Metabolism of Terpenoids in Animal Models and Humans
K. Hüsnü Can Başer, Gerhard Buchbauer in Handbook of Essential Oils, 2020
1,8-Cineole is widely distributed in plants and found in high concentrations in the essential oils of Eucalyptus globulus and Laurus nobilis. It is extensively used in cosmetics and for ointments against cough, muscular pain, and rheumatism (O'Neil, 2006; Bornscheuer et al., 2014). In rat liver microsomes, 1,8-cineole is predominantly metabolized to 3-hydroxy-1,8-cineole and, to a lesser extent, to 2- and 9-hydroxy-1,8-cineole, respectively. (Miyazawa et al., 2001a). In the urine of rabbits and koalas, various 7- and 9-oxydated metabolites were found (Boyle et al., 2001). In human liver microsomes, however, only the 2- and 3-hydroxylated products catalyzed by the isoenzyme CYP3A4 could be identified (seen Figure 10.9. (Miyazawa and Shindo, 2001; Miyazawa et al., 2001a). Both metabolites could also be also found in the urine of three human volunteers after oral administration of a cold medication containing 1,8-cineole (Miyazawa et al., 2001b); these metabolites are therefore excellent biomarkers for the 1,8-cineole intake in humans. Besides these main biotransformation products, Horst and Rychlik could also identify small amounts of 7- and 9-hydroxy-1,8-cineole in human urine (Horst and Rychlik, 2010).
Essential oils and aromas that affect mood and cognition
Philip N. Murphy in The Routledge International Handbook of Psychobiology, 2018
Studies investigating the oral bioavailability of essential oil constituents are also generally limited, and the results for the different essential oil constituents that have been investigated are often variable. One study revealed that when capsules containing limonene, 1,8-cineole, and α-pinene were administered to human volunteers, only 1,8-cineole could be detected in sufficient quantities in plasma (Kohlert et al., 2000). In a separate study, oral bioavailability of 1,8-cineole was reported to be low when administered to possums, although at higher doses, oral bioavailability was increased (McLean et al., 2007). More promising bioavailability results were also reported for limonene in a different study, since following oral administration to rodents, limonene was reported to have a half-life of 337 minutes, whilst oral bioavailability was 43% (Chen et al., 1998). The sesquiterpene hydrocarbon α-cedrene (a component of cedar wood oil) has also been associated with good oral absorption in vivo(49–85% bioavailability), a relatively long half-life, and was highly distributed in tissues, including the brain (Kim et al., 2015), which would be relevant to mediate effects in the CNS. However, another sesquiterpene hydrocarbon, α-humulene, was only 18% bioavailable following oral administration in vivo in a separate study, although it had an elimination half-life of 55 minutes and was distributed in the liver, kidneys, heart, lungs, spleen, and also the brain (Chaves et al., 2008). α-Humulene can also be absorbed following topical administration, as was concluded from a study in which cream and aerosol formulations containing 0.5% Cordia verbenacea (a synonym of C. curassavica) oil were applied to mouse ear skin and the component α-humulene was subsequently detected (Chaves et al., 2008).
Monoterpenes Modulating IL-10
Parimelazhagan Thangaraj in Phytomedicine, 2020
1,8-cineole (eucalyptol) is a major monoterpenoid present in many plant volatile/essential oils, principally, the Rosmarinus and Eucalyptus species which are mainly used by the pharmaceutical industry in drug formulations, as a percutaneous penetration enhancer, and for its decongestant and anti-tussive effects, and in aromatherapy as a skin stimulant (Elaissi et al. 2012; Lima et al. 2013b). Santos et al. (2004) identified 1,8-cineole as a substance with analgesic, anti-inflammatory, and hepatoprotective properties, and to attenuate the colonic damage in rats with acute trinitrobenzene sulfonic acid-induced colitis, an animal model of the inflammatory bowel disease of humans. We found two previous studies of this 1,8-cineole compound in cerulein-induced acute pancreatitis (Lima et al. 2013b) and the amelioration of bacterial vaginosis and vulvovaginal candidiasis in mice by inhibiting the bacterial growth and NF-κB activation (Trinh et al. 2011). Lima et al. (2013b) reported that 1,8-cineole (100, 200, and 400 mg/kg, per oral (p.o.) significantly (p < 0.05) lowered the cerulein-induced elevation of the serum amylase and lipase at all doses, a significant decrease in pancreatic edema was observed only at 200 and 400 mg/kg. Meanwhile, cerulein significantly (p > 0.05) elevated the serum levels of TNF-α, IL-1β, and IL-6, whereas the level of serum IL-10 was decreased. Treatment with 1,8-cineole (100, 200, and 400 mg/kg, p.o.) and thalidomide (200 mg/kg, p.o.) effectively decreased the levels of TNF-α, IL-1β, and IL-6, but the levels of IL-10 were increased. Also, the authors concluded that these changes in cytokine levels were significantly mitigated by 1,8-cineole pre-treatment, suggesting that it may have an important role in the inhibition of the pro-inflammatory response in Acute Pancreatitis (AP). By creating a balance between pro-inflammatory and anti-inflammatory cytokines, 1,8-cineole might exercise a therapeutic benefit for the control of acute pancreatitis. Trinh et al. (2011) also studied this compound and recommended that 1,8-cineole inhibited the expressions of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), cyclooxygenase (COX)-2, Inducible Nitric Oxide Synthase (iNOS), and the activation of NF-κB and increased the expression of the anti-inflammatory cytokine IL-10.
Development of galangal essential oil-based microemulsion gel for transdermal delivery of flurbiprofen: simultaneous permeability evaluation of flurbiprofen and 1,8-cineole
Published in Drug Development and Industrial Pharmacy, 2020
Jie Dong, Xue-min Zhu, Feng-ye Wu, Bing-qing Yang, Han Feng, Yun-fei Dong, Wei Gu, Jun Chen
1,8-cineole, also known as eucalyptol, a colorless liquid, is a natural organic compound. It is an oxygenated monoterpene compound with a refreshing eucalyptus and menthol-like odor and originally identified in many aromatic herbs, such as eucalyptus, camphor laurel, bay leaves, sweet bail and rosemary. 1,8-cineole is a common active agent with anti-inflammatory effects. It ameliorates the inflammatory phenotype of human umbilical vein endothelial cells by mediating NF-ĸB expression [33]. Furthermore, the anti-inflammatory properties of 1,8-cineole have been proposed to reduce or prevent gastrointestinal inflammation and ulceration [34]. In addition, 1,8-cineole has also been confirmed to possess comparable analgesic activity to that of morphine [35]. However, despite its promising pharmacological effects, 1,8-cineole still cannot exert the expected efficacy owing to its poor water-solubility and the absence of a satisfactory oral delivery system. ME has been proved to be a good carrier for the development of 1,8-cineole formulation. 1,8-Cineole-loaded self-microemulsifying drug delivery system was found to attenuate lipopolysaccharide-induced endothelial injury, and was thus proposed as a promising agent for the treatment of inflammatory cardiovascular disease via oral administration [36]. Curcumin-loaded ME formulation was also prepared using 1,8-cineole as an ingredient of ME for transdermal delivery [21]. Although several analgesic pharmaceutical formulations containing 1,8-cineole have been dispensed for external use [37], to the best of our knowledge, the pharmacokinetic profiles of 1,8-cineole after transdermal or dermal administration are still unclear.
Design and development of essential oil based nanoemulsion for topical application of triclosan for effective skin antisepsis
Published in Pharmaceutical Development and Technology, 2022
Pratibha G. Kakadia, Barbara R. Conway
The amount of TSN recovered from skin appendages through cyanoacrylate biopsy was dependent on the concentration of the oil used in the formulations. As the concentration of oil increased from 5 to 10% (w/w) in OO-based NEs, there was a 2-fold increase in TSN concentration from 1.02 ± 0.19 to 2.02 ± 0.12 µg/mg, while for EO-based NEs, the concentration of TSN increased from 1.35 ± 0.17 to 3.79 ± 0.14 µg/mg in the appendages. It was observed that TSN retention in the skin was higher for EO-NEs compared to the OO-NEs, which aligns with skin permeation data. Hence, this result suggests that a combination of TSN and EO may be a potential method to improve skin antisepsis in clinical practice. EO contains 1,8-cineole, which has been shown to bind in large quantities to the SC (Cornwell et al. 1996). It is thought to enhance lipophilic drug penetration by increasing the coefficient (partitioning of drug between vehicle and SC), as well as hydrophilic drug penetration by increasing the diffusion coefficient (Cal et al. 2001). It has been also shown that 1,8-cineole partitioning in the skin lipids is heterogeneous, leading to both ordered and disordered areas in SC lipids (Williams et al. 2006). Furthermore, as is evident from some in vitro assays, 1,8-cineole does not permeate through the skin but tends to be retained within the skin (Cornwell et al. 1996; Cal et al. 2006). Increased skin penetration of steroid hormones using an EO (45% v/v) microemulsion for topical delivery has been reported (Biruss et al. 2007). Results showed the ability of EO to augment percutaneous absorption by SC lipid extraction and loosening the hydrogen bond between the ceramides leading to fluidisation of lipid bilayers (Chen et al. 2014).
Nasal odorant metabolism: enzymes, activity and function in olfaction
Published in Drug Metabolism Reviews, 2019
Jean-Marie Heydel, Philippe Faure, Fabrice Neiers
Although this review focuses on the function of odorant metabolism in olfactory tissues, one should note that odorants are also ingested with foods and undergo systemic metabolism. Odorants and their metabolites may activate extraolfactory odorant receptors, some of which were identified and found to be involved in cell–cell adhesion, sperm migration or skeletal muscle regeneration (Kang and Koo 2012). Accordingly, it has been shown that after the ingestion of 1,8-cineole, its odorant metabolites can be found in mother’s milk and be potentially potent stimuli for breastfed children (Kirsch et al. 2012; Kirsch and Buettner 2013).
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