Wednesday, December 23, 2015

The Resin For The Season

Biology concepts – sap, resin, latex, mucilage

Frankincense is a solid material than starts out as a 
liquid that oozes from a tree. In the presence of air, 
the resin turns hard. When burned, many 
fragrant and brain altering compounds are released.
We saw last week that gold doesn't just look good, it has a significant place in biology. This week we take a look at frankincense, a natural tree product prized for its use in sacred rituals. The Catholic Church is the number one purchaser of frankincense, but that may be about to change, especially for medicine. The wise men must have done some heavy thinking before they made their gift choices for Jesus – gift cards are so impersonal.

A 2008 study may have defined just why frankincense is used in religious rituals. Burning the resin releases incensole acetate (IA), one of the resin’s key components, which activates transient receptor potential vanilloid (TRPV3) ion channels in the skin and brain. This ion channel is responsible for mediating a warm feeling in the skin, but TRPV3 channels also mediate brain activity.

The researchers in Israel found that IA activates the cFos transcription factor in the brain, leading to anxiolytic (anxio = anxiety, and lytic = destroying) and anti-depressive feelings. Mice without TRPV3 channels did not show cFos activation or behavior changes when exposed to IA. It appears that burning frankincense makes one feel happier and more in tune with whatever activity is going on at the time, including religious rituals.

The fact that there is a psychoactive agent in frankincense is amazing enough, but there’s more biology to this second gift. Recent evidence indicates that the oils and other compounds in frankincense may save lives– if the trees that produce frankincense don’t disappear in the next 50 years. Unfortunately, their extinction is a distinct possibility – we must save this precious sap, or resin, or whatever it is.

Trees can produce various oozings and liquids. Pancake syrup most often comes from the sap of a maple tree, while your stick of Wrigley’s spearmint uses the latex that exude from many different kinds of plants. Gum drippings may also be used in chewing gum (Chiclets used chicle gum), but gums are now more commonly found in paints and erasers. The aloe vera you use on burns is a type of mucilage, rich in glycoproteins. But many plants, especially coniferous trees, exude resins when they are under attack or are damaged.

Amber is fossilized resin. Scientists learn much from organisms caught 
in it and thus preserved. Recent evidence also shows that amber can 
help us track bug attacks on plants from the days of dinosaurs. 
Gum is semi-solid, and rubbery. The gum shown is chicle, used 
for many years in Chiclets gum. Mucilage is produced by 
many pants, including as a treat and trap for insects in carnivorous
plants like this sundew. Maple sap is clear and dilute when tapped from
a tree. It must be boiled for hours to reduce it to syrup. Latex rubber is 
naturally white. The first car and bicycle tires were all white, not
just white-walled.
Gums can also be used for defense, but are made directly from disintegrating internal plant material. They harden to a certain degree after being exuded from the plant tissue, but are more known for their ability to increase the viscosity of a liquid, due to their long polysaccharide molecules. Bacterial agar plates use a gum from seaweed to grow microorganisms.

Sap is the sugary fluid that travels up and down in the xylem of vascular plants, providing the different structures with carbohydrate to produce ATP at the cellular level. Therefore, sap is a nutritive liquid and all trees produce it – but not all taste good.

Mucilage is similar to sap. It also contains glycoproteins and other carbohydrate-containing molecules, and is important for food and water storage in almost all plants, especially cacti. However, mucilage can be used for other purposes, like luring insects into carnivorous plant traps, such as the flypaper plant.

People used to lick mucilage everyday, but technology has reduced its role in our lives. When mixed with water, mucilage is an adhesive, like on the backs of stamps. You don’t have to lick your computer screen to send an e-mail, so mucilage is less important to us in these modern times.

Resins become definite solids when exposed to air. They are not nutritive, and contain primarily the byproducts and secondary metabolites of other cellular processes. While gums and saps are soluble (will dissolve) in water or fat, resins are stable in water but will dissolve in alcohol.

The reason for resin production is not fully understood. They may play a role in defense or tissue injury, but may instead serve to rid the plant of unneeded or unwanted waste products. Indeed, when trees are cut to harvest frankincense, the first resin produced is discarded, because it contains many toxins and foul smelling chemicals.

The Boswellia sacra tree grows in a harsh
environment. The roots can grip onto stones and
they grow out of the ground as buttresses to keep
the tree stable on the cliff sides.
Resins are produced mostly by coniferous trees (like pine trees). This makes frankincense an exception, since it comes from the Boswellia sacra tree, a deciduous tree (trees that lose their leaves in the winter). Frankincense is different from other resins in another aspect as well, it is technically a gum resin, since it has many compounds that are of the gum variety within its resin. The gum-like essential oils in frankincense are one of the reasons it is sought after as an incense.

B. sacra grows only in the middle eastern countries of Yemen and Oman, and possibly in Somalia. The tree is only 2-7 meters (6-23 ft.) when fully grown, and starts producing resin at a fairly young age of 8-10 years. Its small stature may be due in part to the arid climate that it lives in; there is so little water to be had that B. sacra survives only on the moisture it absorbs from fog.

However uninviting its environment might seem, B. sacra is well adapted to this area and is very finicky in growing anywhere else. In fact, a recent study indicates that they are more finicky than even previously believed. Though living in two different areas (Oman/Yemen vs. Somalia), it had been accepted that these plants were the same species. But based on chemical evaluation of the essential oils of the resins from trees in these two regions, the Oman/Yemen trees of B. sacra are truly different than the B. carterii trees of Somalia.

Initial gas chromatography-mass spectrum analysis did not show significant differences in the kinds of volatile molecules present, but there were large differences in the amounts of the individual compounds in the resin from each species of tree. Later experiments also showed chemical differences in the same compounds from each species.

Yemen and Oman are side by side and Somalia is
just across the Gulf of Aden. But recent studies show
that the frankincense trees that grow in Yemen and
Oman are distinctly different from those in Somalia.
This speciation difference shows that B. sacra REALLY likes to stay close to home. There’s nothing wrong with that, except that the small area that it grows in happens to be one of the most unstable parts of the world. The trees have been over harvested for resin, and this affects the rate at which the trees reproduce. Heavily tapped trees have seeds that germinate only 8-16% of the time, while trees that have not been tapped for resin germinate seeds at a rate of over 80%.

Add goats grazing on the existing trees, global warming, fires, and low genetic diversity in individual stands of trees to the low rate of propagation and this spells trouble for the B. sacra species. Estimates are as dire as a 50% decrease in frankincense production in the next 15 years, to a 90% loss of trees in the next 50 years – but there is hope.

A recent DNA study shows that trees from different parts of the Dhofar region are genetically distinct, and that there is a low level of heterozygosity in the trees of a single area. This low level of genetic diversity results in trees less able to survive changes in environment or biology (genetic diversity is key to natural selection). But some stands show more genetic diversity and arguments are now being made to initiate conservation efforts for the diverse stands, while increasing cross-pollination of the least genetically diverse trees. It is hoped that these efforts, as well as attempts to grow B. sacra in the Sonora Desert of North America, could stave off extinction of B. sacra.
The hippocampus is important in your sense of well-
being. Studies have shown that in people with
depression, the hippocampus is smaller, perhaps from
poor neurogenesis or from increased cell death. Why
the seahorse? In Greek, hippocampus means, “horse sea
monster.” I can see the resemblance.
Why is it important that we save the frankincense trees? Because it is becoming evident that the resinous compounds in frankincense could have great medical benefits to humans – and unhappy mice.

We mentioned above that IA (incensole acetate) of frankincense acts on the brain to increase feelings of well-being. Mice bred to be submissive and to give up (quit) earlier in a test of depressive activity show a much stronger will to live and more positive behaviors when given IA. Recent research in Israel shows that IA influences brain molecular biology, especially in the hippocampus, altering depressive behaviors as much as other chemical interventions. It is hoped that IA may be a viable anti-depressant drug in the future.

This same group showed in 2008 that IA was a significant anti-inflammatory agent, through its inhibitor action on an important transcription factor (called NF-kB) that stimulates expression of inflammatory proteins. In mice with traumatic brain injuries, IA administration resulted in reduced inflammation and pressure on the brain, reduced neuron degeneration, and prevented loss of cognitive function. Their more recent study also indicates that IA is protective in stroke and in the damage that can come after strokes by reintroducing oxygen into the damage part of the brain (when blood flow resumes).

Boswellic acid is also of use in myeloid leukemia, a type
of cancer of the white blood cells. It seems that BA can
induce the cancer cells to commit suicide, and die after a
period of time like most cells do. BA trigger apoptosis by
stimulating the release of important compounds from the
mitochondria, suggesting to the cell that its energy making
organelles are irreparably damaged.
Another compound in frankincense is showing promise as an anti-cancer drug. An essential oil molecule called Boswellic Acid (BA) has been shown to slow the rate of cancer cell growth. A recent study has delineated at least part of the mechanism of BA-mediated inhibition of colorectal tumor growth.

Cancer is the result of mutations in genes that code for the production of proteins that keep cells living, growing, and dividing forever. BA stops the synthesis of some of these proteins. It turns out that BA stimulates production of a micro RNA (miRNA, a short RNA molecule of about 22 nucleotides) that can bind to the messages transcribed from DNA that would be translated into pro-cancer proteins and stop the proteins from being made. Do you think the three kings had any idea that they were giving a gift that can stop inflammation, depression, and cancer – or they did they just think it smelled nice?

Next week – The third of the original gifts, myrrh. There's a biologic reason frankincense and myrrh were given together as gifts, but science didn't figure it out until just a couple of years ago.

Takahashi, M., Sung, B., Shen, Y., Hur, K., Link, A., Boland, C., Aggarwal, B., & Goel, A. (2012). Boswellic acid exerts antitumor effects in colorectal cancer cells by modulating expression of the let-7 and miR-200 microRNA family Carcinogenesis, 33 (12), 2441-2449 DOI: 10.1093/carcin/bgs286

Moussaieff, A., Gross, M., Nesher, E., Tikhonov, T., Yadid, G., & Pinhasov, A. (2012). Incensole acetate reduces depressive-like behavior and modulates hippocampal BDNF and CRF expression of submissive animals Journal of Psychopharmacology, 26 (12), 1584-1593 DOI: 10.1177/0269881112458729

Coppi, A., Cecchi, L., Selvi, F., & Raffaelli, M. (2010). The Frankincense tree (Boswellia sacra, Burseraceae) from Oman: ITS and ISSR analyses of genetic diversity and implications for conservation Genetic Resources and Crop Evolution, 57 (7), 1041-1052 DOI: 10.1007/s10722-010-9546-8
For more information, see:

Resin –

Sap –

Gum –

Latex –

Mucilage –

Boswellia sacra –

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