The Cannaconnection. lists three strains that are high in geraniol without giving other terpenes. It would almost be easier to just supplement with an essential oil such as rose oil. Citronella oil, like rose oil, is rich in geraniol and its chemical cousin citronellol. The featured paper will mention nerol, also found in lemongrass and rose oil. Both nerol and geraniol are citronelol with an extra double bond. Geraniol has a trans double bond whereas nerol has a cis double bond.
Introduction to response elements
The featured study does not make sense until one reads background information from the laboratory published in 2000. The upstream regulatory portion of the COX-2 gene (nucleotide −327/+59) was hooked to the protein coding portion of the gene for luciferase. When the cell thinks it is making Cox2 it makes a bioluminescent enzyme called luciferase.  Another construct was used to measure PPAR activity tk-PPREx3-Luc, This is three tandem peroxisome proliferator response elements,
Response elements are short sequences in the promoters of genes that bind to proteins that sense changes in the cell’s environment. The promoter is upstream of the part of the gene that codes for protein. When transcription factors bind to the response elements enzymes that transcribe the gene sequence into mRNA are recruited. mRNA is what gets translated into proteins.
- NFκ-B is a DNA that lives inside the cell. It is activated by dangerous events that occur outside the cell such as ionizing radiation, reactive oxygen species, and lipopolysaccharide (LPS) from the cell membranes of bacteria.
- The NF-IL6 binds the transcription faction CEBPB that controls their transcription of the interleukin 6 (IL6) as well as the IL-1 gene.
- CRE is the cyclic AMP response element. It is the binding site of the cAMP response element binding protein CREB. Wikipedia authors report 750,000 palindromic and half-site CREs in the human genome that remain turned off due to methylation. The CRE upstream of the Cox2 gene may be part of the anti-inflammatory effect of THC that will be explored later.
- The PPARs are activated by numerous derivatives of arachidonic acid and responsible for controlling the transcription of genes involved in metabolism. There has got to be an endocannabinoid connection somewhere.
Terpenes geraniol and citronellol control response selements
This study came out of Department of Food Science and Nutrition, Nara Womens University, Nara Japan Department of Food Science and Nutrition, Nara Womens University, Nara Japan. This particular group has a history of analyzing the biological action of components of essential oils. The principal constituents are geraniol and citronelliol. Rose oil has a tradition of being used as an anti inflammatory. Is this due to inhibition of cyclooxygenase 1, the constituent isoform, or Cox2, the deducible isoform? Second, what is the upstream mechanism? Let’s tale a tour of the paper figure by figure.
Figure 1. from ref , Just rose oil…
1A Rose oil reverses LPS activation of Cox2 promoter
the COX-2 Promoter activity measured by luciferase activity in bovine aorta endothelial cells (BAEC) generically engineered to express PPAR transcription factors. BAEC were incubated for 5 h with 0.01% rose oil and 1 mg/mL LPS. p<0:05, p<0:01, p < 0:001, compared with cells treated with 1 mg/mL of LPS .The rose oil does not bring things down to the level of the control, but it cuts in half the full LPS response.
1B Rose oil turns on PPARs
BAECs were transiently transfected with not only human PPAR expression systems to ramp up production of these transcription factors but also a PPRE-luc reporter system to determine if the PPAR transcription factors were being activated. BAEC were incubated for 24 hours with 0.01% rose oil. The cells were harvested, lysed, and assayed for their luciferase activity. Data are means SD. *p<0.05, **p<0.01, ***p < 0:001, compared with ethanol as the control . Because the PPAR expression system is constant and some other controls that are not being discussed on this post, the luciferase activity reflects only rose oil components binding to PPARs.
C. Rose oil contains…
Rose oil was analyzed by GC and GC-MS. Only three of the top 15 components are shown here.
Figure 2 Citronellol goes trans or cis
In the review of  we are back to our BAEC cells expressing constant large amounts of PPARα or PPARγ. The authors examined the 3x PPRE-luciferase activity in the presence of the top three components of rose oil
Starting with citrolellol and the stared carbon carbon bond: Adding a trans double bond of to produce geraniol only slightly reduces the activity. Adding a cis double bond at the same location to produce nerol destroys the ability to activate PPAR.
Figure 3, What happens to LPS induced inflammation?
The switch to PPARγ when PPARα is more active is on the surface confusing. Previous work from this laboratory showed that 15-deoxy-Δ12,14PGJ2 binds to PPARγ.  These authors discussed other studies that demonstrated 15d-PGJ2, but not PPARγ agonist Troglitazone, inhibited IκB kinase which is an intermediate in the process that leads to LPS induced NF-κB activation.  Scroll back up to the intro Figure 0. NFκ-B also response to reactive oxygen species according to the authors of the Wikipedia page.
There are a bewildering number of crystal structures of PPARγ and small molecules on the rcsb.org protein structure database. One has to ask, What does not bind to PPARγ ? Resveratrol, of red wine fame, and metabolites bind to PPARγ. 4JAZ This interaction was predicted to be antagonistic. Citronellol is one carbon short of being close to half of 15-deoxy-Δ12,14PGJ2 . Perhaps geraniol is simply acting as a scavenger of oxygen radicals in a manner that bypasses whatever unvaerified mechanism it is using to inhibit Cox2 expression. When citronellol binds, it results in a conformational change similar to 15-deoxy-Δ12,14PGJ2 .
Thoughts on medical cannabis
Recall that phyto- and endo-cannabinoids act to shut down cAMP production. Recall from Figure 0 that the cAMP response element also has a say in transcription of the Cox2 gene. The THC component might be acting on this response element of Cox2 gene rranscription together with shutting down NF-κB. We are still a very long way of knowing the right dose of this rose oil food ingredient. Perhaps we will eventually be able to create a rose oil plus cannabis entourage effect for patients seeking relief of inflammation.
- Inoue H, Tanabe T, Umesono K. Feedback control of cyclooxygenase-2 expression through PPARgamma. J Biol Chem. 2000 Sep 8;275(36):28028-32. PMC free article
- Katsukawa M, Nakata R, Koeji S, Hori K, Takahashi S, Inoue H. Citronellol and geraniol, components of rose oil, activate peroxisome proliferator-activated receptor α and γ and suppress cyclooxygenase-2 expression. Biosci Biotechnol Biochem. 2011;75(5):1010-2. PMC free article