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1.
Int J Mol Sci ; 25(11)2024 May 29.
Article in English | MEDLINE | ID: mdl-38892121

ABSTRACT

Dermatology and cosmetology currently prioritize healthy, youthful-looking skin. As a result, research is being conducted worldwide to uncover natural substances and carriers that allow for controlled release, which could aid in the battle against a variety of skin illnesses and slow the aging process. This study examined the biological and physicochemical features of novel hydrogels containing cannabidiol (CBD) and α-terpineol (TER). The hydrogels were obtained from ε-caprolactone (CL) and poly(ethylene glycol) (PEG) copolymers, diethylene glycol (DEG), poly(tetrahydrofuran) (PTHF), 1,6-diisocyanatohexane (HDI), and chitosan (CHT) components, whereas the biodegradable oligomers were synthesized using the enzyme ring-opening polymerization (e-ROP) method. The in vitro release rate of the active compounds from the hydrogels was characterized by mainly first-order kinetics, without a "burst release". The antimicrobial, anti-inflammatory, cytotoxic, antioxidant, and anti-aging qualities of the designed drug delivery systems (DDSs) were evaluated. The findings indicate that the hydrogel carriers that were developed have the ability to scavenge free radicals and impact the activity of antioxidant enzymes while avoiding any negative effects on keratinocytes and fibroblasts. Furthermore, they have anti-inflammatory qualities by impeding protein denaturation as well as the activity of proteinase and lipoxygenase. Additionally, their ability to reduce the multiplication of pathogenic bacteria and inhibit the activity of collagenase and elastase has been demonstrated. Thus, the developed hydrogel carriers may be effective systems for the controlled delivery of CBD, which may become a valuable tool for cosmetologists and dermatologists.


Subject(s)
Cannabidiol , Hydrogels , Skin , Hydrogels/chemistry , Hydrogels/pharmacology , Cannabidiol/pharmacology , Cannabidiol/chemistry , Skin/drug effects , Skin/metabolism , Humans , Cyclohexane Monoterpenes/chemistry , Cyclohexane Monoterpenes/pharmacology , Antioxidants/pharmacology , Antioxidants/chemistry , Antioxidants/chemical synthesis , Regeneration/drug effects , Polymers/chemistry , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Keratinocytes/drug effects , HaCaT Cells , Drug Carriers/chemistry , Drug Delivery Systems , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry
2.
Toxicol Appl Pharmacol ; 487: 116978, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38795847

ABSTRACT

Non-small cell lung cancer (NSCLC) is a complex malignancy with a high degree of heterogeneity, representing approximately 85% of all lung cancer cases. The treatment landscape for NSCLC has been revolutionised by incorporating targeted and immunotherapies; however, novel therapeutic modalities are consistently needed to enhance the treatment outcomes. Indeed, alternative anti-cancer therapies involving natural products have drawn the attention of clinicians and scientists owing to their remarkable chemopreventive potential, often displaying minimal toxicity. D-carvone (CN) is one such natural product that has exhibited numerous promising therapeutic benefits, yet its efficacy against NSCLC remains enigmatic. In the present study, network pharmacological studies and molecular docking in conjunction with in-vitro validation were used to elucidate the underlying mechanism of action of CN comprehensively. Different databases revealed a total of 77 putative anti-NSCLC targets of CN. The identified core targets were utilised to construct a "Compound- Target- Disease" network by Cytoscape (v3.9.0). Further analysis identified 5 core/ hub targets of CN including JAK2, ERK1, ESR1, GSK3B and HSP90AA1. Molecular docking indicated a strong binding interaction of the compound with these core targets. Also, Gene Ontology and KEGG analysis validated the involvement of multiple biological processes. Additionally, CN significantly inhibited cell proliferation, clonogenicity, and wound healing potential while promoting apoptosis in a dose-dependent manner in H1299 and A549 cell lines as examined by flow cytometry, morphological assessment, and western blotting. In conclusion, this study delineates the therapeutic effects of CN on NSCLC, thus highlighting CN as a putative drug candidate for further analysis.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Cyclohexane Monoterpenes , Lung Neoplasms , Molecular Docking Simulation , Network Pharmacology , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Cyclohexane Monoterpenes/pharmacology , A549 Cells , Cell Line, Tumor , Signal Transduction/drug effects , Cell Proliferation/drug effects , Protein Interaction Maps , Apoptosis/drug effects , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry
3.
Molecules ; 29(9)2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38731415

ABSTRACT

Investigations have shown that storage bugs seriously harm grains during storage. In the interim, essential oils (EOs) have been proven to be a good botanical pesticide. The anti-Lasioderma serricorne properties of Elsholtzia ciliata essential oil, which was obtained by steam distillation, were evaluated using DL-limonene, carvone, and their two optical isomer components using contact, repelling, and fumigation techniques. Simultaneously, the fumigation, contact, and repellent activities of carvone and its two optical isomers mixed with DL-limonene against L. serruricorne were evaluated. The results showed that E. ciliata, its main components (R-carvone, DL-limonene), and S-carvone exhibited both fumigations (LC50 = 14.47, 4.42, 20.9 and 3.78 mg/L) and contact (LD50 = 7.31, 4.03, 28.62 and 5.63 µg/adult) activity against L.serricorne. A binary mixture (1:1) of R-carvone and DL-limonene displayed an obvious synergistic effect. A binary mixture (1:1) of carvone and its two optical isomers exhibited an obvious synergistic effect, too. Furthermore, the repellent activity of the EO, carvone, and its two optical isomers, DL-limonene, and a combination of them varied. To stop insect damage during storage, E. ciliata and its components can be utilized as bio-insecticides.


Subject(s)
Insecticides , Lamiaceae , Oils, Volatile , Oils, Volatile/chemistry , Oils, Volatile/pharmacology , Lamiaceae/chemistry , Animals , Insecticides/chemistry , Insecticides/pharmacology , Limonene/chemistry , Limonene/pharmacology , Insect Repellents/chemistry , Insect Repellents/pharmacology , Cyclohexane Monoterpenes/chemistry , Cyclohexane Monoterpenes/pharmacology , Drug Synergism , Fumigation
4.
Neurochem Res ; 49(7): 1863-1878, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38753259

ABSTRACT

The study aimed to assess 𝛾-Terpinene's (𝛾-TER) neuroprotective potential in acute cerebral ischemia, characterized by reduced cerebral blood flow in rats. Middle cerebral artery occlusion (MCAO), a standard method for inducing cerebral ischemia, was employed in male Wistar rats. 𝛾-TER at varying doses (5, 10, and 15 mg/kg) were intraperitoneally administered during reperfusion onset. Neurological outcomes, cerebral infarct size, edema, and enzymatic activities (SOD, GPx, and catalase) in the brain were evaluated using diverse techniques. The study examined gene expression and pathways associated with neuroinflammation and apoptosis using Cytoscape software, identifying the top 10 genes involved. Pro-inflammatory and pro-apoptotic factors were assessed through real-time PCR and ELISA, while apoptotic cell rates were measured using the TUNEL and Flow cytometry assay. Immunohistochemistry assessed apoptosis-related proteins like Bax and bcl-2 in the ischemic area. 𝛾-TER, particularly at doses of 10 and 15 mg/kg, significantly reduced neurological deficits and cerebral infarction size. The 15 mg/kg dose mitigated TNF-α, IL-1ß, Bax, and caspase-3 gene and protein levels in the cortex, hippocampus, and striatum compared to controls. Furthermore, Bcl-2 levels increased in these regions. 𝛾-TER show cased neuroprotective effects by suppressing inflammation, apoptosis, and oxidation. In conclusion, 𝛾-TER, possessing natural anti-inflammatory and anti-apoptotic properties, shields the brain against ischemic damage by reducing infarction, edema, oxidative stress, and inflammation. It modulates the expression of crucial genes and proteins associated with apoptosis in diverse brain regions. These findings position 𝛾-TER as a potential therapeutic agent for ischemic stroke.


Subject(s)
Apoptosis , Neuroprotective Agents , Rats, Wistar , Animals , Male , Apoptosis/drug effects , Neuroprotective Agents/therapeutic use , Neuroprotective Agents/pharmacology , Rats , Infarction, Middle Cerebral Artery/drug therapy , Infarction, Middle Cerebral Artery/metabolism , Infarction, Middle Cerebral Artery/pathology , Brain Ischemia/drug therapy , Brain Ischemia/metabolism , Brain Ischemia/pathology , Oxidative Stress/drug effects , Inflammation/drug therapy , Inflammation/metabolism , Cyclohexane Monoterpenes/therapeutic use , Cyclohexane Monoterpenes/pharmacology , Oxidation-Reduction/drug effects , Brain/drug effects , Brain/metabolism , Brain/pathology
5.
J Nat Prod ; 87(4): 861-868, 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38438305

ABSTRACT

PC-A (1), a bromo nor-eremophilane, showed selective antiproliferative activity against a triple-negative breast cancer (TNBC) cell line. This unique activity prompted us to establish a total synthesis to facilitate a structure-activity relationship (SAR) study and selectivity optimization. An enantioselective first total synthesis of 1 was achieved starting from (R)-carvone through a side chain extension with a Mukaiyama aldol reaction and decalin construction. The synthesized decalin derivatives and debromo PC-A (2) were evaluated for antiproliferative activity against five human tumor cell lines, including TNBC, to assess preliminary SAR correlations.


Subject(s)
Drug Screening Assays, Antitumor , Triple Negative Breast Neoplasms , Humans , Structure-Activity Relationship , Molecular Structure , Triple Negative Breast Neoplasms/drug therapy , Stereoisomerism , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cyclohexane Monoterpenes/pharmacology , Cyclohexane Monoterpenes/chemistry , Monoterpenes/pharmacology , Monoterpenes/chemistry , Monoterpenes/chemical synthesis , Sesquiterpenes/pharmacology , Sesquiterpenes/chemical synthesis , Sesquiterpenes/chemistry , Female , Cell Line, Tumor , Polycyclic Sesquiterpenes/pharmacology , Polycyclic Sesquiterpenes/chemistry , Polycyclic Sesquiterpenes/chemical synthesis
6.
Food Funct ; 15(8): 4292-4309, 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38526853

ABSTRACT

Asthma is a chronic inflammatory disorder in airways with typical pathologic features of airway inflammation and mucus hypersecretion. α-Terpineol is a monocyclic terpene found in many natural plants and foods. It has been reported to possess a wide range of pharmacological activities including anti-inflammatory and expectorant effects. However, the role of α-terpineol in asthma and its potential protective mechanism have not been well elucidated. This study is designed to investigate the pharmacological effect and mechanism of α-terpineol on asthmatic mice using the metabolomics platform. A murine model of asthma was established using ovalbumin (OVA) sensitization and then challenged for one week. The leukocyte count and inflammatory cytokines in the bronchoalveolar lavage fluid (BALF), lung histopathology, inflammatory  infiltrate and mucus secretion were evaluated. An ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS)-based metabolomics study was performed on lung tissues and serum to explore endogenous small molecule metabolites affected by α-terpineol in asthmatic mice. After α-terpineol treatment, leukocyte count, inflammatory cytokines in the BALF, and peribronchial inflammation infiltration were significantly downregulated. Goblet cell hyperplasia and mucus secretion were attenuated, with the level of Muc5ac in BALF decreased. These results proved the protective effect of α-terpineol against airway inflammation, mucus hypersecretion and Th1/Th2 immune imbalance. To further investigate the underlying mechanisms of α-terpineol in asthma treatment, UPLC-MS/MS-based metabolomics analysis was performed. 26 and 15 identified significant differential metabolites were found in the lung tissues and serum of the control, model and α-terpineol groups, respectively. Based on the above differential metabolites, enrichment analysis showed that arachidonic acid (AA) metabolism was reprogrammed in both mouse lung tissues and serum. 5-Lipoxygenase (5-LOX) and cysteinyl leukotrienes (CysLTs) are the key enzyme and the end product of AA metabolism, respectively. In-depth studies have shown that pretreatment with α-terpineol can alleviate asthma by decreasing the AA level, downregulating the expression of 5-LOX and reducing the accumulation of CysLTs in mouse lung tissues. In summary, this study demonstrates that α-terpineol is a potential agent that can prevent asthma via regulating disordered AA metabolism.


Subject(s)
Arachidonic Acid , Asthma , Bronchoalveolar Lavage Fluid , Cyclohexane Monoterpenes , Lung , Metabolomics , Mice, Inbred BALB C , Animals , Asthma/drug therapy , Asthma/metabolism , Mice , Cyclohexane Monoterpenes/pharmacology , Arachidonic Acid/metabolism , Lung/drug effects , Lung/metabolism , Female , Disease Models, Animal , Cytokines/metabolism , Ovalbumin , Tandem Mass Spectrometry , Mucin 5AC/metabolism , Chromatography, High Pressure Liquid
7.
Oxid Med Cell Longev ; 2022: 4509204, 2022.
Article in English | MEDLINE | ID: mdl-35295720

ABSTRACT

Major depressive disorder (MDD) is a progressive deteriorating mental state with a feeling of worthlessness and frequent mood swings. Several studies reported the favorable effects of natural drug substances on MMD associated oxidative stress and neuroinflammation. The present study is attempted to examine whether carveol could affect lipopolysaccharide- (LPS-) induced depression, and if so, how nuclear factor E2-related factor (Nrf2) contributed to the neuroprotective effects of carveol mechanistically. Two experimental cohorts were used using the SD rats: first to evaluate the promising dose of carveol (whether 20 mg/kg or 50 mg/kg) and secondly to determine the effect of carveol on Nrf2-mediated antidepression. Significant neuronal alterations were noticed in the cortex and hippocampus regions in the LPS-treated group, accompanied by elevated inflammatory cytokine levels such as tumor necrosis factor-alpha (TNF-α), cyclooxygenase (COX-2), and c-Jun N-terminal kinase (p-JNK). Moreover, amassing of free radicals exacerbated lipid peroxidase (LPO) and oxidative stress with a limited antioxidant capacity. Carveol (20 mg/kg) significantly ameliorated these detrimental effects by promoting the antioxidant Nrf2 gene and protein, which critically regulate the downstream antioxidant and anti-inflammatory pathway. To further elaborate our hypothesis, we employed all-trans retinoic acid (ATRA), an Nrf2 inhibitor, and we found that ATRA exaggerated LPS-induced depressive-like effects associated with elevated neuroinflammatory markers. Our results demonstrated that carveol (20 mg/kg) could activate the endogenous antioxidant Nrf2, which regulates the downstream antioxidant signaling pathway, eventually leading to amelioration of LPS-induced neuroinflammation and neurodegeneration.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Cyclohexane Monoterpenes/therapeutic use , Depressive Disorder, Major/drug therapy , NF-E2-Related Factor 2/drug effects , Animals , Anti-Inflammatory Agents/pharmacology , Cyclohexane Monoterpenes/pharmacology , Humans , Male , Rats , Rats, Sprague-Dawley
8.
Food Funct ; 13(6): 3110-3132, 2022 Mar 21.
Article in English | MEDLINE | ID: mdl-35212344

ABSTRACT

Spearmint belongs to the genus Mentha in the family Labiatae (Lamiaceae), which is cultivated worldwide for its remarkable aroma and commercial value. The aromatic molecules of spearmint essential oil, including carvone, carveol, dihydrocarvone, dihydrocarveol and dihydrocarvyl acetate, have been widely used in the flavors and fragrances industry. Besides their traditional use, these aromatic molecules have attracted great interest in other application fields (e.g., medicine, agriculture, food, and beverages) especially due to their antimicrobial, antioxidant, insecticidal, antitumor, anti-inflammatory and antidiabetic activities. This review presents the sources, properties, synthesis and application of spearmint aromatic molecules. Furthermore, this review focuses on the biological properties so far described for these compounds, their therapeutic effect on some diseases, and future directions of research. This review will, therefore, contribute to the rational and economic exploration of spearmint aromatic molecules as natural and safe alternative therapeutics.


Subject(s)
Cyclohexane Monoterpenes/pharmacology , Mentha spicata/chemistry , Oils, Volatile/chemistry , Animals , Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Antioxidants/chemistry , Antioxidants/metabolism , Antioxidants/pharmacology , Biosynthetic Pathways , Central Nervous System Agents/chemistry , Central Nervous System Agents/pharmacology , Cyclohexane Monoterpenes/chemistry , Cyclohexane Monoterpenes/metabolism , Cyclohexane Monoterpenes/toxicity , Humans , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/pharmacology , Hypolipidemic Agents/chemistry , Hypolipidemic Agents/pharmacology , Insecticides , Protective Agents/chemistry , Protective Agents/pharmacology
9.
Molecules ; 27(3)2022 Jan 25.
Article in English | MEDLINE | ID: mdl-35164037

ABSTRACT

Aseries of novel 1,4-disubstituted 1,2,3-triazoles were synthesized from an (R)-carvone terminal alkyne derivative via a Cu (I)-catalyzed azide-alkyne cycloaddition reaction using CuSO4,5H2O as the copper (II) source and sodium ascorbate as a reducing agent which reduces Cu (II) into Cu (I). All the newly synthesized 1,2,3-triazoles 9a-h were fully identified on the basis of their HRMS and NMR spectral data and then evaluated for their cell growth inhibition potential by MTS assay against HT-1080 fibrosarcoma, A-549 lung carcinoma, and two breast adenocarcinoma (MCF-7 and MDA-MB-231) cell lines. Compound 9d showed notable cytotoxic effects against the HT-1080 and MCF-7 cells with IC50 values of 25.77 and 27.89 µM, respectively, while compound 9c displayed significant activity against MCF-7 cells with an IC50 value of 25.03 µM. Density functional calculations at the B3LYP/6-31G* level of theory were used to confirm the high reactivity of the terminal alkyne as a dipolarophile. Quantum calculations were also used to investigate the mechanism of both the uncatalyzed and copper (I)-catalyzed azide-alkyne cycloaddition reaction (CuAAC). The catalyzed reaction gives complete regioselectivity via a stepwise mechanism streamlining experimental observations. The calculated free-energy barriers 4.33 kcal/mol and 29.35 kcal/mol for the 1,4- and 1,5-regioisomers, respectively, explain the marked regioselectivity of the CuAAC reaction.


Subject(s)
Cyclohexane Monoterpenes/chemistry , Triazoles/chemistry , Carbon-13 Magnetic Resonance Spectroscopy , Cell Line, Tumor , Cycloaddition Reaction , Cyclohexane Monoterpenes/pharmacology , Density Functional Theory , Drug Screening Assays, Antitumor , Humans , In Vitro Techniques , Proton Magnetic Resonance Spectroscopy , Triazoles/chemical synthesis , Triazoles/pharmacology
10.
Life Sci ; 290: 120087, 2022 Feb 01.
Article in English | MEDLINE | ID: mdl-34740575

ABSTRACT

Alpha-terpineol (TPN) is one of the major components of the resin obtained from Protium heptaphyllum. This plant has been utilized as medicine by Brazilian indigenous tribes to treat cardiovascular diseases. Scientific reports have shown that the TPN possesses vasorelaxant and antihypertensive effects. This study was conducted to assess the cardioprotective action of TPN against isoproterenol (ISO)-induced cardiotoxicity. Wistar rats were randomly divided into six groups. Rats were orally administered with TPN (25, 50, and 75 mg/kg, respectively) for 15 days, and ISO was administered (85 mg/kg, subcutaneously) on the 14th and 15th days. At the end of the experiment, the hemodynamic, baroreflex test, ECG, biochemical, histological, and morphometric changes were monitored from control and experimental groups, i.e., on the 15th day. ISO-induced myocardial infarcted rats showed an increase in mortality rates, cardiac marker enzymes, tachycardia, hypertrophy, myocardium necrosis, edema, hemorrhagic areas, infiltration of inflammatory cells like lymphocytes, and increased myocardial infarct size. However, pretreatment with TPN significantly inhibited these effects of ISO. The histopathological findings obtained for the myocardium further confirmed the biochemical results. Thus, the present study provides evidence for the efficacy of TPN against ISO-induced myocardial infarction in rats.


Subject(s)
Cardiotoxicity/drug therapy , Cyclohexane Monoterpenes/pharmacology , Animals , Antioxidants/pharmacology , Biomarkers/metabolism , Cardiotonic Agents/pharmacology , Cardiotoxicity/metabolism , Cardiovascular Diseases/drug therapy , Cyclohexane Monoterpenes/metabolism , Heart/drug effects , Hemodynamics/drug effects , Isoproterenol/pharmacology , Lipid Peroxidation/drug effects , Male , Myocardial Infarction/pathology , Myocardium/metabolism , Rats , Rats, Inbred WKY
11.
Carbohydr Polym ; 277: 118825, 2022 Feb 01.
Article in English | MEDLINE | ID: mdl-34893242

ABSTRACT

Biomedical implants-associated bacterial infections have become a major threat to human health. Therefore, it is meaningful to develop new antibacterial strategies to solve this problem. In this study, we conjugated acetylated lentinan (AceLNT) with α-terpineol (AceLNT-g-α-ter), a highly effective natural antibacterial compound, to constitute a novel AceLNT-g-α-ter membrane (AceLNT-g-α-terM). Compared with AceLNT membrane (AceLNTM), the adhesion amount of E. coli and P. aeruginosa in AceLNT-g-α-terM decreased by 80% and 85% after 7 d incubation in fluid bacterial medium. Moreover, the number of E. coli and P. aeruginosa biofilm on AceLNT-g-α-terM surface decreased by 70% and 71%. At the meanwhile, α-terpineol grafting modification of AceLNT had limited effect on its stimulating activity on macrophages and had no more cytotoxicity. In summary, our study firstly confirmed that AceLNT-g-α-terM could effectively inhibit gram-negative bacteria adhesion and biofilm formation, and provided a novel strategy for preventing infection of biomedical implants.


Subject(s)
Anti-Bacterial Agents/pharmacology , Cyclohexane Monoterpenes/pharmacology , Escherichia coli/drug effects , Lentinan/pharmacology , Pseudomonas aeruginosa/drug effects , Acetylation , Animals , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Bacterial Adhesion/drug effects , Biofilms/drug effects , Cyclohexane Monoterpenes/chemistry , Cytokines/metabolism , Lentinan/chemistry , Macrophages/drug effects , Macrophages/metabolism , Mice , Microbial Sensitivity Tests , Molecular Structure , NIH 3T3 Cells , RAW 264.7 Cells , Tumor Necrosis Factor-alpha/metabolism
12.
Biomolecules ; 11(12)2021 12 01.
Article in English | MEDLINE | ID: mdl-34944447

ABSTRACT

Carvone is a monoterpene ketone contained in the essential oils of several aromatic and medicinal plants of the Lamiaceae and Asteraceae families. From aromatic plants, this monoterpene is secreted at different concentrations depending on the species, the parts used, and the extraction methods. Currently, pharmacological investigations showed that carvone exhibits multiple pharmacological properties such as antibacterial, antifungal, antiparasitic, antineuraminidase, antioxidant, anti-inflammatory, and anticancer activities. These studies were carried out in vitro and in vivo and involved a great deal of knowledge on the mechanisms of action. Indeed, the antimicrobial effects are related to the action of carvone on the cell membrane and to ultrastructural changes, while the anti-inflammatory, antidiabetic, and anticancer effects involve the action on cellular and molecular targets such as inducing of apoptosis, autophagy, and senescence. With its multiple mechanisms, carvone can be considered as natural compounds to develop therapeutic drugs. However, other investigations regarding its precise mechanisms of action as well as its acute and chronic toxicities are needed to validate its applications. Therefore, this review discusses the principal studies investigating the pharmacological properties of carvone, and the mechanism of action underlying some of these properties. Moreover, further investigations of major pharmacodynamic and pharmacokinetic studies were also suggested.


Subject(s)
Anti-Infective Agents/pharmacology , Anti-Inflammatory Agents/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Antioxidants/pharmacology , Cyclohexane Monoterpenes/pharmacology , Animals , Anti-Infective Agents/pharmacokinetics , Anti-Inflammatory Agents/pharmacokinetics , Antineoplastic Agents, Phytogenic/pharmacokinetics , Antioxidants/pharmacokinetics , Autophagy , Cell Membrane/chemistry , Cell Survival/drug effects , Cyclohexane Monoterpenes/chemistry , Cyclohexane Monoterpenes/therapeutic use , Ethnopharmacology , Humans , Oils, Volatile/chemistry , Plant Oils/chemistry
13.
Molecules ; 26(23)2021 Nov 25.
Article in English | MEDLINE | ID: mdl-34885712

ABSTRACT

Mandarin is a favorite fruit of the citrus family. Mandarin seeds are considered a source of nontraditional oil obtained from byproduct materials. This investigation aimed to assess the biomolecules of mandarin seeds and evaluated their antimycotic and antimycotoxigenic impact on fungi. Moreover, it evaluated the protective role of mandarin oil against aflatoxin toxicity in cell lines. The two types of extracted oil (fixed and volatile) were ecofriendly. The fatty acid composition, tocopherol, sterols, and carotenoids were determined in the fixed oil, whereas volatiles and phenolics were estimated in the essential oil. A mixture of the two oils was prepared and evaluated for its antimicrobial impact. The reduction effect of this mixture was also investigated to reduce mycotoxin secretion using a simulated experiment. The protective effect of the oil was evaluated using healthy strains of cell lines. Fixed oil was distinguished by the omega fatty acid content (76.24%), lutein was the major carotenoid (504.3 mg/100 g) and it had a high ß-sitosterol content (294.6 mg/100 g). Essential oil contained limonene (66.05%), α-pinene (6.82%), ß-pinene (4.32%), and γ-terpinene (12.31%) in significant amounts, while gallic acid and catechol were recorded as the dominant phenolics. Evaluation of the oil mix for antimicrobial potency reflected a considerable impact against pathogenic bacteria and toxigenic fungi. By its application to the fungal media, this oil mix possessed a capacity for reducing mycotoxin secretion. The oil mix was also shown to have a low cytotoxic effect against healthy strains of cell lines and had potency in reducing the mortality impact of aflatoxin B1 applied to cell lines. These results recommend further study to involve this oil in food safety applications.


Subject(s)
Bacteria/drug effects , Citrus/chemistry , Oils, Volatile/chemistry , Plant Oils/chemistry , Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Bacteria/pathogenicity , Bicyclic Monoterpenes/chemistry , Bicyclic Monoterpenes/pharmacology , Cyclohexane Monoterpenes/chemistry , Cyclohexane Monoterpenes/pharmacology , Fruit/chemistry , Fungi/drug effects , Humans , Limonene/chemistry , Limonene/pharmacology , Mycotoxins/antagonists & inhibitors , Mycotoxins/chemistry , Oils, Volatile/pharmacology , Phytosterols/chemistry , Phytosterols/pharmacology , Plant Oils/pharmacology , Sitosterols/chemistry , Sitosterols/pharmacology
14.
J Environ Pathol Toxicol Oncol ; 40(3): 75-85, 2021.
Article in English | MEDLINE | ID: mdl-34587406

ABSTRACT

BACKGROUND: Parkinson's disease (PD) is the most prevalent disease linked with age-associated neuronal degeneration. Phytotherapeutic compounds or agents have gained increased importance because of their increased specificity and minimal side effects. Isopulegol, a monoterpene, was utilized in the present study because of its wide range of therapeutic properties. Our aim was to examine the underlying mechanism of anti-neuroinflammatory action and neuroprotective efficacy of isopulegol in cell lines and in an experimental animal model of PD. METHODS: The MTT assay was performed in microglial BV-2 cells subjected to lipopolysaccharides (LPS). The release of NO and synthesis of ROS intracellularly in BV-2 cells were detected. C57BL/6 mice induced with MPTP were examined for motor function and coordination. Expression of proinflammatory mediators was also assessed both in vivo and in vitro. Histopathological sections of brain and expression of iNOS and COX-2 were also analyzed. RESULTS: BV-2 cells did not exhibit noticeable toxicity at selected concentrations and LPS-incubated cells showed marked elevation of NO levels and increased production of intracellular ROS. Increased expression of proinflammatory cytokines was also observed. Motor function and coordination deficits were observed in mice induced with MPTP. Histopathological abnormalities and increased iNOS and COX-2 expression were noted in MPTP-induced mice. Administration of isopulegol reversed the changes brought about by LPS and MPTP. CONCLUSION: The study indicated that isopulegol is a potential therapeutic drug against clinical complications of PD.


Subject(s)
Cyclohexane Monoterpenes/pharmacology , Neuroprotective Agents/pharmacology , Parkinson Disease/drug therapy , Animals , Brain/drug effects , Brain/pathology , Cell Line , Cell Survival/drug effects , Cyclooxygenase 2/genetics , Cytokines/metabolism , Inflammation Mediators/metabolism , Lipopolysaccharides/toxicity , MPTP Poisoning/drug therapy , MPTP Poisoning/genetics , MPTP Poisoning/physiopathology , Male , Mice, Inbred C57BL , Microglia/drug effects , Microglia/metabolism , Motor Activity/drug effects , Nitric Oxide/metabolism , Nitric Oxide Synthase Type II/genetics , Parkinson Disease/pathology , Reactive Oxygen Species/metabolism
15.
Oxid Med Cell Longev ; 2021: 9966663, 2021.
Article in English | MEDLINE | ID: mdl-34422216

ABSTRACT

Epilepsy is a neurodegenerative brain disorder characterized by recurrent seizure attacks. Numerous studies have suggested a strong correlation between oxidative stress and neuroinflammation in several neurodegenerative disorders including epilepsy. This study is aimed at investigating the neuroprotective effects of the natural compound carveol against pentylenetetrazole- (PTZ-) induced kindling and seizure model. Two different doses of carveol (10 mg/kg and 20 mg/kg) were administered to male rats to determine the effects and the effective dose of carveol and to further demonstrate the mechanism of action of nuclear factor E2-related factor (Nrf2) in PTZ-induced kindling model. Our results demonstrated reduced levels of innate antioxidants such as superoxide dismutase (SOD), catalase, glutathione-S-transferase (GST), and glutathione (GSH), associated with elevated lipid peroxidation (LPO) and inflammatory cytokines level such as tumor necrosis factor-alpha (TNF-α), and mediators like cyclooxygenase (COX-2) and nuclear factor kappa B (NFκB). These detrimental effects exacerbated oxidative stress and provoked a marked neuronal alteration in the cortex and hippocampus of PTZ-intoxicated animals that were associated with upregulated Nrf2 gene expression. Furthermore, carveol treatment positively modulated the antioxidant gene Nrf2 and its downstream target HO-1. To further investigate the role of Nrf2, an inhibitor of Nrf2 called all-trans retinoic acid (ATRA) was used, which further exacerbated PTZ toxicity. Moreover, carveol treatment induced cholinergic system activation by mitigating acetylcholinesterase level which is further linked to attenuated neuroinflammatory cascade. The extent of blood-brain barrier disruption was evaluated based on vascular endothelial growth factor (VEGF) expression. Taken together, our findings suggest that carveol acts as an Nrf2 activator and therefore induces downstream antioxidants and mitigates inflammatory insults through multiple pathways. This eventually alleviates PTZ-induced neuroinflammation and neurodegeneration.


Subject(s)
Cyclohexane Monoterpenes/pharmacology , Epilepsy/complications , Kindling, Neurologic/pathology , NF-E2-Related Factor 2/metabolism , Neuroinflammatory Diseases/prevention & control , Pentylenetetrazole/toxicity , Seizures/prevention & control , Animals , Antioxidants/pharmacology , Epilepsy/chemically induced , Epilepsy/pathology , Kindling, Neurologic/drug effects , Lipid Peroxidation , Male , NF-E2-Related Factor 2/genetics , Neuroinflammatory Diseases/etiology , Neuroinflammatory Diseases/pathology , Neuroprotective Agents/pharmacology , Oxidative Stress , Rats , Rats, Sprague-Dawley , Seizures/etiology , Seizures/pathology
16.
Biomed Res Int ; 2021: 5522964, 2021.
Article in English | MEDLINE | ID: mdl-34337019

ABSTRACT

Ziziphora (Cacotti in Persian) belongs to the Lamiaceae family (mint group) and is vastly found in Iran and Asia. This traditional medicinal plant is normally used as analgesic and for treatment of particular gastrointestinal diseases. Since colorectal cancer is one of the most common causes of death in the world and the second leading cause of cancer death among adults, there is a pressing need to inhibit this malignancy by using methods with minimal side effects. One of these methods is the use of natural resources such as medical plants. This study is aimed at investigating the expression of apoptosis-related genes in the adjacent culture of colorectal cancer epithelial cells (HT-29) with Ziziphora essential oil (ZEO). The essential oil was extracted from Ziziphora leaves, and its compounds were determined and then added to the HT-29 culture medium at different concentrations. After 24 hours, the HT-29 cells were harvested from the medium and cytotoxicity was analyzed by MTT assay. After MTT assay and determination of the percentage of apoptosis by flow cytometry, RNA extraction was performed and the expression levels of Bax, Bcl-2, caspase 3 (C3), and caspase 9 (C9) were analyzed using newly designed primers by reverse transcription (RT) qPCR method and GeniX6 software. Also, specific antibodies were used for western blot analyses of those molecules. GC analysis revealed 42 different compounds in the ZEO, including pulegone (26.65%), menthone (5.74%), thymol (5.51%), and menthol (1.02%). MTT assay showed that the concentration of 200 µg/ml of ZEO had the highest HT-29 cell death during 24 hours. After incubation with the concentration of 50 µg/ml of ZEO for 24 and 48 hours, caspase 3 and 9 gene expressions in the treated group increased compared to those in the control group (P < 0.001), while the Bcl-2 expression decreased. The results showed that having anticancer compounds, ZEO can increase C3 and C9 and decrease Bcl-2 expressions, causing apoptosis in HT-29 cells in vitro. This can lead to the use of ZEO as a factor for colorectal cancer treatment.


Subject(s)
Apoptosis , Colorectal Neoplasms/pathology , Lamiaceae/chemistry , Oils, Volatile/pharmacology , Apoptosis/drug effects , Cell Line, Tumor , Cell Survival/drug effects , Cyclohexane Monoterpenes/pharmacology , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Epithelial Cells/pathology , Gas Chromatography-Mass Spectrometry , Gene Expression Regulation, Neoplastic/drug effects , Humans , Models, Biological , bcl-2-Associated X Protein/metabolism
17.
Molecules ; 26(16)2021 Aug 20.
Article in English | MEDLINE | ID: mdl-34443651

ABSTRACT

Caraway (Carum carvi L.) essential oil is a candidate for botanical herbicides. A hypothesis was formulated that the sand-applied maltodextrin-coated caraway oil (MCEO) does not affect the growth of maize (Zea mays L.). In the pot experiment, pre-emergence application of five doses of MCEO was tested on four maize cultivars up to the three-leaf growth stage. The morphological analyses were supported by the measurements of relative chlorophyll content (SPAD), two parameters of chlorophyll a fluorescence, e.g., Fv/Fm and Fv/F0, and fluorescence emission spectra. The analyzed MCEO contained 6.5% caraway EO with carvone and limonene as the main compounds, constituting 95% of the oil. The MCEO caused 7-day delays in maize emergence from the dose of 0.9 g per pot (equal to 96 g m-2). Maize development at the three-leaf growth stage, i.e., length of roots, length of leaves, and biomass of shoots and leaves, was significantly impaired already at the lowest dose of MCEO: 0.4 g per pot, equal to 44 g m-2. A significant drop of both chlorophyll a fluorescence parameters was noted, on average, from the dose of 0.7 g per pot, equal to 69 g m-2. Among the tested cultivars, cv. Rywal and Pomerania were less susceptible to the MCEO compared to the cv. Kurant and Podole. In summary, maize is susceptible to the pre-emergence, sand-applied MCEO from the dose of 44 g m-2.


Subject(s)
Oils, Volatile/pharmacology , Plant Oils/pharmacology , Zea mays/drug effects , Zea mays/growth & development , Biomass , Carum/chemistry , Chlorophyll A/metabolism , Cyclohexane Monoterpenes/chemistry , Cyclohexane Monoterpenes/pharmacology , Fluorescence , Herbicides/pharmacology , Limonene/chemistry , Limonene/pharmacology , Photosynthesis/drug effects , Plant Leaves/drug effects , Plant Leaves/growth & development , Plant Leaves/metabolism , Plant Roots/drug effects , Plant Roots/growth & development , Plant Roots/metabolism , Zea mays/metabolism
18.
Int J Biol Macromol ; 186: 873-885, 2021 Sep 01.
Article in English | MEDLINE | ID: mdl-34293359

ABSTRACT

In this work, two combinations of double EOs, i.e., α-terpineol: eugenol (α-T:Eu) and carvacrol:eugenol (CA:Eu), are used to develop the active antibacterial films of double EOs@yam starch/microcrystalline cellulose (EOs@SC). The hydrogen-bonded networks in SC matrix are conducive to thermostability enhancement and the film of SC25 is determined for EO incorporation. The interactions between EOs and SC matrix are also hydrogen bonds and the double EOs@SC are smooth at ratio of ≤2:2 for α-T:Eu or CA:Eu. The ultimate film properties are dependent on the incorporated EOs. The release of EOs is well controlled by two mechanisms of diffusion (predominant) and swelling (secondary). Synergetic antibacterial activity occurs on double EOs@SC. The shelf life of pork can be extended by 1 day at 25 °C by the two typical films of α-T2:Eu2@SC and CA2:Eu2@SC. Moreover, EOs@SC can be well degraded in humus soil. Thereby, the target films will have great potential in active packaging to extend the shelf life of food.


Subject(s)
Anti-Bacterial Agents/pharmacology , Cellulose/pharmacology , Dioscorea , Escherichia coli/drug effects , Food Microbiology , Food Packaging , Food Preservation , Oils, Volatile/pharmacology , Pork Meat/microbiology , Staphylococcus aureus/drug effects , Anti-Bacterial Agents/chemistry , Cellulose/chemistry , Cyclohexane Monoterpenes/chemistry , Cyclohexane Monoterpenes/pharmacology , Cymenes/chemistry , Cymenes/pharmacology , Diffusion , Escherichia coli/growth & development , Eugenol/chemistry , Eugenol/pharmacology , Hydrogen Bonding , Oils, Volatile/chemistry , Staphylococcus aureus/growth & development , Time Factors
19.
Molecules ; 26(13)2021 Jun 25.
Article in English | MEDLINE | ID: mdl-34202378

ABSTRACT

In the present study the ability of supercritical carbon dioxide (SCO2) extracts of M. longifolia L. leaves to modulate low-density lipoprotein receptor (LDLR) and proprotein convertase subtilisin/kexin type 9 (PCSK9) expression was evaluated in cultured human hepatoma cell lines Huh7 and HepG2. Two SCO2 extracts, one oil (ML-SCO2) and a semisolid (MW-SCO2), were subjected to detailed chemical characterization by mono- and bidimensional nuclear magnetic resonance (1D, 2D-NMR), gas chromatography coupled with mass spectrometry (GC-MS) and liquid chromatography coupled with mass spectrometry (LC-MS). Chemical analysis revealed significant amounts of fatty acids, phytosterols and terpenoids. ML-SCO2 was able to induce LDLR expression at a dose of 60 µg/mL in HuH7 and HepG2 cell lines. Furthermore, ML-SCO2 reduced PCSK9 secretion in a concentration-dependent manner in both cell lines. Piperitone oxide, the most abundant compound of the volatile constituent of ML-SCO2 (27% w/w), was isolated and tested for the same targets, showing a very effective reduction of PCSK9 expression. The overall results revealed the opportunity to obtain a new nutraceutical ingredient with a high amount of phytosterols and terpenoids using the SCO2 extraction of M. longifolia L., a very well-known botanical species used as food. Furthermore, for the first time we report the high activity of piperitone oxide in the reduction of PCSK9 expression.


Subject(s)
Carbon Dioxide/chemistry , Cyclohexane Monoterpenes , Mentha/chemistry , Plant Extracts/chemistry , Proprotein Convertase 9/biosynthesis , Receptors, LDL/biosynthesis , Cyclohexane Monoterpenes/chemistry , Cyclohexane Monoterpenes/isolation & purification , Cyclohexane Monoterpenes/pharmacology , Hep G2 Cells , Humans
20.
Molecules ; 26(10)2021 May 12.
Article in English | MEDLINE | ID: mdl-34066034

ABSTRACT

The chemical composition of three Citrus limon oils: lemon essential oil (LEO), lemon terpenes (LT) and lemon essence (LE), and their influence in the virulence factors production and motility (swarming and swimming) of two Pseudomonas aeruginosa strains (ATCC 27853 and a multidrug-resistant HT5) were investigated. The main compound, limonene, was also tested in biological assays. Eighty-four compounds, accounting for a relative peak area of 99.23%, 98.58% and 99.64%, were identified by GC/MS. Limonene (59-60%), γ-terpinene (10-11%) and ß-pinene (7-15%) were the main compounds. All lemon oils inhibited specific biofilm production and bacterial metabolic activities into biofilm in a dose-dependent manner (20-65%, in the range of 0.1-4 mg mL-1) of both strains. Besides, all samples inhibited about 50% of the elastase activity at 0.1 mg mL-1. Pyocyanin biosynthesis decreases until 64% (0.1-4 mg mL-1) for both strains. Swarming motility of P. aeruginosa ATCC 27853 was completely inhibited by 2 mg mL-1 of lemon oils. Furthermore, a decrease (29-55%, 0.1-4 mg mL-1) in the synthesis of Quorum sensing (QS) signals was observed. The oils showed higher biological activities than limonene. Hence, their ability to control the biofilm of P. aeruginosa and reduce the production of virulence factors regulated by QS makes lemon oils good candidates to be applied as preservatives in the food processing industry.


Subject(s)
Anti-Bacterial Agents/pharmacology , Citrus/chemistry , Oils, Volatile/pharmacology , Plant Oils/pharmacology , Pseudomonas aeruginosa/drug effects , Pseudomonas aeruginosa/pathogenicity , Quorum Sensing/drug effects , Anti-Bacterial Agents/chemistry , Bacterial Proteins/metabolism , Bicyclic Monoterpenes/chemistry , Bicyclic Monoterpenes/pharmacology , Biofilms/drug effects , Cyclohexane Monoterpenes/chemistry , Cyclohexane Monoterpenes/pharmacology , Drug Resistance, Multiple, Bacterial/drug effects , Gas Chromatography-Mass Spectrometry , Limonene/chemistry , Limonene/pharmacology , Oils, Volatile/chemistry , Pancreatic Elastase/metabolism , Plant Oils/chemistry , Pseudomonas aeruginosa/metabolism , Pyocyanine/biosynthesis , Signal Transduction/drug effects , Virulence , Virulence Factors , Volatile Organic Compounds/chemistry , Volatile Organic Compounds/pharmacology
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