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D-limonene induces apoptosis of gastric cancer cells
Abstract
To investigate the apoptosis effect induced by D-limonene on BGC-823 gastric cancer cells.
The expression of p53, bc1-2 in BGC-823 cells and qualitative, quantitative index of cell apoptosis were detected with MTT, electron microscopy, flow cytometry and immunohistochemical method.
D-limonene could induce the formation of apoptotic bodies in a dose- and time-dependent manner. The expression of bcl-2 protein decreased and p53 protein increased in BGC-823 cells treated with D-limonene, compared with the control cells.
D-limonene exerts its cytotoxic effect on BGC-823 gastric cancer cells by inducing apoptosis.
... In mitochondria, Bcl-2 and Bcl-xL are anti-apoptotic members and Bax and Bak have been identified as pro-apoptotic members (Jeong & Seol, 2008). In all apoptotic analyzes, LIM was able to increase Bax protein expression, cytochrome c release from mitochondria to cytosol, and decrease Bcl-2 protein expression, confirming its pro-apoptotic activity (Chaudhary et al., 2012;Jia et al., 2013;Lu et al., 2003;Yang et al., 2008;Ye et al., 2020;Yu et al., 2018;Zhang et al., 2014). LIM also induced a remarkable loss of ΔΨm, as revealed by the reduction of Rh 123 FI (Zhang et al., 2014) reaffirming its mitochondrial apoptotic potential against cancer. ...
... To increase the apoptotic signal and intensify the mitochondrial pathway of death, LIM has been shown to inactivate the overexpression of oncogenes such as c-jun and c-myc (Giri et al., 1999), inhibit the YY1 protein (Parija & Das, 2003), and increase the expression of the p53 protein (Lu et al., 2003). The expression of the c-myc protein when deregulated leads to a consolidation of oncogenesis and is considered a milestone for most human cancers (Stefan & Bister, 2017). ...
Limonene (LIM) is a monoterpene, which is abundant in essential oils of Citrus fruits peels (Rutaceae). More recently, LIM, as a potential natural anticancer compound, has attracted major attention and exerted a chemopreventive activity, stimulating the detoxification of carcinogenic compounds and limiting tumor growth and angiogenesis in various cancer models. Twenty‐six (26) articles were selected based on previously established criteria. Anticancer activity of LIM was related to the inhibition of tumor initiation, growth, and angiogenesis and the induction of cancer cells apoptosis. LIM was able to increase Bax expression, release cytochrome c, and activate the caspase pathway. In addition, LIM increased the expression of p53 and decreased the activity of Ras/Raf/MEK/ERK and PI3K/Akt pathways. LIM also decreased the expression of VEGF and increased the activities of the Man‐6‐P / IGF2R and TGF‐βIIR receptors. These results highlight LIM as an abundant natural molecule with low toxicity and pleiotropic pharmacological activity in cancer cells, targeting various cell‐signaling pathways critically involved in the initiation, growth, and chemoresistance of cancer cells.
... Yu et al. found that D-limonene inhibits the proliferation of lung cancer cells and through induction of autophagy increases apoptosis of lung cancer cells (13). Previously, Lu et al. confirmed the effect of D-limonene on induction of apoptosis in BGC-823 gastric cancer cells (14). D-Limonene is also effective in primary chemotherapy for hepatocellular carcinoma (15). ...
... Many researchers have demonstrated that D-limonene possess anticancer activity (14,31). However, low solubility of D-limonene in biological fluids is a crucial problem and has limited its application in cancer treatment. ...
The low solubility of the plant-extracted agent like D-limonene in cancer therapy is a critical problem. In this study, we prepared D-limonene-loaded niosomes (D-limonene/Nio) for cancer therapy through in vitro cytotoxicity assay of HepG2, MCF-7, and A549 cell lines. The niosomal formulation was prepared by film hydration technique with Span® 40: Tween® 40: cholesterol (35:35:30 molar ratio) and characterized for vesicle distribution size, morphology, entrapment efficiency (EE %), and in vitro release behaviour. The obtained niosomes showed a nanometric size and spherical morphology with EE% about 87 ± 1.8%. Remarkably prolonged release of D-limonene from niosomes compared to free D-limonene observed. The loaded formulation showed significantly enhanced cytotoxic activity with all three cancer cell lines (HepG2, Macf-7 and A549) at the concentration of 20 µM. These results indicated that niosome loaded with phytochemicals can be a promising nano-carrier for cancer therapy applications.
... Moreover, it inhibited the growth of mouse H22 and S180 tumor and the formation of new blood vessels in tumor tissues in vivo [65]. d-limonene is a known anticarcinogenic compound that it was proved to have antitumor activity [66][67][68][69][70]. In recent studies, d-limonene showed able to inhibit the growth of human gastric cancer cell in vitro through a mechanism of inducing the apoptosis of tumor cells [70]. ...
... d-limonene is a known anticarcinogenic compound that it was proved to have antitumor activity [66][67][68][69][70]. In recent studies, d-limonene showed able to inhibit the growth of human gastric cancer cell in vitro through a mechanism of inducing the apoptosis of tumor cells [70]. ...
Essential oils are odoriferous substances traditionally used in the perfumery, food, and pharmaceutical industries. The most volatile fraction (constituting 90–95 % of total oil) comprises, in most cases, complex mixtures that may contain hundreds of compounds, which are composed mainly of terpenoids. Each of these constituents contributes for the biological effects of these essential oils. In this chapter, a total of 20 essential oil constituents, which presented positive results on cytotoxic drug screening, were selected; among them, ascaridole, α-bisabolol, (E)-caryophyllene, β-elemene, β-eudesmol, d-limonene, terpinen-4-ol, and thymol have been extensively studied with promissory results. Herein, we highlighted the recent advances in the knowledge of the chemical and anticancer properties of these compounds, establishing new goals for future research.
... Te treatment with the extract of Heliopsis longipes SF Blake (Asteraceae), in which spilanthol is also the major phytochemical, inhibited breast cancer angiogenesis and could increase p53 levels, the latter related to apoptosis, resulting in a reduction in the tumor's size [43]. Another study investigated the efect of D-limonene on BGC-823 gastric cancer cells, using p53 expression, showing also an apoptotic cytotoxic efect [44]. Te modulation of p53 by scopoletin is related to the induction of autophagy, showing the afnity of these compounds with TP53 expression enhancers [45]. ...
Acmella oleracea (L.) R. K. Jansen, popularly known as jambu in Northern Brazil, is widely used in folk medicine and local cuisine. Its consumption in different ways reinforces the need for safety assessments. In this study, the major compounds found in the hydroethanolic extract of A. oleracea flowers (EHFAO) were characterized by ultra-performance liquid mass spectrometry (UHPLC-ESI-QTOF-MS/MS). The effects of oral administration of 100/mg/kg of EHFAO extract over 60 days in male spontaneously hypertensive (SHR) and Wistar (WR) rats and the in silico ADME/Tox predictions, lipophilicity, and water solubility were accomplished for the compounds identified. Spilanthol was detected as the foremost major compound at a concentration of 97.7%, followed by 1.53% scopoletin and 0.77% d-limonene. The treatment with EHFAO did not alter the animals´ weight over the studied period. Moderate alterations were observed solely in the hepatic enzymes AST (WR = 97 UI/L and SHR = 150 UI/L ∗p<0.05) and ALT (WR = 55 UI/L and SHR = 95 UI/L ∗p<0.05), while no relevant histopathological alterations were found. The in-silico study confirmed the in vivo findings, as the identified compounds were considered highly bioactive orally, due to their drug similarity profiles, adequate lipid solubility, bioavailability, and pharmacokinetics. Therefore, the chronic treatment with EHFAO was found safe at the concentration of 100/mg/kg, with no interference in the blood pressure levels neither appreciable toxic effects.
... In addition, limonene is used in the cosmetic area for aromatic property, in dermatology for percutaneous transfer of drugs, and in food as sweetening (Bacanlı et al., 2018). Many previous studies reported that it has anti-inflammatory and antioxidant features and treatment of many types of cancer such as lung, gastric, hepatocellular carcinoma (Guyton & Kensler, 2002;Lu et al., 2003;Yu et al., 2018;Hajizadeh et al., 2019;Souto et al., 2020). However, low solubility of limonene is a major problem in biological fluids and leads to limited treatment options in cancer therapy (Murali et al., 2013;Hajizadeh et al., 2019). ...
Copolymerization is a very important method in the synthesis of products having the physical and chemical properties sought in industrial sense. In this paper, the copolymerization of N-(4-nitrophenyl) acrylamide monomer with D-limonene was carried out and LIM-co-NPA copolymer was synthesized by free radical chain polymerization reaction. The structure of sustainable copolymer of limonene was chemically characterized by FT-IR, 1H-NMR spectroscopic techniques. In addition, thermal stability of copolymer investigated by TGA/DTG/DTA simultaneous thermal analysis methods. The spectroscopic results are compatible with the amide or limonene polymers synthesized in the literature. From the important thermal results of the sustainable copolymer, it has been found that the initial decomposition temperature is 226°C, and the maximum decomposition temperatures is 329°C, glass transition temperature at 261°C and crystallization temperature at 340°C. It can be said that this promising sustainable copolymer is suitable for other mechanical, physical and biological study and research fields.
... D-limonene was regarded as a major functional constituent in T A B L E 3 Antimicrobial activity of essential oil obtained from peel powder and fresh peel with and without albedo of Citrus jambhiri using HD and USHD essential oils, which suppresses the mitochondrial death pathway and PI3K/Akt pathway that results in apoptosis of human colon cancer cells (Jia et al., 2013). This component has also repressed the escalation of gastric and lung cancer cells (Lu, Feng, Zhan, & Yu, 2003;Yu et al., 2018). From Table 4, the essential oils from USHD were examined to have a higher amount of oxygenated monoterpenes due to the synergistic effect of ultrasound and HD. ...
Citrus jambhiri processing generates 40% peel waste with considerable waste man-
agement constraints. Interestingly, these peels are a rich source of essential oil.
Hence, in this study, the essential oil was extracted from fresh peels and peel
powder (PP) of C. jambhiri using hydrodistillation (HD) and ultrasound-assisted
hydrodistillation (USHD). Kinetic study, physicochemical, antimicrobial, and chemical
composition of the essential oil obtained from PP and fresh peel with albedo (FPA)
and without albedo (FPWA) using HD and USHD was studied. The kinetic study was
further experimentally validated using the first and second-order kinetic model. The
integrated equations were used to test the fitting of the model with obtained experi-
mental data. Kinetics of oil extraction from PP using USHD showed that extraction
process best fitted in second-order kinetic model with a high coefficient of determi-
nation (R2 = .999), yield (3.63%) and extraction rate constant (K2 = 0.0306), showing
that it validated the process thoroughly. The physicochemical properties of essential
oils obtained from both extraction methods fall within an acceptable range. Specific
gravity, acid value, and total phenolic content showed no significant difference
between both extraction methods while others differed significantly. The antioxidant
and antimicrobial activity increased with ultrasound treatment. GC–MS analysis of
different oil samples revealed that 10 compounds extracted from each extraction
with the highest amount of D-limonene (61.29%) were obtained from PP using
USHD. USHD stands as a fast, efficient, and economical method for extracting essen-
tial oil and can be a potential source for nutraceutical and pharmaceutical industries.
... It has been shown that derivatives of limonene, such as perillyl alcohol and perillyl aldehyde, inhibit proliferation and migration of breast cancer cells [7] and cause cell cycle arrest in G1 and apoptosis of human carcinoma cell lines [8]. D-limonene is also capable of inducing apoptosis in gastric cancer cells [9]. The anticancer activities of limonene, the major components of the oil, were evaluated against A-549 and DLD-1 cell lines. ...
Leaf volatile components of Bursera simaruba (L.) Sarg., a native tree from tropical America used in traditional medicine, were extracted by hydrodistillation. The essential oil was analyzed by GC-MS. We have identified 38 compounds in this oil, of which limonene (46.7%), β-caryophyllene (14.7%), α-humulene (13.2%) and germacrene D (7.6%) are the major components. The anticancer activity of the essential oil was tested on human lung carcinoma cell line A-549 and human colon adenocarcinoma cell line, DLD-1. B. simaruba leaf essential oil was found to be active against both tumor cell lines, with a GI50 of 42 ± 2 μg/mL for A-549 and 48 ± 2 μg/mL for DLD-1. The evaluation of the cytotoxic properties of the major constituents of the oil indicates that α-humulene is possibly responsible for this activity.
... It has been reported in the literature that derivatives of limonene, such as perillyl alcohol and perillyl aldehyde, inhibit proliferation and migration of breast cancer cells [4] and cause cell cycle arrest in G1 and apoptosis of human carcinoma cell lines [5]. D-limonene is also capable of inducing apoptosis in gastric cancer cells [6]. Terpinen-4-ol can induce caspase-dependent apoptosis in human melanoma cells [7], and has been shown to cause differentiation of human myelocytic cell line HL-60 [8]. ...
The essential oil of Hedyosmum arborescens Sw. (Chloranthaceae), a native plant of the Caribbean archipelago, was extracted by hydrodistillation. The chemical composition of the volatile fraction was determined by GC and GC-MS analyses and 50 components were identified. The major components are α-phellandrene (11.4%), bicyclogermacrene (10.6%) and sabinene (9.7%). The anticancer activities of these extracts were assessed against human lung carcinoma cell line A-549 and human colon adenocarcinoma cell line DLD-1. The leaf essential oil of H. arborescens was found to be moderately active against both cancer cell lines with GI50 values of 158 ± 7 μg/mL for A-549 and 178 ± 9 μg/mL for DLD-1.
... henonis were the monoterpene compound (62.96%, 63.44% and 71.36%, respectively), followed by sesquiterpene compounds (31.52%, 33.13% and 23.58%, respectively). Limonene and (+)-epi-bicyclosesquiphellandrene were the main constituents in the all species.Lu et al. (2003) reported that limonene showed antiangiogenic and proapoptotic effects on human gastric cancer implanted in nude mice, thus inhibiting tumor growth and metastasis.Misra et al. (2013) reported that (+)-epi-bicyclosesquiphellandrene showed antimicrobial and anticancer activities.Kim et al. (2004) reported that the tea tree (Melaleuca alter ...
Natural plant extract has been the subject of intense research aiming in elucidating the underlying mechanisms of their chemoprevenlive effects upon various forms of human cancers. The objective of our study was to evaluate the natural antioxidants and anticancer agent potential of Phyllostachys. The chemical composition of steam extract from Phyllostachys was carried out using GC-MS. The steam extract of Phyllostachys was dominated by monoterpenes (62.96% - 71.36%) and sesquiterpenes (23.58% - 33.13%) as the main compounds. The antioxidant activities of the steam extract was determined using a DPPH scavenging and hydrogen peroxide scavenging activity test systems. Furthermore, the amounts of total phenolics in steam extract were determined spectrometrically The steam extract of P. pubescens and P. bambusoides were presented the high activity (69.4% and 64.0%. respectively.). The steam extract from Pyllostachys species showed a hydrogen peroxide scavenging activity of approximately 50.4% - 54.6% when compared to that of the standard gallic acid. The anticancer activities of steam extract were determined using a MTT assay. Assessment of the cytotoxic effect of the steam extract on PC-3 cells showed that the P. bambusoides (20.85%) and P. pubescens (20.41%) were superior in induced cytotoxicity compared with the steam extract of P nigra var. henonis (1.15%). Findings from this study indicated that steam extract of P. bambusoides and P. pubescens possessed potential as medicinal drug especially in prostate cancer treatment.
... In addition, D-limonene augments the antineoplastic effects of other chemotherapeutic agents such as 5-fluorouracil. 5 It is obvious from the above examples that D-limonene has significant proapoptotic and antiangiogenesis effects. Further research is needed to fully harness its antineoplastic effects. ...
... Areche et al. [36] showed that spathulenol was cytotoxic to gastric adenocarcinoma cells (AGS). Limonene inhibits the growth of human gastric cancer cells through a mechanism of inducing their apoptosis [37]. In addition, limonene showed anti-metastatic and anti-angiogenic effects in animal models [38]. ...
Xylopia laevigata, popularly known as "meiú" and "pindaíba", is a medicinal plant used in the folk medicine of the Brazilian Northeast for several purposes. The chemical constituents of the essential oil from leaves of X. laevigata, collected from wild plants growing at three different sites of the remaining Atlantic forest in Sergipe State (Brazilian Northeast), were analyzed by GC/FID and GC/MS. The effect of the essential oil samples was assessed on tumor cells in culture, as well on tumor growth in vivo. All samples of the essential oil were dominated by sesquiterpene constituents. A total of 44 compounds were identified and quantified. Although some small differences were observed in the chemical composition, the presence of γ-muurolene (0.60-17.99 %), δ-cadinene (1.15-13.45 %), germacrene B (3.22-7.31 %), α-copaene (3.33-5.98 %), germacrene D (9.09-60.44 %), bicyclogermacrene (7.00-14.63 %), and (E)-caryophyllene (5.43-7.98 %) were verified as major constituents in all samples of the essential oil. In the in vitro cytotoxic study, the essential oil displayed cytotoxicity to all tumor cell lines tested, with the different samples displaying a similar profile; however, they were not hemolytic or genotoxic. In the in vivo antitumor study, tumor growth inhibition rates were 37.3-42.5 %. The treatment with the essential oil did not significantly affect body weight, macroscopy of the organs, or blood leukocyte counts. In conclusion, the essential oil from the leaves of X. laevigata is chemically characterized by the presence of γ-muurolene, δ-cadinene, germacrene B, α-copaene, germacrene D, bicyclogermacrene, and (E)-caryophyllene as major constituents and possesses significant in vitro and in vivo anticancer potential.
... duced cancers (Elson et al., 1988; Maltzman et al., 1989). Dietary limonene also inhibits the development of ras oncogene-induced mammary carcinomas in rats. There are many reports that the development of azoxymethane-induced aberrant crypt foci in the colon of rats was significantly reduced when they were given 0.5% limonene in the drinking water. Lu et al. (2003) demonstrated that d-limonene can inhibit the growth of human gastric cancer cells in vitro through a mechanism of inducing the apoptosis of tumor cells. Therefore, d-limonene has been applied to precaution and treatment in chemical-induced animal model, such as colon cancer, breast cancer, gastric cancer, pancreatic cancer, and hepatic ...
Cancer is a major public health problem in India and many other parts of the world. Its two main characteristics are uncontrolled cell growth and metastasis. Natural products represent a rich source of compounds that have found many applications in various fields of medicines and therapy including cancer therapy. Effective ingredients in several plant-derived medicinal extracts are terpenoid compounds and many terpenes have biological activities and are used for the treatment of human diseases.
This review attempted to collect all available published scientific literature of eight naturally occurring terpenoids and their effect on inhibition of tumor progression.
The present review is about eight potent naturally occurring terpenoids that have been studied for their pharmacological properties in our lab and this review includes 130 references compiled from all major databases.
Literature survey revealed that triterpenoids, such as glycyrrhizic acid, ursolic acid, oleanolic acid, and nomilin, the diterpene andrographolide, and the monoterpenoids like limonene and perillic acid had shown immunomodulatory and antitumor activities. All of them could induce apoptosis in various cancer cells by activating various proapoptotic signaling cascades. Many of these terpenoids found to inhibit metastatic progression and tumor-induced angiogenesis. The molecular mechanisms that involved in these activities include inhibition of various oncogenic and anti-apoptotic signaling pathways and suppression or nuclear translocation of various transcription factors including nuclear factor kappa B (NF-κB).
The chemopreventive and chemoprotective effects of these compounds point toward their possible role in modern anticancer therapies.
... Chinese herbs can not only relieve clinical symptoms of GPL [11][12][13] , but also regulate the expression of related oncogenes to some extent in GPL [14][15][16][17] . Bcl-2 is one of the oncogenes and has a close correlation with apoptosis, its abnormal expression is usually observed during the development of GPL [18][19][20][21][22][23][24][25] . Although overexpression of bcl-2 oncogene is found in GPL, it is different in same tissues of different sufferers and the regulating effect of Chinese herbs is different too. ...
To observe the protein and mRNA expression of bcl-2 oncogene in gastric precancerous lesions (GPL) and to analyze its correlation with syndromes in traditional Chinese medicine (TCM).
Sixty-seven patients with GPL confirmed by gastroscopy and pathology were studied, including 39 cases of moderate gastric mucosal dysplasia, 19 cases of severe gastric mucosa dysplasia, 9 cases of incomplete colon metaplasia. In syndrome differentiation of TCM, 17 cases belonged to the syndrome of qi and yin deficiency of the spleen and stomach complicated by qi stagnation, 21 cases belonged to the syndrome of qi and yin deficiency of the spleen and stomach complicated by stomach heat, 29 cases belonged to the syndrome of qi and yin deficiency of the spleen and stomach complicated by blood stasis. Protein and mRNA expression of bcl-2 oncogene were detected by labeled streptavidin biotin (LSAB) immunohistochemistry and in situ hybridization respectively.
Abnormal expression of protein and mRNA on bcl-2 oncogene was found in GPL, which increased gradually with the course of lesions. In moderate and severe gastric mucosal dysplasia and incomplete colon metaplasia, there was no difference in the expression of bcl-2 oncogene (P>0.05). In different accompanying syndromes, the expression of protein and mRNA on bcl-2 oncogene increased gradually in the following order: deficiency of both qi and yin of the spleen and stomach accompanying qi stagnation-->stomach heat-->blood stasis. In GPL, compared with accompanying blood stasis, there was an obvious difference in the expression of bcl-2 oncogene between the syndrome of qi and yin deficiency of the spleen and stomach and accompanying stomach heat, so did accompanying qi stagnation (the level of protein: chi(2) = 8.45, P<0.05; the level of mRNA: chi(2) = 7.35, P<0.05).
Apoptosis-associated bcl-2 oncogene is abnormally expressed in GPL, which correlates with different accompanying syndromes in TCM.
... d-Limonene showed antiangiogenic and proapoptotic effects on human gastric cancer implanted in nude mice, thus inhibiting tumor growth and metastasis (Guang et al., 2004). d-Limonene can also induce the formation of apoptotic bodies on BGC-823 gastric cancer cells in a dose-and time-dependent manner (Guang et al., 2003) and its efficacy was increased by combining it with cytotoxic agents such as 5-fluorouracil. Administration of chow pellets containing 1% or 2% d-limonene to male Sprague-Dawley rats resulted in significant reductions in chemically induced, hepatocellular carcinomas (Kaji et al., 2001). ...
Essential oils and their volatile constituents are used widely to prevent and treat human disease. The possible role and mode of action of these natural products is discussed with regard to the prevention and treatment of cancer, cardiovascular diseases including atherosclerosis and thrombosis, as well as their bioactivity as antibacterial, antiviral, antioxidants and antidiabetic agents. Their application as natural skin penetration enhancers for transdermal drug delivery and the therapeutic properties of essential oils in aroma and massage therapy will also be outlined.
Species of the genus Citrus are cultivated in many regions of China and are widely used for medicinal purposes. In the present study, essential oils (EOs) were extracted from four different Citrus species using steam distillation. The chemical components of these four essential oils were separated using gas chromatography‐mass spectrometry, and 56 compounds were confirmed. D‐limonene was found to be the most abundant compound. All four essential oils demonstrated varied but remarkable radical scavenging capacity (IC50; 0.77–13.9%). Citrus paradisi essential oil exhibited excellent antioxidant activity. Compared to ibuprofen, topical application of the four Citrus spp. essential oils significantly inhibited ear edema formation in mice. Furthermore, essential oils from the four Citrus species reduced the expression levels of interleukin‐6 (IL‐6), cyclooxygenase‐2 (COX‐2) and nuclear transcription factor kappa B p65 (NF‐κB) to different degrees. The cytotoxicity of the four essential oils on BV2 microglial cells was determined using the MTT assay (IC50; 321.37–1558.87 μg/mL), wherein Citrus limon essential oil showed the lowest cytotoxicity. The essential oils of Citrus limon, Citrus reticulata, and Citrus paradisi had an inhibitory effect on the lung cancer cell line H1299 by inducing a G0/G1 cell cycle arrest. Cluster and principal component analyses were used to determine the relationship among the Citrus species. These results suggest that the four Citrus essential oils have potential for use as active ingredients in functional foods or cosmeceutical products.
In this study, inhibitory effect of limonene on Staphylococcus aureus (S. aureus) and its antibacterial mechanism was explored, respectively. The results showed that limonene effectively inhibited bacterial growth at a minimum inhibitory concentration (MIC) of 20 ml/L. Scanning electron microscopy (SEM), the reduction of AKP activity and fluorescence microscope observation confirmed that limonene caused the destruction of the cell morphology and cell wall integrity of S. aureus. The reduction of MFI in fluorescein diacetate staining experiment and leakage of biological macromolecules (nucleic acids and proteins) indicated that limonene damaged the cell membrane and increased membrane permeability. Besides, the reduction of membrane potential (MP) further confirmed that the damage to membrane and the reduction of respiratory metabolic activity. Furthermore, the respiratory depression test confirmed that the pathway of limonene affecting the respiratory metabolism of S. aureus is TCA pathway, followed by EMP. In addition, the disorder of succinate dehydrogenase (SDH), malate dehydrogenase (MDH), pyruvate kinase (PK), ATPase (T-ATPase, Na⁺-K⁺-ATPase, Ca²⁺-Mg²⁺-ATPase), and ATP concentration demonstrated that limonene could result in a slowdown of metabolism and metabolic dysfunction, thus inhibiting ATP synthesis.
In this study, ultrasound-assisted hydro-distillation (UAHD) extraction of essential oil (EO) from Iberis amara seeds was optimized using response surface methodology (RSM). The maximum recovery of EO was 0.42 ± 0.05% (v/w) using the optimal extraction parameters (extraction time of 240 min, ultrasonic power of 75 W and solvent-to-sample ratio of 6.7 mL/g). UAHD showed a significantly higher amount of EO compared to the traditional methods hydro-distillation (HD) (0.26 ± 0.07% (v/w)) and steam distillation (SD) (0.19 ± 0.04% (v/w)) (P < 0.05). Scanning electron microscope (SEM) images revealed that the seeds were crushed into tiny particles after UAHD, which is believed to facilitate secretion of EO. Subsequently, 28 kinds of compounds were identified by GC–MS for the EOs extracted by UAHD, HD and SD and with similar quantitative characters. The principal constituents were 4-Carvomenthenol (18.75 − 22.13%), Menthone (10.95 − 12.36%), Neodihydrocarveol (9.78 − 11.38%) and α-Curcumene (9.37 − 10.81%). Further study on bioactivity of EO samples was carried out. The oils obtained with the three techniques exerted slightly different but good antioxidant and anti-inflammatory effects, cytotoxicity on human colon cancer cells, as well as antibacterial and anti-feedant effects against Pieris rapae larvea. In conclusion, this study suggests that UAHD is an excellent technology for EO extraction and may have industrial applications. In addition, Iberis amara seed extracts can become more available as a natural resource for food and pharmaceutical industries.
The chemical composition of ethanolic extracts of Zingiber officinale rhizome and Moringa oleifera seeds was examined
and their individual and combined toxicity assayed against some aspects of the developmental biology of Callosobruchus chinensis.
GC-MS revealed forty-one (41) chemical components in ethanolic extract of Z. officinale rhizome and thirteen (13) chemical
components in ethanolic extract of M. oleifera seed. 1-(4-Hydroxy-3-methoxyphenyl)-dec-en-3-one (12.40%) and
1-(4-Hydroxy-3-methoxyphenyl) tetradec-4-en-3-one (9.05%) were the most abundant components ethanolic extract of Z. officinale
accounting for about 22% of the total oil. Hexadecanoic acid, ethyl ester (22.33%) and 11-Octadecenoic acid, methyl ester (18.09%)
were the most abundant components in M. oleifera accounting for about 40% of the total oil. Z. officinale oil was more toxic to C.
chinensis than M. oleifera oil (LC50: Z. officinale = 24.00 µl; M. oleifera = 38.00 µl). By contrast, the median lethal time (LT50)
required to kill 50% of C. chinenesis by extract mixture (Z. offcinale and M. oleifera) (36.36 h) was significantly lower (p < 0.05)
than those gotten at singular exposure of Z. officinale (64.61 h) and M. oleifera (76.44 h). Thus, the results exemplify the individual
applicability of ethanolic extracts of Zingiber officinale and Moringa oleifera as C. chinensis biocide. When combined, the results
confirm the synergistic potentials of the oils. This knowledge may facilitate the discovery of components that are essential in the
design of an effective cum sustainable biopesticide with multiple modes of actions.
The aim of this study is to elucidate the anti-inflammatory activities of chopi (Zanthoxylum piperitum A.P. DC.) essential oil. Essential oil (EO) of chopi was extracted by steam distillation method, and its major constituents were limonene and geranyl acetate. Chopi-EO decreased approximately 38% of nitrite production, as compared to the lipopolysaccharde (LPS)-induced nitrite production. However, chopi-EO and its components did not quench nitric oxide (NO) chemically in cellfree system, and markedly inhibited approximately 40.4% of inducible nitric oxide synthase (iNOS) mRNA transcription. In addition, the inhibition of E-selectin gene transcription by chopi-EO caused the suppression of cellular adhesion. These results suggest that chopi-EO may exert potential anti-immunological inflammatory activity.
The second edition of this book is virtually a new book. It is the only comprehensive text on the safety of essential oils, the first review of essential oil/drug interactions, and it provides detailed essential oil constituent data not found in any other text. Much of the existing text has been re-written, and 80% of the text is completely new. There are 400 comprehensive essential oil profiles and almost 4000 references. There are new chapters on the respiratory system, the cardiovascular system, the urinary system, the digestive system and the nervous system. For each essential oil there is a full breakdown of constituents, and a clear categorization of hazards and risks, with recommended maximum doses and concentrations. There are also 206 Constituent Profiles. There is considerable discussion of carcinogens, the human relevance of some of the animal data, the validity of treating an essential oil as if it was a single chemical, and the arbitrary nature of uncertainty factors. There is a critique of current regulations.
To investigate the effects and mechanism of d-limonene on the growth and metastasis of gastric cancer in vivo.
Metastatic model simulating human gastric cancer was established by orthotopic implantation of histologically intact human tumor tissue into gastric wall of nude mice. One percent d-limonene was orally administered at dose of 15 ml/kg every other day for seven weeks. Eight weeks after implantation, tumor weight, inhibition rate, apoptotic index (AI), microvessel density (MVD), vascular endothelial growth factor (VEGF), variation of ultrastructure, and the presence of metastasis were evaluated, respectively, after the mice were sacrificed.
The tumor weight was significantly reduced in 5-FU group (2.55+/-0.28 g), d-limonene group (1.49+/-0.09 g) and combined treatment group (1.48+/-0.21 g) compared with the control group(2.73+/-0.23 g, P<0.05). In 5-FU group, d-limonene group, combined treatment group, the inhibition rates were 2.60%,47.58% and 46.84% and 0, respectively; AI was (3.31+/-0.33)%, (8.26+/-1.21)%, (20.99+/-1.84)% and (19.34+/-2.19)%, respectively; MVD was (8.64+/-2.81), (16.77+/-1.39), (5.32+/-4.26) and (5.86+/-2.27), respectively; VEGF expression was (45.77+/-4.79), (41.34+/-5.41), (29.71+/-8.92) and (28.24+/-8.55), respectively. The incidences of peritoneal metastasis also decreased significantly in 5-FU group(77.8%), d-limonene group (20.0%) and combined group (22.2%) compared with control group (100%) versus 62.5%,30% and 22.2%) (P<0.05). Liver metastasis was also inhibited and the incidences decreased significantly in 5-FU group, d-limonene group and combined group than that in control group (87.5% vs 55.5%, 20.0% and 22.2% respectively)(P<0.05). The incidence of ascites in control group, 5-FU group, d-limonene group and combined group was 25.0%, 22.2%, 0, 0, respectively and 12.5%, 11.1% 0, 0, with respect to the metastasis rate to other organs.
d-limonene has antiangiogenic and proapoptotic effects on gastric cancer, thereby inhibits tumor growth and metastasis. Combination of d-limonene with cytotoxic agents may be more effective.
Bcl-2 is an anti-apoptotic protein. If the level of Bcl-2 protein can be reduced sufficiently in tumors using RNA interference (RNAi) to target the gene message, the apoptosis of tumor cells may be promoted. In this study, we synthesized 19 nucleotides (nts) small interference RNA (siRNA) constructs suppressing bcl-2 gene expression in human tumor cells (HeLaB2 and BGC-823 cell lines) in vitro. The bcl-2 gene expression levels were significantly reduced when these siRNA were transfected into experimental two tumor cells for 72 hours. The apoptosis process was also examined in the tumor cells. Here we synthesized siRNA from a DNA template under the control of the RNA polymerase III promoter in transfected tumor cells. Using this DNA vector-based approach, we found that the siRNA efficiently and specifically inhibited the synthesis of protein encoded by the bcl-2 gene in HeLaB2 and BGC-823 tumor cells. Tumor growth was inhibited by 66.5% with 2mg/kg pSilencer 3.1H1-bcl-2 in mouse liver tumor-bearing BALB/c mice. This approach may prove to be a valuable clinical technique for the analysis of specific gene functions and gene therapy of malignant tumors that utilize the bcl-2 gene via RNA interference.
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