Article

Antioxidant Activity of Limonene on Normal Murine Lymphocytes: Relation to H 2 O 2 Modulation and Cell Proliferation

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Abstract

Limonene is a monoterpene present in citrus fruit and is used as flavouring agents of foods. It was shown that monoterpenes possess antioxidant activity. Previously, it was demonstrated that limonene exerts anti-proliferative action on a lymphoma cell line without modifying normal lymphocyte viability. H(2)O(2) has a modulator role in cell proliferation. In the present study, the effect of limonene on normal lymphocytes proliferation and its relation with H(2)O(2) level modulation was analysed, evaluating its effect on the activity of cell antioxidant enzymes, such as catalase, peroxidase and superoxide dismutase. Limonene exerted a biphasic effect on cell proliferation; the increase in cell proliferation was related to the decrease in H(2)O(2) level by the increase in catalase and peroxidase activities. Moreover, limonene protected the cells to the oxidative stress induced by exogenous addition of H(2)O(2). In view of these results, it is possible that limonene could protect normal lymphocytes from diseases related to oxidative stress, including cancer, but further research is necessary to establish the role of limonene as a potential antioxidant that can effectively protect lymphocytes from oxidative stress and mitochondrial dysfunction.

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... Limonene may also have been involved in the antioxidant activities of C. edulis extracts [50]. Limonene exerts its free radical scavenging activities by donating hydrogen or electrons, thereby breaking radical chain reactions [50,51]. Moreover, limonene enhances SOD and catalase expression [52]. ...
... Moreover, limonene enhances SOD and catalase expression [52]. In rat models, limonene upregulated glutathione S-transferase and induced the activities of glutathione peroxidase in the oesophagus [51]. This may have been attributed to limonene-mediated increase in expressions of genes encoding SOD and CAT enzymes [53] Research on antioxidant activities of Mentha piperita extracts revealed the main compound was menthol, which conferred hydrogen donating abilities to the extract [54]. ...
Article
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Herbal medications are gaining popularity due to their long history of use in traditional medicine. They serve as a reservoir for a diverse array of phytocompounds linked to amelioration of oxidative stress. Oxidative stress is a disturbance in the balance between generation and elimination of reactive species in human body. Moreover, reactive species are implicated in the onset and progression of chronic disorders. The current therapeutic approaches despite showing efficacy are characterized by several limitations such as adverse effects and prohibitive costs. This drives the need to explore alternatives that can inhibit, ameliorate or reverse conditions caused by oxidative stress. Several studies have evaluated antioxidant effects of diverse plant extracts. C. edulis and P. capensis are used as traditional therapy among the African communities to manage oxidative stress-related ailments. However, there is limited research on the antioxidant effects of these medicinal plants. The current study, therefore, sought to evaluate the antioxidant and phytochemical profile, of C. edulis and P. capensis extracts. Samples were collected from Embu County, Kenya. In vitro antioxidant properties of the extracts were evaluated through ferric reduction, Iron chelating, hydroxyl radical, and DPPH radical scavenging activities. Activities of catalase, superoxide dismutase and glutathione reductases of the extracts were further determined. Phytochemical profiles were determined using Liquid Chromatography Mass Spectrophotometer (LC-MS) and Gas Chromatography Mass Spectrophotometer (GC-MS) analyses. The extracts displayed concentration dependent antioxidant activities. Phytochemical analyses revealed presence compounds which are associated with antioxidant activities including flavonoids, phenolics, tocopherols and terpenoids. The findings provide a scientific validation for the folklore use of C. edulis and P. capensis in management of oxidative stress. Nevertheless, there is a need for further purification and characterization of phytochemicals associated with antioxidant activities.
... Recently, studies have shown that D-limonene (LIM), a natural monocyclic monoterpene widely found in citrus fruits, has powerful antioxidant and anti-inflammatory properties (Roberto et al., 2010;Santana et al., 2020;Vieira et al., 2018). In addition, Hirota et al. (2010) demonstrated that it anti-inflammatory effects involves cytokines and reactive oxygen species (ROS) inhibition and inactivation of eosinophil migration (Hirota et al., 2010). ...
... These antioxidant actions of LIM were similar to those found in other studies. Durço et al. (2019) showed that LIM (10 μmol, i.p.) completely abolished oxidative stress damage induced by isoproterenol in the hearts of Swiss mice, while Roberto et al. (2010) reported that LIM (10 and 50 μg/ml) suppressed oxidative stress in lymphoid cell suspensions from BALB/c mice. Taken together, these data reinforce the hypothesis that LIM is a potent antioxidant agent. ...
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Background Despite some advances in the discovery of novel therapies, smoke inhalation injury remains a difficult to treat critical health issue due to its physiopathological complexity. Natural products, such as D-limonene (LIM), are becoming an important potential source of new treatments in many health problems. LIM has been shown to have antioxidant, anti-inflammatory and protective effects in respect of several diseases, including respiratory conditions Objective The aim of this study was to evaluate the effects of inhaled LIM on acute smoke-induced lung injury in rats Methods Thirty minutes after smoke inhalation, adult male Wistar rats were treated with vehicle or LIM (0.01 mg/kg) for 30 min. Blood samples, and the liver, lungs, and trachea were collected for analysis Results The results showed that LIM minimized the injuries, reducing oxidative and inflammatory damage by improving catalase (CAT) (p < 0.05), and superoxide dismutase (SOD) activities (trachea: p < 0.01; lung: p < 0.05) and reducing interleukin-1 beta (IL-1β) level (p < 0.01) caused by smoke inhalation. LIM was also able to ameliorate damage in both trachea and lung tissues Conclusions The results indicate that LIM has a beneficial effect on lung injury, mainly by reducing oxidative stress, anti-inflammatory response and histological damage.
... A wide range of therapeutic properties and health benefits has been attributed to DL as the major constituent of citrus essential oils. These therapeutic properties and health benefits can be summarized as an antiinflammatory , Kummer, Fachini-Queiroz et al. 2013, Yu, Yan et al. 2017, antioxidant (Roberto, Micucci et al. 2010, Murali, Karthikeyan et al. 2013, anticancer , Ye, Liang et al. 2020), antibacterial (Hąc-Wydro, Flasiński et al. 2017, antiviral (Astani and Schnitzler 2014), antinociceptive (do Amaral, atilde et al. 2007), and antidiabetic activities (Murali and Ravanan, 2012, Murali, Karthikeyan et al. 2013, More, Kulkarni et al. 2014) as well as treating metabolic syndromes (Victor Antony Santiago, Jayachitra et al. 2012), beneficial effects on GIT (de Souza, Vieira et al. 2019) and respiratory tract (Chi, Wei et al. 2013), and wound healing activity in preclinical or clinical studies. Several articles have reviewed some of these activities and health benefits (Miller, Thompson, Hakim, Chow, & Thomson, 2011;Santana et al., 2020;Vieira et al., 2018). ...
... A wide range of therapeutic properties and health benefits has been attributed to DL as the major constituent of citrus essential oils. These therapeutic properties and health benefits can be summarized as anti-inflammatory , Kummer, Fachini-Queiroz et al. 2013, antioxidant (Roberto, Micucci et al. 2010, Murali, Karthikeyan et al. 2013, anticancer , Ye, Liang et al. 2020), antibacterial (Hąc-Wydro, Flasiński et al. 2017, antiviral (Astani and Schnitzler 2014), antinociceptive (do Amaral, atilde et al. 2007), and antidiabetic activities (Murali and Ravanan, 2012, Murali, Karthikeyan et al. 2013, More, Kulkarni et al. 2014) as well as treating metabolic syndromes (Victor Antony Santiago, Jayachitra et al. 2012), beneficial effects on GIT (de Souza, Vieira et al. 2019), respiratory tract (Chi, Wei et al. 2013), and wound healing activity in preclinical or clinical studies. As summarized in Fig. 3, several articles have reviewed some of these activities and health benefits (Vieira et al., 2018). ...
... Coinciding with the reports by other Hirai et al. [25], Aguilar et al. [26], Perdones et al. [27] and Campolo et al. [28], limonene was the most abundant component in LEO while its content may vary. LEO was rich in constituents with monoterpene structure (limonene, α-pinene, etc.) which have been proven to possess antioxidant activity [29]. For example, limonene was shown to prevent neuronal suffering [30], oxidative stress on lymphocytes, and mitochondrial dysfunction [29] through its antioxidant activity. ...
... LEO was rich in constituents with monoterpene structure (limonene, α-pinene, etc.) which have been proven to possess antioxidant activity [29]. For example, limonene was shown to prevent neuronal suffering [30], oxidative stress on lymphocytes, and mitochondrial dysfunction [29] through its antioxidant activity. In addition, LEO components present in other studies were not detected in this experiment such as β-phellandrene [25], camphene, and sabinene [26]. ...
Article
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Lemon essential oil (LEO) is a kind of citrus essential oil with antioxidant, anti-inflammatory, and antimicrobial activities, but low water solubility and biological instability hinder its industrial application. In this study, LEO was nanoemulsified to solve these problems. The preparation procedure of lemon essential oil nanoemulsions (LEO-NEs) was optimized, and the physicochemical characterization and antioxidant activities were explored. Single-factor experiments (SFEs) and response surface methodology (RSM) were conducted for the effects on the mean droplet size of LEO-NEs. Five factors of SFE which may influence the droplet size were identified: HLB value, concentration of essential oil, concentration of surfactant, ultrasonic power, and ultrasonic time. On the basis of the SFE, the RSM approach was used to optimize the preparation procedure to obtain LEO-NEs with the smallest droplet size. LEO-NEs exhibited good antioxidant activity when the HLB value was 13, content of surfactant was 0.157 g/mL, ultrasonic time was 23.50 min, and ultrasonic power was 761.65 W. In conclusion, these results can provide a good theoretical basis for the industrial application of lemon essential oil.
... A wide range of therapeutic properties and health benefits has been attributed to DL as the major constituent of citrus essential oils. These therapeutic properties and health benefits can be summarized as an antiinflammatory , Kummer, Fachini-Queiroz et al. 2013, Yu, Yan et al. 2017, antioxidant (Roberto, Micucci et al. 2010, Murali, Karthikeyan et al. 2013, anticancer , Ye, Liang et al. 2020), antibacterial (Hąc-Wydro, Flasiński et al. 2017, antiviral (Astani and Schnitzler 2014), antinociceptive (do Amaral, atilde et al. 2007), and antidiabetic activities (Murali and Ravanan, 2012, Murali, Karthikeyan et al. 2013, More, Kulkarni et al. 2014) as well as treating metabolic syndromes (Victor Antony Santiago, Jayachitra et al. 2012), beneficial effects on GIT (de Souza, Vieira et al. 2019) and respiratory tract (Chi, Wei et al. 2013), and wound healing activity in preclinical or clinical studies. Several articles have reviewed some of these activities and health benefits (Miller, Thompson, Hakim, Chow, & Thomson, 2011;Santana et al., 2020;Vieira et al., 2018). ...
... A wide range of therapeutic properties and health benefits has been attributed to DL as the major constituent of citrus essential oils. These therapeutic properties and health benefits can be summarized as anti-inflammatory , Kummer, Fachini-Queiroz et al. 2013, antioxidant (Roberto, Micucci et al. 2010, Murali, Karthikeyan et al. 2013, anticancer , Ye, Liang et al. 2020), antibacterial (Hąc-Wydro, Flasiński et al. 2017, antiviral (Astani and Schnitzler 2014), antinociceptive (do Amaral, atilde et al. 2007), and antidiabetic activities (Murali and Ravanan, 2012, Murali, Karthikeyan et al. 2013, More, Kulkarni et al. 2014) as well as treating metabolic syndromes (Victor Antony Santiago, Jayachitra et al. 2012), beneficial effects on GIT (de Souza, Vieira et al. 2019), respiratory tract (Chi, Wei et al. 2013), and wound healing activity in preclinical or clinical studies. As summarized in Fig. 3, several articles have reviewed some of these activities and health benefits (Vieira et al., 2018). ...
Article
One of the major challenges in processing food products is preserving flavor-producing compounds. D-Limonene (DL) is a safe and common additive in the food and cosmetics industry. However, the high sensitivity of DL to oxidation reduces the intensity of its aroma and even the production of bad taste compounds, making the use of this additive problematic. Encapsulation may be an efficient way to introduce sensitive compounds such as DL into food products. In nanoencapsulation technology, by reducing the size of the carrier to nanometers, the surface-to-volume ratio increases dramatically, leading to increased encapsulation efficiency, improved bioavailability, and controlled release of encapsulated material. Hence, this review refers to updated information regarding DL nano-scaled delivery systems using different nanocarriers, its bioavailability, release rates as well as its application in functional food products and its toxicity when loaded into nanocarriers.
... Decreased activities/concentrations of SOD, catalase, and GSH in ROT-injected rats resulted from the inactivation of these enzymatic and non-enzymatic antioxidants by H 2 O 2 . Previous studies have revealed that LMN is a potent scavenger of toxic free radicals, such as hydrogen peroxide (H 2 O 2 ), superoxide, and hydroxyl free radicals, in vitro [40,41]. However, LMN treatment to ROT-injected rats showed near normalized activities/concentrations of SOD, catalase, and GSH ascribed to its potent antioxidant activity. ...
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Rotenone (ROT) is a naturally derived pesticide and a well-known environmental neurotoxin associated with induction of Parkinson’s disease (PD). Limonene (LMN), a naturally occurring monoterpene, is found ubiquitously in citrus fruits and peels. There is enormous interest in finding novel therapeutic agents that can cure or halt the progressive degeneration in PD; therefore, the main aim of this study is to investigate the potential neuroprotective effects of LMN employing a rodent model of PD measuring parameters of oxidative stress, neuro-inflammation, and apoptosis to elucidate the underlying mechanisms. PD in experimental rats was induced by intraperitoneal injection of ROT (2.5 mg/kg) five days a week for a total of 28 days. The rats were treated with LMN (50 mg/kg, orally) along with intraperitoneal injection of ROT (2.5 mg/kg) for the same duration as in ROT-administered rats. ROT injections induced a significant loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc) and DA striatal fibers following activation of glial cells (astrocytes and microglia). ROT treatment enhanced oxidative stress, altered NF-κB/MAPK signaling and motor dysfunction, and enhanced the levels/expressions of inflammatory mediators and proinflammatory cytokines in the brain. There was a concomitant mitochondrial dysfunction followed by the activation of the Hippo signaling and intrinsic pathway of apoptosis as well as altered mTOR signaling in the brain of ROT-injected rats. Oral treatment with LMN corrected the majority of the biochemical, pathological, and molecular parameters altered following ROT injections. Our study findings demonstrate the efficacy of LMN in providing protection against ROT-induced neurodegeneration.
... The antioxidant activity could be partially explained by the presence of some main components in the essential oil. It has been reported that monoterpenes such as β-ocimene, 3-carene, limonene and myrcene showed antioxidant activities [42,43]. Eucalyptol (or 1,8-cineole) also exhibited antioxidant activity in the oxygen radical absorbance capacity assay [44]. ...
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Lindera glauca is a shrub or small tree mostly distributed in China, Japan and Korea. However, reports on the biological activities of Lindera glauca fruit essential oil (LGFEO) are limited. The study on its chemical composition, and antioxidant and cholinesterase inhibitory activities were performed, along with molecular docking of six selected compounds. The LGFEO was extracted by hydro distillation and analyzed by GC-MS and GC-FID. Antioxidant activities of LGFEO were evaluated by three methods with different mechanisms. Acetylcholinesterase and butyrylcholinesterase inhibitory activities of LGFEO were tested. A total of 48 components were identified representing 95.74% of the total composition of LGFEO in which the major compounds were (E)-β-ocimene (41.53%), α-copaene (13.17%), δ-cadinene (6.20%), 3-carene (5.89%) and eucalyptol (3.57%). Weak antioxidant activities of LGFEO in three assays (9.52, 11.36 and 38.98 μmol TE/g, respectively) were observed. LGFEO showed obvious cholinesterase inhibitory activities at the final concentrations of 50 and 20 μg/mL. IC50 values for acetylcholinesterase and butyrylcholinesterase were 46.48 and 34.85 μg/mL, respectively. Molecular docking revealed that geranyl acetate, β-caryophyllene and limonene had lower binding affinities in the range of −7.1 to −6.1 kcal/mol through hydrophobic interactions and hydrogen bond. Six compounds including 3-carene, limonene, eucalyptol, (E)-β-ocimene, geranyl acetate and β-caryophyllene could contribute together to cholinesterase inhibitory activities of LGFEO. This essential oil indicated low potential as natural antioxidant, but it could be potentially used as cholinesterase inhibitor with possible application in food, aromatherapy and pharmaceutical industries.
... Limonene production in different organisms is given in Table 17.2. Limonene is used for rice bran oil extraction (Mamidipally and Liu 2004), agrofood industry (Ibáñez et al. 2020), therapeutics (Kousar et al. 2017), and as insecticide (Karr and Coats 1988), antimicrobial (Vuuren and Viljoen 2007;Han et al. 2019), antioxidant (Roberto et al. 2010), anti-inflammatory (d'Alessio et al. 2013, anticancer (Mukhtar et al. 2018;Araújo-Filho et al. 2021), and antidepressant ) agent. Korman et al. (2017) have produced various monoterpenes, valuable products that find wide usage as flavors, pharmaceuticals, biofuels, and fragrances. ...
Chapter
Cell-free system is an easy, rapid, sensitive platform for production of various chemicals and biofuels. The system lacks membrane-bound barriers, but it possesses all of the necessary substrates, biomolecules, and machinery that are needed for the production of desired products. In addition, cell-free system offers an alternative to existing in vivo production systems. Biological experiments can be easily created with cell-free systems under a variety of reaction conditions, which makes it a powerful tool, but cell-free system has its own limitations such as narrow reaction time and deficiency of exchange of materials and energy from cell surroundings. The system is being used for the production of various important biofuels such as ethanol, butanol, hydrogen, isoprene, bisabolene, limonene, pinene and farnesene. In this chapter, we discuss recent progress and uses of cell-free system for production of biofuels toward industrial applications.KeywordsCell-free systemEnzymesSynthetic biologyAdvanced biofuelsBiofuels
... Nonetheless, the oil demonstrated weaker anti-H. pylori activity, most of the compounds are well-established antioxidant agents such as limonene, pinene, and borneol [90,91]. Investigations in vivo and in vitro have revealed that compounds with high antioxidant activity, not only scavenge free radicals but also exhibit antibacterial activity against H. pylori [92]. ...
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Due to its rising antibiotic resistance and associated inflammations, Helicobacter pylori poses a challenge in modern medicine. Salvia officinalis, a member of the Lamiaceae family, is a promising medicinal herb. In this regard, a phytochemical screening followed by GC-MS and LC-MS was done to evaluate the chemical profile of the total ethanolic extract (TES) and the essential oil, respectively. The anti-H. pylori and the anti-inflammatory activities were evaluated by a micro-well dilution technique and COX-2 inhibition assay. Potential anti-H. pylori inhibitors were determined by an in silico study. The results revealed that the main metabolites were flavonoids, sterols, volatile oil, saponins, and carbohydrates. The LC-MS negative ionization mode demonstrated 12 compounds, while GC-MS showed 21 compounds. Carnosic acid (37.66%), epirosmanol (20.65%), carnosol1 (3.3%), and 12-O-methyl carnosol (6.15%) were predominated, while eucalyptol (50.04%) and camphor (17.75%) were dominant in LC-MS and GC-MS, respectively. TES exhibited the strongest anti-H. pylori activity (3.9 µg/mL) asymptotic to clarithromycin (0.43 µg/mL), followed by the oil (15.63 µg/mL). Carnosic acid has the best-fitting energy to inhibit H. pylori (−46.6769 Kcal/mol). TES showed the highest reduction in Cox-2 expression approaching celecoxib with IC50 = 1.7 ± 0.27 µg/mL, followed by the oil with IC50 = 5.3 ± 0.62 µg/mL. Our findings suggest that S. officinalis metabolites with anti-inflammatory capabilities could be useful in H. pylori management. Further in vivo studies are required to evaluate and assess its promising activity.
... It was reported that LIM had low toxicity and showed no evidence of risk in animal studies [15]. Therefore, LIM has been used to evaluate many biological activities, such as anti-oxidation, anti-inflammation, and the ability to regulate blood pressure [16][17][18]. Previous studies have shown that LIM has antiobesity properties in 3T3-L1 adipocytes and high-fat diet-induced obese rats [19,20]. ...
Article
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D-limonene (LIM) is a common monoterpene compound, principally found in citrus essential oils. This study investigated the anti-obesity effect of LIM on the 5′-adenosine monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway in 3T3-L1 adipocytes and high-calorie diet-induced obese rats and confirmed the optimally effective dose of LIM. The 3T3-L1 adipocytes were treated with 0.05–0.4 mg/mL LIM for 10 days and oil red O and triglyceride (TG) content were used to determine the levels of lipid accumulation. The results showed that more than 0.05 mg/mL LIM inhibited lipid accumulation by reducing oil red O in 3T3-L1 adipocytes. Masses of 0.2 and 0.4 mg/mL LIM also decreased the TG contents in 3T3-L1 adipocytes. On the other hand, Wistar rats were given high-calorie diets, combined with LLIM (154 mg/kg) and HLIM (1000 mg/kg) treatments, for 16 weeks. The result shows that LLIM and HLIM decreased body weight, total fat tissue weight, and serum low-density lipoprotein-cholesterol (LDLc) levels. HLIM reduced serum TG and increased serum lipase and high-density lipoprotein-cholesterol (HDLc) levels. Moreover, the anti-obesity metabolic pathway showed that LIM (>0.05 mg/mL) in 3T3-L1 adipocytes and LIM (>154 mg/kg) in high-calorie diet-induced obese rats could activate the AMPK signaling pathway. The activated AMPK regulated the mRNA expression related to adipogenesis (PPARγ, C/EBPα, FABP4), lipogenesis (SREBP-1c, ACC, FAS), and lipolysis (ATGL, HSL) to inhibit obesity. This finding demonstrates that LIM has anti-obesity properties. Namely, it is seen that LIM acts by regulating the AMPK signaling pathway in 3T3-L1 adipocytes and high-calorie diet-induced obese rats. In terms of dose–response, LIM (154 mg/kg) would be an optimal effective dose for anti-obesity induced by a high-calorie diet.
... An example is zidovudine, nucleoside antiretroviral drugs, due to their similarity to nitrogenous bases (thymidine), is a potent inhibitor of HIV replication (Paton et al., 2021). According to the study by Roberto et al. (2010), there was a reduction in thymidine concentration in cells exposed to D-limonene. In addition, perillic acid, a majoritarian limonene metabolite detected in human plasma, also has an inhibitory effect through thymidine incorporation, which presented a dose-dependent effect (Mukhtar et al., 2018). ...
Article
The COVID-19 pandemic has substantially impacted the world health systems, causing public health concerns, and the search for new compounds with antiviral activity is of extreme interest. Natural molecules with bioactive potential are a trend, with essential oils (Eos) being the focus of recent studies. Thus, this study evaluates in chemico the d-limonene inhibitory activities in the viral genome of SARS-CoV-2 and analyzes the cytotoxic potential and safety profile of d-limonene and lime and orange EOs with a high content of d-limonene. The EOs were extracted and characterized, and the in chemico computational analysis for the determination as a potential anti-SARS-CoV-2 was performed with d-limonene, the major compound in EOs. The cytotoxicity analysis of EOs and d-limonene was carried out with MRC-5 and HaCaT, and the preliminary safety profile was also evaluated by the HET-CAM assay. d-limonene was suggested as a promising compound for anti-SARS-CoV-2 research, since the molecule does not provide mutagenic and cytotoxic fragments, and does not have irritating potential when diluted, in addition to having favorable pharmacokinetic characteristics, through in chemico analysis. Collectively, the results reveal the antiviral potential of lime and orange EOs, as well as their major compound. In this sense, further studies should be conducted to understand the antiviral mechanisms.
... Antioxidant activity of the composites D-limonene is a monocyclic terpene that is consumed by humans largely as an ingredient of traditional food such as citrus fruits, carrots, coffee, orange and nutmeg (Roberto et al. 2010). Moreover, d-limonene is generally recognized as a safe flavoring agent that can be found in common food items such as fruit juices, soft drinks, baked goods, ice cream and puddings. ...
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Pulp fibers are among the most abundant and cost effective cellulose source for the fabrication of polymer-cellulose composites. A straightforward method is to impregnate pulp fibers into thermoplastic films by hot press forming. As such, tissue materials made from hard or soft wood lignin-free Kraft fibers are attractive. In this work, we prepared cellulose fiber-polylactic acid (PLA) composite films by impregnating PLA films into a 40 g/m² tissue paper texture. A PLA film was sandwiched between single and multiple layers of cellulose tissues by hot pressing, forming composite films. Up to 40 wt% cellulose could be incorporated into PLA in this way. The effect of cellulose fiber content on the composite thermomechanical properties has been studied and reported. A natural terpene, limonene, was infused into the cellulose fibers by immersion coating to produce antioxidant composites. Limonene-modified composites demonstrated long-term antioxidant release and activity for three days, verified by 2, 2-Diphenyl-1-picrylhydrazyl (DPPH), cupric ion reducing antioxidant capacity (CUPRAC) and free iron ions (Fe²⁺)/ferrozine chelating assays separately. The short-term (2 h) antioxidant activity of the biocomposites reached 50–70% levels depending on the cellulose fiber concentration for the DPPH and CUPRAC assays but remained lower at 20–55% levels in the metal chelating assay. Due to sustained release of limonene from the composites, at the end of the 5-day period, the iron chelating antioxidant activity of the composites improved reaching 75%, whereas for DPPH and CUPRAC assay, 90% activity was recorded. These biocomposite films can be used in active protective packaging of both food (fruit) and cosmetic products. Graphical abstract
... Recent studies have shown that D-limonene possesses anti-oxidant activity and protects lymphocytes from oxidative stress induced by hydrogen peroxide. 26,27 Moreover, numerous reports have shown that D-limonene has anticancer activity on various types of cancer as it can trigger apoptosis and regulate the cell cycle. 28,29 In addition, a study conducted by Rehman et al. showed that D-limonene can be used as a protective agent against the nephrotoxic effect of DOX. 30 However, D-limonene suffered from low water solubility due to its hydrophobic nature, which hampered its use and efficacy. ...
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Self-assembled nanoparticles present unique properties that have potential applications in the development of a successful drug delivery system. Doxorubicin (DOX) is an important anti-neoplastic anthracycline chemotherapeutic drug widely described. However, it suffers from serious dose-dependent cardiotoxicity. d-Limonene is a major constituent of numerous citrus oils that is considered a specific monoterpene against free radicals producing antioxidant activity. Herein, we aimed to design three types of self-assembled nanodelivery systems (nanoemulsion, niosomes, and polylactide nanoparticles) for loading both DOX and d-limonene to enhance the solubilization of d-limonene and provide antioxidant activity with excellent anticancer activity. As confirmed by dynamic light scattering and transmission electron microscopy, the nanoparticles were prepared successfully with diameter sizes of 52, 180, and 257 nm for the DOX-loaded nanoemulsion, niosomes, and polylactide nanoparticles, respectively. The zeta potential values were above -30 mV in all cases, which confirms the formation of stable nanoparticles. The loading efficiency of DOX was the highest in the case of the DOX-loaded nanoemulsion (75.8%), followed by niosomes (62.8%), and the least was in the case of polylactide nanoparticles with a percentage of 50.2%. The in vitro release study of the DOX-loaded nanoparticles showed a sustained release profile of doxorubicin with the highest release in the case of DOX-loaded PDLLA nanoparticles. The kinetic release model for all developed nanoparticles was the Peppas-Sahlin model, demonstrating DOX release through Fickian diffusion phenomena. Moreover, all developed nanoparticles maintain the antioxidant activity of d-limonene. The cytotoxicity study of the DOX-loaded nanoparticles showed concentration-dependent anticancer activity with excellent anticancer activity in the case of the DOX-loaded nanoemulsion and polylactide nanoparticles. These nanoparticles will be further studied in vivo to prove the cardioprotective effect of d-limonene in combination with DOX.
... Likewise, the radical quenching properties are also attributed to the Curcuma leaf essential oils [17,35]. Furthermore, the bioactive compounds including eucalyptol, α-lemenone, α-phellandrene, 2carene and α-curcumene are also reported to act as chain breaking antioxidants [36,37]. Since the role of antioxidants in alleviating chronic diseases and preventing infectious disease are evident [38,39], the leaf essential oils from different Curcuma spp. ...
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Curcuma species are widely used as a food additive and also in various medicinal purposes. The plant is a rich source of essential oil and is predominantly extracted from the rhizomes. On the other hand, the leaves of the plants are usually considered as an agrowaste. The valorization of these Curcuma leaf wastes into essential oils is becoming accepted globally. In the present study, we aim to extract essential oils from the leaves of Curcuma longa (LEO), C. aromatica (REO), and C. anguistifolia (NEO). The chemical composition of these essential oils was analyzed by GC-MS. Free radical scavenging properties were evaluated against the radical sources, including DPPH, ABTS, and hydrogen peroxide. The antibacterial activity was assessed by the disc diffusion method and Minimum inhibitory concentration analysis against Gram positive (Staphylococcus aureus) and Gram negative (Escherichia coli, Pseudomonas aeruginosa and Salmonella enterica) bacteria. Results identified the compounds α-phellandrene, 2-carene, and eucalyptol as predominant in LEO. The REO was predominated by camphor, 2-bornanone, and curdione. The main components detected in NEO were eucalyptol, curzerenone, α-lemenone, longiverbenone, and α-curcumene. Antioxidant properties were higher in the LEO with IC50 values of 8.62 ± 0.18, 9.21 ± 0.29, and 4.35 ± 0.16 µg/mL, against DPPH, ABTS, and hydrogen peroxide radicals. The cytotoxic activity was also evident against breast cancer cell lines MCF-7 and MDA-MB-231 cells; the LEO was found to be the most active against these two cell lines (IC50 values of 40.74 ± 2.19 and 45.17 ± 2.36 µg/mL). Likewise, the results indicated a higher antibacterial activity for Curcuma longa essential oil with respective IC50 values (20.6 ± 0.3, 22.2 ± 0.3, 20.4 ± 0.2, and 17.6 ± 0.2 mm). Hence, the present study confirms the possible utility of leaf agrowastes of different Curcuma spp. as a possible source of essential oils with pharmacological potential.
... Kalpana et al. [37] found hesperidin produced radioprotection by effectively decreasing MN frequency, dicentric aberrations and comet attributes, and correlated this activity with the ability for ROS scavenging. Limonene inhibited the genotoxicity of H 2 O 2 , behaving as a reductor agent that would protect cells from H 2 O 2 -induced oxidative stress [38,39]. Costa and Nepomuceno [40] indicated that a mixture of vitamins and elements such as copper, selenium and zinc protects against the genotoxic effects of the chemotherapeutic free-radical generator Doxorubicin using the wing spot test in Drosophila melanogaster. ...
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Betula pendula belongs to the Betulaceae family and is most common in the northern hemisphere. Various birch species have exhibited antimicrobial, antioxidant and anticancer properties. In the present study, we investigated the genotoxic and cytotoxic activity as well as the antigenotoxic potential against the mutagenic agent mitomycin-C (MMC) of two commercial products, i.e., a Betula pendula aqueous leaf extract product (BE) and a Betula pendula product containing aqueous extract of birch leaves at a percentage of 94% and lemon juice at a percentage of 6% (BP) using the cytokinesis block micronucleus (CBMN) assay. The most prevalent compounds and elements of BE and BP were identified using UHPLC-MS and ICP-MS/MS, respectively. All mixtures of BE with MMC demonstrated a decrease in the MN frequencies, with the lowest and highest concentrations inducing a statistically significant antigenotoxic activity. BP lacked genotoxic potential, while it was cytotoxic in all concentrations. Its mixtures with MMC demonstrated statistically significant antigenotoxic activity only at the lowest concentration. UHPLC-MS and ICP-MS/MS showed the presence of various elements and phytochemicals. Our results reveal antigenotoxic and cytotoxic potential of both BE and BP, while the variations observed could indicate the importance of the interactions among different natural products and/or their compounds.
... sinensis) [75]. Many of these monoterpenes have been shown to have potential in medicinal applications to reduce inflammation [76] and as natural antioxidants [77] with numerous antimicrobial and antifungal properties [78][79][80][81][82][83][84][85]. Our GC-MS analysis also detected carene in the EO of both tested citrus species, whereas carvone was found in C. reticulata only. ...
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Aphids are serious pests of a wide range of agricultural crops, including pomegranates and grapevines. In addition, due to the negative environmental impacts of chemical insecticides, these pests are developing important resistance against aphicides. Therefore, one alternative method to control aphids is the use of essential oils (EO). The present study aimed to evaluate the insecticidal activity of Citrus aurantium and C. reticulata peel EO at different concentrations and with different exposure periods to pomegranate and grapevine aphids, Aphis punicae and A. illinoisensis via the topical application method under laboratory conditions. The results reveal that C. aurantium L. EO had greater toxicity against pomegranate and grapevine aphids, with LC50 of 0.37 and 0.82 μL/mL, respectively, at 48 h after application. The highest repellence effect was estimated for C. aurantium EO, at 2.5 μL/cm2, on A. punicae, with a value of 100% after an exposure time of 3 h, in contrast to the 88% repellence estimated for A. illinoisensis. The GC-MS investigation of both essential oils identified limonene, 3-carene, pinene, and p-cymene as active substances that could be attributed to the effects observed. Overall, our results offer a potential tool to control the two aphid species and could help in the development of integrated insect management in pomegranate and grapevine fields.
... D-limonene has a proven impact on different types of cancer (17). Also, it possesses antioxidant, anti-diabetic, anti-apoptotic, and lipid peroxidation inhibitory effects, prevents mitochondrial dysfunction, and inhibits ROS (18,19). Published research has shown different biological activities of D-limonene, including hypolipidemic and immunomodulatory activities and hepatoprotective and dermatoprotective effects (20)(21)(22). ...
Article
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Background and Objective: Reactive oxygen species are the main factors involved in kidney damage during renal ischemia-reperfusion (RIR). Since D-limonene has antioxidant, anti-diabetic, anti-apoptotic, and lipid peroxidation effects, it prevents mitochondrial dysfunction and inhibits ROS, this study was conducted to evaluate the effects of pretreatment with D-limonene on oxidative stress and antioxidant activity in RIR injury. Methods: In this experimental study, 24 male Wistar rats were randomly divided into 3 groups: control, RIR (ischemia was induced by clamping of renal pedicles for 45 minutes and reperfusion was considered 24 hours after ischemia), and RIR+D-limonene (100 mg/kg by oral gavage for 12 days). Serum and kidney were used to evaluate malondialdehyde (MDA), myeloperoxidase (MPO), paraoxonase1 (PON1), glutathione (GSH), catalase (CAT), glutathione peroxidase (GPX), and nitric oxide (NO). Findings: Serum and renal levels of MDA ([18.2±98.77 vs. 9.21±1.77] and [19.85±3.39 vs. 9.84±1.65]) and MPO ([67.25±32.67 vs. 40.21±6.1] and [18.44±2.86 vs. 10.42±1.68]) and serum level of NO (31.3±36.1 vs. 27.88±2.6) significantly increased in the RIR group compared with the control group (p<0.05). Serum and kidney levels of GSH, activities of CAT and GPX in serum and kidney, and serum activity of PON1 significantly decreased in the RIR group compared with the control group (p<0.05). Pretreatment with D-limonene could significantly ameliorate serum and renal levels of MDA, serum levels of GSH and NO, and serum activity of CAT in rats pretreated with D-limonene in comparison with RIR rats (p<0.05). Conclusion: This study indicated that pretreatment with D-limonene could ameliorate RIR injuries in rats through its antioxidant activities.
... These results are related to those observed in previous study, in which we demonstrated the ability of EO or limonene to stimulate in vitro the proliferation of human lymphocytes similar to phytohemagglutinin (Cariddi et al., 2011). Similarly, Roberto et al. (2010), demonstrated that limonene (5, 10 and 50 μg/ml) significantly stimulated the proliferation of murine lymphocytes (1 × 10 6 cells/well) after 24 h incubation. ...
Article
Design of innovative adjuvant strategies with an appropriate safety profile is relevant to developed subunit or inactivated microorganism vaccines for bovine mastitis. Minthostachys verticillata essential oil (EO) has demonstrated ability to stimulate the innate immune response and adjuvant effect similar to Al(OH)3. Here we evaluated the adjuvant effect of EO and its metabolite, limonene (L) alone and microencapsulated by spray-drying, using an inactivated Enterococcus faecium strain bovine-mastitis inducer. The gas chromatography–mass spectrometry analysis showed that microencapsulation process did not alter the EO or L chemistry. Microencapsulated EO (McEO) or L (McL) (2.0, 2.5 and 5.0 mg/ml) decreased the viability of bovine mammary gland epithelial cells in a dose-dependent way. Balb/c mice (n = 32) were subcutaneously inoculated (day 0) and revaccinated (day 14 and 28) with saline solution, inactivated bacteria alone or combined with Incomplete Freund's Adjuvant; EO or L (2.5 mg/ml); McEO or McL (5.0 mg/ml); or microcapsule wall material (Mc) alone (2.5 mg/ml). EO, L, McEO and McL stimulated E. faecium-specific IgG (IgG1 or IgG2a) with opsonizing capacity and increased the proportion of CD4⁺ and CD8⁺ T cells producers of IFN-γ. Microencapsulation was an effective strategy to increase the adjuvant potential of EO or L. These new adjuvants deserve further study to evaluate their incorporation into vaccines for bovine mastitis.
... Limonene (1%) has antibacterial, antifungal, anti-inflammatory, antioxidant, and tumor-suppressive activity [42][43][44][45][46]. ...
Article
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The leaves of Rubus idaeus L., a by-product of the fruit food industry, are a known source of bioactive molecules, although the chemical composition has only been partially investigated. The main objective of this study was to examine the biological activities and the chemical composition of the extract of leaves of R. idaeus (RH), obtained by steam distillation (SD). The antioxidant capacity; the total phenolic content (TPC); the cytotoxic activity against tumor cell lines; and the antibacterial activity, in addition to the study of the chemical fingerprinting, carried out by Gas/Chromatography-Mass-Spectrometry (GC/MS) and Headspace (HS)-GC/MS, were established. The extract showed a strong antioxidant capacity and a modest antibacterial activity against two bacterial strains, as well as significant cytotoxic activity against tumor cell lines (Caco-2 and HL60) and being proliferative on healthy cells. Many of the GC-identified volatile molecules (1,8-cineol, β-linalool, geraniol,caryophyllene, τ-muurolol, citral, α-terpineol, 3- carene, α-terpinen-7-al, etc.) can explain most of the biological properties exhibited by the extract of R. idaeus L. The high biological activity of the RH and the high compatibility with the various matrices suggest good prospects for this extract, both in the food and cosmetic fields or in dietary supplements for improving human health.
... In the last years, numerous studies have found that limonene and orange oil possess powerful antioxidative properties and protect organisms from oxidative damage (67)(68) . In particular, they're rapidly and nearly all absorbed in the gastrointestinal tract, both humans and animals (69) , and also an effective anti-carcinogen (70) hepatoprotective, immunomodulatory, and anti-inflammatory properties (71) . Antimicrobial and antifungal effects of orange peel essential oil (72) may come from limonene content. ...
Article
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The valorization of agro-industrial waste like orange peel presents an economic and environmental due to the enormous amounts generated during orange juice production. This study focuses on the encapsulation of orange peel oil and its main constituent, limonene, using different wall combinations using spray drying. The increase of gum Arabic (GA) provided higher viscosity (136.33cP) and stability (0.9%) in the orange oil emulsion before spray-drying, whereas the predominance of maltodextrin (MD) led to the reverse, 58.67cP, and 13%, respectively. In the spray-dried powder, MD as a prominent in-wall mixture resulted in higher bulk density for orange oil powder (0.33g/cm3), better results in the wettability test (31.67sec.), and the highest oil retention (92.22%) for limonene powder. The encapsulation efficiency was positively influenced by the 10% GA with 85.35 and 85.77% for limonene and orange oil powders, respectively. Significant color changes were undergone according to different CIE-LAB characteristics, especially for limonene powder (b* 7.91), where MD is predominant in the wall combinations. Increasing the GA concentration affects the morphology of the particles with more agglomeration, while the predominant MD leads to more spherical and smooth particles. In the sensory analysis, supplemented sponge cake with encapsulated limonene showed the highest overall preference score (7.87/9), while orange oil flavoring in jelly candies had the superiority (7.9/9) compared to the control. The nutritional data and biochemical parameters showed non-significant results in all groups supplemented with the spray-dried flavorings compared to normal control. The spray-drying of orange peel oil and limonene did not show any adverse effects on the nutritional or the biochemical parameters with enhancing the sensory attributes of the final food products.
... The other Cornus mas fruit cultivars showed comparable antioxidant activity, however slightly weaker than the Słowianin cultivar. The correlation coefficients between TPC and antioxidant activity were not significant (p > 0.05), suggesting that the free-radical scavenging activity of Corni fructus water extracts may be attributed to differences in the activity of phenols and other active compounds, such as ascorbic acid [63], monoterpenes (especially limonene) and iridoids [64,65]. On the other hand, the antioxidant potential for the entire extract, which was tested, is an exponential result of single reactions taking place in the single electron transfer process, which does not fully reflect the reactions taking place in vivo, providing only an estimate of the antioxidant capacity [66]. ...
Article
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As a systemic disease, diabetes mellitus (DM) is characterized by the disruption of many glucose metabolic pathways. Therefore, it seems critical to study new therapies to support treatment to develop therapeutic systems that can operate across a broad metabolic spectrum. The current state of knowledge indicates an essential role of the gut microbiota in the development and course of the disease. Cornus mas fruits have demonstrated a rich biological activity profile and potential for application in the treatment of DM. As part of a preliminary analysis, the activity of four cultivars of Cornus mas fruits was analyzed. The cultivar Wydubieckij was selected as having the highest activity in in vitro conditions for further prebiotic system preparation. The study aimed to develop a unique therapeutic system based, first of all, on the mechanism of α-glucosidase inhibition and the antioxidant effect resulting from the activity of the plant extract used, combined with the prebiotic effect of inulin. The obtained system was characterized in vitro in terms of antioxidant activity and enzyme inhibition capacity, and was then tested on diabetic rats. The study was coupled with an analysis of changes in the intestinal microflora. The system of prebiotic stabilized Cornus mas L. lyophilized extract with inulin offers valuable support for the prophylaxis and treatment of DM.
... Myristicin, a benzodioxole compound, was recognized as an antioxidant agent [33]. On the other side, the two monoterpenes limonene [39] and terpinen-4-ol [40] were noted with a considerable antioxidant property. Notably, Seol et al. demonstrated that the inhalation of linalool (a noncyclic monoterpenoid) could enhance antioxidative activity in patients with carpal tunnel syndrome [41]. ...
Article
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Essential oils (EOs) of Clausena indica fruits, Zanthoxylum rhetsa fruits, and Michelia tonkinensis seeds were analyzed for their phytochemical profiles and biological activities, including anti-diabetes, anti-gout, and anti-leukemia properties. Sixty-six volatile compounds were identified by gas chromatography–mass spectrometry (GC–MS), in which, myristicin (68.3%), limonene (44.2%), and linalool (49.3%) were the most prominent components of EOs extracted from C. indica, Z. rhetsa, and M. tonkinensis, respectively. In addition, only EOs from C. indica inhibited the activities of all tested enzymes comprising α-amylase (IC50 = 7.73 mg/mL), α-glucosidase (IC50 = 0.84 mg/mL), and xanthine oxidase (IC50 = 0.88 mg/mL), which are related to type 2 diabetes and gout. Remarkably, all EOs from C. indica, Z. rhetsa (IC50 = 0.73 mg/mL), and M. tonkinensis (IC50 = 1.46 mg/mL) showed a stronger anti-α-glucosidase ability than acarbose (IC50 = 2.69 mg/mL), a known anti-diabetic agent. Moreover, the growth of leukemia cell Meg-01 was significantly suppressed by all EOs, of which, the IC50 values were recorded as 0.32, 0.64, and 0.31 mg/mL for EOs from C. indica, Z. rhetsa, and M. tonkinensis, respectively. As it stands, this is the first report about the inhibitory effects of EOs from C. indica and Z. rhetsa fruits, and M. tonkinensis seeds on the human leukemia cell line Meg-01 and key enzymes linked to diabetes and gout. In conclusion, the present study suggests that EOs from these natural spices may be promising candidates for pharmaceutical industries to develop nature-based drugs to treat diabetes mellitus or gout, as well as malignant hematological diseases such as leukemia.
... anti-asthmatic [149]; antioxidant [150]; anti-inflammatory [151] O 3 Gingko biloba (Ginkgoaceae) [ kaempferol Anticancer [175]; anti-inflammatory [176] Heat stress C. acuminata [177] 10-hydroxycamptothecin Increase Alkaloids 10-hydroxycamptothecin Anticancer [178] Heat stress Daucus carota (Apiaceae) [179][180][181] α-terpinolene Decrease Terpenoids α-terpinolene Antioxidant and anticancer [182] α-caryophyllene, β-farnesene Increase NA NA anthocyanins, coumaric and caffeic acid; Increase Phenolics p-coumaric acid and caffeic acid Antioxidant [183,184] Heat stress Q. rubra (Fagaceae) [185] isoprene (2-methyl-1,3-butadiene) Increase Terpenoids NA NA Heat stress S. lycopersicon [87,97] β-phellandrene (dominant), 2-carene, α-phellandrene, limonene; increased emission of (E)-β-ocimene after treatment above 46 • C; β-caryophyllene. ...
Article
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Plant secondary metabolites (PSMs) are vital for human health and constitute the skeletal framework of many pharmaceutical drugs. Indeed, more than 25% of the existing drugs belong to PSMs. One of the continuing challenges for drug discovery and pharmaceutical industries is gaining access to natural products, including medicinal plants. This bottleneck is heightened for endangered species prohibited for large sample collection, even if they show biological hits. While cultivating the pharmaceutically interesting plant species may be a solution, it is not always possible to grow the organism outside its natural habitat. Plants affected by abiotic stress present a potential alternative source for drug discovery. In order to overcome abiotic environmental stressors, plants may mount a defense response by producing a diversity of PSMs to avoid cells and tissue damage. Plants either synthesize new chemicals or increase the concentration (in most instances) of existing chemicals, including the prominent bioactive lead compounds morphine, camptothecin, catharanthine, epicatechin-3-gallate (EGCG), quercetin, resveratrol, and kaempferol. Most PSMs produced under various abiotic stress conditions are plant defense chemicals and are functionally anti-inflammatory and antioxidative. The major PSM groups are terpenoids, followed by alkaloids and phenolic compounds. We have searched the literature on plants affected by abiotic stress (primar-ily studied in the simulated growth conditions) and their PSMs (including pharmacological activities) from PubMed, Scopus, MEDLINE Ovid, Google Scholar, Databases, and journal websites. We used search keywords: "stress-affected plants," "plant secondary metabolites, "abiotic stress," "climatic influence," "pharmacological activities," "bioactive compounds," "drug discovery," and "medicinal plants" and retrieved published literature between 1973 to 2021. This review provides an overview of variation in bioactive phytochemical production in plants under various abiotic stress and their potential in the biodiscovery of therapeutic drugs. We excluded studies on the effects of biotic stress on PSMs.
... The antioxidant activities of the oils could be described by the presence of the main bioactive components of the oils. For example, it has been reported that terpenes such as α-terpinene, γ-terpinene, sabinene, terpinolene, and limonene showed antioxidant activities [33,34]. Some oxygenated monoterpenes and sesquiterpenes-such as terpinen-4-ol, α-terpineol, borneol, and spathulenol-also exhibited antioxidant activities [33,35,36]. ...
Article
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The chemical composition and biological activities of the essential oils from the leaves, stems, and roots of Kadsura coccinea (K. coccinea) were investigated. The essential oils were extracted by hydro distillation and analyzed by gas chromatography mass spectrometry (GC-MS) and gas chromatography with flame ionization detector (GC-FID). Antioxidant activities of the essential oils were examined with DPPH radical scavenging assay, ABTS cation radical scavenging assay, and ferric reducing antioxidant power assay. Antimicrobial activities were evaluated by determining minimum inhibitory concentrations (MIC) and minimum microbiocidal concentrations (MMC). Acetylcholinesterase and butyrylcholinesterase inhibitory activity of the essential oils were also tested. A total of 46, 44, and 47 components were identified in the leaf, stem, and root oils, representing 95.66%, 97.35%, and 92.72% of total composition, respectively. The major compounds of three essential oils were α-pinene (16.60–42.02%), β-pinene (10.03–18.82%), camphene (1.56–10.95%), borneol (0.50–7.71%), δ-cadinene (1.52–7.06%), and β-elemene (1.86–4.45%). The essential oils were found to have weak antioxidant activities and cholinesterase inhibition activities. The essential oils showed more inhibitory effects against Staphylococcus aureus (S. aureus) than those of other strains. The highest antimicrobial activity was observed in the root oil against S. aureus, with MIC of 0.78 mg/mL. Therefore, K. coccinea essential oils might be considered as a natural antibacterial agent against S. aureus with potential application in food and pharmaceutical industries.
... Moreover, the two isomers αand β-pinene are well-known monoterpenes present in parsley, and many plant essential oils have antitumor, antioxidant, and anti-inflammatory effect [25]. Also, limonene protected the cells to the oxidative stress induced by exogenous H 2 O 2 [26]. The aim of the current study was to investigate the potential protective effect of essential leaf oil of parsley (Petroselinum crispum) against CCl 4 -induced oxidative stress in mouse testes and thyroid glands. ...
Article
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The aim of the present study was to investigate the ameliorative potential of parsley (Petroselinum crispum) leaf essential oil (PO) against the detrimental effects of carbon tetrachloride (CCl4) on the thyroid gland and testes of mice. Twenty-four adult male mice were divided into four groups and treated for 4 weeks. The 1st control group received 3 mL/kg olive oil intraperitoneally, twice a week followed by 0.5 mL/kg saline intragastrically daily. The 2nd CCl4 group received CCl4 (3 mL/kg intraperitoneally, twice a week). The 3rd PO group received PO (0.5 mL/kg intragastrically daily), while the 4th CCl4+PO group received CCl4 coadministrated with PO at the aforementioned doses. CCl4 group recorded significant (p
... In normal conditions, a dynamic equilibrium exists between ROS activity and defense capacity of antioxidants. [36][37][38][39] The shift in equilibrium in favor of ROS activity results in oxidative stress. This might happen either due to an increase in ROS production or a decrease in defense capacity of antioxidants. ...
Research
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Background: Citrus sinensis is one of the most important and widely known fruits known for its medicinal value. Many medicinal properties of orange peel extract are known to fight viral and bacterial infections. ROS are oxygen-containing, chemically reactive molecules. ROS can kill bacteria but it also destroys the adjacent infected host tissues. The aim of the study was to determine the neutralizing effect of limonene (orange peel extract) on Reactive Oxygen Species (ROS) generated by the mixture when used as an intracanal medicament. Methodology: Aqueous and ethanol extracts prepared from peel of Citrus sinensis were screened for neutralizing effect of limonene (orange peel extract) on Reactive Oxygen Species (ROS) generated by the mixture when used as an intracanal medicament. The groups were analyzed for ROS formation using the mass spectrometer (JEOL GC MATE II) immediately after preparation. Results: The peak value of 3345.6 m/z denotes ROS formation. Group C shows a higher peak value than other groups. Conclusion: The peak value of 3390.8 m/z was probably originated by the production of reactive compounds. Thus decreased ROS formation was noted in orange peel aqueous extract warranting further in vivo clinical studies to determine the exact dosages and its effectiveness in practical situations.
... Likewise, one of herbal medicinal products, silymarin, consisting of optically pure components, showed the crucial role of stereochemistry in inhibiting the aggregation of amyloid-beta (Aβ), a pathogenic hallmark of Alzheimer's disease [15]. Studies have revealed that D-limonene, which is isolated from medicinal plants, has a number of therapeutic effects, including anti-cancerous [16], anti-nociceptive [17], gastroprotective and healing of gastric ulcer [18], antioxidant [19] and anti-inflammatory [20] properties, and effectiveness in improving lung function [21]. ...
Article
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Limonene is a monoterpene confined to the family of Rutaceae, showing several biological properties such as antioxidant, anti-inflammatory, anticancer, antinociceptive and gastroprotective characteristics. Recently, there is notable interest in investigating the pharmacological effects of limonene in various chronic diseases due to its mitigating effect on oxidative stress and inflammation and regulating apoptotic cell death. There are several available studies demonstrating the neuroprotective role of limonene in neurodegenerative diseases, including Alzheimer’s disease, multiple sclerosis, epilepsy, anxiety, and stroke. The high abundance of limonene in nature, its safety profile, and various mechanisms of action make this monoterpene a favorable molecule to be developed as a nutraceutical for preventive purposes and as an alternative agent or adjuvant to modern therapeutic drugs in curbing the onset and progression of neurodegenerative diseases. This manuscript presents a comprehensive review of the available scientific literature discussing the pharmacological activities of limonene or plant products containing limonene which attribute to the protective and therapeutic ability in neurodegenerative disorders. This review has been compiled based on the existing published articles confined to limonene or limonene-containing natural products investigated for their neurotherapeutic or neuroprotective potential. All the articles available in English or the abstract in English were extracted from different databases that offer an access to diverse journals. These databases are PubMed, Scopus, Google Scholar, and Science Direct. Collectively, this review emphasizes the neuroprotective potential of limonene against neurodegenerative and other neuroinflammatory diseases. The available data are indicative of the nutritional use of products containing limonene and the pharmacological actions and mechanisms of limonene and may direct future preclinical and clinical studies for the development of limonene as an alternative or complementary phytomedicine. The pharmacophore can also provide a blueprint for further drug discovery using numerous drug discovery tools.
... In normal conditions, a dynamic equilibrium exists between ROS activity and defense capacity of antioxidants. [36][37][38][39] The shift in equilibrium in favor of ROS activity results in oxidative stress. This might happen either due to an increase in ROS production or a decrease in defense capacity of antioxidants. ...
Article
Full-text available
Background: Citrus sinensis is one of the most important and widely known fruits known for its medicinal value. Many medicinal properties of orange peel extract are known to fight viral and bacterial infections. ROS are oxygen-containing, chemically reactive molecules. ROS can kill bacteria but it also destroys the adjacent infected host tissues. The aim of the study was to determine the neutralizing effect of limonene (orange peel extract) on Reactive Oxygen Species (ROS) generated by the mixture when used as an intracanal medicament. Methodology: Aqueous and ethanol extracts prepared from peel of Citrus sinensis were screened for neutralizing effect of limonene (orange peel extract) on Reactive Oxygen Species (ROS) generated by the mixture when used as an intracanal medicament. The groups were analyzed for ROS formation using the mass spectrometer (JEOL GC MATE II) immediately after preparation. Results: The peak value of 3345.6 m/z denotes ROS formation. Group C shows a higher peak value than other groups. Conclusion: The peak value of 3390.8 m/z was probably originated by the production of reactive compounds. Thus decreased ROS formation was noted in orange peel aqueous extract warranting further in vivo clinical studies to determine the exact dosages and its effectiveness in practical situations.
... Limonene, a common monoterpene found as major component of the active complex of the genus Citrus [15], has been shown to exert anxiolytic, antinociceptive, antioxidant, and anti-inflammatory activity [16][17][18][19][20], as well as to display a protective effect against metabolic syndromes and gastrointestinal and respiratory tract diseases [21,22]. Interestingly, limonene has been suggested to act on the central nervous system, affecting the expression of adenylate cyclase 1 [15], which has been demonstrated to regulate cAMP levels. ...
Article
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Many natural-derived compounds, including the essential oils from plants, are investigated to find new potential protective agents in several neurodegenerative disorders such as Alzheimer’s disease (AD). In the present study, we tested the neuroprotective effect of limonene, one of the main components of the genus Citrus, against the neurotoxicity elicited by Aβ1-42 oligomers, currently considered a triggering factor in AD. To this aim, we assessed the acetylcholinesterase activity by Ellman’s colorimetric method, the mitochondrial dehydrogenase activity by MTT assay, the nuclear morphology by Hoechst 33258, the generation of reactive oxygen species (ROS) by DCFH-DA fluorescent dye, and the electrophysiological activity of KV3.4 potassium channel subunits by patch-clamp electrophysiology. Interestingly, the monoterpene limonene showed a specific activity against acetylcholinesterase with an IC50 almost comparable to that of galantamine, used as positive control. Moreover, at the concentration of 10 µg/mL, limonene counteracted the increase of ROS production triggered by Aβ1-42 oligomers, thus preventing the upregulation of KV3.4 activity. This, in turn, prevented cell death in primary cortical neurons, showing an interesting neuroprotective profile against Aβ1-42-induced toxicity. Collectively, the present results showed that the antioxidant properties of the main component of the genus Citrus, limonene, may be useful to prevent neuronal suffering induced by Aβ1-42 oligomers preventing the hyperactivity of KV3.4.
... Also, the ursolic acid demonstrates a marked therapeutic effect influencing the metabolic, energetic, and oxidative processes in the cell (Li et al. 2013;Kashyap et al. 2016). Flavonoids, terpenoids, and phenolic acids of N. multifida contribute to the manifestation of antihypoxic activity as they have antioxidant activity preventing from generation and injuring effect of the oxygen active forms and thus promoting the efficacy of tissue respiration and oxidative phosphorylation coupling (Roberto et al. 2010;Sato et al. 2011). ...
Article
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The antihypoxic effect of the Nepeta multifida L. dry extract was studied in experiments on white Wistar rats. The life span of animals was determined against the background of acute hypoxias: hypercapnic, hemic, and histotoxic ones. Using the model of acute hypobaric hypoxia/reoxygenation there was evaluated the content of ATP, lactic and pyruvic acids, TBA-active products, reduced glutathione, catalase activity in brain tissue. On the model of acute hypobaric hypoxia/reoxygenation, the content of ATP, lactic and pyruvic acids, reduced glutathione and catalase activity in brain tissue The N. multifida dry extract demonstrated antihypoxic effect at the doses comprised between 100 and 300 mg/kg increasing lifespan of animals in hypercapnic, hemic and histotoxic hypoxias. N. multifida decreases the manifestation of free-radical oxidation processes, increases the activity of the endogenic antioxidant system, and promotes the efficacy of tissue respiration and oxidative phosphorylation coupling in the brain of white rats in hypoxia/reoxygenation.
... PHSE-PNP nanoparticles also displayed significant antioxidant activity (Figure 3) in the current research. This was due to its individual ingredients, such as limonene which is well-known as a strong antioxidant (Roberto et al. 2010, Faridi et al. 2013. In addition to limonene, there are other pecan smoke compounds whose antioxidant effects can inhibit free radicals. ...
Article
Full-text available
Synthesis and investigation of biological activity of Peganum harmala smoke-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles. Peganum harmala smoke-loaded PLGA nanoparticles (PHSE-PNP) were produced by double emulsion solvent evaporation method and characterised by scanning electron microscopy (SEM), dynamic light scattering (DLS), and ζ-potential. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) for toxicity evaluation, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and ferric reducing antioxidant power (FRAP) assay for antioxidant power, chorioallantoic membrane (CAM), qPCR, and scratch assay for angiogenesis and mouse cancer model for antitumor effects of PHSE-PNP's were used. PHSE-PNP with a size of 216.33 nm, polydispersity index (PDI): 0.22 and ζ-potential: -25.41 mV inhibited A2780, PC3, A549, HepG2, Mda-mb-231, HT-29 as cancer cells and HUVEC as an normal cells with half-maximal inhibitory concentration (IC50) at about 208.62, 479.05, 1092.6, 1103.9, 1299.21, 3467.5, and <4000 µg/ml, respectively. Also PHSE-PNP inhibited ABTS (IC50: 0.720 mg/ml), DPPH (IC50: 1.36 mg/ml) free radicals and decreased the size of murine tumours (88.3% in 11 days) and suppressed angiogenesis in the CAM and scratch assays. PHSE-PNP can be considered as a potential chemopreventive agent in cancer therapy.
... Citrus species: modern functional food and nutraceutical-based product ingredient (Figure 3), and D-limonene is the most abundant element. This monocyclic terpene is consumed by humans as an ingredient of traditional foods and is listed in the Code of Federal Regulations, as Generally Recognized as a Safe (GRAS) and used as a flavoring agent (Roberto et al., 2010). ...
Article
Full-text available
Citrus is the most produced tree fruit crop in the world and occupies a place of considerable importance in the country's economy. Almost 33% of the Citrus fruits are processed for juice production, however, a great amount of wastes including peels, segment membrane and seeds are produced. Indeed, Citrus fruits consist of 45% juice, 26% pulp, 27% peels and 2% seeds. Pruning, a cultural practice involving the removal of tree branches and limbs, were applied in order to improve the fruit's quality. From pruning a large amount of leaves are also produced. These agri-food matrices contained a higher wide range of bioactive phytochemicals compared to fruits. The present review article covered the last five years of research on chemistry, healthy properties, applications in food and nutraceutical industries, of all portions of Citrus fruit and its major bioactive compound. Additionally, the patents are included.
... H 2 O 2 is a stable and easily diffused out of the cell [18]. H 2 O 2 has been shown to be involved in cell proliferation [21], cell-cycle arrest [22] and apoptosis [23] and vascular smooth muscle constriction [24]. The multiple responses of the lung to oxygen are a physiological paradigm of the variety of cellular responses to ROS in vitro. ...
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... C 10 H 16 -Inspiration (M. A. Lewis et al., 2018) -Anxiolytic (Komiya et al., 2006) (N. G. P. B. Lima et al., 2013) -Anti-depressant (Komori et al., 1995) (Komiya et al., 2006) -Anti-nociceptive (Do Amaral et al., 2007) -Increasing motility (Buchbauer et al., 1993) -Anti-inflammatory (Lappas & Lappas, 2012) -Anti-carcinogenic (Haag et al., 1992) -Antioxidant (Roberto et al., 2010) -Antifungal, anti-bacterial -Anti-inflammatory (E. B. Russo & McPartland, 2001) -Dries excess fluids (Mihai & Holban, 2017) -May be responsible for dry mouth -Anti-microbial (Da Silva et al., 2012) -Memory enhancing (Kennedy et al., 2011) Piney, dry, woody, resinous, herbal BP:155 °C -Pinene C10H16 -Anxiolytic (Satou et al., 2014) (Yang et al., 2016) -Anti-nociceptive (Him et al., 2008) -Anti-depressant (Guzmán-Gutiérrez et al., 2015) -Bronchodilator (Falk et al. 1990) -Relaxant, anti-spasmodic (Câmara et al., 2003) -Increasing motility (Buchbauer et al., 1993) -Memory enhancing (Kennedy et al., 2011) -AChE inhibitor (F. ...
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The antioxidant activities of a limonene biotransformation extract and of some standard monoterpenes present in the extract were assessed using four antioxidant assays: total antioxidant capacity, based on the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging assay, lipid peroxidation by the thiobarbituric acid (TBA) assay, superoxide anion release by cultured leukemic cells and glutathione S-transferase (GSTs) activity. The limonene biotransformation extract had free radical-scavenging activity (EC50=2.09%, v/v) and inhibited lipid peroxidation (IC50=0.13%, v/v). The extract, perillyl alcohol and α-terpineol inhibited lipid peroxidation by ∼80% at a concentration of 0.02% (v/v). Perillyl alcohol and α-terpineol also reduced the release of superoxide anions by cultured leukemic cells, by 3- and 10-fold, respectively, at concentrations of
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Some time ago, a multiple comparison procedure for comparing several treatments simultaneously with a control or standard treatment was introduced by the present author (Dunnett [1955]). The procedure was designed to be used either to test the significance of the differences between each of the treatments and the control with a stated value 1 - P for the joint significance level, or to set confidence limits on the true values of the treatment differences from the control with a stated value P for the joint confidence coefficient. Thus the procedure has the property of controlling the experimentwise, rather than the per-comparison, error rate associated with the comparisons, in common with the multiple comparison procedures of Tukey [unpublished] and Scheffe [1953]. In the earlier paper, tables were provided enabling up to nine treatments to be compared with a control with joint confidence coefficient either .95 or .99. Tables for both one-sided and two-sided comparisons were given but, as explained in the paper, the two-sided values were inexact for the case of more than two comparisons as a result of an approximation which had to be made in the computations. The main purpose of the present paper is to give the exact tables for making two-sided comparisons. The necessary computations were done on a General Precision LGP-30 electronic computer, by a method described in section 3 below. The tables are given here as Tables II and III; these replace Tables 2a and 2b, respectively, of the previous paper. In addition to providing the exact values, a method is given for adjusting the tabulated values to cover the situation where the variance of the control mean is smaller than the variance of the treatment means, as occurs for example when a greater number of observations is allocated to the control than to any of the test treatments. Furthermore, the number of treatments which may be simultaneously compared with a control has been extended to twenty. 482
Article
d-Limonene was found to be effective in reducing the average number of rat mammary carcinomas that developed in 7,12-dimeihylbenz[a]anthracene-treated rats when the terpene was fed during the initiation or during the promotion/progression stage of carcinogenesis. The time to the appearance of the first tumor was extended only when d-limonene was fed during the initiation stage. These effects could not be attributed to changes in mammary-relevant endocrine functions.
Article
Extracts of three species of eucalyptus leaves (Eucalyptus polyanthemos Schauer, E globulus Labill and E perriniana) and their major volatile components were assessed for antioxidant activity in two different assays. The inhibitory effect of each extract and its components towards aldehyde/carboxylic acid conversion was measured over a period of 30 days. Their inhibitory effects towards malonaldehyde formation from lipid by oxidation with Fenton's reagent were also measured; the extract from E polyanthemos inhibited the oxidation of hexanal completely for 30 days at a level of 200 and 500 µg ml−1. It also inhibited malonaldehyde (MA) formation in cod liver oil by 86% at the 160 µg ml−1 level. At the 500 µg ml−1 level, thymol, 1,8-cineole, benzyl alcohol and terpinen-4-ol identified in the extract from E polyanthemos reduced the extent of hexanal oxidation over a period of 30 days by 100, 96, 82 and 75% respectively. In the lipid/MA assay, thymol, benzyl alcohol, terpinen-4-ol and 1,8-cineole inhibited MA formation by 80, 63, 58 and 26% respectively at the level of 160 µg ml−1. Thymol exhibited potent antioxidant activity comparable to that of the known natural antioxidant α-tocopherol.© 2001 Society of Chemical Industry
Article
This study was aimed to evaluate the antioxidative activities of water (GWE), 50% ethanolic (GE50), and 95% ethanolic (GE95) extracts of Graptopetalum paraguayense. The antioxidant activities, including the radical-scavenging effect, reducing power, and antioxidative effect on Fe/ascorbate-induced lipid peroxidation in a liposome model system, were studied in vitro. The results showed that GWE, GE50 and GE95 possessed antioxidant characteristics including radical scavenging, reducing power, and lipid peroxidation inhibition. It was found that the antioxidative activities of all the extracts increased with increasing concentrations, and the activities correlated with both the total phenol and anthocyanin contents. A comparison of the 50% inhibition concentration (IC50) values of different antioxidative reactions revealed that GE50 was more effective in scavenging α,α-diphenyl-β-picrylhydrazyl (DPPH) radical and showed a higher reducing power than GWE and GE95. However, there were no significant differences (P > 0.05) in the lipid peroxidation-prevention effects among the extracts.
Article
The conventional steam distillation process for oregano (Lippia berlandieri v. Shauer) essential oil extraction produces large volumes of mother liquor. This residual liquid represents a potential value because the soluble antioxidants it contains. Essential oil and ethyl acetate mother liquor extracts (MLEs) were evaluated for antioxidant activity. Total phenolic content and antioxidant activities by the 2-2′-diphenyl-1-picrylhydrazyl (DPPH) method, by the deoxyribose degradation assay, and by oxidation of low density lipoproteins (LDL) with CuSO4 were evaluated. Oil yield was 4.34%. Total phenolic content was 151 ± 2.00 and 150.5 ± 0.98 mg of GAE (gallic acid equivalents)/mL for the essential oil and MLEs, respectively. DPPH assay showed a low radical scavenging activity (RSA) for oregano essential oil. Meanwhile MLEs exhibited no significant RSA at low concentrations, but at higher concentrations (100 μg/mL), it was superior to those exhibited by the controls ascorbic acid and butylated hydroxytoluene (BHT). Deoxy-d-ribose assay results for both essential oil and MLEs showed a good hydroxyl radical RSA at the concentrations tested. Essential oil and MLEs delayed induction time effectively. Solubility problems, chemical constituents, and their hydrophilic–lipophilic distribution are key factors that explain samples behavior for an eventual use of these natural products.
Article
Essential oils extracted by hydrodistillation from the aerial parts of 23 samples of Algerian Origanum glandulosum Desf. were analysed by gas chromatography (GC) and GC–mass spectrometry (MS). Overall, 30 components have been fully characterized. However, all the oils were characterized by the predominance of four components, thymol (18.5–73.1%), carvacrol (7.6–72.6%), p-cymene (1.7–18.5%) and -terpinene (1.1–18.7%). Cluster analysis of the identified components allowed us to establish the presence of three main groups, characterized by carvacrol, thymol and comparable amounts of both compounds, respectively. The free radical scavenging activity of essential oils was determined by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) model system. The SC50 (scavenging concentration) values were in the range 16.2–26.7 µg/ml, representing a good antioxidant effectiveness. The roles of thymol and carvacrol, the main components of all oils, were estimated by measuring their stoichiometric factors. The essential oils were also evaluated for their antimicrobial activity by the agar disc diffusion method and the determination of minimum inhibitory concentration (MIC) against six standard strains (Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Enterococcus hirae, Candida albicans, Candida tropicalis). All microbial strains employed (Gram-positive and Gram-negative bacteria and yeasts) showed a fairly similar degree of susceptibility to the essential oils under investigation, although no evident difference was observed in their sensitivity. Furthermore, a similar level of toxicity was observed for all oils examined, with MIC values of 31.25–125.00 µg/ml. Finally, the addition of the emulsifier Tween 80 to the oil or to the agar markedly decreases the antimicrobial activity of the essential oils against all microbial strains employed, thus suggesting that the antimicrobial activity of the essential oils is dependent on the physicochemical characteristics of their components and also on the microbial strains employed. Copyright © 2006 John Wiley & Sons, Ltd.
Article
Aroma extract from dried clove buds [Syzygium aromaticum (L.) Merr. et Perry] was obtained by using steam-distillation under mild conditions (55°C and 95 mm Hg). The antioxidant property of the aroma extract was evaluated in two different assays. The aroma extract isolated from clove buds inhibited the oxidation of hexanal for 30 days at a level of 50 μg/ml. Clove bud extract inhibited malonaldehyde formation from cod liver oil by 93% at the 160 μg/ml level. Twenty-two compounds were identified in the extracts of clove buds by gas chromatography and gas chromatography/mass spectrometry. The major aroma constituents of clove buds were eugenol (24.371 mg/g) and eugenyl acetate (2.354 mg/g). Eugenol, eugenyl acetate, and benzyl alcohol inhibited the oxidation of hexanal by 99, 99, and 82%, respectively, for a period of 30 days at 500 μg/ml. Eugenol, eugenyl acetate, and benzyl alcohol inhibited malonaldehyde formation from cod liver oil by 88, 79, and 63%, respectively, at 160 μg/ml. The antioxidant activity of clove bud extract and its major aroma components, eugenol and eugenyl acetate, were comparable to that of the natural antioxidant, α-tocopherol (vitamin E).
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BW 5147 (murine lymphoma cell line). We analyzed the effect of H2O2 in cell proliferation testing nitric oxide and apoptosis. Enzymes involved in the regulation of H2O2 levels as superoxide dismutase (SOD) and peroxidase (PER) were analyzed. H2O2 exerted a biphasic effect. The inhibitory effect of H2O2 was related to the activation of the ERK and P38 pathway, NO production and apoptosis. The high proliferation was associated with a low level of H2O2 related to a low SOD and a high PER activities. Drugs capable of producing an increase in H2O2 levels could be used in cancer.
Article
Tilia species are widely used in Europe as medicinal plants. The selective antiproliferative activity of a Tilia cordata flower dichloromethane extract (DME) on a lymphoma cell line has been reported previously and in order to extend this to other unstudied Tilia species, the effect of Tilia x viridis DME on the proliferation of tumor and normal murine lymphocytes was investigated. The bioguided fractionation of DME yielded a fraction rich in limonene (L), alpha-pinene and beta-pinene, which presented a selective antiproliferative action on tumor lymphocytes (EC(50) on tumor cells: 3.8 +/- 0.2 microg/mL; EC(50) on normal cells: 205 +/- 1.8 microg/mL). While all monoterpenes exhibited this activity, limonene proved to be the most active (EC(50) on tumor cells: 35 +/- 2.0 microg/mL; EC(50) on normal cells: 72 +/- 5.0 microg/mL) also exerting a stimulatory effect on non-mitogen stimulated lymphocytes proliferation (% of stimulation respect to control) (mean +/- SEM): L 10 microg/mL: 25 +/- 1.0%; 20 microg/mL: 38.5 +/- 2.5%; L 40 microg/mL: 41 +/- 0.9%; L 60 microg/mL: 58.5 +/- 3%. T. x viridis may thus constitute a potential source of monoterpenes with immunomodulatory activity.
Article
Daily s.c. injection of (-)deprenyl (2.0 mg/kg/day) for three weeks in young male rats caused a threefold increase in superoxide dismutase (SOD) activity in the striatum of the brain compared with the value in saline-injected control rats. Furthermore, the activity of catalase (but not of glutathione peroxidase) was also increased significantly by deprenyl treatment. The results confirmed the previous findings of Knoll on SOD activity and furthermore provided evidence that the activity of catalase is also significantly induced by the drug, which was not found in the previous study.
Article
The effects of D-limonene and citrus fruit oils, i.e. orange oil and lemon oil, on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced neoplasia of the lungs and forestomach of female A/J mice were investigated. D-Limonene and the citrus fruit oils given p.o. 1 h prior to NNK, also administered p.o., inhibited pulmonary adenoma formation and the occurrence of forestomach tumors. In an additional experiment, D-limonene given p.o. 1 h prior to NNK administered i.p. again showed pronounced inhibition of pulmonary adenoma formation. This study provides additional data demonstrating that non-nutrient constituents of the diet can inhibit carcinogen-induced neoplasia when administered at a short time interval prior to carcinogen challenge.
Article
Activated macrophages are known to release a variety of immunoregulatory substances including the low-molecular-weight substances hydrogen peroxide and lactate. We report here that lactate but not hydrogen peroxide is capable of supporting a substantial production of T-cell growth factor (TCGF) in cultures of accessory cell-depleted splenic T-cell populations after stimulation with concanavalin A. Hydrogen peroxide and its biosynthetic precursor superoxide anion (O2-) mediate, however, a strong augmentation of the TCGF production by accessory cell-depleted T-cell populations in the presence of lactate. Lactate inhibits the incorporation of [3H]thymidine in short-term cultures (18-26 hr) of accessory cell-depleted T cells. This confirms the rule that (optimal) production of T-cell growth factor requires a growth inhibitory signal. Concentrations of hydrogen peroxide which augment TCGF production most effectively (i.e., 1 X 10(-5) M) do not inhibit the incorporation of [3H]thymidine; and higher concentrations (3 X 10(-5)-1 X 10(-4) M) of hydrogen peroxide inhibit both the production of TCGF and the incorporation of [3H]thymidine. In agreement with the augmenting effect of hydrogen peroxide on TCGF production, it was observed that the proliferative response in mixed lymphocyte cultures is suppressed by catalase and augmented by 1 X 10(-5) M H2O2. Proliferative and cytotoxic responses in mixed lymphocyte cultures with an external source of interleukin 2 (IL-2) in contrast, are not augmented by 1 X 10(-5) M H2O2. The relatively high concentration of 1 X 10(-4) M hydrogen peroxide was found to inhibit the proliferative responses in mixed lymphocyte cultures with or without external IL-2 but not the cytotoxic response in the presence of IL-2. This indicates that CTL precursor cells may be relatively resistant against H2O2.
Article
d-Limonene was found to be effective in reducing the average number of rat mammary carcinomas that developed in 7,12-dimethylbenz[a]anthracene-treated rats when the terpene was fed during the initiation or during the promotion/progression stage of carcinogenesis. The time to the appearance of the first tumor was extended only when d-limonene was fed during the initiation stage. These effects could not be attributed to changes in mammary-relevant endocrine functions.
Article
The immunotoxicologic effects of d-limonene were determined. This naturally occurring substance is widely used in food flavorings and is a common additive in cosmetics. In the present study, BALB/c mice were treated with d-limonene for 9 wk. Effects on T- and B-cell responses were determined after 4 and 8 wk of treatment. Concanavalin-A responses at 8 wk, but not 4 wk, were suppressed in treated mice. A similar trend was observed for phytohemagglutinin and lipopolysaccharide responses. Evidence was presented that d-limonene had polyclonal activator action. Mice primed with keyhole limpet hemocyanin (KLH) prior to initiation of d-limonene treatment had suppressed primary and secondary anti-KLH responses. Mice treated with d-limonene prior to KLH priming produced significant increased antibody responses. Additional evidence for polyclonal stimulation was obtained by histopathologic examination of secondary lymphoreticular tissue. Significant secondary follicle development and prominent lymphoid nodules and aggregates were found in the pancreas and intestinal mucosa, particularly apparent in mice receiving the highest d-limonene dosage. A subchronic LD50 study was conducted wherein BALB/c mice received 16 daily doses of d-limonene. An LD50 of approximately 0.0850 mg d-limonene/kg (corrected for 82% purity) was determined.
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This article has no abstract.
Article
A new simple colorimetric assay for measurement of peroxidase activity using 3,3′-diaminobenzidine tetrahydrochloride as hydrogen donor is described. The DAB is stable under the usual assay conditions, and its rate of auto-oxidation is negligible. Under optimal conditions, a linear relationship is found between peroxidase concentration and the rate of oxidation of 3,3′-diaminobenzidine tetrahydrochloride (ΔA405nm/min). Using horseradish peroxidase, the DAB method appears more sensitive than the o-dianisidine and the guaiacol assays for peroxidase. This method can also be used for measurement of peroxidase activity in tissue fractions.
Article
Several dietary compounds have been demonstrated to reduce gastrointestinal cancer rates in both humans and animals. We showed that high human gastrointestinal tissue levels of glutathione S-transferase (GST), a family of detoxification enzymes consisting of class Alpha, Mu, Pi and Theta isoforms, were inversely correlated with cancer risk. We now investigated whether the sulforaphane analog compound 30, indole-3-carbinol, D-limonene or relafen, supplemented in the diet for two weeks at 1450, 250, 10,000, and 200 ppm, respectively, influenced (i) GST activity, (ii) GST isoenzyme levels, (iii) GSH levels, or (iv) glutathione peroxidase (GPx) activity in the gastrointestinal tract of male Wistar rats. Sulforaphane analog compound 30 enhanced GST activity in all organs studied (1.2-2.4 x). It induced GST Alpha levels in small intestine and liver, GST Mu levels in stomach and small intestine, GST Pi levels in stomach and small and large intestine, and GSH levels in stomach and proximal and middle small intestine. Indole-3-carbinol induced gastric GST Mu and hepatic GST Alpha levels. D-limonene induced hepatic GST Alpha, colonic GST Pi levels and proximal small intestinal GST enzyme activity and GST Pi levels. Relafen induced hepatic GST Alpha levels, distal small intestinal and gastric GST Pi levels, and oesophageal and proximal small intestinal GSH levels. GPx activity was enhanced by relafen in oesophagus, and in distal small intestine by sulforaphane analog compound 30. Enhancement of GSTs and to a lesser extent GPx and GSH, resulting in a more efficient detoxification, may explain at least in part the anticarcinogenic properties of sulforaphane analog compound 30, and to a much lesser extent of indole-3-carbinol and D-limonene.
Article
Several naturally occurring and synthetic food components reduce gastrointestinal cancer. Many of these compounds are scavengers of free radicals, formed during oxidative stress. Glutathione peroxidases (GPxs) protect against free radicals by catalysing their inactivation, thereby consuming glutathione (GSH). This might be one of the mechanisms leading to cancer prevention. We studied the effect of several dietary anticarcinogens on gastrointestinal GPx enzyme activities in male Wistar rats. Total as well as selenium-dependent and non-selenium-dependent GPx (t-GPx, Se-GPx and nSe-GPx) enzyme activities were determined in cytosolic fractions of oesophagus, gastric and colonic mucosa and liver. d-Limonene induced all three types of GPx activities in the oesophagus. d-Limonene and PEITC induced colonic t-GPX and nSe-GPx activity. beta-Carotene induced all three colonic GPx activities and hepatic t-GPx and Se-GPx activity. Coumarin and alpha-tocopherol induced gastric t-GPx and colonic nSe-GPx activity. Oltipraz enhanced oesophageal and gastric t-GPx and oesophageal, gastric and colonic Se-GPx. All other anticarcinogens induced one type of GPx activity at one site. In conclusion, the specific enhancement of GPx enzyme activities by dietary anticarcinogens might lead to a more efficient reduction of organic hydroperoxides and hydrogen peroxide and thus add to prevention of carcinogenesis in these organs.
Article
Antioxidant activities of volatile extracts isolated from thyme, basil, rosemary, chamomile, lavender, and cinnamon were evaluated by two independent assays: the aldehyde/carboxylic acid assay and the conjugated diene assay. The volatile extracts were prepared from dried herbs and spices using liquid-liquid continuous extraction following steam distillation under reduced pressure (55 degrees C and 95 mmHg). The antioxidant activities of the extracts decreased in the following order in both of the lipophilic assay systems: thyme > basil > rosemary > chamomile > lavender and cinnamon. Thyme and basil extracts inhibited the oxidation of hexanal for 40 days at the levels of 10 microg/mL and 50 microg/mL, respectively. The extracts of thyme and basil were effective in retarding methyl linoleate deterioration at 40 degrees C, with activity increasing with concentration in the range 10-200 microg/mL. At a concentration of 50 microg/mL, thyme extract was similar in antioxidant activity to BHT and alpha-tocopherol in the conjugated diene assay. The antioxidant potentials of the volatile extracts used in this study were accurately measured by the lipophilic systems, such as the aldehyde/carboxylic acid assay and the conjugated diene assay.
Article
We investigated the relationship between the absorptive pathway and the immune responses of the lung, particularly the phagocytic function of alveolar macrophages (Mphi) after oral administration of D-limonene in rats. D-Limonene was orally administered in oily solution with a stomach tube in thoracic duct-cannulated rats, and the lymphatic output of D-limonene was measured. D-Limonene levels reached a maximum in thoracic duct lymph and lung 3 h after its oral administration. It also significantly increased in bronchoalveolar lavage fluid (BALF) and alveolar Mphi, in which there was frequently a focal exudation of lipid droplets containing D-limonene into the alveolar cavity through alveolar capillary walls. Second, D-limonene orally given to rats (250, 500, 1,000 mg/kg/d) for 8 consecutive days resulted in a marked increase in both the number and the phagocytic activity of alveolar Mphi compared to the controls. BALF from rats dosed with D-limonene (1,000 mg/kg/d) enhanced the phagocytic activity of alveolar Mphi from control rats because the dose was prolonged. The activity of alveolar Mphi following in vitro incubation with D-limonene also increased in a dose-dependent manner. An oral administration of D-limonene enhanced the Con A-stimulated proliferation of splenocytes. These results suggest that D-limonene taken up from the thoracic duct lymph moves to the lung and directly activates the immune response of alveolar MO there, or indirectly activates it through activated lymphocytes.
Article
The immunomodulatory activity of some naturally occurring monoterpenes were studied in Balb/c mice. Administration of various monoterpenes such as carvone (100 micromoles/Kg body wt/dose/animal), limonene (100 micromoles/Kg body wt/dose/animal) and perillic acid (50 micromoles/Kg body wt/dose/animal) were found to increase the total white blood cells (WBC) count in Balb/c mice. The maximum total WBC count in carvone treated animals was observed on the 12th day (16,560 cells/cmm) while in limonene (13,783 cells/cmm) and perillic acid (14,437 cells/cmm) treated animals the maximum count was observed on the 9th day after the drug treatment. Administration of terpenoids increased the total antibody production, antibody producing cells in spleen, bone marrow cellularity and alpha-esterase positive cells significantly compared to the normal animals indicating its potentiating effect on the immune system.
Article
Since the discovery of catalase, it has been postulated that aerobic organisms generate enough oxidants to threaten their own fitness and, in particular, their genetic stability. An alternative is that these enzymes exist to defend the cell against more-abundant oxidants imposed by external sources. These hypotheses were tested directly through study of Hpx- (katG katE ahpCF) mutants of Escherichia coli, which lack enzymes to scavenge hydrogen peroxide (H2O2). These strains grew well in anaerobic medium but poorly when they were aerated. The Hpx- bacteria formed filaments and exhibited high rates of mutagenesis, both indicators of DNA damage. An additional recA mutation caused Hpx- cells to die rapidly upon aeration, even though the intracellular H2O2 was <1 microM. Spin-trap experiments detected substantial hydroxyl radicals, and cell-permeable iron chelators eliminated both the phenotypic defects and hydroxyl-radical formation, confirming that the Fenton reaction was responsible. An Hpx- oxyR strain exhibited even more DNA lesions than did the Hpx- mutant, indicating that the OxyR stress response induced protein(s) that suppressed DNA damage. One critical protein was Dps, an iron-sequestration protein, because Hpx- dps mutants exhibited sensitivity similar to that of the Hpx- oxyR mutant. These results reveal that aerobic E. coli generates sufficient H2O2 to create toxic levels of DNA damage. Scavenging enzymes and controls on free iron are required to avoid that fate. The rate constant of the Fenton reaction measured at physiological pH was much higher than under the acidic conditions that were used to determine the commonly cited value.
Article
The traditional view of intracellular oxidation - reduction, or redox, balance in epithelial cells, which is more than three decades old ( 1 ) , emphasizes a dynamic equilibrium between the produc- tion of reactive oxygen species (ROS; these include superoxide anion, O 2 − ; hydrogen peroxide, H 2 O 2 ; and chemical species with the characteristics of the hydroxyl radical, • OH) by a variety of fl avin dehydrogenases that occupy essentially every cellular compartment, and the detoxifi cation of these species by a broad range of antioxidant enzymes and related small molecules ( 2 ) . ROS are produced by the mitochondrial electron transport chain during the course of cellular respiration, by cytochrome P450 - related components of microsomes ( 3 ) , and, in many human tumors, by the recently described family of membrane-bound NADPH oxidases that possess a high degree of homology with components of the NADPH oxidase system of polymorpho nuclear leukocytes and macrophages ( 4 ) . ROS are detoxifi ed by a com- plex and interactive series of proteins and small molecules — including members of the superoxide dismutase, glutathione peroxidase, and peroxiredoxin gene families, as well as catalase — that ultimately reduce O 2 − and H 2 O 2 (or lipid peroxides) to non-
Article
Plant antioxidants are composed of a broad variety of different substances like ascorbic acid and tocopherols, polyphenolic compounds, or terpenoids. They perform several important functions in plants and humans (e.g., carotenoids function as accessory pigments for light harvesting and provide photoprotection and pigmentation in plants). Monoterpenes and diterpenes, which are the main components of essential oils, act as allelopathic agents, attractants in plant-plant or plant-pathogen/herbivore interactions or repellants. For humans, carotenoids play an important role for health, carotenoids with provitamin A activity are important for vision; other carotenoids influence the human immune function and gap-junctional communication (GJC). Additionally, their antioxidative capacity is believed to be responsible for the health promoting properties of fruits and vegetables. Three main ways of antioxidant action of carotenoids have been detected until now (i.e., quenching of singlet oxygen, hydrogen transfer, or electron transfer). These mechanisms and investigation of antioxidant activity in vitro are discussed in detail. The monoterpenes limonene and perillyl alcohol may be promising substances in cancer therapy. Several investigations have studied the antioxidant activity of monoterpenes and diterpenes or essential oils in vitro. Results as well as the action of a newly discovered, very effective antioxidant (i.e., gamma-terpinene) are discussed. An important point when assessing the antioxidant activity of plant antioxidants is to consider their interaction with other antioxidants. Especially combinations of hydrophilic and lipophilic antioxidants may exert synergistic effects, as has been shown for rutin in combination with gamma-terpinene, lutein, or lycopene.
Article
Some coumarins possess enhancing effects on lymphocyte mitogen responsiveness. In this investigation, the activity of scopoletin, a coumarin that has been isolated from different plants and in this case specifically from T. cordata Mill., was evaluated. For this purpose, normal T lymphocytes and a hyperproliferative T lymphoma cell line were used. Scopoletin was found to exert a dual action on tumoral lymphocytes exhibiting both a cytostatic and a cytotoxic effect. These effects varied with the concentrations analysed and the time of cell incubation (EC(50): 251+/-15 microg/ml) and were associated to the induction of apoptosis. Scopoletin induced cell proliferation on normal T lymphocytes (Proliferation stimulation index: 1 microg/ml scopoletin: 1.26+/-0.1; 10 microg/ml scopoletin: 3+/-0.25; 100 microg/ml scopoletin: 1.86+/-0.08); this stimulatory action was found to be due to the interaction with kinase C (PKC) protein. These results indicate that scopoletin could be a potential antitumoral compound to be used for cancer treatment.