By Alex Poplawsky, Editor
Originally published February 2008.
Ingestion of royal jelly by honey bee larvae causes them to differentiate into discrete behavioral castes as adults. Could this regal substance have the same effect on neural stem cells to cause them to metamorphose into neurons and glia? Of course I would be spoiling the story if I just told you yes.
The story of royal jelly begins with its discovery, which most likely corresponds with the history of honey. The harvesting of honey begins throughout the entire world during the early Paleolithic to Neolithic periods when it is first described in ancient cave paintings. These nomadic hunters are thought to have painted their successful looting of bee hives prior to the hunt in hopes that life will mimic their art. As time passes, humans begin to settle down and become rooted in agriculture. Apiculture, or the keeping of bees, is also believed to take place during this time and was initially practiced by simply integrating a wild hive into the home. However, it wasn’t until the great masters of beekeeping like the ancient Egyptians, Greeks and Romans when great technological strides were made to mass produce honey, bees wax, and, you guessed it, royal jelly. In these cultures, the medicinal value of honey was highly regarded and is mostly noted as a strong disinfectant. The Great Alexander was even believed to be mummified in the stuff (myth), while jars of still edible honey have been found in Egyptian tombs (fact). As for royal jelly, it was regarded as a skin ointment in Egypt or an ancient Viagra in China. Unfortunately, the bee business soon went the way of the Dodo as sugar cane became cheaper to produce in the New World. The scientific enlightenment of the 18th century and the isolation of antibiotics in the 20th century was almost the final blow to honey in which the “mysterious” healing properties of honey were replaced by reason. Only recently has there been resurgence in the study of royal jelly in the scientific community that may once again bring the bee back to the people.
Royal jelly is secreted by the hypopharyngeal glands that are located in the head of young female worker bees. Contrary to popular belief, royal jelly is not reserved for the queen but is fed to the entire bee brood during the first three days of life. However, once those three days expire, the future female workers and male drones receive only honey and pollen while the to-bee queen is stock piled with royal jelly. As far as science currently understands, this is the only difference that separates the creation of a queen from her subjects. I think this is where the Neuroscience comes in! Components of royal jelly have recently been identified and are being associated with insect social organization and chemicals mimicking neurotrophic factors in vitro and in vivo.
The eusocial behavior of the honey bee has long been in the eye of science and, with the 2006 completion of the honey bee genome project, a genetic link is beginning to be made. One recent study has examined the genes that encode a novel protein subfamily that makes up ~90% of royal jelly protein. These major royal jelly proteins (MRJP) are believed to have evolved from the more ancient yellow protein family, which was made famous by its multifunctional role in Drosophila. Although, the precise biochemical pathway for MRJPs is unknown in the honey bee, it is interesting to think that they may share commonality with the yellow proteins and their role in the fruit fly. In this species, yellow proteins are thought to influence neighboring cells through a dopaminelike receptor and are necessary to initiate male sexual behavior. In a similar way, the MRJPs can be a genetic messenger to designate the social behaviors specific to the queen through oral administration. But how can this knowledge benefit human health?
To move closer to human application, one research group has looked at how royal jelly affects rat embryonic neural stem cell cultures. They found that application of royal jelly to the cell medium promotes the generation of all types of brain cells, including neurons, astrocytes, and oligodendrocytes. They further hypothesized that a single fatty acid (HDEA) that is unique to royal jelly may be to blame. However, when HDEA was applied to the stem cells, there was only a selective increase in neurons. In this way, it is thought that there are still unknown neurotrophic chemicals in royal jelly that are responsible for differentiation of the glial cell lines. Maybe a look into the major royal jelly proteins is next.
The biggest point to note from the previous study is that even adult rat and human brains have neural stem cells that are primed to differentiate. If they are stimulated by exogenous factors like royal jelly, they may be able to replace dead cells associated with certain neurodegenerative diseases. Unfortunately, these royal agents would have to survive digestion and be able to pass through the almost impregnable blood brain barrier to have any effect.
For this reason, a Japanese research group orally administered royal jelly to examine it as a potential for human therapeutics. They discovered an increase in the mRNA expression of glial cell linederived neurotrophic factor, which can protect against neuron cell death in neurodegenerative disorders. Specifically, this neurotrophin is shown to facilitate midbrain dopaminergic neuron survival and, in this way, may be protective against Parkinson’s disease. Secondly, an increase in neurofilament H mRNA was found in the rat hippocampus, which is a protein exclusively expressed in neural axons. Even though the physiological significance of this result has yet to be determined, it could mean that new neuron development is increasing in this brain structure. Also, the hippocampus is one brain structure known to progressively degenerate in Alzheimer’s disease, which could be counteracted by oral administration of royal jelly.
The sweet power of honey has had a profound effect on man since life in caves, but has only made a recent reappearance in the scientific community through its regal equivalent. The physiological actions of royal jelly on eusocial behaviors are slowly being tapped and may shed light on how our individual genetics may dictate our society as a whole. Components of royal jelly are even being isolated and ascribed to neuro-plastic roles in the mammalian brain. Reevaluating the wisdom of the ancients under the modern microscope has uncovered some reason behind the mysticism of royal jelly.