IngredientesCineole, also known as eucalyptol or cajeputol, is a terpene oxide that serves as a principal constituent of eucalyptus oils. Its systematic IUPAC name is 1,8-epoxy-p-menthane, and it is registered under CAS number 470-82-6. Eucalyptol is a monoterpenoid and cyclic ether, also commonly known as cineole. The cineoles are volatile and colorless liquids. They are symmetrical monoterpenic cyclic ethers usually found as components of essential oils from aromatic plants. 1,8-Cineole has a characteristic fresh and camphoraceous fragrance and pungent taste.
A structural isomer, 1,4-cineole (CAS 470-67-7), exists in nature alongside the 1,8-form. Although 1,8-cineole is traditionally a more abundant and more desirable isomer, 1,4-cineole (1,4-epoxy-p-menthane) is an extensively distributed natural oxygenated monoterpene found in the same plant species. However, it is frequently found in much inferior concentrations than 1,8-cineole. Unless otherwise stated, the name "cineole" in pharmacological and clinical literature invariably refers to the 1,8-isomer.
Eucalyptol is generated from geranyl pyrophosphate (GPP), which isomerises to (S)-linalyl diphosphate (LPP). Ionisation of the pyrophosphate, catalysed by cineole synthase, produces eucalyptol. The process involves the intermediacy of an alpha-terpinyl cation.
1,8-Cineole is a naturally occurring compound derived from botanical sources such as eucalyptus, rosemary, and camphor laurel. The naturally occurring monoterpene 1,8-cineole is a major component of the essential oil in eucalyptus. However, 1,8-cineole is also found in some species of the Mentheae tribe, including mint and thyme. Eucalyptol comprises over 80% of the total in the essential oils from eucalyptus trees, and it is also found in tea tree, mugwort, bay leaves, sweet basil, rosemary, sage, and cannabis. Within the genus Eucalyptus, content is species-dependent: the eucalyptol content of eucalyptus essential oil can be between about 6% and over 80%. Eucalyptus globulus leaves contain not less than 2% (v/w) essential oil, consisting of not less than 70% (w/w) 1,8-cineole; another report states that fresh leaves of Eucalyptus globulus contained 54% to 61% 1,8-cineole.
The essential oil from eucalyptus leaves can be extracted through steam distillation. Beyond eucalyptus, 1,8-cineole was the main compound particularly in fresh leaves of Eucalyptus cinerea in spring (74.98%), dried spring leaves (85.32%), winter flowers (78.76%), and winter fruits (80.97%). Other compounds found in the aerial parts in all seasons include α-pinene (2.41% to 10.13%), limonene (1.46% to 4.43%), α-terpineol (1.73% to 11.72%), and α-terpinyl acetate (3.04% to 20.44%).
Cineole is available and used in several distinct forms:
Aboriginal Australians use eucalyptus leaf infusions (which contain eucalyptus oil) as a traditional medicine for treating body pains, sinus congestion, fever, and colds. This traditional knowledge was foundational to the later scientific and commercial development of eucalyptus oil. The Indigenous Australians' intimate knowledge of the eucalyptus tree was based on a profound understanding of their environment and its healing potentials. This traditional knowledge was passed down through generations and laid the groundwork for the broader acceptance of eucalyptus in medicine.
The eucalyptus tree caught the attention of European explorers in the early 19th century. Its rapid growth and ability to drain swamps were noted as useful traits for land reclamation. It was only a matter of time before the tree's medicinal properties were explored by the scientific community. In the 1850s, French chemist Pierre-Joseph Pelletier and his colleague Joseph Bienaimé Caventou isolated eucalyptus oil and identified its key component, cineole (or eucalyptol). This discovery was pivotal, as cineole was found to have antiseptic and expectorant properties, making eucalyptus oil a valuable tool for treating respiratory conditions.
In 1870, F. S. Cloez identified and ascribed the name "eucalyptol" to the dominant portion of Eucalyptus globulus oil. By the 1870s oil from Eucalyptus globulus, Tasmanian blue gum, was being exported worldwide and eventually dominated world trade. Surgeons were using eucalyptus oil as an antiseptic during surgery by the 1880s. In the 19th century, European practitioners adopted cineole-containing eucalyptus oil as a remedy for coughs, colds, bronchitis, and sinus congestion.
Cineole is found in traditional medicinal plants like Mentha longifolia, which is used for treating digestive disorders. Historically, cineole has been used in traditional medicine for centuries, especially in Australia and Asia, where eucalyptus leaves were utilised for their perceived ability to relieve symptoms of respiratory ailments. For a long time, the Eucalyptus genus has been used in traditional medicine. Eucalyptus plants possess a broad spectrum of biological effects, such as antibacterial, antiseptic, antioxidant, anti-inflammatory, and anticancer activities.
The European Medicines Agency Committee on Herbal Medicinal Products concluded that traditional medicines based on eucalyptus oil can be used for treating cough associated with the common cold, and to relieve symptoms of localised muscle pain. This EMA assessment recognises the long-standing traditional use of cineole-containing preparations, validating their role in respiratory and musculoskeletal symptom relief.
Eucalyptol (1,8-cineole) is the mainly responsible component for the eucalyptus oils' medicinal value. While eucalyptus essential oil contains many other secondary compounds — including α-pinene, limonene, α-terpineol, and terpinyl acetate — the preponderance of pharmacological research has focussed on isolated 1,8-cineole. The mucolytic monoterpene 1,8-cineole (eucalyptol), the major constituent of eucalyptus species, is well known for its anti-inflammatory, antioxidant, bronchodilatory, antiviral, and antimicrobial effects.
The anti-inflammatory mechanisms of 1,8-cineole involve the inhibition of nuclear translocation of NF-κB p65 and PPARγ, leading to the suppression of immune response genes. This regulatory process effectively modulates the expression of key inflammatory mediators, including TNF-alpha, IL-6, IL-8, VCAM-1, and E-selectin.
Juergens (2014) proposed a mechanism of action of 1,8-cineole through reduction of two arachidonic acid pathways, involving 5-LOX and COXs, impairing the production of AA-derived pro-inflammatory mediators, such as LTB4 and PGE2. However, this should be demonstrated, and considering that NF-κB is involved in the transcription of these inflammatory enzymes, their impaired activity could be a consequence of NF-κB inhibition, instead of direct inhibition of these enzymes by 1,8-cineole.
The anti-inflammatory effect of 1,8-cineole in wild-type mice was attributable to the suppression of mast cell activation when compared to mast cell-deficient mice. The mechanism of action was further examined in an in vitro cell system using bone-marrow-derived mast cells, which revealed that 1,8-cineole not only repressed mast cell degranulation but also mitigated allergic dermatitis.
In vitro work has further characterised the cytokine-level effects. In the presence of 1,8-cineol at a concentration of 0.15 μg/ml (10⁻⁶ M), production of TNF-α and IL-1β by monocytes, and of IL-1β and TNF-α by lymphocytes, was significantly inhibited.
The main protective antiviral, anti-inflammatory, and mucolytic mechanisms of 1,8-cineole are the induction of interferon regulatory factor 3 (IRF3), the control of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), along with decreasing mucin genes (MUC2, MUC19). Similar to other aromatic oils, 1,8-cineole is commonly used to treat respiratory tract infections due to its ability to increase the ciliary beat frequency in the mucus membrane and its bronchodilating and anti-inflammatory properties, as evidenced by preclinical studies.
Co-treatment with LPS and 1,8-cineol leads to reduced production of mucin and decreased expression levels of mucin genes closely associated with attenuated NF-κB-activity. Researchers demonstrated for the first time a 1,8-cineol-dependent reduction of mucin-filled goblet cells and MUC2-gene expression associated with an attenuated NF-κB-activity in human nasal slice cultures. These findings suggest that these effects partially account for the clinical benefits of 1,8-cineol-based therapy during rhinosinusitis.
Its protective effects are mainly due to its ability to reduce oxidative stress and inflammation and regulate nuclear factor kappa B (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2). In the present study, the antioxidant mechanisms of action of the monoterpene 1,8-cineole were reported as an important key issue to control pro-oxidative and related pro-inflammatory effects that are not sufficiently controlled by known guided anti-inflammation inhaled airway therapies.
A strong anti-microbial effect of 1,8-cineole in co-administration with chlorhexidine gluconate was observed with regard to methicillin-resistant S. aureus strains and also for E. coli, K. pneumoniae, E. faecalis, and C. albicans strains with a weaker effect. Essential oils extracted by hydrodistillation from the leaf parts of E. globulus revealed significant anti-bacterial properties and caused highly significant decreased microbial counts of S. aureus in agar diffusion assays. The essential oils showed antimicrobial activities against bacteria and yeasts, with the best results found for the dried autumn and winter leaves oils (MIC <0.39 mg/mL) against Streptococcus pyogenes.
After oral administration, 1,8-cineole is absorbed in the small intestine and subsequently metabolised in the liver by human cytochrome P450 enzymes (CYP3A4/5). Its primary metabolites, 2α-hydroxy- and 3α-hydroxy-1,8-cineole, are excreted through urine. In addition to its systemic availability in the bloodstream, 1,8-cineole can reach the bronchial system and be exhaled through the peripheral airways.
It has recently been shown that 1,8-cineole was detectable in nasal tissue samples after its oral administration for 14 days, which indicates the systemic distribution of 1,8-cineole via the gut and the bloodstream. The identification of urinary metabolites following a single 100 mg dose of 1,8-cineole has revealed 2-hydroxy-1,8-cineole and 3-hydroxy-1,8-cineole.
Clinical evidence has shown that 1,8-cineole provides symptom relief, improves lung function, and enhances quality of life, particularly in patients with COPD, asthma, and chronic sinusitis. For COPD specifically, a placebo-controlled double-blind trial by Worth, Schacher, and Dethlefsen (2009) examined cineole as a concomitant therapy. In this placebo-controlled double-blind trial, 242 patients were randomly assigned to one of two treatment groups, with one group receiving capsules containing 100 mg of cineole and the other receiving placebo. Patients were prescribed 2 capsules three times a day, taken half an hour before meals. The cineole group received a total of 600 mg per day. The primary goal of the study was to explore the potential of cineole to reduce the number, severity, and duration of exacerbations in patients with COPD. Secondary outcome measures included lung function, severity of dyspnoea, and quality of life. Patients were seen for evaluation once a month for 6 months.
Evidence strength: The COPD evidence base consists of at least one published randomised double-blind placebo-controlled trial, which is the gold standard study design. However, the evidence is limited by the relatively small number of trials dedicated specifically to this indication, and longer-term, multicentre confirmatory data remain limited.
In the first preliminary placebo-controlled study in severe steroid-dependent asthma (n = 32), following a run-in phase of 2 months to determine the minimal effective dose of daily prednisolone, patients were randomly allocated to receive either 1,8-cineole (3 × 200 mg/day) (Soledum® forte capsules) or placebo, while daily prednisolone was reduced by 2.5 mg every 3 weeks. Results showed, for the first time, significant prednisolone reduction of 36% with active treatment (range 2.5–10 mg, mean 3.75) vs. a decrease of only 7% (2.5–5 mg, mean 0.91 mg) in the placebo group. These results suggested a prednisolone equivalent potency of 1,8-cineole 600 mg of around 2.8 mg that was well tolerated following steroid reduction.
One study involved 32 patients randomly divided into two groups: the cineole group and the placebo group. The cineole group received small gut-soluble capsules containing 200 mg of cineole each, taken 3 times a day. The placebo group took 3 capsules a day using capsules filled with no active ingredient. Study visits took place at 3, 6, 9, and 12 weeks. Cineole was well tolerated, with only two in the cineole group reporting gastritis and heartburn.
Evidence strength: The asthma evidence rests on a small number of randomised controlled trials (one pivotal study of n = 32). While results are promising — particularly regarding steroid-sparing effects — the small sample sizes mean findings should be considered preliminary and in need of replication in larger populations.
In a prospective, randomised, double-blinded, placebo-controlled study with 152 patients with acute nonpurulent rhinosinusitis, researchers assessed 1,8-cineole efficacy and safety. Participants received either 1,8-cineole capsules (3 × 200 mg/day) or placebo capsules for 7 days. The findings indicated that the 1,8-cineole group experienced a significant reduction in their symptoms-sum-score (SSS) and improvements in secondary endpoints, including headache, nasal obstruction, and rhinological secretion.
The first placebo-controlled study with 1,8-cineole (two 100 mg capsules three times daily for 7 days) in acute non-purulent sinusitis showed significant reduction of the mean symptoms sum-score after 4 and 7 days and amelioration of headache among secondary endpoints.
At a mechanistic level, topical application of 1,8-cineol may offer a novel therapeutic approach to reduce bacteria-induced mucus hypersecretion.
Evidence strength: Rhinosinusitis has among the more robust human clinical evidence for 1,8-cineole, with multiple randomised double-blind placebo-controlled trials demonstrating consistent effects on symptom scores. This is also the indication for which the EMA has recognised traditional use.
As part of a double-blind, placebo-controlled, multicentre study, a total of 242 patients with confirmed acute bronchitis was randomly selected to participate. Over a period of 10 days, all patients were administered 3 × 200 mg of cineole, or a respective placebo, per day. As cineole accelerates the beat frequency of the cilia in the mucous membrane, as well as acting both as a bronchodilating and an anti-inflammatory agent, it has been postulated that it will be effective in treating symptoms of acute bronchitis.
Evidence strength: This randomised controlled multicentre trial provides moderately strong evidence for acute bronchitis, though the evidence base remains narrower than for rhinosinusitis and COPD, and further independent replication is warranted.
One study was designed to assess the potential pharmacological relationships between absorbed 1,8-cineole following exposure to rosemary aroma, cognitive performance, and mood. Twenty healthy volunteers performed serial subtraction and visual information processing tasks in a cubicle diffused with the aroma of rosemary. Mood assessments were made pre and post testing, and venous blood was sampled at the end of the session. Pearson correlations were carried out between serum levels of 1,8-cineole, cognitive performance measures, and change in mood scores. The results showed for the first time that performance on cognitive tasks is significantly related to concentration of absorbed 1,8-cineole following exposure to rosemary aroma, with improved performance at higher concentrations.
1,8-Cineole is a monoterpenoid compound which exists in many plant essential oils and has been proven to have neuroprotective activity, though its specific effects and molecular mechanisms require further clarification. Rosemary (Salvia rosmarinus) demonstrated potent acetylcholinesterase inhibitory effects. Key chemical constituents including 1,8-cineole were identified as primary contributors.
Evidence strength: The cognitive evidence is largely preliminary. The key human study is a small observational correlation study (n = 20), not an interventional trial. Preclinical and mechanistic data are more developed but have not been translated into robust clinical trials. This remains an area of active but early-stage investigation.
Evidence indicates that 1,8-cineole effectively modulates inflammatory pathways by inhibiting cytokine release and suppressing arachidonic acid metabolism. 1,8-cineole exhibits a wide range of biological effects, including anti-inflammatory, antioxidant, antibacterial, antiviral, mucolytic/secretolytic, bronchodilatory, analgesic, pro-apoptotic, and numerous other activities crucial for health-promoting properties.
Evidence strength: Mechanistic in vitro evidence for cytokine inhibition is well-established. Translation into controlled human trials examining inflammation as a primary endpoint — outside of the respiratory context — is limited.
Eucalyptus oil has antimicrobial activity against a broad range of food-borne human pathogens and food spoilage microorganisms. In vitro data confirm activity against a range of clinically relevant organisms, though dedicated human infection trials using isolated 1,8-cineole as treatment are largely absent from the literature.
Evidence strength: Primarily in vitro and ex vivo. Clinically, antimicrobial effects are inferred from observational improvements in rhinosinusitis and COPD exacerbation trials. Direct evidence from infection-focused randomised controlled trials is lacking.
Recent evidence has indicated 1,8-cineole's potential role in managing conditions such as Alzheimer's disease, neuropathic pain, and cancer. This bioactive molecule demonstrates significant therapeutic potential for various neurological and respiratory disorders, including cancer, epilepsy, and tracheitis, attributable to its potent antioxidant, anti-inflammatory, and antimicrobial properties.
Eucalyptol (1,8-cineole) exhibits anti-seizure activity potentially via modulation of the nitric oxide pathway. Eucalyptol, a monoterpene ether with antioxidant properties, has shown neuroprotective potential; however, its anti-seizure mechanism is not fully elucidated. One study evaluated the anti-seizure effects of eucalyptol in a pentylenetetrazol (PTZ)-induced seizure model in mice.
Evidence strength: Evidence for neurological indications is confined to preclinical (in vitro and animal) studies. No randomised controlled trials in human neurological patients have been completed, and this area remains exploratory.
1,8-cineole (CIN) is a monoterpene that naturally occurs in many aromatic plants and has been characterised as having gastroprotective action. The aim of one study was to investigate the mechanisms of action involved in the antiulcer and healing activity of CIN. Wistar rats were exposed to different protocols (acute ulceration, gastrointestinal motility, and antisecretory activity). The involvement of nitric oxide and sulphydryl groups was determined, along with the levels of gastric mucus, lipid peroxidation, sulphydryl groups, and myeloperoxidase activity.
Evidence strength: Gastroprotective evidence is preclinical (animal studies). No human clinical trials specifically addressing gastrointestinal protection have been conducted with isolated 1,8-cineole.
Dosages below reflect only those reported in peer-reviewed clinical studies. Therapeutic doses for conditions not yet studied in clinical trials are not reported here, as no verified data exist.
Despite the promising applications of 1,8-cineole, the clinical translation is still in its early stages and faces several complications and limitations. While considered safe and well-tolerated at normal therapeutic doses, excessive use and overdosage of 1,8-cineole through oral ingestion, inhalation, or skin application can be hazardous, leading to potential acute toxicity, including inflammatory gastrointestinal conditions and rare symptoms like nausea, vomiting, and diarrhoea.
Eucalyptol has a toxicity (LD50) of 2.48 grams per kg (rat). Ingestion in significant quantities is likely to cause headache and gastric distress, such as nausea and vomiting. Because of its low viscosity, it may directly enter the lungs if swallowed, or if subsequently vomited.
Preclinical toxicity and reproductive toxicity of 1,8-cineole (CIN) were investigated in Wistar rats. In the repeated-doses toxicity study for 50 days, CIN at doses of 100, 500, or 1000 mg/kg did not produce any signs of toxicity or deaths, but affected body weight gain during the first week of treatment. The haematological and biochemical profiles did not show significant differences except for increases in MCV, platelet, and urea levels or reductions in MCHC, MPV, and alkaline phosphatase. Histopathological analysis showed weak changes in the lungs, liver, kidneys, and uterus. In the reproductive toxicity study, CIN at doses of 250, 500, or 1000 mg/kg produced a reduction in body weight in pregnant rats treated during the pre-implantation or organogenesis periods.
In the asthma trial, cineole was well tolerated with only two in the cineole group reporting gastritis and heartburn. Due to its good safety profile and minimal side effects, it represents a very attractive adjunctive treatment option.
After oral administration, 1,8-cineole is absorbed in the small intestine and subsequently metabolised in the liver by human cytochrome P450 enzymes (CYP3A4/5). Because cineole is both a substrate for and, in some experimental conditions, an inducer of CYP enzymes, there is a theoretical basis for interaction with co-administered drugs that share these metabolic pathways. The disappearance of aminopyrine from plasma was enhanced in 4 out of 5 volunteers submitted for 10 days to treatment with eucalyptol (1,8-cineole) aerosol, an early finding consistent with hepatic enzyme induction. Given the considerably lower doses acquired through the consumption of 1,8-cineole via herbal teas or spices, the significance of dose-dependent metabolism becomes pivotal in a comprehensive assessment encompassing both pharmacological and toxicological dimensions.
A specific and documented safety concern relates to concentrated eucalyptus essential oil (as distinct from pharmaceutical-grade enteric-coated cineole capsules) in young children. Concentrated eucalyptus oil should not be applied near the face or airways of infants and young children, as ingestion or inappropriate topical application has been associated with serious toxicity in case reports and case series in the medical literature. This concern applies to eucalyptus oil preparations as a whole, not to the low-concentration food-grade uses of cineole.
Although preclinical findings are promising, clinical translation is limited by methodological variability and a lack of standardised dosing protocols across trials. Despite the promising applications of 1,8-cineole, the clinical translation is still in its early stages and faces several complications and limitations. Considering the previously reported uses of Eucalyptus essential oils and extracts, there is still an urgent requirement for further in vivo studies using the various Eucalyptus constituents to reveal the secrets beyond its traditional uses in the treatment of a wide spectrum of conditions. Most human evidence is concentrated in respiratory medicine; evidence for neurological, oncological, metabolic, and gastrointestinal indications remains in the preclinical or early translational phase.
Condiciones de salud que cineol puede ayudar a apoyar.
Cineole (1,8-cineole/eucalyptol) has specific clinical trial evidence for acute bronchitis. A double-blind, placebo-controlled multicenter RCT in 242 patients with confirmed acute bronchitis found 3×200 mg/day cineole orally for 10 days significantly improved the Bronchitis Sum Score by day 4 (p=0.0383) and significantly reduced cough frequency (p=0.0001). It also reduces exacerbation rates in COPD and allows steroid reduction in asthma patients.
Cineole (1,8-cineole/eucalyptol) is the main constituent of eucalyptus oil with specific clinical evidence for acute bronchitis from a placebo-controlled double-blind RCT (PMC3842692) demonstrating significantly faster dissipation of acute bronchitis symptoms versus placebo. It acts as a mucolytic, bronchodilator, and NF-κB-inhibiting anti-inflammatory agent.
Cineole (1,8-cineole, eucalyptol) is the primary bioactive terpenoid of eucalyptus oil with robust clinical evidence for COPD and asthma. RCTs have shown 1,8-cineole significantly reduces COPD exacerbation rates, improves FEV1, and allows steroid-sparing in asthma. It is approved by Commission E for upper respiratory tract catarrh.
1,8-Cineole (eucalyptol) is the principal constituent of eucalyptus essential oil with demonstrated mucolytic, expectorant, and anti-inflammatory activity. It inhibits MUC2 and MUC19 mucin gene expression and downregulates NF-κB-mediated inflammatory cascades driving mucus hypersecretion. Clinical studies confirmed significant improvement in asthmatic patients and relief of rhinosinusitis.
Cineole (1,8-cineole, eucalyptol) is the primary mucolytic and anti-inflammatory compound of eucalyptus with robust clinical evidence for rhinosinusitis. A 310-patient non-interventional survey showed significant improvements in all rhinosinusitis symptom dimensions (p<0.001) with oral cineole over 7 days, with 90% rating efficacy as good or very good. It is used in licensed oral preparations in Germany for rhinosinusitis treatment.
1,8-Cineole (eucalyptol) is the pharmacologically active compound in eucalyptus oil with the strongest clinical evidence for sinusitis: a placebo-controlled RCT (Kehrl et al., 2004) found 200 mg three times daily significantly improved rhinosinusitis symptom scores versus placebo after 7 days.
Sistemas corporales que cineol puede ayudar a apoyar.
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