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Limonene: Aroma of innovation in health and disease
Abstract
Natural products obtained in dietary components may aid the prevention and treatment of a variety of diseases. Reports in the scientific literature have demonstrated that the consumption of terpenes is a successful alternative in the treatment of several diseases, triggering beneficial biological effects in clinical and preclinical studies. The monoterpene limonene is largely used in alimentary items, cleaning products, and it is one of the most frequent fragrances used in cosmetics formulation. The therapeutic effects of limonene have been extensively studied, proving anti-inflammatory, antioxidant, antinociceptive, anticancer, antidiabetic, antihyperalgesic, antiviral, and gastroprotective effects, among other beneficial effects in health. In this review, we collected, presented, and analyzed evidence from the scientific literature regarding the usage of limonene and its activities and underlying mechanisms involved in combating diseases. The highlighting of limonene applications could develop a useful targeting of innovative research in this field as well as the development of a limonene-based phytomedicine which could be used in a variety of conditions of health and disease.
... Limonene Regulate the dopamine and GABA pathways by modulating the adenosine A2 A receptor [116] Restore monoaminergic neurons to increase serotonin, norepinephrine, and dopamine neurotransmitters [167] β-linalool Activate 5-HT 1A and α2 adrenergic receptors to increase serotonin and noradrenaline [34] Modulate GABA A receptors that exhibit fast inhibitory neurotransmission in the brain to dampen the neuron's excitability and prevent over-excitation [35] 1,8-cineole Regulates the inhibitory pathway by modulating GABA A and benzodiazepine receptors [153] β-pinene Mediating 5-HT 1A , α2, and dopamine D2-like to increase serotonin, noradrenaline, and dopamine neurotransmitters in the brain [52,155] Eugenol Increase monoamine neurotransmitters and metallothionein-III expression in the brain and hippocampus [55] Directly prevent lipid peroxidation and indirectly increase glutathione L-ascorbate in the striatum to prevent reduction of striatal DA and its metabolites [58] Mediates the gabaergic system in the central amygdala to inhibit the excitability of neurons [87] Antioxidant α-pinene Increases the expression of oxidative phosphorylation proteins in the hippocampus to prevent mitochondrial dysfunction [154] 1,8-cineole It binds with Keap1 to induce Nrf2 protein formation and reduce MPO activity [22] p-cymene Reduce nitrite, which is capable of inhibiting SOD and catalase [12] Eugenol Scavenges ROS species through the donation of phenolic hydroxyl and allyl groups of eugenol [61,117] Guard neuron cells against NDMA and 5-lipoxygenase that cause oxidation and excitotoxic injury [110] Prevention of hexanal oxidation effects, iron-mediated lipid peroxidation, non-enzymatic peroxidation in liver mitochondria, and copper-dependent low-density lipoprotein oxidation [110] Prevents lipid peroxidation and reactive species by forming complexes with reactive metals [61] Enhance glutathione enzyme production to neutralize the toxicity effect of p-quinone [58,110] β-caryophyllene Increase SOD2 and gpx-1 enzymes [43] α-phellandrene Enhance plasma GSH to increase the scavenging activity of free radicals [116] Suppress intracellular NO and O 2 À to regulate oxidative stress [31] Limonene Suppression of IL-1β and TNF-α expressions at the hippocampus to inhibit neuroinflammation [90,116] Reduce reactive species and increase antioxidant enzymes [90,116] container is usually used to store the isolated terpene. [37,77] Moreover, high temperatures can accelerate the degradation process of a terpene, thus a cool environment is need as it capable to extend the shelf life by maintaining the chemical integrity. ...
... [22] This study is supported by recent findings that report the activity of 1,8-cineole to reduce depressive-like symptoms by using glutamatergic systems. [153] It regulates the inhibitory pathway by modulating GABA A and benzodiazepine receptors, which reduce overexcitation of neurons that can lead to neuron death. [153] However, no study has been conducted to assess whether 1,8-cineole modulates the dopaminergic system. ...
... [153] It regulates the inhibitory pathway by modulating GABA A and benzodiazepine receptors, which reduce overexcitation of neurons that can lead to neuron death. [153] However, no study has been conducted to assess whether 1,8-cineole modulates the dopaminergic system. Moreover, in the β-Pinene case, it prevents depression and anxiety by mediating 5-HT 1A , α2, and dopamine D2-like, which lead to an increment of serotonin, noradrenergic, and dopamine neurotransmitters in the brain. ...
This review focus on the terpenoids as potential therapeutic agents for depression and anxiety disorders, which naturally found in a variety of plants and exhibit a wide range of biological activities. Among the terpenoids discussed in this review are α‐pinene, β‐caryophyllene, α‐phellandrene, limonene, β‐linalool, 1, 8‐cineole, β‐pinene, caryophyllene oxide, p‐cymene, and eugenol. All of these compounds have been studied extensively regarding their pharmacological properties, such as neuroprotective effect, anti‐inflammation, antibacterial, regulation of neurotransmitters and antioxidant effect. Preclinical evidence are reviewed to highlight their diverse mechanisms of action and therapeutic potential to support antidepressant and anxiolytic properties. Additionally, challenges and future directions are also discussed to emphasize therapeutic utility of terpenoids for mental health disorders. Overall, this review provides a promising role of terpenoids as novel therapeutic agents for depression and anxiety, with potential implications for the development of more effective and well‐tolerated treatments in the field of psychopharmacology.
... These additives are essential to obtain high-quality, high-performance polypropylene and C-PP/PE films adapted to the needs of different industrial sectors [16][17][18][19][20][21][22][23][24][25][26]. Previously, various extraction techniques have been used for Irgafos P-168 and antioxidant additives in C-PP/PE and PP films [29,30]. These techniques include S extraction, ultrasound-assisted extraction (UAE), and more advanced techniques s microwave-assisted extraction (MAE) and supercritical fluid extraction (SFE) [3 Soxhlet extraction is a classic method where the sample is placed in a cell-shaped e tion cartridge, and a heating and cooling cycle is carried out. ...
... Although organic compounds such chloromethane, cyclohexane, and chloroform are recognized for achieving high rec percentages, their high toxicity represents a significant risk for the personnel invol their handling and the environment in general [33][34][35]. Specifically, dichloromethan known as methylene chloride, is subject to use restrictions due to its harmful pot Therefore, it is essential to select solvents that carefully ensure the extraction pro effectiveness, offer safety for human well-being, and minimize their environmental i Previously, various extraction techniques have been used for Irgafos P-168 and other antioxidant additives in C-PP/PE and PP films [29,30]. These techniques include Soxhlet extraction, ultrasound-assisted extraction (UAE), and more advanced techniques such as microwave-assisted extraction (MAE) and supercritical fluid extraction (SFE) [31][32][33][34]. ...
... Specifically, dichloromethane, also known as methylene chloride, is subject to use restrictions due to its harmful potential. Therefore, it is essential to select solvents that carefully ensure the extraction process's effectiveness, offer safety for human well-being, and minimize their environmental impact [28][29][30][31][32]. Limonene emerges as an up-and-coming option since its toxicity is considerably lower than that of traditional solvents [28][29][30][31][32]. ...
In polypropylene/polyethylene composite (C-PP/PE) production, stabilizing additives such as Irgafos P-168 are essential as antioxidant agents. In this study, an investigation was carried out that covers different solid-liquid extraction methods (Soxhlet, ultrasound, and microwaves); various variables were evaluated, such as temperature, extraction time, the choice of solvents, and the type of C-PP/PE used, and the gas chromatography coupled to mass spectrometry (GC-MS) technique was used to quantify the presence of Irgafos P-168 in the C-PP/PE samples. The results revealed that microwave extraction was the most effective in recovering Irgafos P-168. A recovery of 96.7% was achieved when using dichloromethane as a solvent, and 92.83% was achieved when using limonene as a solvent. The ultrasound technique recovered 91.74% using dichloromethane and 89.71% using limonene. The Soxhlet extraction method showed the lowest recovery percentages of 57.39% using dichloromethane as a solvent and 55.76% with limonene, especially when the C-PP/PE was in the form of pellets. The degradation products that obtained the highest degradation percentages were Bis (di-test-butyl phenyl) phosphate and Mono (di-test-butyl phenyl) phosphate using the microwave method with dichloromethane as a solvent and PP in film. Finally, the possible mechanisms for forming the degradation compounds of Irgafos P-168 were postulated.
... Additionally, it was observed that it also lowers the activity of COX-2, resulting in reduced levels of PGE2, which is attributed to the presence of limonene, 1.8-cineole, and α-terpineol [66]. Limonene diminishes inflammation by decreasing the activity of 5-LOX and lowering the levels of LTB4, thereby preventing the inflammatory process [67]. Additionally, both limonene and terpineol demonstrate antiinflammatory effects by decreasing the levels of pro-inflammatory cytokines such as TNF, IL-6, leptin, and AOPP in a colitis induction model [68]. ...
... Additionally, both limonene and terpineol demonstrate antiinflammatory effects by decreasing the levels of pro-inflammatory cytokines such as TNF, IL-6, leptin, and AOPP in a colitis induction model [68]. Limonene reduces the production of ROS and RNS by increasing the activity of the antioxidant defense system in cells of diabetic rats and an inflammatory state [67]. It also promotes a reduction in MDA [69]. ...
Phytosomes are used as vehicles that carry plant extracts. They exhibit biological activities and possess better bioavailability, bioabsorption, and lower toxicity than drugs. Obesity is an inflammatory state in which oxidative stress is present, which triggers severe effects on the body’s organs. This study aimed to evaluate the impact of the extract and phytosomes of Callistemon citrinus on oxidative stress and inflammation in the liver and heart of Wistar rats fed with a high-fat-fructose diet. Phytosomes containing the extract of leaves of C. citrinus were prepared. The antioxidant, pro-inflammatory enzymes, and biomarkers of oxidative stress were evaluated. Among the groups, only the high-fat-fructose group presented an increase in the COX-2, 5-LOX, and MPO inflammatory enzymes, while the XO enzyme exhibited decreased activity. The groups were fed a hypercaloric diet for 15 weeks while orlistat, C. citrinus extract, and phytosomes were administered at three different concentrations, exhibiting enzyme activities similar to those of the control group. It was also observed that the lowest concentration of phytosomes had a comparable effect to the other concentrations. Callistemon citrinus extract can modulate the activities of enzymes involved in the inflammation process. Furthermore, small doses of phytosomes can serve as anti-inflammatory agents.
... It is known that terpenes are abundant in the volatile oils of citrus plants (Kohzaki et al. 2009); therefore, the SPME method is usually used to determine the monoand sesquiterpenes. The Citrus volatile oil is mainly composed of monoterpene and sesquiterpene hydrocarbons, and also by their oxygenated derivatives, aliphatic aldehydes, alcohols, and esters (Dugo and Giacomo 2002;Tranchida et al. 2012;Vieira et al. 2018). After determining the structure of the volatile components, they were classified as hydrocarbons, carbonylic compounds, monoterpene hydrocarbons, oxygenated monoterpenes, sesquiterpene hydrocarbons, oxygenated sesquiterpenes, fatty acids and derivatives, and others. ...
... Limonene is a colorless liquid and has a pleasant lemon-like odor (Hirota et al. 2010). This makes it widely used as a flavor and fragrance additive in common food items, as well as in the cosmetic industry as soaps, perfumes, and shampoos (Jongedijk et al. 2016;Vieira et al. 2018). When the amounts of limonene in the flowers and leaves of the 5 Citrus species were examined, values were between 1.1% and (Kamatou and Viljoen 2008). ...
Species belonging to the genus Citrus are produced and traded in large amounts around the world. In addition to the consumption of citrus fruits as food due to their high vitamin C content, their use in many areas has become widespread with the development of the plant-based products industry. In this study, the amount and structure of volatile components of leaves and flowers of 5 different citrus species (Citrus aurantium, Citrus limon, Citrus paradisi, Citrus reticulata, and Citrus sinensis) were determined using the solid phase micro extraction. Monoterpene hydrocarbons and their oxygenated derivatives were identified as the most abundant chemical component groups. Limonene was the dominant compound in Citrus limon flowers (36.5%), leaves (22.5%) and Citrus paradisi flowers (22.4%). Linalool, and sabinene were the other major components. Linalool was determined at 50.5% in flowers and 73.3% in leaves of Citrus aurantium. Moreover, sabinene had a high amount in Citrus sinensis flowers (19.7%), leaves (24.7%), and in Citrus paradisi (27.4%) leaves. Apart from these dominant components, γ-terpinene (13.9%) and p-cymene (25.4%) were detected in Citrus reticulata flowers and leaves in an important amount. It was seen that the leaves and flowers of Citrus species gathered from Hatay province were an important source of limonene and linalool compounds.
... ora incarnata L. plant compounds and emphasized that this bicin has antitumor activity. Sharma et al. (2015) [21] discovered Benzenepropanoic acid, 3,5bis(1,1-dimethylethyl)-4-hydroxy-methyl ester compound in the extract of Brassica juncea L. species, and Xian et al. (2018)[22] emphasized in their study that this plant has anti-inflammatory effect.Vieira et al. (2018) [23] comprehensively examined the effects of limonene on health. They emphasized that many studies are revealing the anti-inflammatory, antioxidant, antinociceptive, anticancer, antidiabetic, antiviral, and gastroprotective effects of limonene published in the scientific literature between 2008 and 2017.3.2. Synthesis and characterizati ...
... Sujana et al. (2012) found (3E,5E,7E)-6-Methyl-8-(2,6,6-trimethyl-1-cyclohexenyl)-3,5,7octatrien-2-phenolic acid in Passiflora incarnata L. plant compounds and emphasized that this bicin has antitumor activity. Sharma et al. (2015) [21] discovered Benzenepropanoic acid, 3,5bis(1,1-dimethylethyl)-4-hydroxy-methyl ester compound in the extract of Brassica juncea L. species, and Xian et al. (2018)[22] emphasized in their study that this plant has anti-inflammatory effect.Vieira et al. (2018) [23] comprehensively examined the effects of limonene on health. They emphasized that many studies are revealing the anti-inflammatory, antioxidant, antinociceptive, anticancer, antidiabetic, antiviral, and gastroprotective effects of limonene published in the scientific literature between 2008 and 2017.3.2. ...
Mosses are one of the oldest land plants that constitute the second largest group of the plant kingdom, are found in almost every region, have known therapeutic effects, are rich in secondary metabolites, can withstand harsh climatic conditions and thirst for a long time. Volatile extracts of Hypnum cupressiforme Hedw. were analyzed by gas chromatography-mass spectrometry in this study, and the presence of 18 different phytocompounds was determined as secondary metabolites. Using these extracts, silver nanoparticles (AgNPs) were synthesized using a green synthesis method. The AgNPs that were created were characterized. The extracts and AgNPs were tested for antibacterial, antibiofilm, antioxidant, mutagenic, and DNA-cleavage activity. The tests revealed no evidence of mutagenicity. Antibiofilm and antibacterial activity of AgNPs against P. vulgaris, P. aeruginosa, and E. faecalis were demonstrated. Both oxidatively and hydrolytically, H. cupressiforme the extract was found to have higher antioxidant properties and high DNA cleavage activity.
... Limonene is a cyclic monoterpene hydrocarbon found in citrus fruit oils. The compound has two forms, (D)-(also known as R) and (S)-limonene, which exhibit distinct scents resembling orange and lemon, respectively (Vieira et al., 2018). In addition to its unique aroma, limonene has been extensively studied for its potential therapeutic effects, including antihyperalgesic, anti-in ammatory, antioxidant, antinociceptive, anticancer, antidiabetic, antiviral, and gastroprotective properties, among other health bene ts (Y. ...
Lactobacillus -derived (LAB) exopolysaccharide (EPS) was used as an emulsifier to encapsulate limonene enantiomers, including S- (SL) and D- (DL). EPS and emulsions were analyzed for physiochemical and rheological behavior, followed by emulsifying stability and antimicrobial activity against food-borne pathogens. EPS was extracted and yielded 1.1 g/L amount with an optimized supplementation of 5 % carbon source at pH 6.1 and characterized using fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and thermo-gravimetric analysis (TGA), along with physiochemical properties. At 2 % EPS in 60/40 O/W emulsion, a desired mean particle size and polydispersity index (PDI) were acquired by comparing different O/W ratios. Optimized emulsions showed higher stability under different physiological parameters: temperatures (-20 to 60 ºC), pH (2-9), and salinity. In FTIR analysis, emulsions showed OH and C=O stretching acquired from EPS and the presence of cyclohexane-1-ene group from encapsulated limonene. Notably, our study is among the first to demonstrate LAB-derived EPS as a natural and effective emulsifier for stabilizing limonene, providing both improved stability and antimicrobial efficacy against E. coli and L. monocytogenes compared to free oils. These findings illustrate that LAB-derived EPS is a promising natural emulsifier for encapsulating volatiles, with significant applications in food safety.
... According to Ruiz and Flotats [43], limonene was the dominant compound in various citrus EOs, which is also in accordance with the obtained results. Additionally, prior studies have demonstrated the anti-inflammatory, anti-cancer, antioxidant, antidiabetic, antiviral, and gastroprotective properties of limonene [44,45]. ...
Kumquat is one of the smallest citrus fruits (from the Rutaceae family), and its essential oil’s biological effects have not yet been sufficiently researched, in contrast to the essential oils of its relatives. Therefore, the aim of this large-scale study was to investigate the chemical profile of kumquat essential oils (KEOs) isolated by microwave-assisted distillation (MAD) and Clevenger hydrodistillation using GC-MS analysis. To test the bioaccessibility of their bioactive components, in vitro digestion with commercially available enzymes was performed. The final step of this research was to test their cytotoxic activity against a cervical cancer cell line (HeLa), a human colon cancer cell line (HCT116), a human osteosarcoma cell line (U2OS), and a healthy cell line (RPE1). Two methods were used to test the antioxidant activity: DPPH (2,2-diphenyl-1-picrylhydrazyl) and ORAC (oxygen radical absorbance capacity). The antibacterial activity was tested in relation to the growth and adhesion of Escherichia coli and Staphylococcus aureus on a polystyrene surface. The GC-MS analysis showed that the major compound in both kumquat essential oils was limonene, which was stable before and after in vitro digestion (>90%). The results showed that the cytotoxic activity of the KEOs in all three cancer cell lines tested was IC50 1–2 mg/mL, and in the healthy cell line (RPE1), the IC50 value was above 4 mg/mL. The antibacterial activity of the KEOs obtained after MAD and Clevenger hydrodistillation was 4 mg/mL against E. coli and 1 mg/mL against S. aureus. The KEOs after MAD and Clevenger hydrodistillation reduced the adhesion of E. coli by more than 1 log, while there was no statistically significant effect on the adhesion of S. aureus to the polystyrene surface. Both KEOs exhibited comparable levels of antioxidant activity using both methods tested, with IC50 values of 855.25 ± 26.02 μg/mL (after MAD) and 929.41 ± 101.57 μg/mL (after Clevenger hydrodistillation) for DPPH activity and 4839.09 ± 91.99 μmol TE/g of EO (after MAD) and 4928.78 ± 275.67 μmol TE/g of EO (after Clevenger hydrodistillation) for ORAC. The results obtained show possible future applications in various fields (e.g., in the food, pharmaceutical, cosmetic, and agricultural industries).
... O. gratissimum produces an essential oil (EO) that is valued by the perfumery, cosmetic, pharmaceutical, and food industries [12]. In addition, many biological properties have been reported on the EO of the plant including antiviral, inhibitory, anticoagulant, antitumor, antimicrobial, antimalarial, antioxidant, antiinflammatory, antileishmania, anti-catabolic effects [11,13,14]. However, to the best of our knowledge, no study has been conducted on the antioxidant activity and physicochemical properties of this EO in Burkina Faso. ...
Ocimum gratissimum L. is an aromatic herbaceous plant that is native to tropical countries especially West Africa, India and South America. It has been traditionally used for medicinal, condiment and culinary purposes and many biological properties have been reported on its essential oils (EOs). This study aims to determine the physico-chemical parameters and assess the antioxidant potential of this plant's EO. Thus, fresh leaves of O. gratissimum were collected from the cultivated field of Irsat (Ouagadougou), Burkina Faso at the full blooming stage. These leaves were hydrodistilled and analyzed immediately after collection (fresh) to evaluate the quality of volatile constituents in terms of composition by GC-MS. Physico-chemical properties were determined by using international standards ISO. The antioxidant activity was determined by 2,2'-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and the 2,2' azinobis 3 ethylbenzothiazoline 6 sulfonic acid (ABTS) methods. The study revealed the presence of thymol (29.5%), γ-terpinene (20.5%) and p-cymene (12.9%) as EO major constituents. For physico-chemical parameters, the relative density value was less than 1. A low content of free acids was found. The EO had low light refraction and was found to be dextro-rotatory. The EO was soluble in 7 volumes of ethanol (70%) and values obtained for the acid index and refractive index were less than 2. The antioxidant activity showed DPPH radical inhibition value of 41.16 % at 0.1% of EO concentration with an IC50 value of 3.9 μg/ml. The ABTS radical inhibition value was 36.14 % at 0.1% of EO concentration with an IC50 value of 3.13 mg/ml. The present study has permitted to verification of the quality of O. gratissimum EO produced in Burkina Faso and showed that this oil could be a promising source of antioxidant compounds.
... Limonene is a compound widely used in various industries such as food, pharmaceuticals, flavoring, and solvents. It is the main component of citrus essence and is responsible for its unique aroma and taste (Vieira et al., 2018). The percentage of limonene in this study was evaluated as an important biochemical trait of the fruit. ...
... For example, ether extract from fresh vs. dried C. limon peels resulted in a decrease in limonene from 76.8% to 28.3% [21]. Therefore, fresh sample preparation is preferable to obtain the primary component limonene, which is known to have diverse biological functions [17,90]. The diversity of components in LEO is actually quite high due to the extraction process and sample freshness. ...
Recent studies have explored the antioxidant properties of lemon essential oil (LEO), taking considering factors like plant part, extraction methods, and antioxidant assay. However, due to varied results and limited precision in individual studies, our meta-analysis aims to offer a comprehensive understanding across different experiments, irrespective of location or time. Out of 109 scientific articles published between 1947 and 2024, only 28 successfully validated their data on differences in antioxidant capacity and IC50, using weighted averages of Hedges’ d in meta-analysis. A meta-analysis revealed several key findings: (i) lemon leaf and peel extracts have higher IC50 compared to controls, whereas whole plant extracts show lower values (p < 0.001); (ii) the maceration preserves antioxidant properties better than hydro-distillation and Soxhlet extraction (p < 0.001); (iii) LEO require higher concentrations to achieve comparable free radical inhibition as the standard controls such as AsA, BHT, and quercetin, suggesting lower antioxidant efficiency. This was supported by IC50 result, which showed no significant difference between LEO and other compounds like thymol, Thymus vulgaris EO, and Citrus aurantium EO. However, compared to AsA, BHT, limonene, and trolox, the inhibition efficacy was significantly lower (p < 0.01). These findings consistently demonstrated significant antioxidant activity across multiple assays, including ABTS, β-carotene bleaching, DPPH, and FRAP (p < 0.01). Notably, the predominant components of LEO including α-linoleic acid, D-limonene, limonene, L-limonene, neryl acetate, sabinene, and Z-citral, which demonstrate significant potency as antioxidant agent (p < 0.01). Specifically, limonene and Z-citral make substantial contributions to its antioxidant capacity (p < 0.01). Despite variations in purity among LEO extractions, there is potential for future enhancement through nanoemulsion. In conclusion, LEO show promise as an alternative antioxidant, with emphasis to selecting samples based on leaves or peels and employing maceration extractions for various antioxidant assays. Active components rich in terpenoids, such as limonene and Z-citral, are particularly noteworthy.
Graphical Abstract
... Among the main properties of the most abundant terpenes in C. sativa, noteworthy is the ability of aand b-pinene, D-limonene, b-caryophyllene, and a-humulene to inhibit the activity of acetylcholinesterase, which is the basis of the insecticidal activity of these terpenes (López and Pascual-Villalobos 2010). D-limonene also exhibits potent anti-inflammatory, antioxidant, anti-cancer, antidiabetic, and anti-nociceptive properties (Vieira et al. 2018), whereas anxiolytic, antioxidant, anti-ageing, anti-inflammatory, and analgesic properties have been recognized to b-myrcene (Surendran et al. 2021). Interestingly, b-caryophyllene is the only terpene known to interact with the human endocannabinoid system, by acting as agonist of the CB2 receptor; this gives b-caryophyllene its therapeutic potential by mediating anti-inflammatory and immunomodulatory effects (Gertsch et al. 2008). ...
Cannabis sativa L. is an annual dioecious species native from Central Asia, which has mainly been used for medical purposes by many ancient cultures and is currently used for the treatment of several diseases. The pharmacological properties of C. sativa are related to cannabinoids, a class of secondary metabolites entirely unique to this crop that are produced and stored at high levels in the inflorescences and leaves. In addition to cannabinoids, C. sativa plants also produce a large number of non-cannabinoid secondary metabolites including terpenes, phenolic compounds and others, which have also been associated with health-promoting activities. In recent decades, the interest in secondary metabolites from C. sativa has been increasing due to their potential applications not only as pharmaceuticals, but also as nutraceuticals, food additives, drugs, fragrances, and biopesticides. This has generated a significant increase in the development of effective strategies for improving the production of such bioactive compounds. In this context, elicitation has emerged as an effective tool based on the application of abiotic or biotic factors that induce physiological changes and stimulate defense or stress-related responses in plants, including the biosynthesis of secondary metabolites. The current review gives a comprehensive overview of the available studies on the different elicitation approaches used to enhance the accumulation of the major bioactive compounds in C. sativa, and highlights challenges and opportunities related to the use of external elicitors for improving the added value of this crop.
... It can be applied in many industrial sectors such as the food or cosmetic industry as fragrance as well as biobased additive in thermoplastic processing. Moreover, it is an interesting molecule due to its antimicrobial properties [15][16][17]. Limonene can be extracted from OPs with different solvents and under various conditions. Most commonly, the petrochemical and toxic solvent hexane is applied in this process, however to reduce the environmental footprint, other solvents can perform successfully as well [18]. ...
... Roasting of rice with olive oil was conducted in Pilaf method, which increased the temperature and the heating rate, and hence had a contributing effect on limonene level. Limonene has anti-inflammatory, antioxidant, anticancer, antidiabetic, antiallergic, antistress, and antinociceptive properties, and beneficial effects on gastric ulcers, colitis, airway inflammation, and asthma [58]. Therefore, cooking practices for the high retention of this compound is important. ...
A rice dish is a complex food item with different dimensions affected by variety, cooking technique, and the presence of other ingredients and their interactions. Baldo, Osmancik, and Cammeo are the most popular rice varieties, and Salma and Pilaf techniques are two of the most common cooking methods used in the culinary applications in Türkiye. Therefore, rice dishes were prepared with these rice varieties, and cooked via Salma and Pilaf techniques in this study. Butter, olive oil, margarine, and sunflower oil were included in the formulations as different fat types. The samples prepared with Osmancik rice, Salma method, and olive oil (O-S-O); Baldo rice, Pilaf method, and olive oil (B-P-O); and Cammeo rice, Salma method, and olive oil (C-S-O) were the top three dishes in terms of overall acceptability scores. Squalene, limonene, isopropyl myristate, cyclotetradecane, acetic acid, acetol, and nonanal were detected as volatile compounds in these rice dishes. Methyl oleate, methyl palmitate, methyl linoleate, methyl stearate, methyl palmitoleate, methyl linolenate, and methyl eicosanate are the common fatty acid components in these most liked rice dishes and olive oil used. Methyl benzoate and benzaldehyde were quantified using the Salma technique in O-S-O and C-S-O but not in B-P-O cooked with Pilaf method. Complicated chemical reactions among rice components are closely associated with the development of cooked rice aromas. This study is the first to investigate volatiles and fatty acid-derived compounds in rice dishes cooked with Baldo, Osmancik, and Cammeo varieties using Salma and Pilaf procedures together with sensory evaluation.
... 5989-54-8, dipentene CAS no. 138-86-3) is also a terpene fragrance referred to as a lemon-like smell or citrus taste (37,38). Air oxidation of limonene can also occur in a similar way, as described for linalool (39). ...
Fragrance materials are widely used in various types of products in daily life and many of them can be contact sensitizers. Contact allergy to fragrances has been reported to be common worldwide. Unlike other groups of contact allergens such as metals and preservatives, fragrance materials in consumer products can be present as single fragrance chemicals or in the form of mixtures known as natural complex substances. Due to the complexity of the fragrance materials and the high number of fragrance substances known to cause contact sensitization, selecting suitable materials for patch testing is challenging. Emerging fragrance markers have been additionally introduced in different baseline series for screening to enhance the rate of fragrance contact allergy detection. Moreover, there have been continual updates on basic knowledge, clinical perspectives, sources of exposure, and regulations on the use of fragrance materials. Avoiding pitfalls while performing patch testing with fragrance test materials is also crucial and should not be overlooked. Therefore, this review aims to update knowledge to provide a high-quality holistic approach to fragrance contact allergy diagnosis and management.
... The antifungal efficiency of menthol against C. albicans corresponds to amphotericin B, with a minimum inhibitory concentration (MIC) of 125.0 μg/mL, and also targets dental germs (Al-Bayati 2009;Mikaili et al. 2013). Limonene is a colorless substance that exhibits two optical isomers (Siti 2015;Vieira et al. 2018). Limonene exhibits significant potential for application in antimicrobial and food storage domains owing to its wideranging bactericidal properties, favorable safety profile, and minimal toxicity (Kim et al. 2013;Han et al. 2019). ...
Monoterpenoids, compounds found in various organisms, have diverse applications in various industries. Their effectiveness is influenced by the oil’s chemical composition, which in turn is influenced by plant genotype, environmental conditions, cultivation practices, and plant development stage. They are used in various industries due to their distinctive odor and taste, serving as ingredients, additives, insecticides, and repellents. These compounds have synergistic properties, resulting in superior combined effects over discrete ones, potentially beneficial for various health purposes. Many experimental studies have investigated their interactions with other ingredients and their antibacterial, insecticidal, antifungal, anticancer, anti-inflammatory, and antioxidant properties. This review discusses potential synergistic interactions between monoterpenoids and other compounds, their sources, and biological functions. It also emphasizes the urgent need for more research on their bioavailability and toxicity, underlining the importance and relevance of this comprehensive study in the current scientific landscape.
Graphical Abstract
... Seventeen compounds comprising 99.99% of the total oil were identified of which limonene (33.50%) and α-pinene (28.79%) were recognized as major constituents of cone. Limonene is popularly used for digestive problems and abdominal pain, and as a cough suppressant [44] and is considered a safe treatment option with low toxicity, since it is rapidly absorbed and metabolized without posing a mutagenic, carcinogenic, or nephrotoxic risk in the gastrointestinal tract [45]. Additionally, Hirota et al. [46] reported its use in treating respiratory tract diseases among the public. ...
Abies is an important genus of the family Pinaceae, with about 50 species found in the highlands of Asia, Europe, North Africa, and North and Central America. The principal aim of the present work was to investigate the chemical content and biological potential of the resin and cone from Abies nordmanniana subsp. bornmulleriana and Abies nordmanniana subsp. equi-trojani, respectively. The flavonoid and phenolic contents of the resin and cones were evaluated using liquid chromatography-high resolution mass spectrometry (LC-HRMS). Additionally, the essential oil and fatty acid compositions were analyzed using gas chromatography-mass spectrometry (GC-MS) and gas chromatography-flame ionization detector (GC-FID), respectively. Cytotoxicity of the extracts and essential oils were screened against certain cancer cell lines, namely, human prostate adenocarcinoma cell line (PC3), human lung adenocarcinoma cell line (A549), human pancreatic cancer cell line (PANC-1), human hepatocellular carcinoma cell line (HepG2), human breast cancer cell line (MDA-MB231), and normal human lung fibroblast cell line (CCD-34-LU), with MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide] assay. According to the MTT results, hexane extracts of both cone (CH) and resin (RH), ethanol-water (CEW), dichloromethane (CD), and acetone (CA) extracts of the cone mostly inflict cytotoxicity in HepG2 cell line. Antiviral activities of Abies nordmanniana subsp. extracts at doses of 5 μg/g and 10 μg/g were also evaluated in ovo for their virucidal activity against avian coronavirus. Abies nordmanniana subsp. extracts exhibited concentration-dependent antiviral activity on specific pathogen-free embryonated chicken eggs. Significantly, cone acetone extract (CA), cone ethanol extract (CE), and cone dichloromethane extract (CD) of Abies nordmanniana subsp. exhibited strong inhibition of the virus at a concentration of 10 μg/g. The most potent virucidal activity was observed with ethanol-water extract of conifer form (CEW). According to these results, it was proved that Abies nordmanniana species could be a potential, sustainable, and renewable drug source, especially considering the impressive antiviral and significant cytotoxic activity potentials.
... Numerous studies have been conducted on the therapeutic effect of limonene and the compound has demonstrated an array of health benefits, including anti-inflammatory, antioxidant, antinociceptive, anticancer, antidiabetic, antihyperalgesic, antiviral, and gastroprotective properties. [50,51] Linalool ...
Rheumatoid Arthritis (RA) is an immune-mediated inflammatory condition. It occurs when the immune system attacks the tissue surrounding joints due to the release of specific chemicals and enzymes that start consuming away the cartilage and bones. The ant-arthritis of Coriandrum sativum (CS) has 96 were examined. Docking scores depicted that, anethole, beta-pinene, camphor, and geraniol phytochemicals demonstrated a commendable potential as inhibitors of 2AXJ molecule. The score hierarchy is camphor (-6.9 kcal/mol), beta-pinene (-5.9 kcal/mol), geraniol (-5.3 kcal/mol), and anethole (-5.2 kcal/mol). The four phytochemicals also appear to have good drug-likeness properties and oral bioavailability. Therefore the in vitro and in vivo studies have demonstrated that CS has strong potential as anti-arthritics and anti-inflammatory. However, clinical trials for both fresh and extracted CS are also necessary to validate the findings.
... To address this issue, we turned to limonene, a natural cyclic terpene found in citrus fruit peels. Limonene boasts several advantageous properties, including mild and pleasant aroma, low viscosity, and antibacterial activity [30][31][32]. Furthermore, existing research has investigated the polymerization and modification of limonene through thiol-ene click reactions [32][33][34][35]. ...
Compared to traditional invasive techniques for wound closure, photocrosslinkable surgical adhesives with antibacterial properties offer significant advantages. These include ease of application, a controllable and efficient curing reaction, reduced risk of pain and infection, and effective leakage prevention. This study introduces a novel soybean oil-based nonisocyanate polyurethane prepolymer for use in such adhesives. The prepolymer, a hydroxyurethane functionalized with methacrylate and quaternary ammonium groups (QAs), was characterized through spectroscopic methods. The resulting UV-curable bioadhesives, synthesized via thiol-ene-methacrylate click-photopolymerization, incorporated limonene as a reactive diluent, a tetra-functional thiol crosslinker, and a photoinitiator. Elemental analysis confirmed the uniform distribution of QAs and sulfur atoms, indicating a homogeneous network structure, corroborated by high gel content values in both organic (84–92%) and aqueous media (91–99%), and a consistent tan δ peak as per DMTA. The optimized adhesives exhibited strong adhesion (up to 377 kPa) to gelatin sheets—a tissue-analogous substrate—and displayed suitable surface free energy (45–52 mN/m) as determined by contact angle measurements, suggesting favorable thermodynamic adhesion to skin. Additionally, the adhesives showed satisfactory cytocompatibility with L-929 fibroblast cells and antimicrobial efficacy against two gram-positive and gram-negative bacterial strains, indicating promising biological activity.
... Numerous studies have been conducted on the therapeutic effect of limonene and the compound has demonstrated an array of health benefits, including anti-inflammatory, antioxidant, antinociceptive, anticancer, antidiabetic, antihyperalgesic, antiviral, and gastroprotective properties. [50,51] Linalool ...
Rheumatoid Arthritis (RA) is an immune-mediated inflammatory condition. It occurs when the immune system attacks the tissue surrounding joints due to the release of specific chemicals and enzymes that start consuming away the cartilage and bones. The ant-arthritis of Coriandrum sativum (CS) has not been summarized before, so this review aims to assess further and explore its efficacy in RA disorders. The online literature search was performed using databases such as ScienceDirect, PubMed, Google Scholar, Wiley Online, Library, Springer, and Taylor& Francis for review. Articles published from January 2010 to January 2024 were composed. Additionally, the molecular docking of the eight selected CS phytochemicals was carried out against the AR protein target (PDB ID: 2AXJ) to support the review. Different parameters such as docking score, oral bioavailability, drug-likeness, absorption, distribution, metabolism, excretion, and toxicity (ADMET) were examined. Docking scores depicted that, anethole, beta-pinene, camphor, and geraniol phytochemicals demonstrated a commendable potential as inhibitors of 2AXJ molecule. The score hierarchy is camphor (-6.9 kcal/mol), beta-pinene (-5.9 kcal/mol), geraniol (-5.3 kcal/mol), and anethole (-5.2 kcal/mol). The four phytochemicals also appear to have good drug-likeness properties and oral bioavailability. Therefore the in vitro and in vivo studies have demonstrated that CS has strong potential as anti-arthritics and anti-inflammatory. However, clinical trials for both fresh and extracted CS are also necessary to validate the findings.
... Numerous studies exploring the chemical constituents and bioactivity of different Citrus oils have consistently reported robust radical scavenging activity [39,40]. In the current study, the essential oils (EOs) are primarily comprised of monoterpene hydrocarbons, notably limonene, and the antioxidant properties of limonene have been previously documented [41][42][43]. Investigations into the chemical composition of essential oils extracted from C. aurantium align with our findings, suggesting that the primary components of the oil of the peel are monoterpene hydrocarbons such as limonene [20,44]. A study conducted by Hsouna et al., reported that C. aurantium L. flower extract displayed superior DPPH scavenging activity, with an IC 50 of 1.85 µg/ml [45]. ...
Background
Bitter orange (Citrus aurantium) is a fruiting shrub native to tropical and subtropical countries around the world and cultivated in many regions due to its nutraceutical value. The current study investigated the metabolic profiling and enzyme inhibitory activities of volatile constituents derived from the C. aurantium peel cultivated in Egypt by three different extraction methods.
Methods
The volatile chemical constituents of the peel of C. aurantium were isolated using three methods; steam distillation (SD), hydrodistillation (HD), and microwave-assisted hydrodistillation (MAHD), and then were investigated by GC-MS. The antioxidant potential was evaluated by different assays such as DPPH, ABTS, FRAP, CUPRAC, and phosphomolybdenum and metal chelating potential. Moreover, the effect of enzyme inhibition of the three essential oils was tested using BChE, AChE, tyrosinase, glucosidase, as well as amylase assays.
Results
A total of six compounds were detected by GC/MS analysis. The major constituent obtained by all three extraction methods was limonene (98.86% by SD, 98.68% by HD, and 99.23% by MAHD). Differences in the composition of the compounds of the three oils were observed. The hydrodistillation technique has yielded the highest number of compounds, notably two oxygenated monoterpenes: linalool (0.12%) and α-terpineol acetate (0.1%).
Conclusion
In our study differences in the extraction methods of C. aurantium peel oils resulted in differences in the oils’ chemical composition. Citrus essential oils and their components showed potential antioxidant, anticholinesterase, antimelanogenesis, and antidiabetic activities. The presence of linalool and α-terpineol acetate may explain the superior activity observed for the oil isolated by HD in both radical scavenging and AChE inhibition assays, as well as in the enzyme inhibition assays.
... The most abundant cannabinoids found in cannabis are ∆ 9 -tetrahydrocannabinolic Natasha Damiana Spadafora and Simona Felletti contributed equally to this work. a perfuming and a flavouring agent [29]; however, it has shown immune-modulatory properties, antitumor, and antiinflammatory effects [30]. Terpinolene is widely used as a flavouring agent in the industry [31]. ...
The increasing interest in hemp and cannabis poses new questions about the influence of drying and storage conditions on the overall aroma and cannabinoids profile of these products. Cannabis inflorescences are subjected to drying shortly after harvest and then to storage in different containers. These steps may cause a process of rapid deterioration with consequent changes in precious secondary metabolite content, negatively impacting on the product quality and potency. In this context, in this work, the investigation of the effects of freeze vs tray drying and three storage conditions on the preservation of cannabis compounds has been performed. A multi-trait approach, combining both solid-phase microextraction (SPME) two-dimensional gas chromatography coupled to mass spectrometry (SPME-GC × GC–MS) and high-performance liquid chromatography (HPLC), is presented for the first time. This approach has permitted to obtain the detailed characterisation of the whole cannabis matrix in terms of volatile compounds and cannabinoids. Moreover, multivariate statistical analyses were performed on the obtained data, helping to show that freeze drying conditions is useful to preserve cannabinoid content, preventing decarboxylation of acid cannabinoids, but leads to a loss of volatile compounds which are responsible for the cannabis aroma. Furthermore, among storage conditions, storage in glass bottle seems more beneficial for the retention of the initial VOC profile compared to open to air dry tray and closed high-density polyethylene box. However, the glass bottle storage condition causes formation of neutral cannabinoids at the expenses of the highly priced acid forms. This work will contribute to help define optimal storage conditions useful to produce highly valuable and high-quality products.
Graphical Abstract
... One of the most common smells used in cosmetic formulations, limonene is a monoterpene that is mostly found in cleaning and food products. Limonene has the therapeutic effects such as anti-inflammatory, antioxidant, antinociceptive, anticancer, antidiabetic, antiviral, and gastroprotective properties 63 . Essential oils are complex combinations of constituents from multiple functional group groups. ...
The pharmacological effects of limonene, especially their derivatives, are currently at the forefront of research for drug development and discovery as well and structure-based drug design using huge chemical libraries are already widespread in the early stages of therapeutic and drug development. Here, various limonene derivatives are studied computationally for their potential utilization against the capsid protein of Herpes Simplex Virus-1. Firstly, limonene derivatives were designed by structural modification followed by conducting a molecular docking experiment against the capsid protein of Herpes Simplex Virus-1. In this research, the obtained molecular docking score exhibited better efficiency against the capsid protein of Herpes Simplex Virus-1 and hence we conducted further in silico investigation including molecular dynamic simulation, quantum calculation, and ADMET analysis. Molecular docking experiment has documented that Ligands 02 and 03 had much better binding affinities (− 7.4 kcal/mol and − 7.1 kcal/mol) to capsid protein of Herpes Simplex Virus-1 than Standard Acyclovir (− 6.5 kcal/mol). Upon further investigation, the binding affinities of primary limonene were observed to be slightly poor. But including the various functional groups also increases the affinities and capacity to prevent viral infection of the capsid protein of Herpes Simplex Virus-1. Then, the molecular dynamic simulation confirmed that the mentioned ligands might be stable during the formation of drug-protein complexes. Finally, the analysis of ADMET was essential in establishing them as safe and human-useable prospective chemicals. According to the present findings, limonene derivatives might be a promising candidate against the capsid protein of Herpes Simplex Virus-1 which ultimately inhibits Herpes Simplex Virus-induced encephalitis that causes interventions in brain inflammation. Our findings suggested further experimental screening to determine their practical value and utility.
... Limonene, a shared compound in all hydrosols, although it may not be considered a discriminant compound in PCA due to its presence in significant percentages across all samples, is recognized for its therapeutic effect, including anti-inflammatory, antioxidant, and antiviral effects, besides its use as flavor and fragrance additive owing to its pleasant lemon-like odor [83]. ...
In the circular economy framework, hydrosols, by-products of the essential oil industry, are gaining attention for their potential in waste reduction and resource reuse. This study analyzed hydrosols from six edible flowers, investigating their chemical composition (VOC-Hyd) and antibacterial properties alongside volatile organic compounds of fresh flowers (VOC-Fs) and essential oils (EOs). Antirrhinum majus exhibited ketones as major VOC-Fs (62.6%) and VOC-Hyd (41.4%), while apocarotenoids dominated its EOs (68.0%). Begonia cucullata showed alkanes (33.7%) and aldehydes (25.7%) as primary VOC-Fs, while alkanes were prevalent in both extracts (65.6% and 91.7% in VOC-Hyd and in EOs, respectively). Calandula officinalis had monoterpenoids in VOC-Fs and VOC-Hyd (89.3% and 49.7%, respectively), while its EOs were rich in sesquiterpenoids (59.7%). Dahlia hortensis displayed monoterpenoid richness in both VOC-Fs and extracts. Monocots species’ VOC-Fs (Polianthes tuberosa, Tulbaghia cominsii) were esters-rich, replaced by monoterpenoids in VOC-Hyd. P. tuberosa EO maintained ester richness, while T. cominsii EOs contained a significant percentage of sulfur compounds (38.1%). Antibacterial assays indicated comparable minimum inhibitory concentration profiles across VOC-Hyd: B. calcullata and P. tuberosa against Staphylococcus aureus and Salmonella enterica ser. typhimurium, T. cominsii against Escherichia coli and S. enterica, A. majus and C. officinalis against S. aureus, and D. hortensis against S. enterica.
... Limonene is one of the most common terpenes found in nature, with a pleasant lemon-like odor and is therefore often used as a flavoring and fragrance in food and cosmetics. Apart from its flavoring properties, it has been extensively studied for its other beneficial biological properties, namely its anti-inflammatory, antioxidant, antiviral anticancer, antidiabetic, and gastroprotective effects [21]. Table 2. ...
Sea fennel (Crithmum maritimum L.) is one of the most abundant and widespread Mediterranean halophytes, traditionally harvested and used in the summer months. As the plant bioactive metabolites are strongly influenced by the plant vegetation period and environmental conditions, we investigated some of the main bioactive compounds from sea fennel leaves over a one-year period to gain a deeper insight into their annual changes. A comprehensive phytochemical analysis of the essential oils using GC-MS, as well as the major phenolic and carotenoid compounds using HPLC, was performed. The results showed a high positive correlation between temperature and all major bioactive compounds, especially phenolic acids, cryptochlorogenic acid, and chlorogenic acid (r = 0.887, p = 0.0001 and r = 0.794, p = 0.002, respectively), as well as the limonene content in the essential oil (r = 0.694, p = 0.012). PCA analysis clearly distinguishes the period from February to April from the rest of the year, which contained the least bioactive metabolites overall. The overall data analyzed show great variations in sea fennel phytochemicals during the period of a year, with β-carotene content being the least effected. Therefore, it can be concluded that the plant can be used as a functional food or in other industries, such as the cosmetic and/or pharmaceutic industries, beyond its typical harvest period (early to midsummer).
... NA Antioxidant, antidiabetic, anticancer, anti-inflammatory (limonene) [122,123], anti-fungal (β-phellandrene) [124], antioxidant and antitumour properties (viridiflorene) [125,126], insect repellent (E-β-farnesene) [127] antioxidant activity (copaene) [115]. ...
The Australian Wet TropicsWorld Heritage Area (WTWHA) in northeast Queensland is
home to approximately 18 percent of the nation’s total vascular plant species. Over the past century, human activity and industrial development have caused global climate changes, posing a severe and irreversible danger to the entire land-based ecosystem, and the WTWHA is no exception. The current average annual temperature of WTWHA in northeast Queensland is 24 ◦C. However, in the
coming years (by 2030), the average annual temperature increase is estimated to be between 0.5 and 1.4 ◦C compared to the climate observed between 1986 and 2005. Looking further ahead to 2070, the anticipated temperature rise is projected to be between 1.0 and 3.2 ◦C, with the exact range depending on future emissions. We identified 84 plant species, endemic to tropical montane cloud forests (TMCF)
within the WTWHA, which are already experiencing climate change threats. Some of these plants are used in herbal medicines. This study comprehensively reviewed the metabolomics studies conducted on these 84 plant species until now toward understanding their physiological and metabolomics responses to global climate change. This review also discusses the following: (i) recent developments in plant metabolomics studies that can be applied to study and better understand the interactions of wet tropics plants with climatic stress, (ii) medicinal plants and isolated phytochemicals with structural diversity, and (iii) reported biological activities of crude extracts and isolated compounds.
Rheumatoid arthritis (RA) is a persistent autoimmune disorder predominantly affecting the joint structures, eliciting inflammatory responses, and ultimately leading to degenerative changes without proper medical intervention. Ultimately, this can severely impair joint function and impact the patient's quality of life. Current treatment approaches include disease‐modifying anti‐rheumatic drugs, non‐steroidal anti‐inflammatory drug, corticosteroids, and biologic therapies for RA management. The current study contributes to the ongoing advancements in RA treatment. d ‐Limonene is a monocyclic monoterpene. It is present in essential oils of various aromatic plants, such as Lippia alba and Artemisia dracunculus , and in citrus fruits such as lemon and orange. It has reported anti‐inflammatory and anti‐nociceptive properties and was selected for the current study as a potential anti‐arthritic candidate. It was administered at three dosages (25, 50, 100 mg/kg, b.w., p.o) in Complete Freund's adjuvant‐induced arthritic rats over 28 days. The efficacy of the compound was compared to piroxicam, a widely used standard drug for treating RA. The anti‐arthritic activity of the compound was assessed by measuring arthritic scoring and plethysmometry at both baseline and post‐intervention stages. Additional confirmation of the investigation was sought by performing biochemical and hematological activities. Moreover, quantitative polymerase chain reaction was employed to determine the levels of messenger RNA expression for transcription factors such as tumor necrosis factor‐α, interleukin (IL)‐1β, nuclear factor‐κB, matrix metalloproteinase‐3, IL‐6, and IL‐4 in the blood. The levels of PGE2 were evaluated by enzyme‐linked immunosorbent assay. The histopathological and radiographic studies were also carried out for further confirmation. The results of these findings supported our assertion regarding the anti‐arthritic potential of the compound.
The feasibility of using different forms of limonene biosolvents as dyeing medium in rhamnolipid (RL) biosurfactant-based reverse micellar dyeing system for cotton fabrics is investigated, with different dyeing profiles. Experimental results reveal that limonene-dyed fabrics can achieve generally higher colour yield than water-dyed fabrics while samples dyed by one-step dyeing method could obtain higher colour yield, but poorer relative unlevelness index (RUI) values when compared with samples dyed by two-step method. The CIE L*a*b* value and reflectance of water-dyed and limonene-dyed samples were examined. The pH value of aqueous and non-aqueous dye liquor was measured. SEM images of limonene-dyed cotton fabrics and TEM images of reverse micelle morphology were evaluated. Washing and crocking fastness of the dyed samples were also assessed. The resulting evidence validate that limonene is feasible for reverse micellar reactive dyeing of cotton fabric with the use of RL biosurfactant and it can be one of the alternative solvents, making the dyeing process more natural, more biodegradable and environmentally more sustainable.
Aquaculture faces challenges from Aeromonas hydrophila, causing Motile Aeromonas Septicaemia, particularly affecting Labeo rohita (Rohu) in Pakistan. This study explores potential herbal antibacterials targeting A. hydrophila, molecular docking of Trachyspermum ammi (ajwain) phytocompounds against pathogen. The cell wall synthesis ligase, D-alanine-D-alanine ligase (PDB ID 6ll9) was processed in BIOVIA Discovery Studio and docked with 13 antibacterial phytocompounds found after QSAR analysis of T. ammi. Binding energies were calculated using PyRx to assess complex stability. ADME-TOX assessment for selected phytocompounds and parameterisation in CHARMM-GUI were performed. Docking the two best ligands with highest binding energies and ADME-TOX compliance, we found carvacrol and limonene formed most stable protein-ligand complexes, with raw and processed protein. Our findings suggest these herbal compounds can inhibit D-alanine-D-alanine ligase. These in-silico results support the potential of 'ajwain' in managing A. hydrophila, further in-vivo experiments are necessary to validate these inhibitory properties.
The major commercial crops in Pakistan are citrus fruit trees, which are farmed extensively and serve as the country's principal source of foreign exchange. A local citrus plant, Citrus paradisi, variety Foster is famous for its valuable fruit and fruit juice, however, tons of peels of this fruit are thrown as waste, which otherwise can be utilized in formulating nutraceutical and cosmetics. In the present study, essential oil of fruit peels was obtained through hydro-distillation, which was then analyzed through GC-MS analysis and studied for its antioxidant and enzyme inhibition potential. GCMS analysis revealed the presence of several components; major were found to be limonene, α-terpineol, caryophyllene, δ-amorphene, elemol, γ-eudesoml, nootkatone and di-isooctyl phthalate. Although, the oil showed weak free radical inhibition, it was potentially active in CUPRAC, FRAP, phosphomolybdenum and metal chelating antioxidant assays. The oil also exhibited anti-glucosidase, anti-amylase activities and also exhibited potent inhibition of the enzyme tyrosinase, which makes it strong candidate for nutraceuticals and skin care products. The docking studies also substantiate our results and caryophyllene, γ-eudesoml and nootkatone showed good binding affinity α-glucosidase and α-amylase and all tested compounds showed the higher binding affinity towards the enzyme tyrosinase.
Limonene, a dietary monocyclic monoterpene commonly found in citrus fruits and various aromatic plants, has garnered increasing interest as a gastrointestinal protectant. This study aimed to assess the effects of limonene on intestinal epithelial barrier function and investigate the involvement of cannabinoid receptor type‐1 (CB1R) in vitro. Additionally, the study focused on examining the metabolomic changes induced by limonene in the intestinal epithelial cells (Caco‐2). Initial analysis of transepithelial electrical resistance (TEER) revealed that both l ‐limonene and d ‐limonene, isomers of limonene, led to a dose‐ and time‐dependent increase in TEER in normal cells and those inflamed by pro‐inflammatory cytokines mixture (CytoMix). Furthermore, both types of limonene reduced CytoMix‐induced paracellular permeability, as demonstrated by a decrease in Lucifer yellow flux. Moreover, d ‐limonene and l ‐limonene treatment increased the expression of tight junction molecules (TJs) such as occludin, claudin‐1, and ZO‐1, at both the transcriptional and translational levels. d ‐Limonene upregulates E‐cadherin, a molecule involved in adherens junctions (AJs). Mechanistic investigations demonstrated that d ‐limonene and l ‐limonene treatment significantly inhibited CB1R at the protein, while the mRNA level remained unchanged. Notably, the inhibitory effect of d ‐limonene on CB1R was remarkably similar to that of pharmacological CB1R antagonists, such as rimonabant and ORG27569. d ‐limonene also alters Caco‐2 cell metabolites. A substantial reduction in β‐glucose and 2‐succinamate was detected, suggesting limonene may impact intestinal epithelial cells' glucose uptake and glutamate metabolism. These findings suggest that d ‐limonene's CB1R antagonistic property could effectively aid in the recovery of intestinal barrier damage, marking it a promising gastrointestinal protectant.
Introduction: Pharmacotherapeutic targets for breast cancer include the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (EGFR). Inhibitors of these receptors could be interesting therapeutic candidates for the treatment and management of breast cancer (BC). Aim: This study used GC-MS and HPLC to identify bioactive compounds in Pleurotus ostreatus (P. ostreatus) extracts and applied in silico methods to identify potent EGFR, ER, and PR inhibitors from the compounds as potential drug candidates. Method: GC-MS and HPLC were used to identify bioactive chemicals in P. ostreatus extracts of aqueous (PO-A), methanol (PO-M), ethanol (PO-E), chloroform (PO-C), and n-hexane (PO-H). The ER, PR, and EGFR model optimization and molecular docking of compounds/control inhibitors in the binding pocket were simulated using AutoDock Vina in PyRx. The drug-likeness, pharmacokinetic, and pharmacodynamic features of prospective docking leads were all anticipated. Result: The results indicated the existence of 29 compounds in PO-A, 36 compounds in PO-M and PO-E, 42 compounds in PO-C, and 22 compounds in PO-H extracts. With ER, only o-tolylamino-acetic acid (4-nitro-benzylidene)-hydrazide (−7.5 kcal mol⁻¹) from the ethanolic extract could bind to the receptor. PR and EGFR, on the other hand, identified several compounds with higher binding affinities than the control. Ergotaman-3′,6′,18-trione (−8.1 kcal mol⁻¹), 5,10-diethoxy-2,3,7,8-tetrahydro-1H,6H-dipyrrolo[1,2-a:1′,2′-d]pyrazine (−7.8 kcal mol⁻¹) from the aqueous extract; o-tolylamino-acetic acid (4-nitro-benzylidene)-hydrazide (−8.4 kcal mol⁻¹) from the ethanolic extract had better binding affinity compared to progesterone (−7.7 kcal mol⁻¹). Likewise, ergotaman-3′,6′,18-trione (−9.7 kcal mol⁻¹) from the aqueous extract and phenol, 2,4-bis(1,1-dimethyl ethyl) (−8.2 kcal mol⁻¹) from the chloroform extract had better binding affinities compared to the control, gefitinib (−7.9 kcal mol⁻¹) with regards to EGFR. None of the PO-H or PO-M extracts outperformed the control for any of the proteins. Phenols and flavonoids such as quercetin, luteolin, rutin, chrysin, apigenin, ellagic acid, and naringenin had better binding affinity to PR and EGFR compared to their control. Conclusion: The identified compounds in the class of phenols and flavonoids were better lead molecules due to their ability to strongly bind to the proteins' receptors. These compounds showed promising drug-like properties; they could be safe and new leads for creating anticancer medicines.
Rosemary (Salvia rosmarinus Spenn.), an indigenous medicinal and aromatic plant within the Mediterranean
region, yields essential oils renowned for their antimicrobial, antioxidant, anticancer, and anti-inflammatory
properties. When subjected to various stress conditions, rosemary intensifies the production of essential oils as
a defensive mechanism, as occurs when it is subjected to drought stress, making it a potentially interesting crop
for marginal dryland areas of Sicily and other Mediterranean areas. Managing rosemary cultivation through
controlled drought stress close to the balsamic period may increase the concentration and quality of essential oils
and optimize the use of limited resources like water. We conducted two on-farm field experiments in Sicily,
southern Italy, to assess the effect of controlled drought stress on rosemary biomass, essential oil yield, and
composition. The hypothesis was that drought could improve the concentration of essential oils and modify their
chemical composition by increasing valuable aromatic components without negatively impacting crop biomass
production, increasing interest in cultivating this species. The experiments were co-designed with farmers
selecting dedicated field experiments, cultivars, and crop management. Drought stress was applied during
autumn and spring in correspondence with medium-high temperatures and rainwater scarcity. The irrigation
input was reduced for three weeks during the balsamic period for each trail. Under stressed conditions,
morphometric traits were measured. At harvest time, essential oils were extracted using microwave-assisted
extraction. Under the same farm conditions, the canopy height was significantly higher in ‘Barbeque’ than
‘Tuscan Blue cv. (67.3 cm vs. 43.8 cm) This indicates a genotype influence on stress response. Essential oil yield
increased by 30 % in plants of Tuscan blue cv. subjected to stress conditions in one of two farms. Additionally,
drought stress altered the aromatic profile of the essential oil, resulting in differing percentages of key com�pounds between stressed and unstressed plants. Generally, there was a higher α-pinene percentage in unstressed
plants and higher bornyl-acetate and β-caryophyllene concentrations in drought-stressed plants. In the Scicli
farm, α-pinene decreased in response to water stress, while camphene and myrcene increased. Our results
summarized that controlled drought stress had a minimal impact on rosemary growth, increasing the percentages
of some terpenes in its essential oils. No severe decrease was observed in the synthesis of essential oils, suggesting
that rosemary is suitable for marginal soils in many Mediterranean countries to protect soils and diversify crops
in farms.
Chronic venous disease (CVD) significantly impacts global health, presenting a complex challenge in medical management. Despite its prevalence and the burden it places on healthcare systems, CVD remains underdiagnosed and undertreated. This review aims to provide a comprehensive analysis of the bioactive compounds in the Citrus genus, exploring their therapeutic potential in CVD treatment and addressing the gap in current treatment modalities. A narrative review methodology was adopted, focusing on the pharmacological effects of Citrus-derived bioactive compounds, including flavonoids and terpenes. Additionally, the review introduced the DBsimilarity method for analyzing the chemical space and structural similarities among Citrus compounds. The review highlights the Citrus genus as a rich source of pharmacologically active compounds, notably flavonoids and terpenes, which exhibit significant anti-inflammatory, antioxidant, and veno-protective properties. Some of these compounds have been integrated into existing therapies, underscoring their potential for CVD management. The DBsimilarity analysis further identified many clusters of compounds with more than 85% structural similarity. Citrus-derived bioactive compounds offer promising therapeutic potential for managing CVD, showcasing significant anti-inflammatory, antioxidant, and veno-protective effects. The need for further comparative studies, as well as safety and efficacy investigations specific to CVD treatment, is evident. This review underlines the importance of advancing our understanding of these natural compounds and encouraging the development of novel treatments and formulations for effective CVD management. The DBsimilarity method's introduction provides a novel approach to exploring the chemical diversity within the Citrus genus, opening new pathways for pharmacological research.
Rice dish is a complex food item with different dimensions affected by variety, cooking technique, and presence of other ingredients together with their interactions. In this study, rice dishes were prepared with Baldo, Osmancik, and Cammeo rice varieties, and with butter, olive oil, margarine, and sunflower oil by S alma and Pilaf cooking techniques. Samples prepared with Osmancik- Salma method-olive oil (O-S-O), Baldo-Pilaf method-olive oil (B-P-O), and Cammeo- Salma method-olive oil (C-S-O) were the top three dishes in terms of overall acceptability scores. Squalene, limonene, isopropyl myristate, cyclotetradecane, acetic acid, acetol, and nonanal were detected volatiles in rice dishes. Methyl oleate, methyl palmitate, methyl linoleate, methyl stearate, methyl palmitoleate, methyl linolenate, and methyl eicosanate were the common fatty acid components in rice dishes and olive oil. Methyl benzoate and benzaldehyde were quantified in the samples with Salma technique but not in the sample cooked with Pilaf method. Complicated chemical reactions among rice components like Maillard reaction, caramelization reaction, lipid oxidation, thermal degradation, enzymatic/non-enzymatic hydrolysis are closely associated to the cooked rice aroma development. This study is the first study to investigate volatiles, and fatty acid derived compounds of rice dishes cooked with Baldo, Osmancik, and Cammeo varieties with Salma and Pilaf procedure accompanied with sensory evaluation.
Antibiotics at sub-therapeutic levels are often used as feed additives to increase the efficiency of feed conversion into milk
and meat and/or to prevent disease and metabolic problems. Under realistic feeding conditions, ionophoric antibiotics such
as monensin have proven to be the most efficient manipulators of rumen microbiota and fermentation. Despite these desirable
effects on animal performance, the use of antibiotics in animal diets has become a public health concern because of their
potential role in the emergence of antibiotic-resistant bacteria. In recent years, there has been public concern about restricting
or limiting the use of these antibiotics in animal feed and replacing them with natural sources such as essential oils (EO).
Essential oils produced by many aromatic plants have antimicrobial effects on a range of microorganisms. Considerable
research has been devoted to utilizing the antimicrobial properties of EO to manipulate rumen microbial fermentation to
improve feed utilization and reduce the greenhouse gas (GHG) emissions to decrease adverse environmental impacts of
the livestock production. Despite in vitro studies have demonstrated antibacterial activity of essential oils, exhibiting their
ability to induce changes in rumen fermentation and improve feed utilization, most in vivo studies have failed to show
significant effects on nutrient utilization and animal performance owing to the delayed adaptation within the rumen microbial
communities. Current review underscores the opportunities and challenges associated with the use of EO as a potential feed
additive for ruminant animals to enhance their health and productive performance. Additionally, this review also highlights
the challenges related to the practical application functional efficacy of EO
The discovery of antibiotics and pesticides has greatly contributed to the social and economic development of human society but, due to the long-term irrational application, it has led to drug-resistant microorganisms, environmental damage, and other hazards, so the selection of alternative natural, safe, and non-hazardous bioactive substances is an effective solution for this problem. D-limonene is a bioactive compound widely present in various plant essential oils, exhibiting excellent broad-spectrum bioactivity and promising prospects for development and clinical application. This review provides a detailed overview of the biological activities of D-limonene, emphasizing its antimicrobial, anthelmintic, insecticidal, and medicinal potential. While nanoencapsulation technology shows promise in improving the physicochemical properties of D-limonene and enhancing its practical applications, it is also crucial to comprehensively evaluate the potential side effects of D-limonene before use.
Aromatherapy is a medical practice that uses aromatic compounds or essential oils to influence mood and health. Essential oils used in aromatherapy are created from a wide variety of medicinal plants, flowers, herbs, roots, and trees that are found all over the world and have significant, well-documented benefits on enhancing physical, emotional, and spiritual wellbeing.
This book is a comprehensive reference on aromatic compounds present in essential oils and their therapeutic use. Starting from fundamentals of essential oil biosynthesis the book guides the reader through their basic biochemistry, toxicology, profiling, blending and clinical applications. The concluding chapters also present focused information about the therapeutic effects of essential oils on specific physiological systems, plant sources, skin treatment and cancer therapeutics.
The combination of basic and applied knowledge will provide readers with all the necessary information for understanding how to develop preclinical formulations and standard clinical therapies with essential oils. This is an essential reference for anyone interested in aromatherapy and the science of essential oils.
Humulus lupulus, often referred to as "hop," is a plant member of the Cannabaceae family. The plant is dioecious in nature and is a perennial fauna reported for its therapeutic properties. It is used largely in the pharmaceuticals and food industries including breweries. Some of the plant’s metabolites have been studied for their application in the treatment of metabolic syndrome. Extensive studies on the plant have established its importance as a product of commercial significance, thereby boosting the economic value of this plant. The present review provides a compact account of the plant’s phytocompound profile and the remedial properties of its secondary metabolites. Although this plant can be explored as a high-profit-generating resource due to increased market demand and growing market acceptance, challenges faced in the cultivation of this plant limit its availability as an industrially suitable resource. This review, therefore, aimed to shed light on the function of hop secondary metabolites used in therapeutics, hop plant demography, and the problems associated with the cultivation of hop. Limited land availability and the expanding population create the need to develop a cost-effective strategy for cultivating this plant with enhanced yield.
Melaleuca linariifolia Sm. (Genus: Melaleuca; Family: Myrtaceae) cultivated for its ornamental usages in the Kumaun Himalayan region of Uttarakhand is commercially known as flax-leaved paper bark tree. The present study analyzes the chemical variation of the essential oils obtained from aerial parts and flowers of M. linariifolia. The effect of post-harvest shade drying on the essential oil composition was also assessed in the study. Total of 16 compounds accounting for 94.2 % and 94.6 % were identified in the aerial parts and flowers essential oil, respectively. 1,8-Cineole (71.8 %–73.8 %) was identified as the predominant compound in both the studied essential oils followed by limonene (1.7 %–9.3 %) and α-terpineol (4.2 %–6.7 %). Moreover, the fresh aerial parts had 73.8% of 1,8-cineole content which increased up to 79.2% post-harvest drying. The study revealed oxygenated monoterpenes as the major class constituents with 1,8-cineole as the marker component ranging from 67.7 % to 79.2 % during the post drying analysis. While assessing the biological activities, the antioxidant activity of the oils was investigated in vitro using three assays: DPPH radical scavenging activity, Iron(II) complexing activity, and H2O2 radical scavenging activity. The oil also inhibited the activity of α-amylase with IC50 of 3.26 ± 0.04 μg/ml and protein denaturation with IC50 of 3.0 ± 0.03 g/ml. This is the first-time report of essential oil analysis of M. linariifolia flowers and post-harvest drying study from bhabar region of the Kumaun Himalayas. The high essential oil yield, rich chemical composition and biological activities suggest the cultivation of Melaleuca species as an industrial crop.
Forest bathing has beneficial effects on human health via showering of forest aerosols as well as physical relaxation. Terpenes that consist of multiple isoprene units are the largest class of organic compounds produced by various plants, and one of the major components of forest aerosols. Traditionally, terpene-containing plant oil has been used to treat various diseases without knowing the exact functions or the mechanisms of action of the individual bioactive compounds. This review categorizes various terpenes easily obtained from forests according to their anti-inflammatory, anti-tumorigenic, or neuroprotective activities. Moreover, potential action mechanisms of the individual terpenes and their effects on such processes, which are described in various in vivo and in vitro systems, are discussed. In conclusion, the studies that show the biological effectiveness of terpenes support the benefits of forest bathing and propose a potential use of terpenes as chemotherapeutic agents for treating various human diseases.
Aims:
We have investigated the antihyperalgesic effects of limonene in mice that received intrathecal injection of gp120.
Main methods:
Male Swiss mice received gp120, IL-1β or TNF-α intrathecally or sterile saline as a control. A mechanicalsensitivity test was performed at 2 and 3h after the injection. Spinal cord and blood samples were isolated for protein quantification.
Key findings:
Intrathecal administration of gp120 increased mechanical sensitivity measured with an electronic Von Frey apparatus, at 2 and 3h after the injections. Limonene administered orally prior to gp120 administration significantly decreased this mechanical sensitivity at 3h after the gp120 injection. In addition, intrathecal injection of gp120 increased IL-1β and IL-10 in serum, and limonene prevented the ability of gp120 to increase these cytokines. Limonene also inhibited TNF-α and IL-1β-induced mechanical hyperalgesia. Western blot assay demonstrated limonene was capable of increasing SOD expression in the cytoplasm of cells from spinal cord at 4h after intrathecal IL-1β injection.
Significance:
These results demonstrate that gp120 causes mechanical hyperalgesia and a peripheral increase in IL-1β and IL-10, and that prior administration of limonene inhibits these changes. Also limonene modulates the activation of SOD expression in the spinal cord after spinal IL-1β application. The ability of limonene to inhibit the mechanical hyperalgesia induced by gp120, TNF-α and IL-1β emphasizes the anti-inflammatory action of limonene, specifically its ability to inhibit cytokine production and its consequences.
Inhalation of indoor air pollutants may cause airway irritation and inflammation and is suspected to worsen allergic reactions. Inflammation may be due to mucosal damage, upper (sensory) and lower (pulmonary) airway irritation due to activation of the trigeminal and vagal nerves, respectively, and to neurogenic inflammation. The terpene, d-limonene, is used as a fragrance in numerous consumer products. When limonene reacts with the pulmonary irritant ozone, a complex mixture of gas and particle phase products is formed, which causes sensory irritation. This study investigated whether limonene, ozone or the reaction mixture can exacerbate allergic lung inflammation and whether airway irritation is enhanced in allergic BALB/cJ mice. Naïve and allergic (ovalbumin sensitized) mice were exposed via inhalation for three consecutive days to clean air, ozone, limonene or an ozone-limonene reaction mixture. Sensory and pulmonary irritation was investigated in addition to ovalbumin-specific antibodies, inflammatory cells, total protein and surfactant protein D in bronchoalveolar lavage fluid and hemeoxygenase-1 and cytokines in lung tissue. Overall, airway allergy was not exacerbated by any of the exposures. In contrast, it was found that limonene and the ozone-limonene reaction mixture reduced allergic inflammation possibly due to antioxidant properties. Ozone induced sensory irritation in both naïve and allergic mice. However, allergic but not naïve mice were protected from pulmonary irritation induced by ozone. This study showed that irritation responses might be modulated by airway allergy. However, aggravation of allergic symptoms was observed by neither exposure to ozone nor exposure to ozone-initiated limonene reaction products. In contrast, anti-inflammatory properties of the tested limonene-containing pollutants might attenuate airway allergy.
We studied the R-limonene (LMN) metabolism and elimination kinetics in a human in vivo study. Four volunteers were orally exposed to a single LMN dose of 100–130 µg kg−1 bw. In each case, one pre-exposure and subsequently all 24 h post-exposure urine samples were collected. From two subjects, blood samples were drawn up to 5 h after exposure. The parent compound was analysed in blood using headspace GC–MS. The metabolites cis- and trans-carveol (cCAR), perillyl alcohol (POH), perillic acid (PA), limonene-1,2-diol (LMN-1,2-OH), and limonene-8,9-diol (LMN-8,9-OH) were quantified in both blood and urine using GC-PCI-MS/MS. Moreover, GC-PCI-MS full-scan experiments were applied for identification of unknown metabolites in urine. In both matrices, metabolites reached maximum concentrations 1–2 h post-exposure followed by rapid elimination with half-lives of 0.7–2.5 h. In relation to the other metabolites, LMN-1,2-OH was eliminated slowest. Nonetheless, overall renal metabolite elimination was completed within the 24-h observation period. The metabolite amounts excreted via urine corresponded to 0.2 % (cCAR), 0.2 % (tCAR), <0.1 % (POH), 2.0 % (PA), 4.3 % (LMN-1,2-OH), and 32 % (LMN-8,9-OH) of the orally administered dose. GC-PCI-MS full-scan analyses revealed dihydroperillic acid (DHPA) as an additional LMN metabolite. DHPA was estimated to account for 5 % of the orally administered dose. The study revealed that human LMN metabolism proceeds fast and is characterised by oxidation mainly of the exo-cyclic double bond but also of the endo-cyclic double bond and of the methyl side chain. The study results may support the prediction of the metabolism of other terpenes or comparable chemical structures.
Oxidative stress, as mediated by ROS, is a significant factor in initiating the development of age-associated cataracts; D-limonene is a common natural terpene with powerful antioxidative properties which occurs naturally in a wide variety of living organisms. It has been shown to have antioxidant effect; we found that D-limonene can effectively prevent the oxidative damage caused by H
2
O
2
and propose that the main mechanism underlying the inhibitory effects of D-limonene is the inhibition of HLECs apoptosis. In the present study, we used confocal-fluorescence microscopy, flow cytometry analysis, Hoechst staining, H
2
DCFDA staining, transmission electron microscopy, and immunoblot analysis; the results revealed that slightly higher concentrations of D-limonene (125–1800
μ
M) reduced the H
2
O
2
-induced ROS generation and inhibited the H
2
O
2
-induced caspase-3 and caspase-9 activation and decreased the Bcl-2/Bax ratio. Furthermore, it inhibited H
2
O
2
-induced p38 MAPK phosphorylation. Thus, we conclude that D-limonene could effectively protect HLECs from H
2
O
2
-induced oxidative stress and that its antioxidative effect is significant, thereby increasing the cell survival rate.
Aim
To study the effects of d- and l-limonene on pregnant rat myometrial contractility in vitro, and investigate how these effects are modified by other agents. D- and l-limonene (10−13-10−8 M) caused myometrial contraction in a dose-dependent manner.
Methods
Contractions of uterine rings from 22-day-pregnant rats were measured in an organ bath in the presence of d- or l-limonene (10−13-10−8 M) and nifedipine (10−8 M), tetraethyl-ammonium (10−3 M), theophylline (10−5 M), or paxilline (10−5 M). Uterine cyclic adenosine monophosphate (cAMP) level was detected by enzyme immunoassay. Oxidative damage was induced by methylglyoxal (3 × 10−2 M) and the alteration was measured via noradrenaline (1 × 10−9 to 3 × 10−5 M) -induced contractions.
Results
Pre-treatment with nifedipine (10−8 M), tetraethylammonium (10−3 M), and theophylline (10−5 M) attenuated the contracting effect of d- and l-limonene, while in the presence of paxilline (10−5 M) d- and l-limonene were ineffective. The two enantiomers decreased the myometrial cAMP level, but after paxilline pretreatment the cAMP level was not altered compared with the control value. Additionally, l-limonene (10−6 M) diminished consequences of oxidative damage caused by methylglyoxal (3 × 10−2 M) on contractility, whereas d-limonene was ineffective.
Conclusion
Our findings suggest that l-limonene has an antioxidant effect and that both d-and l-limonene cause myometrial contraction through activation of the A2A receptor and opening of the voltage-gated Ca²⁺ channel. It is possible that limonene-containing products increase the pregnant uterus contractility and their use should be avoided during pregnancy.
Essential oils are complex mixtures containing compounds of several different functional- group classes. Depending on the structure, we can distinguish monoterpenes, phenylpropanes, and other components. Here in this study two monoterpene compounds of essential oils, i.e. β-pinene and limonene were examined for their antiviral activity against herpes simplex virus type 1 (HSV-1) in vitro.
All antiviral assays were performed using RC-37 cells. Cytotoxicity was determined in a neutral red assay, antiviral assays were performed with HSV-1 strain KOS. The mode of antiviral action was evaluated at different periods during the viral replication cycle. Acyclovir was used as positive antiviral control.
Beta-pinenene and limonenen reduced viral infectivity by 100 %. The mode of antiviral action has been determined, only moderate antiviral effects were revealed by monoterpenes when these drugs were added to host cells prior infection or after entry of HSV into cells. However, both monoterpenes exhibited high anti-HSV-1 activity by direct interaction with free virus particles. Both tested drugs interacted with HSV-1 in a dose-dependent manner thereby inactivating viral infection.
These results suggest that monoterpenes in essential oils exhibit antiherpetic activity in the early phase of viral multiplication and might be used as potential antiviral agents.
Increasing demand of cosmetics all over the world from teen to adult has increased awareness related to safety issue. The objective of this paper is to indicate the ingredients that possess health effect that can be found in cosmetics and personal care products. The ingredient was segmented to three parts which are preservatives, fragrances and heavy metal impurities. The related paper was reviewed in terms of the chemicals that commonly identified in the cosmetic and personal care product. This paper also highlighted the health risk possesses by such ingredients in the products. From the papers reviews, many chemicals remained arguable in term of safety and its presence in the products. The chemicals are either added for it intentional purposes or appears unintentionally due to the nature of chemical itself or due to the manufacturing processes. It is suggested that consumers aware over the ingredients used in their cosmetic and personal care products and the side effects it possesses.
Abstract Osteoarthritis is a progressive joint disease and a major cause of disability for which no curative therapies are yet available. To identify compounds with potential anti-osteoarthritic properties, in this study, we screened one sesquiterpene, E-caryophyllene, and two monoterpene, myrcene and limonene, hydrocarbon compounds for anti-inflammatory, anti-catabolic and pro-anabolic activities in human chondrocytes. At non-cytotoxic concentrations, myrcene and limonene inhibited IL-1β-induced nitric oxide production (IC50=37.3 μg/ml and 85.3 µg/ml, respectively), but E-caryophyllene was inactive. Myrcene, and limonene to a lesser extent, also decreased IL-1β-induced NF-κB, JNK and p38 activation and the expression of inflammatory (iNOS) and catabolic (MMP-1 and MMP-13) genes, while increasing the expression of anti-catabolic genes (TIMP-1 and −3 by myrcene and TIMP-1 by limonene). Limonene increased ERK1/2 activation by 30%, while myrcene decreased it by 26%, relative to IL-1β-treated cells. None of the compounds tested was able to increase the expression of cartilage matrix-specific genes (collagen II and aggrecan), but both compounds prevented the increased expression of the non-cartilage specific, collagen I, induced by IL-1β. These data show that myrcene has significant anti-inflammatory and anti-catabolic effects in human chondrocytes and, thus, its ability to halt or, at least, slow down cartilage destruction and osteoarthritis progression warrants further investigation.
Essential oils are complex mixtures isolated from aromatic plants which may possess antioxidant and anti-inflammatory activities of interest in thye food and cosmetic industries as well as in the human health field. In this work, a review was done on the most recent publications concerning their antioxidant and anti-inflammatory activities. At the same time a survey of the methods generally used for the evaluation of antioxidant activity and some of the mechanisms involved in the anti-inflammatory activities of essential oils are also reported.
Objectives:
Previous studies have shown that essential oil containing (R)-(+)-limonene and α-phellandrene, extracted from fruits of Schinus terebinthifolius Raddi, exhibit anti-inflammatory activity. This work aimed to verify the antihyperalgesic and antidepressive actions of (R)-(+)-limonene, α-phellandrene, and essential oil from S. terebinthifolius fruits in spared nerve injury (SNI) model of neuropathic pain in rats.
Methods:
In the present work, essential oil from fruits of S. terebinthifolius, as well as the pure (R)-(+)-limonene and α-phellandrene compounds, were assayed for their effects on SNI-induced mechanical and cold hyperalgesia, and depressive-like behavior (immobility in forced swim test) in rats. The locomotor activity was evaluated in open-field test.
Results:
Oral administration for up to 15 days of essential oil of S. terebinthifolius (100 mg/kg), (R)-(+)-limonene (10 mg/kg), α-phellandrene (10 mg/kg), and also subcutaneous 10 mg/kg dose of ketamine (positive control) significantly inhibited SNI-induced mechanical hyperalgesia and increased immobility in the forced swim test. On the 15th day of oral treatment, α-phellandrene, but neither the essential oil from S. terebinthifolius nor (R)-(+)-limonene, prevented the SNI-induced increase in sensitivity to a cold stimulus. The oral treatment with essential oil (100 mg/kg) or with compounds (10 mg/kg) did not interfere on locomotor activity.
Discussion:
Together, the results of the present work show that essential oil of S. terebinthifolius and compounds present in this oil, including (R)-(+)-limonene and α-phellandrene, exhibit antihyperalgesic effects against mechanical hyperalgesia, and are antidepressive, while only α-phellandrene inhibited cold hyperalgesia in SNI rats.
d-limonene is a naturally occurring monoterpene and has been found to posses numerous therapeutic properties. In this study, we used d-limonene as a protective agent against the nephrotoxic effects of anticancer drug doxorubicin (Dox). Rats were given d-limonene at doses of 5% and 10% mixed with diet for 20 consecutive days. Dox was give at the dose of 20 mg/kg body weight intraperitoneally. The protective effects of d-limonene on Dox-induced oxidative stress and inflammation were investigated by assaying oxidative stress biomarkers, lipid peroxidation, serum toxicity markers, proinflammatory cytokines, and expression of nuclear factor kappa B (NFκB), cyclo-oxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) and Nitrite levels. Administration of Dox (20 mg/kg body weight) in rats enhanced renal lipid peroxidation; depleted glutathione content and anti-oxidant enzymes; elevated levels of kidney toxicity markers viz. kidney injury molecule-1 (KIM-1), blood urea nitrogen (BUN), and creatinine; enhanced expression of NFκB, COX-2, and iNOS and nitric oxide. Treatment with d-limonene prevented oxidative stress by restoring the levels of antioxidant enzymes, further both doses of 5% and 10% showed significant decrease in inflammatory response. Both the doses of d-limonene significantly decreased the levels of kidney toxicity markers KIM-1, BUN, and creatinine. d-limonene also effectively decreased the Dox induced overexpression of NF-κB, COX-2, and iNOS and nitric oxide. Data from the present study indicate the protective role of d-limonene against Dox-induced renal damage.
Abstract Previous studies have described the gastroprotective effects of essential oils that are derived from Citrus aurantium (OEC) and its main compound d-limonene (LIM) in a model of chemically induced ulcers in rats. However, these studies do not address the compound's healing effects on the gastric mucosa. Thus, the aim of this work was to evaluate the healing activity of OEC and LIM in acetic acid-induced gastric ulcers in rats, a model that reproduces human chronic ulcers. The obtained results demonstrated that lower effective doses of OEC (250 mg/kg) and LIM (245 mg/kg) induced gastric mucosal healing with a cure rate of 44% and 56%, respectively, compared with the control group (P<.05). During the 14 days of OEC or LIM treatment, none of the groups demonstrated toxicity in terms of body and organ weight or serum biochemical parameters. Both OEC and LIM treatment promoted an increase in epithelial healing, as confirmed by immunohistochemistry, which was greater in the animals that were treated with the positive control. In addition, both treatments increased cellular proliferation as measured by proliferating cell nuclear antigen and cyclooxygenase 2 expression in the gastric mucosa, vascular endothelial growth factor-mediated blood vessel formation in the margin of the ulcer, and production of gastric mucus, which fortifies the gastric protective barrier. We concluded that OEC and LIM, two common flavoring agents, promote gastric mucosal healing without any apparent toxic effect, resulting in better gastric epithelial organization in the treated rats.
The genus Citrus (Rutaceae) includes several species of plants that produce some of the most cultivated fruits in the world, providing an appreciable content of essential oil. In folk medicine, they are used as a cholagogue, antipyretic, anti-inflammatory, sedative, and antitoxic effects. Lemon essential oil has been used since ancient times for its antiseptic, carminative, diuretic, and eupeptic effects. In this study, we investigated the anti-inflammatory activity of Citrus latifolia Tanaka essential oil (CLEO) and its main constituent LIM. In the cell viability assay, CLEO and LIM (3, 10, 30, and 90 μ g/mL) had low cytotoxicity. In zymosan-induced peritonitis, LIM (500 mg/kg) decreased the infiltration of peritoneal exudate leukocytes and decreased the number of polymorphonuclear leukocytes. In vitro chemotaxis revealed that CLEO and LIM (1, 3, and 10 µg/mL) promoted a significant reduction of neutrophil migration toward fMLP and LTB4. LIM (500 mg/kg) also reduced TNF- α levels but did not alter IL-10 levels in the peritoneal exudate. In conclusion, this study showed that LIM isolated from CLEO had potential anti-inflammatory effects, likely by inhibiting proinflammatory mediators present in inflammatory exudate and leukocyte chemotaxis.
Disruption of lipid and carbohydrate homeostasis is an important factor in the development of prevalent metabolic diseases such as diabetes, obesity, and atherosclerosis. Therefore, small molecules that could reduce insulin dependence and regulate dyslipidemia could have a dramatic effect on public health. The grapefruit flavonoid naringenin has been shown to normalize lipids in diabetes and hypercholesterolemia, as well as inhibit the production of HCV. Here, we demonstrate that naringenin regulates the activity of nuclear receptors PPARα, PPARγ, and LXRα. We show it activates the ligand-binding domain of both PPARα and PPARγ, while inhibiting LXRα in GAL4-fusion reporters. Using TR-FRET, we show that naringenin is a partial agonist of LXRα, inhibiting its association with Trap220 co-activator in the presence of TO901317. In addition, naringenin induces the expression of PPARα co-activator, PGC1α. The flavonoid activates PPAR response element (PPRE) while suppressing LXRα response element (LXRE) in human hepatocytes, translating into the induction of PPAR-regulated fatty acid oxidation genes such as CYP4A11, ACOX, UCP1 and ApoAI, and inhibition of LXRα-regulated lipogenesis genes, such as FAS, ABCA1, ABCG1, and HMGR. This effect results in the induction of a fasted-like state in primary rat hepatocytes in which fatty acid oxidation increases, while cholesterol and bile acid production decreases. Our findings explain the myriad effects of naringenin and support its continued clinical development. Of note, this is the first description of a non-toxic, naturally occurring LXRα inhibitor.
Aims:
To further explore the anti-inflammatory properties of d-Limonene.
Main methods:
A rat model was used to compare evolution of TNBS (2,5,6-trinitrobenzene sulfonic acid)-induced colitis after oral feeding with d-Limonene compared to ibuprofen. Peripheral levels of TNF-α (Tumor Necrosis Factor alpha) were assessed in all animals. Cell cultures of fibroblasts and enterocytes were used to test the effect of d-Limonene respectively on TNFα-induced NF-κB (nuclear factor-kappa B) translocation and epithelial resistance. Finally, plasmatic inflammatory markers were examined in an observational study of diet supplementation with d-Limonene-containing orange peel extract (OPE) in humans.
Key findings:
Administered per os at a dose of 10mg/kg p.o., d-Limonene induced a significant reduction of intestinal inflammatory scores, comparable to that induced by ibuprofen. Moreover, d-Limonene-fed rats had significantly lowered serum concentrations of TNF-α compared to untreated TNBS-colitis rats. The anti-inflammatory effect of d-Limonene also involved inhibition of TNFα-induced NF-κB translocation in fibroblast cultures. The application of d-Limonene on colonic HT-29/B6 cell monolayers increased epithelial resistance. Finally, inflammatory markers, especially peripheral IL-6, markedly decreased upon OPE supplementation of elderly healthy subjects submitted or not to 56 days of dietary supplementation with OPE.
Significance:
In conclusion, d-Limonene indeed demonstrates significant anti-inflammatory effects both in vivo and in vitro. Protective effects on the epithelial barrier and decreased cytokines are involved, suggesting a beneficial role of d-Limonene as diet supplement in reducing inflammation.
Background
Peripheral nerve injury can have long-term consequences including pain-related manifestations, such as hypersensitivity to cutaneous stimuli, as well as affective and cognitive disturbances, suggesting the involvement of supraspinal mechanisms. Changes in brain structure and cortical function associated with many chronic pain conditions have been reported in the prefrontal cortex (PFC). The PFC is implicated in pain-related co-morbidities such as depression, anxiety and impaired emotional decision-making ability. We recently reported that this region is subject to significant epigenetic reprogramming following peripheral nerve injury, and normalization of pain-related structural, functional and epigenetic abnormalities in the PFC are all associated with effective pain reduction.
In this study, we used the Spared Nerve Injury (SNI) model of neuropathic pain to test the hypothesis that peripheral nerve injury triggers persistent long-lasting changes in gene expression in the PFC, which alter functional gene networks, thus providing a possible explanation for chronic pain associated behaviors.
Results
SNI or sham surgery where performed in male CD1 mice at three months of age. Six months after injury, we performed transcriptome-wide sequencing (RNAseq), which revealed 1147 differentially regulated transcripts in the PFC in nerve-injured vs. control mice. Changes in gene expression occurred across a number of functional gene clusters encoding cardinal biological processes as revealed by Ingenuity Pathway Analysis. Significantly altered biological processes included neurological disease, skeletal muscular disorders, behavior, and psychological disorders. Several of the changes detected by RNAseq were validated by RT-QPCR and included transcripts with known roles in chronic pain and/or neuronal plasticity including the NMDA receptor (glutamate receptor, ionotropic, NMDA; grin1), neurite outgrowth (roundabout 3; robo3), gliosis (glial fibrillary acidic protein; gfap), vesicular release (synaptotagmin 2; syt2), and neuronal excitability (voltage-gated sodium channel, type I; scn1a).
Conclusions
This study used an unbiased approach to document long-term alterations in gene expression in the brain following peripheral nerve injury. We propose that these changes are maintained as a memory of an insult that is temporally and spatially distant from the initial injury.
Limonene is a bioactive food component found in citrus peel oil that has demonstrated chemopreventive and chemotherapeutic activities in preclinical studies. We conducted an open label pilot clinical study to determine the human breast tissue disposition of limonene and its associated bioactivity. We recruited forty-three women with newly diagnosed operable breast cancer electing to undergo surgical excision to take 2 grams of limonene daily for 2 - 6 weeks before surgery. Blood and breast tissue were collected to determine drug/metabolite concentrations and limonene-induced changes in systemic and tissue biomarkers of breast cancer risk or carcinogenesis. Limonene was found to preferentially concentrate in the breast tissue, reaching high tissue concentration (mean=41.3 µg/g tissue) while the major active circulating metabolite, perillic acid, did not concentrate in the breast tissue. Limonene intervention resulted in a 22% reduction in cyclin D1 expression (P=0.002) in tumor tissue but minimal changes in tissue Ki67 and cleaved caspase 3 expression. No significant changes in serum leptin, adiponectin, TGF-β1, IGFBP-3 and IL-6 levels were observed following limonene intervention. There was a small but statistically significant post-intervention increase in IGF-1 levels. We conclude that limonene distributed extensively to human breast tissue and reduced breast tumor cyclin D1 expression that may lead to cell cycle arrest and reduced cell proliferation. Further placebo-controlled clinical trials and translational research are warranted to establish limonene's role for breast cancer prevention or treatment.
D-limonene is recognized as a potential chemotherapeutic agent, however, the details of this mechanism remain unclear. In this study, we investigated the effects of d-limonene on colon cancer cell viability and its potential mechanism of action in vitro. After 48 h of treatment, d-limonene suppressed the viability of LS174T cells in a dose-dependent manner and caused a dose-dependent apoptotic cell death. D-limonene activated caspase-3 and -9 and PARP cleavage in a dose-dependent manner. Moreover, an increase in Bax protein and cytosol cytochrome c from mitochondria and a decrease in bcl-2 protein were observed following treatment with d-limonene. In addition, d-limonene decreased the levels of p-Akt (Ser473), p-Akt (Thr308) and p-GSK-3β (Ser9), suggesting that d-limonene induced apoptosis via the mitochondrial death pathway and the suppression of the PI3K/Akt pathway.
For the past 40 years, the ecology and evolution of plant secondary metabolites have been major foci of investigation. We use one class of secondary metabolites, the terpenes, as a case study for exploring the factors regulating the evolution of metabolite function. Evolution of function can occur as a result of change at any of several scales of biological organization. Changes in gene sequence and/or genetic architecture underlie several important evolutionary changes in function, and changes in gene regulation that alter terpene quantities also are linked with functional shifts. In addition, changes in the spatial distribution of terpenes within plants and in the structures used for terpene storage can be involved with functional shifts. Finally, as volatile compounds, terpenes play important roles as signaling compounds, and evolution of function can occur through changes in organisms that receive signals as well as the organisms that send them. In terpenes, significant changes in function have occurred as insects have learned to use terpenes as attractant or deterrent cues. A complete understanding of the evolution of function in secondary metabolites requires studying the regulation of function across all of these scales.
Limonene is one of the main flavonoids which is reported to inhibit the inflammatory response by suppressing the production of reactive oxygen species. The aim of this study was to evaluate whether limonene can inhibit Dermatophagoides farinae-induced airway hyperresponsiveness (AHR), eosinophilic infiltration and other histological changes in the lung, T helper (Th) 2 cytokine production and airway remodeling in a mice model of asthma. Treatment with limonene significantly reduced the levels of IL-5, IL-13, eotaxin, MCP-1, and TGF-β₁ in bronchoalveolar lavage fluid. The goblet cell metaplasia, thickness of airway smooth muscle, and airway fibrosis were markedly decreased in limonene-treated mice. Furthermore, AHR to acetylcholine was significantly abrogated in limonene-treated mice. These results indicate that limonene has a potential to reduce airway remodeling and AHR in asthma model.
Research toward renewable and sustainable energy has identified specific terpenes capable of supplementing or replacing current petroleum-derived fuels. Despite being naturally produced and stored by many plants, there are few examples of commercial recovery of terpenes from plants because of low yields. Plant terpene biosynthesis is regulated at multiple levels, leading to wide variability in terpene content and chemistry. Advances in the plant molecular toolkit, including annotated genomes, high-throughput omics profiling, and genome editing, have begun to elucidate plant terpene metabolism, and such information is useful for bioengineering metabolic pathways for specific terpenes. We review here the status of terpenes as a specialty biofuel and discuss the potential of plants as a viable agronomic solution for future terpene-derived biofuels.
Background:
TRPA1 is a Ca-permeable nonselective cation channel expressed in sensory neurons and acts as a nocisensor. Recent reports show that some monoterpenes, a group of naturally occurring organic compounds, modulate TRP channel activity. Here, we report that limonene, being contained in citrus fruits and mushrooms, shows a unique bimodal action on TRPA1 channel.
Methods:
We examine the effects of limonene on sensory neurons from wild-type, TRPV1- and TRPA1-gene-deficient mice and on heterologously expressed channels in vitro. Molecular determinants were identified with using mutated channels. Cellular excitability is monitored with ratiometric Ca imaging. Nociceptive and analgesic actions of limonene are also examined in vivo.
Results:
In wild-type mouse sensory neurons, limonene increased the intracellular Ca(2+) concentration ([Ca(2+) ]i ), which was inhibited by selective inhibitors of TRPA1 but not TRPV1. Limonene-responsive neurons highly corresponded to TRPA1 agonist-sensitive ones. Limonene failed to stimulate sensory neurons from the TRPA1 (-/-) mouse. Heterologously expressed mouse TRPA1 was activated by limonene. Intraplantar injection of limonene elicited acute pain, which was significantly less in TRPA1 (-/-) mice. Systemic administration of limonene reduced nociceptive behaviours evoked by H2 O2 . In both heterologously and endogenously expressed TRPA1, a low concentration of limonene significantly inhibited H2 O2 -induced TRPA1 activation. TRPA1 activation by limonene was abolished in H2 O2 -insensitive cysteine-mutated channels.
Conclusions:
Topically applied limonene stimulates TRPA1, resulting in elicitation of acute pain, but its systemic application inhibits nociception induced by oxidative stress. Because limonene is a safe compound, it may be utilized for pain control due to its inhibition of TRPA1 channels. What does this study add: Limonene, a monoterpene in essential oils of various plants, has been known for its antitumor and anti-inflammatory properties. However, molecular basis of their actions has not been identified. This study shows that limonene activates nociceptive TRPA1 and elicits acute pain, when it is topically applied. In addition, systemic application of limonene exerts inhibitory effects on nociception induced by an oxidative stress-induced TRPA1 activation.
Objectives: Naringin, a bioflavonoid isolated from grapefruit, is well known to possess lipid-lowering and insulin-like properties. We assessed whether naringin treatment ameliorates insulin resistance (IR), [beta]-cell dysfunction, hepatic steatosis and kidney damage in high-fat diet (HFD)-streptozotocin (STZ)-induced type 2 diabetic rats. Design and Methods: Wistar albino male rats were fed a HFD (55 % energy from fat and 2 % cholesterol) to develop IR and on the 10th day injected with a low dose of streptozotocin (40 mg/kg i.p.) to induce type 2 diabetes. After confirmation of hyperglycaemia (>13[middle dot]89 mmol/l) on the 14th day, different doses of naringin (25-100 mg/kg per d) and rosiglitazone (5 mg/kg per d) were administered orally for the next 28 d while maintaining the HFD. Results: Naringin significantly decreased IR, hyperinsulinaemia, hyperglycaemia, dyslipidaemia, TNF-[alpha], IL-6, CRP and concomitantly increased adiponectin and [beta]-cell function in a dose-dependent manner. Naringin increased PPAR[gamma] expression in liver and kidney; phosphorylated tyrosine insulin receptor substrate 1 in liver; and heat shock protein-27 and 72 in pancreas, liver and kidney. In contrast, NF-[kappa]B expression in these tissues along with sterol regulatory element binding protein-1c and liver X receptor- expressions in liver were significantly diminished. Additionally, microscopic observations validated that naringin effectively rescues [beta]-cells, hepatocytes and kidney from HFD-STZ-mediated oxidative damage and pathological alterations. Conclusions: This seminal study provides evidence that naringin ameliorates IR, dyslipidaemia, [beta]-cell dysfunction, hepatic steatosis and kidney damage in type 2 diabetic rats by partly regulating oxidative stress, inflammation and dysregulated adipocytokines production through up-regulation of PPAR[gamma], HSP-27 and 72.
Asthma is a common disease that affects 300 million people worldwide. Given the large number of eosinophils in the airways of people with mild asthma, and verified by data from murine models, asthma was long considered the hallmark T helper type 2 (TH2) disease of the airways. It is now known that some asthmatic inflammation is neutrophilic, controlled by the TH17 subset of helper T cells, and that some eosinophilic inflammation is controlled by type 2 innate lymphoid cells (ILC2 cells) acting together with basophils. Here we discuss results from in-depth molecular studies of mouse models in light of the results from the first clinical trials targeting key cytokines in humans and describe the extraordinary heterogeneity of asthma.
Reactive oxygen intermediers (ROI) play a role in the signal transduction of beta-adrenergic receptors. We investigated whether an antioxidant (limonene) can reduce the beta-mimetic effect of terbutaline in beta-2-adrenergic receptor (β2-AR)-regulated smooth muscles. Tissue samples were collected from nonpregnant (trachea) and 22-day-pregnant (myometrium and cervix) rats. Tissue contractility was investigated in an isolated organ bath. In separate groups of animals, the tracheal and uterine β2-AR activities were upregulated by 17-beta-estradiol valerate (E2) and progesterone (P4), respectively. The total oxidant (TOS) and total antioxidant status (TAS) were also measured. The oxidative stress index (OSI) was defined as the ratio ofTOS and TAS. Terbutaline (10(-10) - 10(-5) M) decreased the spontaneous contractions in the nontreated and the P4-pretreated myometria. The concentration-response curves for terbutaline in the presence of 10-3 M limonene were shifted to the left, but the maximum inhibitory effect was unchanged. Terbutaline (10(-6) M) increased the cervical resistance both in the nontreated and in the P4-treated samples, while limonene reduced this action only in the P4-treated cervices. Terbutaline (10(-9) - 10(-4) M) reduced the tracheal tones both in the nontreated and in the E2-treated tissues, while limonene reduced these effects. The OSI was highest in the trachea and lowest in the pregnant myometrium. Limonene has various influence on terbutaline induced effects in certain tissues. Higher OSI value means, that the antioxidants have greater role in the beta-adrenergic signalmechanism. We assume that the significance of ROI in the signalling process of the β2-ARs are divergent in the various tissues. Our results suggest that the antiasthmatic effect of beta-mimetics may worsen during parallel limonene administration.
Limonene is a lipophilic monoterpene found in high levels in citrus peel. Limonene demonstrates anti-cancer properties in preclinical models with effects on multiple cellular targets at varying potency. While of interest as a cancer chemopreventive, the biological activity of limonene in humans is poorly understood. We conducted metabolite profiling in 39 paired (pre/post-intervention) plasma samples from early-stage breast cancer patients receiving limonene treatment (2 g QD) before surgical resection of their tumor. Metabolite profiling was conducted using ultra-performance liquid chromatography (UPLC) coupled to a linear trap quadrupole (LTQ) system and gas chromatography mass spectrometry (GC-MS). Metabolites were identified by comparison of ion features in samples to a standard reference library. Pathway-based interpretation was conducted using the human metabolome database (HMDB) and the MetaCyc database. Of the 397 named metabolites identified, 72 changed significantly with limonene intervention. Class-based changes included significant decreases in adrenal steroids (P's<0.01), and