Limonene: Aroma of innovation in health and disease
Graphical abstract
Introduction
Plant-derived compounds show important biological properties that can be used for promotion and maintenance of health. Compounds commonly found in dietary products offer protection against diseases, and they are therapeutically important because of their properties, such as antioxidant and anti-inflammatory potential. A regular dietary intake of fruits and vegetables in the diet has protective effects against different pathologies [1].
The international definition for essential oil is the product obtained by hydrodistillation, steam distillation or dry distillation or by a suitable mechanical process without heating (for Citrus fruits) of a plant or some part of it [2]. Essential oils are volatile oily liquids, rarely colored and characterized by a strong odor [3]. This aroma results from the combination of the aromas of each molecule which composes the oil [4]. Typically, essential oils are composed by terpenes, including monoterpenes, which are the most common constituent [3].
The genus Citrus (Rutaceae) includes the most cultivated fruits in the world, such as orange, lemon, and mandarin [5]. In Citrus species, the fruit peel contains secretory cavities filled with essential oil [6]. The extraction of essential oils from Citrus fruits dates from the sixteenth century. Nowadays, the extraction process can be basically summarized in the following steps: rupture of the peel utricles by mechanical action, enabling the oil release, a water flow transports the essential oil and, at last, essential oil and water are separated by centrifugation [7].
Citrus essential oils are characterized by a volatile and a non-volatile fraction, which can be composed of more than 200 compounds. The volatile fraction is mainly composed of monoterpene and sesquiterpene hydrocarbons, also by their oxygenated derivatives, aliphatic aldehydes, alcohols and esters, forming until 99% of the essential oil. The non-volatile fraction could contain hydrocarbons, sterols, fatty acids, waxes, carotenoids, coumarins, psoralens, and flavonoids [7,8].
Terpenes, the main components of essential oil, are produced by various species of plants and present diverse functions, such as defense mechanism against herbivores and pathogens and plant developmental physiology. The terpene basic chemical structure consists of an isoprene unit [9]. Terpenes can present diverse chemical structure and they are synthesized by metabolic pathways by several types of specialized plant cells [10,11]. Terpenes are employed in disease prevention and treatment, offering various biological effects such as antimicrobial, anti-allergenic, antioxidant, anti-inflammatory and immunomodulatory properties [12]. The terpenes large use in health can also be explained by its favorable pharmacokinetic properties, such as lipophilicity and low molecular weight [3,13].
Limonene is one of the most common terpenes in nature and a major constituent of numerous essential oils from Citrus. Limonene is a colorless liquid and it exists as two optical isomers, named d- or l-limonene, and as a racemic mixture [14]. Limonene possesses a pleasant lemon-like odor, which makes it widely used as a flavor and fragrance additive in common food items, such as fruit juices, candies, chewing gums, soft drinks, ice creams. Limonene is one of the most frequent and inexpensive fragrances used in cosmetics formulation, and can be found in many types of beauty products such as soaps, perfumes, shampoos, hair conditioners, and shower gels [[15], [16], [17]], cleaning products and ecofriendly pesticides [18]. In addition, it is considered safe for food preservation [19] and could be used as a green solvent for the extraction of natural products [20].
After oral administration, limonene is rapidly absorbed in the gastrointestinal tract, distributed and metabolized. Limonene is considered safe, presenting low toxicity to humans, without inducing mutagenic, carcinogenic, or nephrotoxic risk to humans [19].
Schmidt and Göen [21] investigated the limonene metabolism and elimination kinetics in humans. The authors found that the metabolites carveol, perillic acid, limonene-1,2-diol, and limonene-8,9-diol, but not perillyl alcohol or limonene itself, were detectable in the volunteers' blood after 5 h of an oral dose of limonene, evidencing a rapid first-pass metabolism. The urinary profile of metabolites is very similar to that in blood. The product of exocyclic oxidation limonene-8,9-diol was the main renal metabolite. Limonene or its metabolites also underwent respiratory elimination, leaving a characteristic odor in the exhaled air. Human limonene metabolism occurs rapidly, and the body is almost entirely cleared from the metabolites after 24 h of limonene ingestion.
Numerous therapeutic properties have been attributed to limonene (1-methyl-4-(1-methylethenyl) cyclohexane), a naturally occurring 10-carbon cyclohexanoid monoterpene derivative [22]. The present review article covers the last ten years (2008–2017) of publications about limonene therapeutic effects published in the scientific literature, aiming to disseminate the knowledge about this useful compound and shed light in future researches regarding its biological activities in preclinical and clinical studies.
Section snippets
Anti-inflammatory activity
Kummer et al. [5] investigated the anti-inflammatory activity of limonene from Citrus latifolia Tanaka fruit bark essential oil using zymosan-induced peritonitis and in vitro assays. Using gas chromatography-mass spectrometry technique, the authors confirmed that limonene was the main compound present (62%) in the essential oil of Citrus latifolia. Limonene, as well as the essential oil, did not present in vitro cytotoxicity on neutrophils derived from the peritoneal cavity of BALB/c mice.
Conclusion and perspectives
Nowadays, researchers have made extensive efforts on natural products as an alternative or complementary medicine because of attractive factors such as relative easy acquisition, efficacy, safety, and low cost. The results reported here validate the growing interest in the biological activities of limonene. We reported and analyzed more than sixty articles published in the last ten years regarding different effects offered by limonene. It can be affirmed that limonene presents
Conflicts of interest
None.
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