*2.5. Vitamins, Minerals, and Bioactive Substances*

Pantothenic acid (vitamin B5) is the most abundant vitamin in RJ (52.8 mg/100 g), followed by niacin (42.42 mg/100 g). RJ contains small amounts of various B group vitamins (B1, B2, B6, B8, B9, and B12), ascorbic acid (vitamin C), vitamin E, and vitamin A [18,22]. Gardner (1948) noted that pantothenic acid of RJ is a lifespan-extending agent [54].

Mineral salts constitute 1.5% of RJ content [18]. Inductively coupled plasma optical emission spectroscopy and double focusing magnetic sector field inductively coupled plasma mass spectrometry indicate that RJ contains small amounts of various minerals and trace elements such as K, Na, Mg, Ca, P, S, Cu, Fe, Zn, Al, Ba, Sr, Bi, Cd, Hg, Pb, Sn, Te, Tl, W, Sb, Cr, Mn, Ni, Ti, V, Co, and Mo. Whereas concentrations of trace and mineral elements in honey vary according to botanical origin, RJ content of trace elements and minerals is highly constant. In this respect, RJ can be considered a form of larval lactation that possesses homeostatic adjustment, same as mammalian and human breast milk [55].

RJ contains high amounts of acetylcholine (Ach, 4–8 mM), and RJ concentration of Ach is highly conserved because of its acidic pH [56]. It is well-known that Ach acts as a neurotransmitter that plays a major role in memory formation and cognitive functioning. Glucose metabolism and insulin contribute to Ach synthesis by controlling the activity of choline acetyltransferase [57]. In this respect, consumption of RJ may prevent the development of cognitive dysfunction thanks to its Ach content. In addition, Ach content of RJ has a survival promoting effect [56].

RJ is rich in nucleotides such as free bases (e.g., adenosine, uridine, guanosine, iridin, and cytidine) and phosphates (e.g., adenosine diphosphate (ADP), adenosine triphosphate (ATP), and adenosine monophosphate (AMP)). Nucleotides constitute 2682.9 mg/kg and 3152.8 mg/kg in fresh and commercial RJ, respectively. Levels of ADP, ATP, and AMP are higher in fresh RJ, and therefore, they can signify RJ freshness. These compounds are necessary for organisms' physiological activities e.g., metabolic degradation of intracellular ATP is essential to provide cells with energy necessary for transport systems and enzymatic activities of proteins [22,58]. Among all nucleotides, AMP N1-oxide is considered a unique active component that exists nowhere in nature except in RJ. AMP N1-oxide demonstrates neurogenic and neurotrophic activities: it stimulates neurite outgrowth and induces differentiation of PC12 cells into neurons similar to sympathetic neurons. This action is similar to that of nerve growth factor, which functions through activation of two cascades of cellular signaling *MAPK*/extracellular signal-regulated kinase 1 or 2 (*ERK1*/*2*) and phosphatidylinositol 3-kinase/*Akt* pathways. The neurite outgrowth-promoting activity of AMP N1-oxide is mediated by adenylate cyclase-coupled adenosine A2A receptors, which are highly expressed in the brain (striatum in particular)—adenosine A2A receptors prevent radical formation and apoptosis, and they contribute to early neuronal development and regulation of synaptic plasticity [18,59].
