Bioactive Molecules of Mandarin Seed Oils Diminish Mycotoxin and the Existence of Fungi.

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.

The terpenes camphene and alpha-bisabolol inhibit inflammatory and neuropathic pain via Cav3.2 T-type calcium channels.

T-type calcium channels are known molecular targets of certain phytocannabinoids and endocannabinoids. Here we explored the modulation of Cav3.2 T-type calcium channels by terpenes derived from cannabis plants. A screen of eight commercially available terpenes revealed that camphene and alpha-bisabolol mediated partial, but significant inhibition of Cav3.2 channels expressed in tsA-201 cells, as well as native T-type channels in mouse dorsal root ganglion neurons. Both compounds inhibited peak current amplitude with IC50s in the low micromolar range, and mediated an additional small hyperpolarizing shift in half-inactivation voltage. When delivered intrathecally, both terpenes inhibited nocifensive responses in mice that had received an intraplantar injection of formalin, with alpha-bisabolol showing greater efficacy. Both terpenes reduced thermal hyperalgesia in mice injected with Complete Freund's adjuvant. This effect was independent of sex, and absent in Cav3.2 null mice, indicating that these compounds mediate their analgesic properties by acting on Cav3.2 channels. Both compounds also inhibited mechanical hypersensitivity in a mouse model of neuropathic pain. Hence, camphene and alpha-bisabolol have a wide spectrum of analgesic action by virtue of inhibiting Cav3.2 T-type calcium channels.

Chemical Composition and Biological Activities of Essential Oils from the Leaves, Stems, and Roots of Kadsura coccinea.

The chemical composition and biological activities of the essential oils from the leaves, stems, and roots of Kadsura coccinea (K. coccinea) were investigated. The essential oils were extracted by hydro distillation and analyzed by gas chromatography mass spectrometry (GC-MS) and gas chromatography with flame ionization detector (GC-FID). Antioxidant activities of the essential oils were examined with DPPH radical scavenging assay, ABTS cation radical scavenging assay, and ferric reducing antioxidant power assay. Antimicrobial activities were evaluated by determining minimum inhibitory concentrations (MIC) and minimum microbiocidal concentrations (MMC). Acetylcholinesterase and butyrylcholinesterase inhibitory activity of the essential oils were also tested. A total of 46, 44, and 47 components were identified in the leaf, stem, and root oils, representing 95.66%, 97.35%, and 92.72% of total composition, respectively. The major compounds of three essential oils were α-pinene (16.60-42.02%), ß-pinene (10.03-18.82%), camphene (1.56-10.95%), borneol (0.50-7.71%), δ-cadinene (1.52-7.06%), and ß-elemene (1.86-4.45%). The essential oils were found to have weak antioxidant activities and cholinesterase inhibition activities. The essential oils showed more inhibitory effects against Staphylococcus aureus (S. aureus) than those of other strains. The highest antimicrobial activity was observed in the root oil against S. aureus, with MIC of 0.78 mg/mL. Therefore, K. coccinea essential oils might be considered as a natural antibacterial agent against S. aureus with potential application in food and pharmaceutical industries.

Myrtenal and ß-caryophyllene oxide screened from Liquidambaris Fructus suppress NLRP3 inflammasome components in rheumatoid arthritis.

BACKGROUND: Liquidambaris Fructus (LF) is the infructescence of Liquidambar formosana. In Traditional Chinese Medicine, LF has been used to treat joint pain, a common symptom of arthritis and rheumatism; however, a lack of pharmacological evidence has limited its applications in modern clinics. Therefore, this study aims to explore the protective effect of LF on rheumatoid arthritis (RA) and to identify its active ingredients. METHODS: Rats with adjuvant-induced arthritis (AIA) were divided into 4 groups and administered petroleum ether extract of LF (PEL), ethyl acetate extract of LF (EEL), water extract of LF (WEL), or piroxicam (PIR) respectively for 3 weeks. Two additional groups were used as normal control (NC) and model control (MC) and administered distilled water as a placebo. The clinical scores for arthritis, bone surface, synovial inflammation and cartilage erosion were used to evaluate the therapeutic efficacy of each treatment. The serum IL-1ß and TNF-α level and the expression of NLRP3, IL-1ß and caspase-1 p20 in the synovial tissue of AIA rats were evaluated by ELISA and Western blot. The active ingredients of LF were investigated using network pharmacology and molecular docking methods, and their inhibition of NLRP3 inflammasome activation was verified in the human rheumatoid arthritis fibroblast-like synovial cells (RA-FLS) model. RESULTS: PEL could alleviate paw swelling, bone and joint destruction, synovial inflammation and cartilage erosion in the AIA rats, with significantly superior efficacy to that of EEL and WEL. PEL reduced IL-1ß and TNF-α serum levels, and attenuated the upregulation of NLRP3, IL-1ß and caspase-1 p20 expression in the synovial tissue of AIA rats. Network pharmacology and molecular docking results indicated that myrtenal and ß-caryophyllene oxide were the main two active ingredients of PEL, and these two compounds showed significant inhibition on TNF-α, NLRP3, IL-1ß and caspase-1 p20 expression in RA-FLS. CONCLUSIONS: Myrtenal and ß-caryophyllene oxide screened from PEL could suppress the activation of NLRP3 inflammasome, thereby alleviating RA symptoms.

Lemon Oils Attenuate the Pathogenicity of Pseudomonas aeruginosa by Quorum Sensing Inhibition.

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.

Wound Healing Activity of α-Pinene and α-Phellandrene.

Bursera morelensis is used in Mexican folk medicine to treat wounds on the skin. Recently, it was shown that the essential oil (EO) of B. morelensis has wound healing activity, accelerating cutaneous wound closure and generating scars with good tensile strength. α-pinene (PIN) and α-phellandrene (FEL) are terpenes that have been found in this EO, and it has been shown in different studies that both have anti-inflammatory activity. The aim of this study was to determine the wound healing activity of these two terpenes. The results of in vitro tests demonstrate that PIN and FEL are not cytotoxic at low concentrations and that they do not stimulate fibroblast cell proliferation. In vivo tests showed that the terpenes produce stress-resistant scars and accelerate wound contraction, due to collagen deposition from the early stages, in wounds treated with both terpenes. Therefore, we conclude that both α-pinene and α-phellandrene promote the healing process; this confirms the healing activity of the EO of B. morelensis, since having these terpenes as part of its chemical composition explains part of its demonstrated activity.

Therapeutic potential of α,ß-thujone through metabolic reprogramming and caspase-dependent apoptosis in ovarian cancer cells.

The therapeutic potential of α,ß-thujone, a functional compound found in many medicinal plants of the Cupressaceae, Asteraceae, and Lamiaceae families, has been demonstrated, including in inflammation and cancers. However, its pharmacological functions and mechanisms of action in ovarian cancer remain unclear. We investigated the anticancer properties of α,ß-thujone in ES2 and OV90 human ovarian cancer cells and its effect on sensitization to cisplatin. α,ß-thujone inhibited cancer cell proliferation and induced cell death through caspase-dependent intrinsic apoptotic pathways. Moreover, α,ß-thujone-mediated endoplasmic reticulum stress was associated with the loss of mitochondrial functions and altered metabolic landscape of ovarian cancer cells. α,ß-Thujone attenuated blood vessel formation in transgenic zebrafish, implying it has significant antiangiogenic potential. In addition, α,ß-thujone sensitized ovarian cancer cells to cisplatin, causing synergistic pharmacological effects. Collectively, our results suggest that α,ß-thujone has therapeutic potential in human ovarian cancer and functions via regulating multiple intracellular stress-associated metabolic reprogramming and caspase-dependent apoptotic pathways.

Industrial, CBD, and Wild Hemp: How Different Are Their Essential Oil Profile and Antimicrobial Activity?

Hemp (Cannabis sativa L.) is currently one of the most controversial and promising crops. This study compared nine wild hemp (C. sativa spp. spontanea V.) accessions with 13 registered cultivars, eight breeding lines, and one cannabidiol (CBD) hemp strain belonging to C. sativa L. The first three groups had similar main essential oil (EO) constituents, but in different concentrations; the CBD hemp had a different EO profile. The concentration of the four major constituents in the industrial hemp lines and wild hemp accessions varied as follows: ß-caryophyllene 11-22% and 15.4-29.6%; α-humulene 4.4-7.6% and 5.3-11.9%; caryophyllene oxide 8.6-13.7% and 0.2-31.2%; and humulene epoxide 2, 2.3-5.6% and 1.2-9.5%, respectively. The concentration of CBD in the EO of wild hemp varied from 6.9 to 52.4% of the total oil while CBD in the EO of the registered cultivars varied from 7.1 to 25%; CBD in the EO of the breeding lines and in the CBD strain varied from 6.4 to 25% and 7.4 to 8.8%, respectively. The concentrations of δ9-tetrahydrocannabinol (THC) in the EO of the three groups of hemp were significantly different, with the highest concentration being 3.5%. The EO of wild hemp had greater antimicrobial activity compared with the EO of registered cultivars. This is the first report to show that significant amounts of CBD could be accumulated in the EO of wild and registered cultivars of hemp following hydro-distillation. The amount of CBD in the EO can be greater than that in the EO of the USA strain used for commercial production of CBD. Furthermore, this is among the first reports that show greater antimicrobial activity of the EO of wild hemp vs. the EO of registered cultivars. The results suggest that wild hemp may offer an excellent opportunity for future breeding and the selection of cultivars with a desirable composition of the EO and possibly CBD-rich EO production.

Biological Evaluation of Essential Oils from Selected Medicinal Plants and Their Main Components against Phytomonas davidi (Kinetoplastea: Trypanosomatidae).

Eight essential oils (EOs) from selected medicinal plants have been tested for their activity against Phytomonas davidi, a plant trypanosomal parasite. In the present research, the EOs have been tested on promastigote forms of P. davidi ATCC® 30287™ strain, along with their major components, both separately and in binary combinations, using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay. The EOs with the highest antipromastigote activity were from Origanum virens and Salvia lavandulifolia. Thymol and ß-pinene were the most active pure compounds. The study of the activity of the pure compounds in combination indicated the existence of antagonistic and synergistic effects depending on the concentration tested. In general, the combinations at low concentrations favored the activity.

Effect of the Association and Evaluation of the Induction to Adaptation of the (+)-α-pinene with Commercial Antimicrobials against Strains of Escherichia coli.

BACKGROUND: The increasing and inappropriate use of antibiotics has increased the number of multidrug-resistant microorganisms to these drugs, causing the emergence of infections that are difficult to control and manage by health professionals. As an alternative to combat these pathogens, some monoterpenes have harmful effects on the bacterial cell membrane, showing themselves as an alternative in combating microorganisms. Therefore, the positive enantiomer α -pinene becomes an alternative to fight bacteria, since it was able to inhibit the growth of the species Escherichia coli ATCC 25922, demonstrating the possibility of its use as an isolated antimicrobial or associated with other drugs. AIMS: The aim of this study is to evaluate the sensitivity profile of E. coli ATCC 25922 strain against clinical antimicrobials associated with (+) -α-pinene and how it behaves after successive exposures to subinhibitory concentrations of the phytochemicals. METHODS: The minimum inhibitory concentration (MIC) was determined using the microdilution method. The study of the modulating effect of (+) -α-pinene on the activity of antibiotics for clinical use in strains of E. coli and the analysis of the strain's adaptation to the monoterpene were tested using the adapted disk-diffusion method. RESULTS: The results demonstrate that the association of monoterpene with the antimicrobials ceftazidime, amoxicillin, cefepime, cefoxitin and amikacin is positive since it leads to the potentiation of the antibiotic effect of these compounds. It was observed that the monoterpene was able to induce crossresistance only for antimicrobials: cefuroxime, ceftazidime, cefepime and chloramphenicol. CONCLUSION: It is necessary to obtain more concrete data for the safe use of these combinations, paying attention to the existence of some type of existing toxicity reaction related to the herbal medicine and to understand the resistance mechanisms acquired by the microorganism.

Protective effect of alpha-pinene against isoproterenol-induced myocardial infarction through NF-κB signaling pathway.

Monoterpenes present in the essential oils exhibit anti-inflammatory properties. In this study, we investigated the preventive effect of alpha-pinene (AP), a monoterpene, against isoproterenol (ISO)-induced myocardial infarction and inflammation in Wistar rats. Male Wistar rats were pretreated with AP (50 mg/kg body weight (bw)) administration for 21 days and ISO (85 mg/kg bw) was administered subcutaneously for last two consecutive days (20th day and 21st day). We noticed that there was an increased activity of cardiac marker enzymes in ISO-treated rats. We also observed that elevated levels of lipid peroxidative indices decreased activities of antioxidant status in plasma, erythrocyte, and heart tissue in ISO-induced rats. Furthermore, ISO-treated rats showed an increase in the levels of inflammatory mediators like tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the serum. Besides, we confirmed the upregulated expression of TNF-α, IL-6, and nuclear factor kappa-light-chain-enhancer of activated B cells in ISO-induced rat heart tissue. Conversely, we found that AP pretreatment significantly decreased levels of cardiac markers like serum cardiac troponin T and cardiac troponin I, lipid peroxidative markers, and restored antioxidants status in ISO-treated rats. Besides, AP administration attenuated ISO-induced inflammatory marker expression. The present findings demonstrated that AP significantly protects the myocardium and exerts cardioprotective and anti-inflammatory effects in experimental rats.

Bergamot essential oil nanoemulsions: antimicrobial and cytotoxic activity.

Bergamot essential oil (BEO) is well-known for its food preservation activity, as well as anticancer efficacy. However, the poor BEO water solubility and deriving low bioaccessibility have limited its wider applications. The incorporation in nanoemulsions of BEO and its refined fractions was investigated to enhance its dispersibility in water to promote its antimicrobial activity, tested against Escherichia coli, Lactobacillus delbrueckii, and Saccharomyces cerevisiae, and its cytotoxicity already at low concentrations. Different nanoemulsion formulations were tested based on food-grade ingredients, which were characterized in terms of hydrodynamic diameter and polydispersity index, and physical stability. The antimicrobial activity against all the tested micro-organisms was observed to be higher for BEO in its initial composition, than the light fraction, richer in d-limonene, ß-pinene, and γ-terpinene, or the heavy fraction, richer in linalyl acetate and linalool. Remarkably, the use of BEO nanoemulsions notably enhanced the antimicrobial activity for all the tested oils. BEO exhibited also a measurable cytotoxic activity against Caco-2 cells, which was also enhanced by the use of the different nanoemulsions tested, in comparison with free oil, which discourages the direct use of BEO nanoemulsions as a food preservative. Conversely, BEO nanoemulsions might find use in therapeutic applications as anticarcinogenic agents.

α-Pinene odor exposure enhances heat stress tolerance through Daf-16 in Caenorhabditis elegans.

Aromatherapy has been widely used as complementary and alternative medicine to reduce pain and induce sleep. However, the scientific evidence regarding the biological effects of odor is scarce and the underlying molecular mechanisms have not been clarified. We treated worms with contactless S-(-)- and R-(+)-α-pinene and analyzed heat stress tolerance. Odor stimulation induced motility recovery after incubation at 35 °C for 4 h. This increase in heat stress tolerance was not present in odr-3 mutants and daf-16 mutants. S-(-)- and R-(+)-α-pinene expanded health span and increased fat accumulation. Moreover, S-(-)- and R-(+)-α-pinene modulated the expression of 84 and 54 genes, respectively. These results show that α-pinene odor stimulation is related to stress tolerance, lipid metabolism, and health span via some specific signaling pathways. This study may provide a potential target for antiaging and disease prevention.

α,ß-Thujone suppresses human placental choriocarcinoma cells via metabolic disruption.

α,ß-Thujone is a natural terpenoid found in many medicinal herbs, such as Artemisia absinthium (wormwood), that exhibits antioxidant, anti-diabetic, and anti-tumorigenic effects. α,ß-Thujone has numerous functions; it serves as a food ingredient, cosmetic additive, and medicinal remedy. Although the therapeutic properties of α,ß-thujone were previously revealed, a comprehensive description of the mechanisms of its anti-cancer potential in choriocarcinoma is yet to be provided. To our knowledge, this study is the first to demonstrate that α,ß-thujone attenuates JEG3 and JAR choriocarcinoma cells through a caspase-dependent intrinsic apoptotic pathway. Moreover, α,ß-thujone was demonstrated to induce a global mitochondrial defect and ER stress in choriocarcinoma by causing mitochondrial depolarization, calcium overload, and metabolic alterations, thereby leading to energy deprivation, which eventually contributes to the increase in apoptosis of choriocarcinoma cells. Herein, we also revealed the synergistic anti-cancer activity of α,ß-thujone via its sensitization effect on paclitaxel in choriocarcinoma cells. Altogether, our findings suggest that α,ß-thujone is a novel, natural pharmacological compound that can be used to treat human placental choriocarcinoma.

Antioxidant and Antiproliferative Potential of Bioactive Molecules Ursolic Acid and Thujone Isolated from Memecylon edule and Elaeagnus indica and Their Inhibitory Effect on Topoisomerase II by Molecular Docking Approach.

The present study aimed to evaluate the antioxidant and antiproliferative potential of ursolic acid and thujone isolated from leaves of Elaeagnus indica and Memecylon edule and their inhibitory effect on topoisomerase II using molecular docking study. The isolated ursolic acid and thujone were examined for different types of free radicals scavenging activity, the antiproliferative potential on U-937 and HT-60 cell lines by adopting standard methods. Further, these compounds were docked with the active site of the ATPase region of topoisomerase II. The findings of the research revealed that ursolic acid harbor strong antioxidant and antiproliferative capacity with low IC50 values than the thujone in all tested methods. Moreover, ursolic acid shows significant inhibition effect on topoisomerase II with a considerable docking score (-8.0312) and GLIDE energy (-51.86 kca/mol). The present outcome concludes that ursolic acid possesses significant antioxidant and antiproliferative potential, which can be used in the development of novel antioxidant and antiproliferative agents in the future.

Sedative effects of the essential oil from the leaves of Lantana camara occurring in the Republic of Benin via inhalation in mice.

Lantana camara Linn. (Verbenaceae) is used traditionally for its numerous medicinal properties such as antimalarial, antibacterial, anticancer and anti-inflammatory. In the present study, we investigated the chemical composition of essential oil from the leaves of L. camara (LCEO) occurring in the Republic of Benin (West Africa) in comparison with LCEOs from other regions; evaluated its sedative effects in mice via inhalation administration; and identified the compounds responsible for activity. LCEO was extracted by hydrodistillation and chemical analyses of the oil were performed by GC and GC/MS. The oil was dominated by monoterpene hydrocarbons (60.58%) and oxygenated monoterpenes (33.39%), among which sabinene (38.81%) and 1,8-cineole (28.90%) were the most abundant. LCEO administered via inhalation to mice significantly decreased locomotor activity in a dose-dependent manner, mainly at the doses of 0.0004 and 0.04 mg per 400 µL of triethyl citrate (TEC). The oil was fractionated to give two fractions, which were further investigated, and revealed that both sabinene and 1,8-cineole were the principal active compounds. The results of the present study indicated that via inhalation administration, LCEO and its main constituents could be considered as promising candidates for the management of dementia, insomnia, attention deficit hyperactivity disorder and other central nervous system-associated diseases.

Cytisus scoparius and Ulex europaeus Produce Volatile Organic Compounds with Powerful Synergistic Herbicidal Effects.

New herbicides based on natural products are claimed to address weed resistance and environmental concerns related to synthetic herbicides. In our previous studies, certain volatile organic compounds (VOCs) produced by Ulex europaeus and Cytisus scoparius were argued to be responsible for the phytotoxicity of both shrub species. Interactions among VOCs were hypothesized to explain the inconsistency between the effects of the identified pure compounds and those naturally emitted from fresh plant material. In this work, eugenol, verbenone, terpinen-4-ol, α-terpineol, and linalool were assayed as binary mixtures of Amaranthus retroflexus and Digitaria sanguinalis. Powerful synergistic inhibitory effects were revealed for germination and early growth. Only 3.1 ppm of verbenone was enough to inhibit A. retroflexus germination when paired to other VOCs. Eugenol was capable of exacerbating the effects of terpinen-4-ol on A. retroflexus, even though it was innocuous when acting alone at 12.5 ppm. The verbenone and linalool pair produced very significant synergistic effects in terms of D. sanguinalis germination. The synergistic effects were predominantly irreversible for D. sanguinalis, since seeds exposed to paired VOCs were unable to recover their germination capacity after removing the phytotoxins or produced damaged seedlings. Both shrub species have been revealed as sources of natural herbicide molecules, with promising synergistic modes of action that deserve to be studied in depth.

Chemical Composition and Antimicrobial Activity of Essential Oils from the Aerial Parts of Pinus eldarica Grown in Northwestern Iran.

Pinus eldarica (Pinaceae), an evergreen plant, is distributed across the warm and dry climates of western Asia, including Asia Minor, the Middle East, and land surrounding the Caspian Sea. Essential oils (EOs) from different aerial parts of this tree have been used in traditional medicine. We aimed to investigate the chemical profile and antimicrobial activity of the EO from P. eldarica grown in northwestern Iran. EO from the needles, bark, and pollen were extracted with boiling water using a Clevenger apparatus at yield of 0.7-1.2 cm3/100 g of dry plant material. The main chemical components of the EO from the needles were D-germacrene (18.17%), caryophyllene (15.42%), γ-terpinene (12.96%), and ß-pinene (10.62%); those from the bark were limonene (16.99%), caryophyllene oxide (13.22%), and drimenol (13.2%); and those from the pollen were α-pinene (25.64%) and limonene (19.94%). In total, 83 constituents were characterized in the EOs, using gas chromatography mass spectrometry analysis; mainly, sesquiterpene hydrocarbons in needle EO and monoterpene hydrocarbons in pollen and bark EOs. ß-Pinene, ß-myrcene, limonene, and caryophyllene were identified in the EOs from all three plant parts. The antibacterial and antifungal properties of the EOs were examined: pollen EO exhibited antibacterial activity against Escherichia coli; bark EO inhibited the growth of Candida albicans and Staphylococcus aureus; and the needle EO inhibited the growth of S. aureus. Thus, the EOs from aerial parts of P. eldarica can benefit the EO industry and antibiotic development.

A Fragrant Environment Containing α-Pinene Suppresses Tumor Growth in Mice by Modulating the Hypothalamus/Sympathetic Nerve/Leptin Axis and Immune System.

The environment is thought to affect outcomes in patients with cancer; however, this relationship has not been proven directly. Recently, an enriched environment, as a model of a positive environment, has been shown to suppress tumor growth by lowering leptin production through a pathway involving the hypothalamus/sympathetic nerve/leptin axis. We previously reported that a fragrant environment (FE) containing α-pinene suppressed tumor growth in mice; however, the underlying mechanism has not been elucidated. Accordingly, in this study, we investigated changes in the neuroendocrine and immune systems following exposure to an FE. Mice were exposed to α-pinene (5 h/day) for 4 weeks prior to tumor implantation with murine melanoma cells and 3 weeks after transplantation. In addition to the evaluation of tumor growth, the blood, spleen, and hypothalamus were collected 3 weeks after transplantation, and neuroendocrinological and immunological parameters were measured. Tumor size was ~40% smaller in mice exposed to FE. Moreover, plasma noradrenaline concentrations, which reflected sympathetic nervous activity, tended to increase, and leptin levels were significantly decreased in FE-exposed mice. Levels of stress hormones, such as plasma corticosterone and adrenaline, did not change in the 2 groups. In the hypothalamus, brain-derived neurotrophic factor protein levels and glucose-1-phosphate concentrations were decreased in the FE group. Additionally, numbers of B cells, CD4+ T cells, CD8+ T cells, and natural killer cells increased in the FE-exposed mice. These neurohormonal and immunological changes in the FE-exposed mice suggested that the FE may activate the hypothalamus/sympathetic nerve/leptin axis and immune system, thereby retarding tumor growth.