocytoma cells (16), and identified AMP N 1 -oxide as one of the active components (17). AMP N 1 -oxide is a unique compound not found in natural products other than RJ; and it suppresses the proliferation of PC12 cells and stimulates the expression of neurofilament M, a specific protein of mature neurons, thus demonstrating that AMP N 1 -oxide can induce neuronal differentiation of PC12 cells (17). PC12 cells have become a principal model for the study about biological activities related to neuronal differentiation.…”

AMP N1-oxide potentiates astrogenesis by cultured neural stem/progenitor cells through STAT3 activation

“…Earlier we reported that an extract of RJ induces neurite outgrowth from cultured PC12 cells, a cell line of rat pheochromocytoma, via adenosine A 2A receptors and identified adenosine monophosphate (AMP) N 1 -oxide as the first active component in royal jelly that affects the nervous system (7). AMP N 1 -oxide is a unique compound not found in natural products other than RJ; and it suppresses the proliferation of PC12 cells and stimulates the expression of neurofilament M, a specific protein of mature neurons in them, thus demonstrating that AMP N 1 -oxide can induce neuronal differentiation of these cells (7). A recent investigation has added the new idea that the AMP N 1 -oxide-induced neurite outgrowth requires integrin signaling (5).…”