Pulegone Research Articles

Pulegone ameliorates inflammation and oxidative stress in L-arginine-induced acute pancreatitis in mice by regulating the activation of p38 MAPK pathway

Purpose: To evaluate the effects of pulegone (PLG) on inflammation and oxidative stress in L-arginineinduced acute pancreatitis (AP), and determine its molecular mechanism.Methods: Hematoxylin-Eosin (H & E) staining assay were performed, and histopathological score, blood glucose concentration, and serum amylase level were evaluated in order to assess the effects of PLG on pancreatic injury in L-arginine-induced AP mice. Enzyme linked immunosorbent assay (ELISA) was conducted to assess the levels of myeloperoxidase (MPO), malonaldehyde (MDA) and inflammatory factors (IL-6, TNF-α and IL-1β) in L-arginine-induced AP mice. Serum lactate dehydrogenase (LDH) and relative levels of ROS generation in L-arginine-induced AP mice were determined using an LDH kit and immunofluorescence assay, respectively. The effect of pulegone (PLG) on the activation of p38 MAPK pathway in L-arginine-induced AP mice was evaluated by Western blot.Results: Significant pancreatic tissue injury occurred in L-arginine-induced AP mice was revealed. PLG alleviated the pathological injury of pancreatitis, and decreased the blood glucose concentration and serum amylase level in L-arginine-induced AP mice. In addition, PLG inhibited oxidative stress and inflammatory responses, and was enabled to inhibit the activation of p38 MAPK pathway in L-arginineinduced AP mice. Furthermore, PLG exhibited protective effect against the development of pancreatic injury in L-arginine-induced AP mice.Conclusion: PLG ameliorates L-arginine-induced inflammation and oxidative stress in AP mice in vivo by inhibiting p38 MAPK pathway, and therefore, is a potential therapeutic agent for the management of acute pancreatitis.

The specific effect of (R)-(+)-pulegone on growth and biofilm formation in multi-drug resistant Escherichia coli and molecular mechanisms underlying the expression of pgaABCD genes

E. coli is associated with high rates of infection and resistance to drugs not only in China but also the rest of the world. In addition, the number of E. coli biofilm infections continue to increase with time. Notably, biofilms are attractive targets for the prevention of infections caused by multidrug-resistant bacteria. Moreover, the pgaABCD-encoded Poly-β-1,6-N-acetyl-d-glucosamine (PNAG) plays an important role in biofilm formation. Therefore, this study aimed to explore the specific effect of the (R)-(+)-pulegone (PU) on growth and biofilm formation in multi-drug resistant E. coli. The molecular mechanisms involved were also examined. The results showed that PU had significant antibacterial and antibiofilm formation activity against E. coli K1, with MIC and MBC values of 23.68 and 47.35 mg/mL, respectively. On the other hand, the maximum inhibition rate for biofilm formation in the bacterium was 52.36 % at 94.70 mg/mL of PU. qRT-PCR data showed that PU significantly down-regulated expression of the pgaABCD genes (P < 0.05). PU was also broadly effective against biofilm formation in MG1655 and MG1655/ΔpgaABCD, exhibiting the maximum inhibition rates were 98.23 % and 93.35 %, respectively. In addition, PU destroyed pre-formed mature biofilm in both MG1655 and MG1655/ΔpgaABCD about 95.03 % and 92.4 %, respectively. The study therefore verified that pgaA was a potential and key target for PU in E. coli although it was not the only one. Overall, the findings indicated that PU is a potential and novel inhibitor of drug resistance, This therefore gives insights on new ways of preventing and treating biofilm-associated infections in the food industry as well as in clinical practice.

Towards a development of novel bioinsecticides for organic control of Planococcus ficus in vineyards

The mealybug species, Planococcus ficus Signoret (Hemiptera: Pseudococcidae) is a pest that mainly affects grapevine plantations (Vitis vinifera L.), causing huge economic losses in the world. The numerous problems caused by the use of synthetic pesticides on the environment and human health have motivated the development and implementation of natural pesticides. The objective of this work was to develop effective and efficient contact bioinsecticide formulations for the control of P. ficus in vineyards. Anti-mealybug formulations were developed using (R)-(+)-pulegone as an active principle, TWEEN® 20 and soy lecithin powder as surfactants, and limonene and diatomaceous earth (DE) as insect waxy layer reducers. The insecticidal properties of formulations against vine mealybugs and their grapevine leaf phytotoxicity were evaluated in laboratory conditions. Pulegone+DE+Lecithin and Pulegone+Limonene+DE+Lecithin formulations showed the highest mortality rates of P. ficus (more than 70 % mortality) at 24 h and 48 h of treatment. This high mortality is probably due to an interaction between pulegone, DE and soy lecithin that allows more molecular mobility and increases the efficiency of the active substance, making it enter and act on the insect. In conclusion, the Pulegone+DE+Lecithin and Pulegone+Limonene+DE+Lecithin formulations can be an efficient tool for the organic control of P. ficus in vineyards.

Chemical composition and antibacterial effects of some essential oils individually and in combination with sodium benzoate against methicillin-resistant Staphylococcus aureus and Yersinia enterocolitica.

Side effects of chemical preservatives and drug resistance have raised interest in use of herbal products. This study aimed to examine the chemical composition and antibacterial effects of Cuminum cyminum, Mentha spicata, and Mentha longifolia essential oils individually and in combination with sodium benzoate against methicillin-resistant Staphylococcus aureus and Yersinia enterocolitica. The essential oils were analyzed by gas chromatography-mass spectrometry. Disc diffusion and microdilution assays were used for in vitro antimicrobial screening. The main components were cumin aldehyde, carvone, and pulegone in C. cyminum, M. spicata, and M. longifolia essential oils, respectively. Antibacterial data analysis showed significant differences between different antibacterial effects of essential oils individually and in combination with sodium benzoate. In terms of individual effects, antibacterial effect of M. longifolia and C. cyminum essential oils were the highest against methicillin-resistant S. aureus and Y. enterocolitica, respectively. The antibacterial effects of sodium benzoate combined with essential oils showed significant differences with the individual effect of sodium benzoate in most cases. The results indicated that the combined effect of these essential oils with sodium benzoate could reduce the use of sodium benzoate as an antimicrobial agent, which could decrease its possible side effects. Thus, for more significant effects, these essential oils could be combined with other agents for the preservation of drug and food products.

COMPARISON OF CHEMICAL COMPOSITION AND ANTIBACTERIAL ACTIVITY OF MENTHA PULEGIUM ESSENTIAL OIL FROM TWO ECOTYPES (EL BAYADH AND DJELFA)

Mentha pulegium, collected from two different sites in Algerian high plains (El Bayadh and Djelfa), were analyzed to determine essential oil constituency. Essential oils were extracted by hydrodistillation and subsequently analyzed by GC and GC/MS. Quantitative differences were recorded between the percentages of some constituents between plants from the two geographical origin. The most important major components were: 1,8-cineole, menthone, menthol, cis-Pulegone and Pulegone. The antimicrobial activity of the essential oils was tested using the disc-diffusion assay. The results showed that the essential oil of Mentha pulegium had great potential of antibacterial activity against selected bacteria

Effects of the mint monoterpene (R)-(+)-pulegone evaluated by functional observational battery: A potential short method

Background: Pulegone (PUL) is one of the major constituents of peppermint and pennyroyal. Objective: The main purpose of this study was to investigate the early effects of toxicity of PUL. Materials and Methods: We assessed single doses of toxicity of PUL (2, 0.3 and 0.05 g/kg body weight), administrated by gavage in C57BL/6 mice, evaluated at 1, 6, and 24 h, their clinical status and behavioral, by functional observational battery (FOB), ambulatory conditions, sperm motility, pathological signs, and organ/body weight (O/Bw). Results: No mortality was registered in this in vivo study of oral acute toxicity, in which histological changes were found in selected organs, and PUL mainly showed that the highest concentration reduced mice locomotor activity with significant differences when compared with data of the FOB. Sperm motility also diminished, and hepatic as well as renal alterations were found without modifications in clinical status and O/Bw. Conclusions: We concluded that PUL could be responsible for these findings and consider that FOB is a useful tool to detect early signs of modifications of physiological and biological parameters in mice. Abbreviations Used: PUL: Pulegone, FOB: Functional observational battery, CNS: Central nervous system, OECD: Organization for Economic Cooperation and Development, ANOVA: Analysis of variance, MNI: Mononuclear cell infiltrate, LD50: Median lethal dose

Phytochemical-based nano emulsions for stored grain protection:

Stored grain losses caused by pest insects contribute significantly to the global food crisis. Currently, there are two main chemical control methods against stored product insect pests: fumigation with very toxic gases and grain protection by residual contact insecticides. Today, the global tendency is to prevent/reduce the wide use of insecticides, which have high toxicity to humans and harm the environment. Therefore, there is an urgent need to develop alternative eco-friendly approaches for stored insect pest control. Essential oils from Micromeria fruticosa and Mentha rotundifolia (Fam. Labiatae) and their main constituent pulegone which previously were shown by us as very active against stored product insect pests, were encapsulated into coarse and nano emulsions. The insecticidal activity of the developed formulations against primary internal insect rice weevil (Sitophilus oryzae L.) and secondary external pest red flour beetle (Tribolium castaneum Herbst) was evaluated in laboratory and pilot experiments. It was found that the phytochemical-based nano emulsions offered significant advantages and provided powerful and prolonged biological activity compare with the coarse formulations. The developed nano emulsions could serve as a natural, effective, low-toxify for human, and environmentally preferred method for protection stored grain and dry food products from pest insects.

(R)-(+)-pulegone suppresses allergic and inflammation responses on 2,4-dinitrochlorobenzene-induced atopic dermatitis in mice model

Background(R)-(+)-pulegone (PLG), a biotransformation of monoterpene ketones, is one of essential oils of Labiatae family. Although PLG was reported to have anti-inflammatory and anti-histamine effects, the therapeutic effects of PLG on atopic dermatitis (AD) have not been reported yet. ObjectiveThis study investigated the anti-AD effects and underlying mechanisms of PLG in AD-induced mice. MethodsBALB/c male mice were challenged with 2, 4-dinitrochlorobenzene (DNCB, 1%) to induce AD. After 4 days of rest, PLG (0.1, 1 and 10 μM) were topically applied to dorsal skin for 2 weeks with secondary elicitation using 0.5% DNCB. Histological changes were identified by H&E staining and mast cells were evaluated by toluidine blue staining. Pro-inflammatory cytokines and serum IgE levels were analyzed by ELISA. Inflammatory mediators were measured by western blotting assay. ResultsTopical treatment with PLG significantly suppressed skin thickness and scratching behavior compared with control group. Expression of nerve growth factor was also decreased by PLG treatment. PLG administration decreased serum IgE levels and the number of mast cells in mice model of DNCB-induced AD. The levels of IL-4, IFN-γ, IL-6, TNF-α and IL-1β in dorsal skin of PLG-treated group were lower than those in the control group. PLG inhibited the phosphorylation of MAPKs, as well as IκBα degradation and NF-κB activation. ConclusionsPLG attenuated the symptoms of AD by suppressing cytokines production, the phosphorylation of MAPKs and the activation of NF-κB signaling. These data suggest that PLG may be an effective natural compound for the treatment of inflammatory skin diseases.

Effect of (R)-(+) Pulegone on Ovarian Tissue; Correlation with Expression of Aromatase Cyp19 and Ovarian Selected Genes in Mice.

Objective Pulegone (PGN) is a monoterpene ketone, whose metabolites exert several cytotoxic effects in various tissues. The present study was conducted in order to evaluate the (R)-(+) PGN-induced alterations in ovarian aromatization, proto-oncogenes and estrogen receptorα (ERα) and ERβ receptors expressions. Materials and Methods In this experimental study, mature albino mice were divided into experimental (received 25 mg/kg, 50 mg/kg and 100 mg/kg PGN, orally for 35 days) and control (received 2% solution of Tween 80 as a PGN solvent, orally) groups. The mRNA levels of Erα, Erβ, p53, Bcl-2, and cytochrome p450 (Cyp19) as well as ovarian angiogenesis were analyzed through reverse transcription polymerase chain reaction and immunohistochemical techniques, respectively. Moreover, apoptosis of follicular cells, serum estrogen and progesterone levels and mRNA damage were investigated via using terminal transferase and biotin-16-dUTP staining, electrochemilunescence and fluorescent microscopy methods, respectively. Results The PGN reduced Erα, Erβ and Cyp19 expression at 50 mg/kg and 100 mg/kg doses, while significantly elevating p53 and reducing Bcl-2 expression. Finally, PGN impaired ovarian angiogenesis, increased apoptosis, elevated follicular atresia and reduced serum levels of estrogen and progesterone. ConclusionChronic exposure to PGN (50 mg/kg and 100 mg/kg), severely affects ovarian aromatization, proto- oncogenes mRNA levels and expression of ERs.

Chemical composition of the essential oil of Mentha pulegium L. from Taftan Area by means of gas chromatography/mass spectrometry (GC/MS)

The aerial parts of Mentha pulegium L. were collected during the flowering stage from the Taftan aera (Baluchestan, Iran) using hydro distillation. The essential oil was extracted from plants’ aerial parts. The highest ratio of oil yield to dried plant weight was 2.642 (w/w) (when using hexane) and 2.053% w/w for the second oil (without using hexane). The oils were analyzed using gas chromatography/mass spectrometry (GC/MS) technique. In the first oil (when using Hexane), 35 constituents embracing 96.19% of total essential oil were recognized. Oxygen containing monoterpens was the main group of constituents of the oil. Pulegone (65.52%), 1,8 cineole (11.10%), isopulegone (2.53%), beta-pinene (2.45%) were the major components of the first oil extracted from M. pulegium L. In the second oil (without solvent), 42 constituents were recognized consisting of 82.94% of its total essential oil. The main constituents for this specie included; pulegone (48.88%), eucalyptol (3.99%), trans-ocimene (1.58%), camphene (2.29%), spathulenol (6.99%) and unknown compound (0.1%). The findings of the research revealed that the M. pulegium essential oil has a considerable percentage of oxygenated terpenoids with the anti-microbial property. Key words: Menthe pulegium L., essential oil, gas chromatography/mass spectrometry (GC/MS), pulegone, 1,8 cineole, isopulegone.

Pulegone inhibits selectively butyrylcholinesterase and ameliorates memory in rats

Pulegone inhibits selectively butyrylcholinesterase and ameliorates memory in rats

Ethnoecology of wild mints in Turkey

Genus Mentha is represented by 15 taxa in Turkey, most common being Mentha longifolia, M. suaveolens, M. pulegium and M. aquatica. All are perennial herbs, flowering in summer and reproducing with the help of seeds as well as vegetatively. These taxa are widely used by locals as condiment as well as for the preparation of mint tea aginst flue, lung and stomach disorders, whooping cough, and as diuretic. The plants flourish equally well on sunny and shady habitats, however growth on moist habitats and alongside the watercourses is more profuse with dark green coloured bigger leaves, short roots, longer shoots and higher fruit production. The soils are generally of sandy-loam texture, being calcareous or non-calcareous in nature, pH varying between acidic to alkalinee. Major constituents of the mint oil are menthone, isomenthone, pulegone and menthofuran. M. longifolia plants are 40-120 cm long, with white or purplish white coloured flowers, shoots contain 0.22% volatile oil, with 15-29% menthol content in dry matter and terpinolene lies around 20 ppm. M. suaveolens plants are 40-100 cm tall, with white or lilac coloured flowers, volatile oil content being 0.14%. M. pulegium is 10-40 cm tall, with lilac coloured flowers, volatile oil content in shoots is 0.12%, 60% being pulegon. These plants contain 90 ppm terpinolene. Pulegone in the samples growing on open dry flooded habitats is higher. M. aquatica plants are 20-90 cm tall, with lilac coloured flowers, shoots contain 0.42% volatile oil and 5-37% menthol in the dry matter. Only a small amount of Oleum Menthae is produced on the household basis in Turkey and major amount consumed by the pharmaceutical industry is imported. Out of 10 tons of Mentha pulegium exported by some mediterranean countries nearly 2 tons are from Turkey. This paper presents ethnoecological features of these wild mints on comprative basis and possibilities for their industrial evaluation.

Effect of Mentha longifolia L. ssp longifolia essential oil on the morphology of four pathogenic bacteria visualized by atomic force microscopy

The chemical composition and the antibacterial activity of the essential oil ofMentha longifolia L. ssp longifolia are being investigated in the present work. The minimal inhibitory concentration (MIC) of this oil against four gram+ and gram- reference bacteria including Salmonella typhimurium LT2, Escherichia coli ATCC 35218, Microccus luteus NCIMB 8166 and Staphylococcus aureusATCC 25923 was used to study the morphological alteration of bacterial wall cell visualized by atomic force microscopy (AFM). The chemical analysis of the essential oil showed the presence of 34 compounds. The most important ones were: menthol (32.51%), menthone (20.71%), pulegone (17.76%), 1,8-cineole (5.61%), terpineol-4 (4.87%) and piperitone (2.16%). The MIC for bacteria ranged from 0.19 to 1.56 mg/ml. We found that M. longifolia (Menthol chemotype) has a high antibacterial effect. Cell wall of the tested bacteria was damaged at MIC concentrations. This susceptibility is more accentuated in S.typhimurium and E. coli (rod bacteria), whereas the damage is less important in coccoid bacteria (S. aureus and M. luteus). Key words: Mentha longifolia, essential oil, Staphylococcus aureus, Microccus luteus, Escherichia coli, Salmonella typhimurium, cell morphology, atomic force microscope

Evidence for dopamine involvement in ambulation promoted by pulegone in mice

I investigated whether dopamine (DA) is involved in the ambulation promoted by pulegone (PUL), a constituent of peppermint oil, in ICR mouse. Co-administration of PUL and bupropion (BUP) had an additive effect on their ambulation-promoting activities. When administered with PUL, the DA antagonists chlorpromazine, fluphenazine, haloperidol, SCH12679, and spiperone all attenuated the effect of PUL on ambulation. In addition, pretreatment with the DA depletor reserpine produced no subsequent sensitivity to the effect of PUL. Taken together, DA may be involved in the ability of PUL to promote ambulation in ICR mice but PUL may not be a direct DA agonist. The chemical structure of PUL is similar to menthol and menthone, and thus they may all be acting through a common mechanism.

COMPOSITION OF THE ESSENTIAL OILS OF LAVANDULA STOECHAS L. SUBSP. STOECHAS (BOISS.)

Calamintha Miller (Lamiaceae) is represented in Turkey by 9 species and 13 taxa, 6 being endemic. The rate of endemism in Turkey is over 45%. In the present study, aerial parts of the Calamintha nepeta (L.) Savi subsp. nepeta were collected from the regions of Tarsus (A), Silifke (B), Bart (C) and Calamintha nepeta (L.) Savi subsp. glandulosa (Req.) P.W. Ball collected from the regions of the Zonguldak (D) and Manisa (E). Water distilled essential oils from the aerial parts of Calamintha species from Turkey were analysed by GC and GC/MS. Trans-piperitone oxide (44.4 %) and piperitenone oxide (11.7 %) were detected as main constituents in sample A; Pulegone (11.9 %), menthone (11.9 %) and carvacrol (10.0 %) were found as main constituents in sample B; Trans-piperitone oxide ( 30.9 %), caryophyllene oxide (7.8 %) were detected as main constituents in sample C; Pulegone (19.5 %), menthone (9.7 %), caryophyllene oxide (7.9 %) and trans-piperitone oxide (5.7 %) were detected as main constituents in sample D; Trans-piperitone oxide (34.2 %), limonene (17.3 %) and piperitenone oxide (10.8 %) were found as main constituents in sample E.

Microarray analysis of the gene expression profile of HMC-1 mast cells following Schizonepeta tenuifolia treatment (80.14)

Abstract Objective: This study was conducted to evaluate the anti-inflammation mechanism of Schizonepeta tenuifolia (ST) extract and ST purified chemicals on PMA plus A23187-induced stimulation of HMC-1 human mast cells. Methods: In the present study, the anti-inflammatory effects of ST, Rosmarinic acid (RA), Pulegone (PG), and 2¥á,3¥á,24-thrihydrooxylen-12en-28oic acid (TH) on stimulated HMC-1 cells were then evaluated by analyzing IL-6, IL-8, and TNF-¥á secretion. In addition, the effects of ST, RA, PG, and TH on gene expression profiles in stimulated HMC-1 cells were evaluated by microarray and real time RT-PCR (RTRP). Results: ST, RA, PG, and TH treated HMC-1 cells were significantly suppressed pro-infalmmatory cytokines in dose dependent manner. In addition, the results of the microarray and RTRP revealed that ST regulates several pathways, including cytokine-cytokine receptor interaction (CCRI), MAPK, and the Toll-like receptor (TLR) signaling pathways. Conclusions: ST may have potential efficacy for the treatment of inflammation disease through anti-inflammation activity that occurs via inhibition of the CCRI, MAPK, and TLR signaling pathways.

Hydrogenation of (-)-menthone, (+)-isomenthone, and (+)-pulegone with platinum/tin catalysts

Fil: Vetere, Virginia. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - La Plata. Centro de Investigacion y Desarrollo en Ciencias Aplicadas "Dr. Jorge J. Ronco". Universidad Nacional de la Plata. Facultad de Ciencias Exactas. Centro de Investigacion y Desarrollo en Ciencias Aplicadas; Argentina

Toxicity of Peppermint Monoterpenes to the Variegated Cutworm (Lepidoptera: Noctuidae)

Toxicity of five monoterpenes to the variegated cutworm, Peridroma saucia Hubner, was evaluated. Larvae fed for 6 d from the beginning of the fifth stadium on semi defined artificial diet fortified with pule gone (0.05%, 0.1%), menthol (0.1%, 0.2%), or menthone (0.2%) weighed less than controls. Reduced growth was the result of feeding inhibition in larvae fed menthone and pule gone and to molting abnormalities in larvae receiving menthol. Menthol completely inhibited pupation at doses approximating those in peppermint (0.05-0.2% wet wt). Limonene (0.2%), menthone (0.1%, 0.2%), and pule gone (0.1%) also inhibited pupation. Growth, feeding, and pupation were not affected when larvae ingested limonene (0.05% or 0.1%) or α-pinene (0.05-0.2%). Growth, maximum weight, and pupal weight of neonate larvae fed artificial diet fortified with menthol, menthone (0.05%), Iimonene (0.05%), α-pinene (0.05%), or pule gone (0.025%) did not differ from those of controls. However, larval mortality was significantly higher in menthone and pule gone treatments than in the controls. The median lethal dose for pule gone applied topically to sixth instars was 1,077 μg/g; for menthone, 2,478 μg/g; and for a-pinene, 7,925 μg/g. Piperonyl butoxide synergized the latter two effects. Suspensions of midgut microsomesfrom sixth instars metabolized all five monoterpenes as indicated by disappearance of NADPH.

Preparation of (-)-cis-2,4-Dimethylcyclohexanone from (+)-Pulegone

<b>Preparation of (-)-<b><i>cis</i></b>-2,4-Dimethylcyclohexanone from (+)-Pulegone</b>