The word "ledol" comes from the Greek word "ledos" meaning "robe". This likely comes from the "wooly" appearance of the plant, which has hair-like stalks stemming from the flower.[3]
Historical and Traditional Uses
The earliest known written record of Rhododendron plant toxicity dates back to 401 B.C. in China.[4] Despite their toxicity, Rhododendron species have been documented in traditional medicinal practices across various cultures, including Chinese, Ayurvedic, European, and North American practices.
The accounts of Rhododendron from around the world describe numerous health benefits and treatments to various ailments.
R. tomentosum is highly recorded with various uses, like treating rheumatism, coughs, colds, and insect bites. Some common names it has are "wild rosemary", "marsh tea", and "marsh rosemary". Scientists have studied R. tomentosum's shoots, due to the shoots having the highest concentration of essential oils, for potential antidiabetic, antimicrobial, and antioxidant purposes.[5]
Mechanism of Action
An image of Rhododendron tomentosum flowers, hair-like fibers stem from the flower, which inspired the name of the toxic molecule within its essential oils.
Although the ledol mechanism of action is quite under-studied, ledol is a sesquiterpenoid and studies on similar sesquiterpenoids, such as picrotoxinin, have shown that these molecules often target GABA receptors.[6] These sesquiterpenoids act as GABA antagonists on GABA post-synaptic receptors. GABA-A receptors, in particular, function as chloride channels that facilitate the flow of chloride ions across cell membranes.[7]
When GABA is deficient, symptoms can include respiratory difficulty, seizures, delirium, vomiting, nausea, gastrointestinal issues, headaches, increased blood pressure, and muscle cramps.[8] This pattern reflects how known GABA-A receptor antagonists, such as picrotoxinin, affect the body.[9] Ledol has similar—if not identical—effects in the body, albeit milder than those of known GABA-A antagonists, according to sources.[10]
Another sesquiterpenoid, Nootkatone, was proven to exhibit similar effects in insects.[11]
Metabolism
Even though the metabolism of ledol has yet to be elucidated, a 2023 article involving sesquiterpene lactones, such as parthenolide, showed the sesquiterpenes reacting to human liver microsomes.[12] This demonstrates the reactivity with the liver’s CYP3A4 enzyme. Through relation, the metabolism is possibly facilitated through the liver if ingested.
↑ Andrews, Steve; Rindsberg, Katrina (April 2001). Herbs of the Northern Shaman: A Guide to Mind-Altering Plants of the Northern Hemisphere. Loompanics Unlimited. ISBN1-55950-211-8. OCLC780276732.
↑ Dampc, Anna; Luczkiewicz, Maria (2015). "Labrador tea – the aromatic beverage and spice: a review of origin, processing and safety". Journal of the Science of Food and Agriculture. 95 (8): 1577–1583. Bibcode:2015JSFA...95.1577D. doi:10.1002/jsfa.6889. PMID25156477.
↑ Dampc, Anna; Luczkiewicz, Maria (1 March 2013). "Rhododendron tomentosum (Ledum palustre). A review of traditional use based on current research". Fitoterapia. 85: 130–143. doi:10.1016/j.fitote.2013.01.013. PMID23352748.
↑ Popescu, Ruxandra; Kopp, Brigitte (2 May 2013). "The genus Rhododendron: An ethnopharmacological and toxicological review". Journal of Ethnopharmacology. 147 (1): 42–62. doi:10.1016/j.jep.2013.02.022. PMID23454683.
↑ Dampc, Anna; Luczkiewicz, Maria (June 2015). "Labrador tea – the aromatic beverage and spice: a review of origin, processing and safety". Journal of the Science of Food and Agriculture. 95 (8): 1577–1583. Bibcode:2015JSFA...95.1577D. doi:10.1002/jsfa.6889. PMID25156477.
↑ Matsumura, F.; and Ghiasuddin, S. M. (1 January 1983). "Evidence for similarities between cyclodiene type insecticides and picrotoxinin in their action mechanisms". Journal of Environmental Science and Health, Part B. 18 (1): 1–14. Bibcode:1983JESHB..18....1M. doi:10.1080/03601238309372355. PMID6187794.
↑ Dampc, Anna; Luczkiewicz, Maria (1 March 2013). "Rhododendron tomentosum (Ledum palustre). A review of traditional use based on current research". Fitoterapia. 85: 130–143. doi:10.1016/j.fitote.2013.01.013. PMID23352748.
↑ Norris, Edmund J.; Chen, Rui; Li, Zhilin; Geldenhuys, Werner; Bloomquist, Jeffrey R.; Swale, Daniel R. (1 May 2022). "Mode of action and toxicological effects of the sesquiterpenoid, nootkatone, in insects". Pesticide Biochemistry and Physiology. 183 105085. Bibcode:2022PBioP.18305085N. doi:10.1016/j.pestbp.2022.105085. PMID35430075.
↑ Grafakou, Maria-Eleni; Barda, Christina; Skaltsa, Helen; Heilmann, Joerg (2 June 2024). "Study on the metabolism of natural sesquiterpene lactones in human liver microsomes using LC-Q-TOF-MS/MS". Natural Product Research. 38 (11): 1855–1863. doi:10.1080/14786419.2023.2226301. PMID37354443.
↑ Dampc, Anna; Luczkiewicz, Maria (2015). "Labrador tea – the aromatic beverage and spice: A review of origin, processing and safety". Journal of the Science of Food and Agriculture. 95 (8): 1577–1583. Bibcode:2015JSFA...95.1577D. doi:10.1002/jsfa.6889. PMID25156477.
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