The Effects of Essential Oils on the Nervous System: A Scoping Review.

Essential oils are a mixture of natural aromatic volatile oils extracted from plants. The use of essential oils is ancient, and has prevailed in different cultures around the world, such as those of the Egyptians, Greeks, Persians, and Chinese. Today, essential oils are used in traditional and complimentary medicines, aromatherapy, massage therapies, cosmetics, perfumes and food industries. The screening effect of essential oils has been studied worldwide. They demonstrate a range of biological activities, such as antiparasitic, antifungal, antibacterial, antiviral, antioxidant, anti-inflammatory, anticancer, antiaging, and neuroprotective properties. In this scoping review, we provide a 10-year updated comprehensive assessment of volatile oils and their effects on the nervous system. MEDLINE, Scopus, and Google Scholar were systematically and strategically searched for original studies investigating these effects from 2012 to 2022. Approximately seventy studies were selected as included studies. Among these studies, several outcomes were reported, including antistress, antianxiety, analgesic, cognitive, and autonomic effects. Some essential oils showed developmental benefits, with the potential to induce neurite outgrowth. The neurotransmitter receptor level can also be modified by essential oil application. Physiological and pathophysiological outcome measures were reported. For physiological outcomes, arousal, cognitive performance, circadian eating behavior, emotional modulation, consumer acceptance, preferences, and willingness to buy were investigated. For pathophysiological conditions, pain, depression, anxiety, stress, sleep disorder, mental fatigue, agitated behavior, and quality of life were measured. In conclusion, essential oils showed promising effects on the nervous system, which can be further applied to their use in functional foods, drinks, and alternative therapy.

Effects of Ceftriaxone on Oxidative Stress and Inflammation in a Rat Model of Chronic Cerebral Hypoperfusion.

Ceftriaxone (CTX) exerts a neuroprotective effect by decreasing glutamate excitotoxicity. We further studied the underlying mechanisms and effects of CTX early post-treatment on behavior in a cerebral hypoperfusion rats. The rats' common carotid arteries (2VO) were permanently ligated. CTX was treated after ischemia. Biochemical studies were performed to assess antioxidative stress and inflammation. Behavioral and histological studies were then tested on the ninth week after vessel ligation. The 2VO rats showed learning and memory deficits as well as working memory impairments without any motor weakness. The treatment with CTX was found to attenuate white matter damage, MDA production, and interleukin 1 beta and tumor necrosis factor alpha production, mainly in the hippocampal area. Moreover, CTX treatment could increase the expression of glia and the glial glutamate transporters, and the neuronal glutamate transporter. Taken together, our data indicate the neuroprotective mechanisms of CTX involving the upregulation of glutamate transporters' expression. This increased expression contributes to a reduction in glutamate excitotoxicity and oxidative stress as well as pro-inflammatory cytokine production, thus resulting in the protection of neurons and tissue from further damage. The present study highlights the mechanism of the effect of CTX treatment and of the underlying ischemia-induced neuronal damage.

Oxocrebanine from Stephania pierrei exerts macrophage anti-inflammatory effects by downregulating the NF-κB, MAPK, and PI3K/Akt signalling pathways.

Plant-derived medicinal compounds are increasingly being used to treat acute and chronic inflammatory diseases, which are generally caused by aberrant inflammatory responses. Stephania pierrei Diels, also known as Sabu-lueat in Thai, is a traditional medicinal plant that is used as a remedy for several inflammatory disorders. Since aporphine alkaloids isolated from S. pierrei tubers exhibit diverse pharmacological characteristics, we aimed to determine the anti-inflammatory effects of crude extracts and alkaloids isolated from S. pierrei tubers against lipopolysaccharide (LPS)-activated RAW264.7 macrophages. Notably, the n-hexane extract strongly suppressed nitric oxide (NO) while exhibiting reduced cytotoxicity. Among the five alkaloids isolated from the n-hexane extract, the aporphine alkaloid oxocrebanine exerted considerable anti-inflammatory effects by inhibiting NO secretion. Oxocrebanine also significantly suppressed prostaglandin E2, tumour necrosis factor-α, interleukin (IL)-1ß, IL-6, inducible nitric oxide synthase, and cyclooxygenase (COX)-2 protein expression by inactivating the nuclear factor κB, c-Jun NH2-terminal kinase, extracellular signal-regulated kinase 1/2, and phosphatidylinositol 3-kinase/Akt inflammatory signalling pathways. Molecular docking analysis further revealed that oxocrebanine has a higher affinity for toll-like receptor 4/myeloid differentiation primary response 88 signalling targets and the COX-2 protein than native ligands. Thus, our findings highlight the potential anti-inflammatory effects of oxocrebanine and suggest that certain alkaloids of S. pierrei could be used to treat inflammatory diseases.

Effects of Thai Local Ingredient Odorants, Litsea cubeba and Garlic Essential Oils, on Brainwaves and Moods.

The functional food market is growing with a compound annual growth rate of 7.9%. Thai food recipes use several kinds of herbs. Lemongrass, garlic, and turmeric are ingredients used in Thai curry paste. Essential oils released in the preparation step create the flavor and fragrance of the famous tom yum and massaman dishes. While the biological activities of these ingredients have been investigated, including the antioxidant, anti-inflammatory, and antimicrobial activities, there is still a lack of understanding regarding the responses to the essential oils of these plants. To investigate the effects of essential oil inhalation on the brain and mood responses, electroencephalography was carried out during the non-task resting state, and self-assessment of the mood state was performed. The essential oils were prepared in several dilutions in the range of the supra-threshold level. The results show that Litsea cubeba oil inhalation showed a sedative effect, observed from alpha and beta wave power reductions. The frontal and temporal regions of the brain were involved in the wave alterations. Garlic oil increased the alpha wave power at lower concentrations; however, a sedative effect was also observed at higher concentrations. Lower dilution oil induced changes in the fast alpha activity in the frontal region. The alpha and beta wave powers were decreased with higher dilution oils, particularly in the temporal, parietal, and occipital regions. Both Litsea cubeba and turmeric oils resulted in better positive moods than garlic oil. Garlic oil caused more negative moods than the others. The psychophysiological activities and the related brain functions require further investigation. The knowledge obtained from this study may be used to design functional food products.

1,7­Bis(4­hydroxy­3­methoxyphenyl)­1,4,6­heptatrien­3­one alleviates lipopolysaccharide­induced inflammation by targeting NF­κB translocation in murine macrophages and it interacts with MD2 in silico.

Trienones are curcuminoid analogues and are minor constituents in the rhizomes of numerous Curcuma plant species. Studies investigating the biological activities of trienones, particularly their anti­inflammatory activities, are limited. In the present study, the trienone 1,7­bis(4­hydroxy­3­methoxyphenyl)­1,4,6­heptatrien­3­one (HMPH) was structurally modified from curcumin using a novel and concise method. HMPH was shown to exhibit potential anti­inflammatory effects on lipopolysaccharide (LPS)­activated RAW264.7 macrophages. Furthermore, LPS­induced nitric oxide secretion in RAW264.7 cells was markedly and dose­dependently inhibited by HMPH; in addition, HMPH had a greater efficacy compared with curcumin. This inhibition was accompanied by the suppression of inducible nitric oxide synthase and cyclooxygenase­2 expression, as well as pro­inflammatory cytokine secretion. To elucidate the molecular mechanism underlying the anti­inflammatory effects of HMPH, the effects of this compound on nuclear factor­κB (NF­κB) translocation were assessed. HMPH significantly inhibited the translocation of p65 NF­κB into the nucleus to a greater extent than curcumin, thus indicating that HMPH has more potent anti­inflammatory activity than curcumin. In addition, an in silico modelling study revealed that HMPH possessed stronger binding energy to myeloid differentiation factor 2 (MD2) compared with that of curcumin, and indicated that the anti­inflammatory effects of HMPH may be through upstream inhibition of the inflammatory pathway. In conclusion, HMPH may be considered a promising compound for reducing inflammation via targeting p65 NF­κB translocation and interfering with MD2 binding.

Effects of Tangerine Essential Oil on Brain Waves, Moods, and Sleep Onset Latency.

Tangerine (Citrus tangerina) is one of the most important crops of Thailand with a total harvest that exceeds 100,000 tons. Citrus essential oils are widely used as aromatherapy and medicinal agents. The effect of tangerine essential oil on human brain waves and sleep activity has not been reported. In the present study, we therefore evaluated these effects of tangerine essential oil by measurement of electroencephalography (EEG) activity with 32 channel platforms according to the international 10-20 system in 10 male and 10 female subjects. Then the sleep onset latency was studied to further confirm the effect on sleep activity. The results revealed that different concentrations, subthreshold to suprathreshold, of tangerine oil gave different brain responses. Undiluted tangerine oil inhalation reduced slow and fast alpha wave powers and elevated low and mid beta wave powers. The subthreshold and threshold dilution showed the opposite effect to the brain compared with suprathreshold concentration. Inhalation of threshold concentration showed effectively decreased alpha and beta wave powers and increased theta wave power, which emphasize its sedative effect. The reduction of sleep onset latency was confirmed with the implementation of the observed sedative effect of tangerine oil.

Heme oxygenase-1 alleviates alcoholic liver steatosis: histopathological study.

Excessive alcohol consumption is one of the most important causes of hepatic steatosis, which involves oxidative stress. In particular, increased oxidative stress has been strongly linked to stimulation of the expression of heme oxygenase-1 (HO-1). This study aimed to investigate whether HO-1 could alleviates alcoholic steatosis in rats. Male Wistar rats were randomly divided into 4 groups: 1) the control group, 2) the EtOH group, 3) the EtOH + ZnPP-IX group and 4) the EtOH + Hemin group. Liver histopathology was investigated in weeks 1 and 4 after the start of the treatment period. Alcohol treatment significantly increased the hepatic malondialdehyde (MDA) levels, an oxidative stress marker. In addition, it increased the triglyceride, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in both weeks. Gross examination demonstrated a yellowish and slightly enlarged liver in the alcohol-treated rats. Hematoxylin and eosin (H&E) and Oil Red O staining indicated hepatic steatosis, which was characterized by diffuse, extensive fatty accumulation and discrete lipid droplets of variable size in hepatocytes of the alcohol-treated rats. Administration of the HO-1 inducer hemin resulted in upregulation of hepatic HO-1 gene expression, reduced the MDA, triglyceride, ALT and AST levels and alleviated alcoholic hepatic steatosis, whereas administration of the HO-1 inhibitor zinc protoporphyrin IX (ZnPP-IX) resulted in downregulation of hepatic HO-1 gene expression and could not alleviate alcoholic hepatic steatosis either week. In conclusion, HO-1 could alleviate alcoholic hepatic steatosis in male Wistar rats and may be useful in development of a new therapeutic approach.

Study designs to investigate Nox1 acceleration of neoplastic progression in immortalized human epithelial cells by selection of differentiation resistant cells.

To investigate the role of NADPH oxidase homolog Nox1 at an early step of cell transformation, we utilized human gingival mucosal keratinocytes immortalized by E6/E7 of human papillomavirus (HPV) type 16 (GM16) to generate progenitor cell lines either by chronic ethanol exposure or overexpression with Nox1. Among several cobblestone epithelial cell lines obtained, two distinctive spindle cell lines - FIB and NuB1 cells were more progressively transformed exhibiting tubulogenesis and anchorage-independent growth associated with increased invasiveness. These spindle cells acquired molecular markers of epithelial mesenchymal transition (EMT) including mesenchymal vimentin and simple cytokeratins (CK) 8 and 18 as well as myogenic alpha-smooth muscle actin and caldesmon. By overexpression and knockdown experiments, we showed that Nox1 on a post-translational level regulated the stability of CK18 in an ROS-, phosphorylation- and PKCepilon-dependent manner. PKCepilon may thus be used as a therapeutic target for EMT inhibition. Taken together, Nox1 accelerates neoplastic progression by regulating structural intermediate filaments leading to EMT of immortalized human gingival epithelial cells.

Role of myocyte enhancing factor 2B in epithelial myofibroblast transition of human gingival keratinocytes.

It has recently emerged that the myogenic contribution of the epithelial mesenchymal transition plays a role in neoplastic invasion and metastasis. Myocyte enhancing factor 2B (MEF2B) is the only MEF2 isoform expressed during early embryonic development, and is herein proposed to transactivate the downstream target proteins of the epithelial myofibroblast transition (EMyT). We have previously generated eight preneoplastic cell lines with spindle and cobblestone morphology from human gingival mucosal keratinocytes immortalized by E6/E7 of human papillomavirus type 16. Spindle cells formed tubulogenic morphogenesis on Matrigel and exhibited contractility, anchorage-independent growth and invasiveness to a greater extent than cobblestone cells. Expression of MEF2B mRNA and myofibroblast proteins was higher in spindle cells compared with cobblestone cells. Epidermal growth factor (EGF) treatment of cobblestone cells also induced expression of these genes. Knockdown of MEF2B in a cobblestone cell line abolished EGF-induced upregulation of MEF2, vimentin and non-muscle caldesmon proteins, but enhanced basal expression of mesenchymal vimentin and fibronectin. Differential regulation of intermediate filaments revealed an unrecognized role of MEF2B in myogenic transformation of the epithelial to a myofibroblast phenotype, which occurs as epithelioid variants in some soft tissue sarcomas.

Redox regulation of cytokeratin 18 protein by NADPH oxidase 1 in preneoplastic human epithelial cells.

INTRODUCTION: A catalytic subunit of NADPH oxidase 1 (Nox1) is implicated to be involved in neoplastic progression in human epithelial cancers. We had previously demonstrated that Nox1 overexpression of immortalized epithelial cells was able to induce the generation of progenitor cells that expressed fetal-type cytokeratins 8 and 18. PURPOSE: We aimed to investigate the direct effects and underlying mechanisms of Nox1 on expression of cytokeratin 18 (CK18). METHODS: Immortalized human epithelial GM16 cells with low CK18 were used in Nox1 overexpression experiments. NuB2 cells with high CK18 were used in Nox1 knockdown experiments. Protein expression of CK18, phosphorylated and ubiquitinated CK18 were analyzed by Western blot. RESULTS: With no effects on the mRNA levels, CK18 protein was increased upon Nox1 overexpression and decreased upon Nox1 knockdown. Treatment with proteasome inhibitor MG132 prevented CK18 degradation and increased CK18 protein indicating translational regulation of CK18. Treatment for NuB2 cells with N-acetyl-L: -cysteine, diphenyleneiodonium, or apocynin decreased CK18 protein levels indicating its regulation involving reactive oxygen species and flavoprotein Nox. It has been known that phosphorylation of CK18 regulates CK18 turnover by ubiquination. Consistently, Nox1 modulated CK18 phosphorylation at ser52. Nox1 knockdown and treatment with diphenyleneiodonium accumulated the levels of ubiquinated CK18 enhancing degradation causing decreased CK18 protein. CONCLUSION: We demonstrated that Nox1 was able to induce CK18 stabilization by inhibiting CK18 protein degradation in a phosphorylation-dependent manner. CK18 accumulation induced by Nox1 is consistent with the persistence of fetal-type CK18 protein in many epithelial carcinomas.

Human papillomavirus 16 E6/E7-immortalized human gingival keratinocytes with epithelial mesenchymal transition acquire increased expression of cIAP-1, Bclx and p27(Kip1).

Epithelial mesenchymal transition (EMT) has been implicated in neoplastic invasion and metastasis. We have previously generated six cell lines from human gingival mucosal keratinocytes immortalized by E6/E7 of human papillomavirus type 16. Ldk and NuB1 lines represented EMT phenotype and other four lines represented cobblestone non-EMT phenotype. These cell lines were utilized as model cells to determine whether inhibitors of apoptosis proteins and cell-cycle regulators were molecular players during EMT. EMT cells exhibited increased expression of vimentin, vascular endothelial growth factor (VEGF) receptor1 and the ability to form tubules on Matrigel as well as to grow anchorage independently. We found that EMT cells expressed significantly elevated levels of cIAP-1, Bclx and p27(kip) higher than non-EMT cells. These proteins could therefore be used as intrinsic indicators of EMT of human gingival keratinocytes.