Lavandula angustifolia Mill. inhibits high glucose and nicotine-induced Ca2+ influx in microglia and neuron-like cells via two distinct mechanisms.

Smoking remains a significant health problem in patients with type 2 diabetes mellitus. This study compared intracellular Ca2+ ([Ca2+]i) in microglia, neurons, and astrocytes in the presence of high glucose (HG) and nicotine and evaluated the effects of Lavandula angustifolia Mill. essential oil (LEO) on this process. [Ca2+]i concentrations were measured by monitoring the fluorescence of Fura-2 acetoxymethyl ester. Treatment with HG and nicotine significantly increased [Ca2+]i in both microglia and neurons through Ca2+ influx from extracellular sources. This increased Ca2+ influx in microglia, however, was significantly reduced by LEO, an effect partially inhibited by the Na+/Ca2+ exchanger (NCX) inhibitor Ni2+. Ca2+ influx in neuron-like cells pretreated with HG plus nicotine was also significantly decreased by LEO, an effect partially inhibited by the L-type Ca2+ channel blocker nifedipine and the T-type Ca2+ channel blocker mibefradil. LEO or a two-fold increase in the applied number of astrocytes attenuated Ca2+ influx caused by high glucose and nicotine in the mixed cells of the microglia, neuron-like cells and astrocytes. These findings suggest that LEO can regulate HG and nicotine-induced Ca2+ influx into microglia and neurons through two distinct mechanisms.

Alleviating effect of lavender (Lavandula angustifolia) and its major components on postherpetic pain: a randomized blinded controlled trial.

BACKGROUND: Postherpetic neuralgia (PHN) causes severe pain which can lead to decreased quality-of-life. This study aimed to evaluate the effects of inhalation of lavender (Lavandula angustifolia) oil and its major components (linalool and linalyl acetate) on the pain in patients with PHN. METHODS: This study was performed at an outpatient clinic. Sixty-four patients with postherpetic neuralgia were randomly allocated to a control group (almond oil) or one of three experimental groups (lavender oil, linalool, or linalyl acetate diluted in almond oil at concentration of 1% v/v), and the participants inhaled the aroma by natural breathing. Quality, severity, and intensity of pain were measured before and after the intervention. RESULTS: Six patients discontinued the intervention for personal reasons; hence, data from 58 patients were analyzed (control group, n = 14; 1% lavender oil group, n = 15; 1% linalool, n = 15; 1% linalyl acetate, n = 14). Reduction in sensory pain was greater in the 1% lavender oil group, 1% linalool group, and 1% linalyl acetate group than in the control group (all P < 0.001). Reduction in affective pain was greater in the 1% lavender group (P < 0.001) and the 1% linalool group (P = 0.007) than in the control group. Decreases in pain severity and intensity were significantly greater in all three intervention groups than in the control group. CONCLUSIONS: Inhalation of lavender oil and its major volatile components effectively reduced the quality, severity, and intensity of postherpetic pain, suggesting that lavender oil, linalool, and linalyl acetate may each be an effective intervention for reducing pain in patients with postherpetic neuralgia. TRIAL REGISTRATION: This study was retrospectively registered on the Clinical Research Information Service. REGISTRATION NUMBER: KCT0007772, first registration 06/10/2022.

Inhalation of Origanum majorana L. essential oil while working reduces perceived stress and anxiety levels of nurses in a COVID-19 intensive care unit: a randomized controlled trial.

Background: Nurses caring for patients with coronavirus disease 2019 (COVID-19) experience higher psychosocial distress than other healthcare workers, and this can adversely affect the quality of patient care. There is evidence that inhalation of essential oil from marjoram (Origanum majorana L.) has calming effects, suggesting this intervention may help to reduce the stress and anxiety of nurses working in a COVID-19 intensive care unit (ICU). This study aimed to investigate the effect of inhalation of marjoram essential oil at work on the stress and anxiety levels of nurses in a COVID-19 ICU. Methods: Nurses (n = 57) working in a single COVID-19 ICU were randomly assigned to inhale 3% marjoram essential oil (marjoram group, n = 29) or almond oil (control group, n = 28) for 2 h while at work. Mean arterial pressure (MAP), heart rate, state anxiety score, and score on a visual analog scale for anxiety (VAS-anxiety) and stress (VAS-stress) were measured before and after the intervention. Results: The two groups had similar baseline variables. MAP did not have within-group or between-group differences. Heart rate increased significantly in the marjoram group after the intervention (p = 0.031), but it remained within the normal range and the increase was not clinically meaningful. There was no significant between-group difference in the state-anxiety or VAS-anxiety score after the intervention, but the marjoram group had a significantly lower state-anxiety (p = 0.001) and VAS-anxiety (p = 0.037) score at posttest vs. pretest. The VAS-stress score was significantly lower in the marjoram group at the posttest vs. the pretest (p = 0.026). Conclusion: Nurses caring for patients in a COVID-19 ICU experience significant stress, and strategies are needed to address this important issue. Inhalation of 3% marjoram essential oil while caring for patients in a COVID-19 ICU may be a simple and effective intervention that reduces perceived stress and anxiety in nurses.Clinical Trial Registration: https://cris.nih.go.kr/, KCT0007543.

BodyThink program-based body image education improves Korean adolescents' attitudes toward cosmetic surgery: randomized controlled trial.

BACKGROUND: The aims of this study were to modify the widely used BodyThink program to suit the circumstances of Korean schools and determine its effects on body esteem, body image, appearance stress, depression, and attitudes toward cosmetic surgery. METHODS: Participants were 184 third-grade students from two middle schools in Korea, who were randomly assigned to a control or intervention group. Two of the participants dropped out; hence, data from 182 students were analyzed. The control group received the existing curriculum for 4 sessions, and the experimental group was provided with 4 sessions of the revised BodyThink program. Before and after the intervention, all participants completed questionnaires. RESULTS: In the BodyThink group, improved body image, decreased depression, and positive improvements in attitudes toward cosmetic plastic surgery were observed after the intervention. DISCUSSION: These results suggest that school health nurses can utilize interventions based on BodyThink program in their curricula to improve the physical and emotional health of adolescents. TRIAL REGISTRATION: This study has been retrospectively registered with the Clinical Research information Service (CRIS) in Korea on October 5, 2023 (KCT0008839).

Codonopsis lanceolata Extract Restores Smooth Muscle Vasorelaxation in Rat Carotid Arteries Even under High Extracellular K+ Concentrations.

Recent studies showed that Codonopsis lanceolata (CL) has antihypertensive effects. However, to date, no study has examined the effects of CL on vascular tone under a high extracellular K+ concentration ([K+]o). Thus, the present study examined the effect of an extract of Codonopsis lanceolata (ECL) on the vascular tension of rat carotid arteries exposed to high [K+]o. We used myography to investigate the effect of an ECL on the vascular tension of rat carotid arteries exposed to high [K+]o and the underlying mechanism of action. In arteries with intact endothelia, the ECL (250 µg/mL) had no effect on vascular tension in arteries exposed to normal or high [K+]o. In contrast, the ECL significantly increased vasorelaxation in endothelium-impaired arteries exposed to a physiologically normal or high [K+]o compared with control arteries exposed to the same [K+]o conditions in the absence of ECL. This vasorelaxing action was unaffected by a broad-spectrum K+ channel blocker and an ATP-sensitive K+ channel blocker. The ECL significantly inhibited the vasoconstriction induced by Ca2+ influx through voltage-dependent Ca2+ channels (VDCCs) but not Ca2+ influx induced via receptor-operated Ca2+ channels or the release of Ca2+ from the sarcoplasmic reticulum in the vascular smooth muscle. In summary, our study reveals that the ECL acts through VDCCs in vascular smooth muscle to promote the recovery of vasorelaxation even in arteries exposed to high [K+]o in the context of endothelial dysfunction and provides further evidence of the vascular-protective effects of ECL.

Ginsenoside Rb1 Reduces Hyper-Vasoconstriction Induced by High Glucose and Endothelial Dysfunction in Rat Aorta.

Acute hyperglycemia induces oxidative damage and inflammation, leading to vascular dysfunction. Ginsenoside Rb1 (Rb1) is a major component of red ginseng with anti-diabetic, anti-oxidant and anti-inflammatory properties. Here, we investigated the beneficial effects and the underlying mechanisms of Rb1 on hypercontraction induced by high glucose (HG) and endothelial dysfunction (ED). The isometric tension of aortic rings was measured by myography. The rings were treated with NG-nitro-L-arginine methyl ester (L-NAME) to induce chemical destruction of the endothelium, and Rb1 was added after HG induction. The agonist-induced vasoconstriction was significantly higher in the aortic rings treated with L-NAME + HG50 than in those treated with HG50 or L-NAME (p = 0.011) alone. Rb1 significantly reduced the hypercontraction in the aortic rings treated with L-NAME + HG50 (p = 0.004). The ATP-sensitive K+ channel (KATP) blocker glibenclamide tended to increase the Rb1-associated reduction in the agonist-induced vasoconstriction in the rings treated with L-NAME + HG50. The effect of Rb1 in the aortic rings treated with L-NAME + HG50 resulted from a decrease in extracellular Ca2+ influx through the receptor-operated Ca2+ channel (ROCC, 10-6-10-4 M CaCl2, p < 0.001; 10-3-2.5 × 10-3 M CaCl2, p = 0.001) and the voltage-gated Ca2+ channel (VGCC, 10-6 M CaCl2, p = 0.003; 10-5-10-2 M CaCl2, p < 0.001), whereas Rb1 did not interfere with Ca2+ release from the sarcoplasmic reticulum. In conclusion, we found that Rb1 reduced hyper-vasoconstriction induced by HG and ED by inhibiting the ROCC and the VGCC, and possibly by activating the KATP in rat aorta. This study provides further evidence that Rb1 could be developed as a therapeutic target for ED in diabetes.

Effects of linalyl acetate on oxidative stress, inflammation and endothelial dysfunction: can linalyl acetate prevent mild cognitive impairment?

Mild cognitive impairment (MCI) is a major public health challenge with an increasing prevalence. Although the mechanisms underlying the development of MCI remain unclear, MCI has been reported to be associated with oxidative stress, inflammatory responses, and endothelial dysfunction, suggesting that agents that reduce these factors may be key to preventing MCI. Currently, no agents have been approved for the treatment of MCI, with the efficacy of commonly prescribed cholinesterase inhibitors remaining unclear. Relatively safe natural products that can prevent the development of MCI are of great interest. Linalyl acetate (LA), the major component of clary sage and lavender essential oils, has been shown to have a variety of pharmacological effects, including anti-hypertensive, anti-diabetic, neuroprotective, anti-inflammatory, and antioxidant properties, which may have the potential for the prevention of MCI. The present review briefly summarizes the pathogenesis of MCI related to oxidative stress, inflammatory responses, and endothelial dysfunction as well as the benefits of LA against these MCI-associated factors. The PubMed and Google Scholar databases were used to search the relevant literature. Further clinical research may lead to the development of new strategies for preventing MCI, particularly in high-risk populations with oxidative stress, inflammatory responses, and endothelial dysfunction (e.g., patients with hypertension and/or diabetes mellitus).

Incidence and risk factors for pressure injury in hospitalized non-small cell lung cancer patients: A retrospective observational study.

AIM: This study aimed to identify the incidence and risk factors for pressure injury in patients hospitalized for non-small cell lung cancer (NSCLC). METHODS: This retrospective observational study was conducted in 645 adults who were hospitalized for NSCLC. Clinicopathological characteristics were compared between NSCLC patients with pressure injury and those without pressure injury. RESULTS: Among total 645 patients, 180 patients showed pressure injury with an incidence of 27.9%. Patients with pressure injury showed increased serum C-reactive protein (CRP) levels (P < 0.001), increased neutrophil-lymphocyte ratio (P = 0.002), and increased platelet-lymphocyte ratio (P = 0.001) more often. Increase in serum CRP levels at the time of admission was the major risk factor for development of pressure injury in NSCLC patients (OR = 2.20; 95% CI [1.40-3.45]; P = 0.001). Also, among major inflammatory markers, serum CRP levels at the time of admission showed weak negative correlation with the period from admission to the development of pressure injury (r = -0.216, P = 0.004). CONCLUSION: By checking serum CRP levels at the time of admission, the NSCLC patients at high risk for the development of pressure injury can be identified in advance and the occurrence of pressure injury can be reduced by applying more active preventive nursing care. CLINICAL TRIAL REGISTRATION NUMBER: KCT0006570.

Maternal separation in mice leads to anxiety-like/aggressive behavior and increases immunoreactivity for glutamic acid decarboxylase and parvalbumin in the adolescence ventral hippocampus.

It has been reported that stressful events in early life influence behavior in adulthood and are associated with different psychiatric disorders, such as major depression, post-traumatic stress disorder, bipolar disorder, and anxiety disorder. Maternal separation (MS) is a representative animal model for reproducing childhood stress. It is used as an animal model for depression, and has well-known effects, such as increasing anxiety behavior and causing abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis. This study investigated the effect of MS on anxiety or aggression-like behavior and the number of GABAergic neurons in the hippocampus. Mice were separated from their dams for four hours per day for 19 d from postnatal day two. Elevated plus maze (EPM) test, resident-intruder (RI) test, and counted glutamic acid decarboxylase 67 (GAD67) or parvalbumin (PV) positive cells in the hippocampus were executed using immunohistochemistry. The maternal segregation group exhibited increased anxiety and aggression in the EPM test and the RI test. GAD67-positive neurons were increased in the hippocampal regions we observed: dentate gyrus (DG), CA3, CA1, subiculum, presubiculum, and parasubiculum. PV-positive neurons were increased in the DG, CA3, presubiculum, and parasubiculum. Consistent with behavioral changes, corticosterone was increased in the MS group, suggesting that the behavioral changes induced by MS were expressed through the effect on the HPA axis. Altogether, MS alters anxiety and aggression levels, possibly through alteration of cytoarchitecture and output of the ventral hippocampus that induces the dysfunction of the HPA axis.

Inhalation of Pelargonium graveolens Essential Oil Alleviates Pain and Related Anxiety and Stress in Patients with Lumbar Spinal Stenosis and Moderate to Severe Pain.

Pain in lumbar spinal stenosis (LSS) patients is closely associated with psychological factors, including anxiety, stress, and depression, and is a critical determinant of patient daily functionality and overall quality of life. The present study evaluated the effects of inhalation of Pelargonium graveolens (geranium) essential oil (GEO) on pain and related psychological factors in LSS patients. Fifty-nine patients, categorized as having mild or moderate to severe pain based on pain visual analog scale (VAS) scores, were randomly assigned to inhalation of 1% GEO or placebo control (PC). No significant differences between GEO and PC were observed in patients with mild pain, whereas differences in anxiety-VAS and stress-VAS scores were observed in patients with moderate to severe pain. Anxiety-VAS and stress-VAS scores decreased significantly after GEO but not after PC inhalation. Regardless of the severity of pain, post-intervention pain-VAS scores were significantly lower in the GEO group than in the PC group. In summary, GEO reduced pain and improved anxiety and stress, particularly among patients with moderate to severe pain. These findings suggest that GEO inhalation may have potential as an adjunct therapy for improving pain management and alleviating anxiety and stress in LSS patients with insufficient responses to pharmacological pain control.

Astrocytes Reduce Store-Operated Ca2+ Entry in Microglia under the Conditions of an Inflammatory Stimulus and Muscarinic Receptor Blockade.

Inflammation and loss of cholinergic transmission are involved in neurodegenerative diseases, but possible interactions between them within neurons, astrocytes, and microglia have not yet been investigated. We aimed to compare store-operated Ca2+ entry (SOCE) in neurons, astrocytes, and microglia following cholinergic dysfunction in combination with (or without) an inflammatory stimulus and to investigate the effects of linalyl acetate (LA) on this process. We used the SH-SY5Y, U373, and BV2 cell lines related to neurons, astrocytes, and microglia, respectively. Scopolamine or lipopolysaccharide (LPS) was used to antagonize the muscarinic receptors or induce inflammatory responses, respectively. The concentration of intracellular Ca2+ was measured using Fura-2 AM. Treatment with scopolamine and LPS significantly increased SOCE in the neuron-like cells and microglia but not in the scopolamine-pretreated astrocytes. LA significantly reduced SOCE in the scopolamine-pretreated neuron-like cells and microglia exposed to LPS, which was partially inhibited by the Na+-K+ ATPase inhibitor ouabain and the Na+/Ca2+ exchanger (NCX) inhibitor Ni2+. Notably, SOCE was significantly reduced in the LPS plus scopolamine-pretreated cells mixed with astrocytes and microglia, with a two-fold increase in the applied number of astrocytes. LA may be useful in protecting neurons and microglia by reducing elevated SOCE that is induced by inflammatory responses and inhibiting the muscarinic receptors via Na+-K+ ATPase and the forward mode of NCX. Astrocytes may protect microglia by reducing increased SOCE under the conditions of inflammation and a muscarinic receptor blockade.

Trans-Anethole Alleviates Trimethyltin Chloride-Induced Impairments in Long-Term Potentiation.

Trans-anethole is an aromatic compound that has been studied for its anti-inflammation, anticonvulsant, antinociceptive, and anticancer effects. A recent report found that trans-anethole exerted neuroprotective effects on the brain via multiple pathways. Since noxious stimuli may both induce neuronal cell injury and affect synaptic functions (e.g., synaptic transmission or plasticity), it is important to understand whether the neuroprotective effect of trans-anethole extends to synaptic plasticity. Here, the effects of trimethyltin (TMT), which is a neurotoxic organotin compound, was investigated using the field recording method on hippocampal slice of mice. The influence of trans-anethole on long-term potentiation (LTP) was also studied for both NMDA receptor-dependent and NMDA receptor-independent cases. The action of trans-anethole on TMT-induced LTP impairment was examined, too. These results revealed that trans-anethole enhances NMDA receptor-dependent and -independent LTP and alleviates TMT-induced LTP impairment. These results suggest that trans-anethole modulates hippocampal LTP induction, prompting us to speculate that it may be helpful for improving cognitive impairment arising from neurodegenerative diseases, including Alzheimer's disease.

Ginsenoside Rg-1 prevents elevated cytosolic Ca2+ via store-operated Ca2+ entry in high-glucose-stimulated vascular endothelial and smooth muscle cells.

BACKGROUND: Ginsenoside Rg-1 (Rg-1), a triterpenoid saponin abundantly present in Panax ginseng, is a type of naturally occurring steroid with known anti-diabetic and anti-inflammatory effects. In this study, we sought to confirm the effects and mechanisms of action of Rg-1 on store-operated Ca2+ entry (SOCE) in human vascular endothelial cell line (EA) and murine aortic vascular smooth muscle cell line (MOVAS) cells exposed to high glucose. METHODS: Cytosolic Ca2+ concentrations in EA and MOVAS cells were measured by monitoring fluorescence of the ratiometric Ca2+-indicator, Fura-2 AM. RESULTS: High glucose significantly increased Ca2+ influx by abnormally activating SOCE in EA and MOVAS cells. Notably, this high glucose-induced increase in SOCE was restored to normal levels in EA and MOVAS cells by Rg-1. Moreover, Rg-1 induced reductions in SOCE in cells exposed to high glucose were significantly inhibited by the plasma membrane Ca2+ ATPase (PMCA) blocker lanthanum, the Na+/K+-ATPase blocker ouabain, or the Na+/Ca2+ exchanger (NCX) blockers Ni2+ and KB-R7943. These observations suggest that the mechanism of action of Rg-1 inhibition of SOCE involves PMCA and Na+/K+-ATPase, and an increase in Ca2+ efflux via NCXs in both EA and MOVAS cells exposed to high glucose. CONCLUSIONS: These findings indicate that Rg-1 may protect vascular endothelial and smooth muscle cells from Ca2+ increases following exposure to hyperglycemic conditions.

Linalyl acetate restores colon contractility and blood pressure in repeatedly stressed-ulcerative colitis rats.

BACKGROUND: Ulcerative colitis (UC) is related to stress, but few studies have evaluated the influence of stress on factors affecting colon contractility in rats with UC. Also, there have been no studies investigating beneficial effects of linalyl acetate (LA), the major component of lavender essential oil, in repeatedly stressed-ulcerative colitis rats. Therefore, we investigated the differences in factors affecting colon contractility of UC rats with or without repeated restraint stress (RRS) and the effects of LA on these parameters in repeatedly stressed-UC rats. METHODS: Rats were assigned to following groups: control, RRS, UC, RRS+UC, and RRS+UC treated with LA or sulfasalazine. To induce UC, rats were administered 2% dextran sodium sulfate (DSS) water on days 1-5, followed by tap water on days 6-15 and DSS water on days 16-20. RRS was induced by immobilizing rats for 2 hr/day on days 1-20. LA or sulfasalazine were daily administered on days 16-20. RESULTS: Disease activity index (DAI) was markedly increased in RRS+UC. Serum interleukin-6 levels and acetylcholine-induced colon contraction were higher in RRS+UC than in control, RRS and UC. Colon nitrite levels also significantly increased in RRS+UC compared to the control and RRS. Blood pressure (BP) was higher in RRS+UC than in the control and UC. Both LA and sulfasalazine was effective in decreasing DAI, colon nitrite levels, acetylcholine-induced colon contraction in RRS+UC. Sulfasalazine significantly reduced serum IL-6 levels in RRS+UC with decreasing tendency in RRS+UC treated by LA. Only LA significantly reduced BP in RRS+UC. CONCLUSIONS: Our findings emphasize the importance of stress management in UC patients. Also, LA may be beneficially used in repeatedly stressed-UC patients with high BP.

Activation of ectopic olfactory receptor 544 induces GLP-1 secretion and regulates gut inflammation.

Olfactory receptors are ectopically expressed in extra-nasal tissues. The gut is constantly exposed to high levels of odorants where ectopic olfactory receptors may play critical roles. Activation of ectopic olfactory receptor 544 (Olfr544) by azelaic acid (AzA), an Olfr544 ligand, reduces adiposity in mice fed a high-fat diet (HFD) by regulating fuel preference to fats. Herein, we investigated the novel function of Olfr544 in the gut. In GLUTag cells, AzA induces the cAMP-PKA-CREB signaling axis and increases the secretion of GLP-1, an enteroendocrine hormone with anti-obesity effects. In mice fed a HFD and orally administered AzA, GLP-1 plasma levels were elevated in mice. The induction of GLP-1 secretion was negated in cells with Olfr544 gene knockdown and in Olfr544-deficient mice. Gut microbiome analysis revealed that AzA increased the levels of Bacteroides acidifaciens and microbiota associated with antioxidant pathways. In fecal metabolomics analysis, the levels of succinate and trehalose, metabolites correlated with a lean phenotype, were elevated by AzA. The function of Olfr544 in gut inflammation, a key feature in obesity, was further investigated. In RNA sequencing analysis, AzA suppressed LPS-induced activation of inflammatory pathways and reduced TNF-α and IL-6 expression, thereby improving intestinal permeability. The effects of AzA on the gut metabolome, microbiome, and colon inflammation were abrogated in Olfr544-KO mice. These results collectively demonstrated that activation of Olfr544 by AzA in the gut exerts multiple effects by regulating GLP-1 secretion, gut microbiome and metabolites, and colonic inflammation in anti-obesogenic phenotypes and, thus, may be applied for obesity therapeutics.

Linalyl acetate as a potential preventive agent against muscle wasting in rheumatoid arthritis rats chronically exposed to nicotine.

Cigarette smoking has detrimental effects on rheumatoid arthritis (RA), characterized by muscle wasting. Linalyl acetate (LA), the main component of Lavandula angustifolia Mill (lavender) oil, has anti-inflammatory properties. We investigated the detrimental effects of chronic nicotine exposure in rats with RA, as well as the abilities of lavender oil and LA to prevent muscle wasting. Rats with RA induced by type II collagen were exposed to nicotine for 22 days from day 1. Lavender oil or LA was administered twice a week during the experiment. Compared with control, collagen-induced arthritis (CIA) and chronic nicotine exposure plus CIA (NicoCIA) showed increases in hind paw thickness and serum interleukin (IL)-6 and decreases in body weight and serum insulin-like growth factor (IGF)-1 levels. Moreover, weight and fiber cross-sectional area of the gastrocnemius muscle were much lower, and mitochondrial membrane potential of the gastrocnemius muscle was higher, in the NicoCIA than in the CIA. These alterations in the NicoCIA were prevented by lavender oil and LA. Importantly, LA showed greater activity than lavender oil in preventing IGF-1 reduction in the NicoCIA. These findings suggest that lavender oil and LA may have preventive benefit in RA by counteracting muscle wasting associated with chronic nicotine exposure.

Protection of the neurovascular unit from calcium-related ischemic injury by linalyl acetate.

Calcium-related ischemic injury (CRII) can damage cells of the neurovascular unit (NVU). Here, we investigate the protective effects of linalyl acetate (LA) against CRII-induced NVU damage and evaluate the underlying mechanisms. The protective effects of LA in cell lines representative of NVU components (BEND, SH-SY5Y, BV2, and U373 cells) were evaluated following exposure to oxygen-glucose deprivation/reoxygenation alone (OGD/R-only) or OGD/R in the presence of 5 mM extracellular calcium ([Ca2+]o) to mimic CRII. LA reversed damage under OGD/R-only conditions by blocking p47phox/NADPH oxidase (NOX) 2 expression, reactive oxygen species (ROS) production, nitric oxide (NO) abnormality, and lactate dehydrogenase (LDH) release only in the BEND cells. However, under CRII-mimicking conditions, LA reversed NO abnormality and matrix metalloproteinase (MMP)-9 activation in the BEND murine brain endothelial cells; inhibited p47phox expression in the human SH-SY5Y neural-like cells; decreased NOX2 expression and ROS generation in the BV2 murine microglial cells; and reduced p47phox expression in the U373 human astrocyte-like cells. Importantly, LA protected against impairment of the neural cells, astrocytes, and microglia, all of which are cellular components of the NVU induced by exposure to CRII-mimicking conditions, by reducing LDH release. We found that LA exerted a protective effect in the BEND cells that may differ from its protective effects in other NVU cell types, following OGD/R-induced damage in the context of elevated [Ca2+]o.

Effects of Short-Term Inhalation of Patchouli Oil on Professional Quality of Life and Stress Levels in Emergency Nurses: A Randomized Controlled Trial.

Objectives: The aim of this study was to investigate the effects of patchouli (Pogostemon cablin Benth.) inhalation by emergency nurses on their stress, compassion satisfaction, compassion fatigue, burnout, blood pressure, and heart rate. Design: A randomized controlled trial. Setting/location: University hospital in Incheon. Subjects: This study was performed from May to August 2018 after all subjects provided written informed consent. Fifty eligible emergency nurses were recruited and randomly allocated to inhale 5% patchouli oil in sweet almond oil (patchouli group, n = 25) or pure sweet almond oil (control group, n = 25). Interventions: Nurses in the patchouli group first inhaled patchouli oil at about 10 pm (the end of an afternoon shift) and inhaled patchouli oil a second time at about 10 pm on next day (24-h interval). Nurses in the control group inhaled pure sweet almond oil following the same schedule. Outcome measures: Outcome measured included blood pressure, heart rate, levels of stress, compassion satisfaction, compassion fatigue, and burnout. Results: Although there were no significant differences in blood pressure, heart rate, compassion fatigue, and burnout, levels of stress were significantly lower (0.06 ± 0.48 vs. 1.19 ± 1.19, p < 0.001) and compassion satisfaction significantly higher (0.56 ± 2.50 vs. -2.84 ± 2.43, p < 0.001) in the patchouli than in the control group. In addition, relative to baseline, compassion fatigue was significantly lower in the patchouli group (26.72 ± 4.98 vs. 25.88 ± 4.63, p = 0.016). Conclusions: Inhalation of patchouli oil effectively reduced the levels of stress and increased compassion satisfaction in emergency nurses, suggesting that patchouli oil inhalation may improve the professional quality of life of emergency nurses. ClinicalTrials.gov ID: KCT0004615.

Sex-specific susceptibility to type 2 diabetes mellitus and preventive effect of linalyl acetate.

AIMS: Biological, psychosocial and lifestyle risk factors interact in the development of type 2 diabetes mellitus (T2DM). To date, the effects of sex, chronic stress (CS) and high-fat diet (HFD) on T2DM and the ability of linalyl acetate (LA) to prevent T2DM have not been determined. This study therefore explored the differential effects of CS and HFD on T2DM, as well as the ability of LA to prevent T2DM development, in male and female rats. MAIN METHODS: T2DM was induced in rats by feeding an HFD and placing them under immobilization stress for 2 h/day for 3 weeks. Low-dose streptozotocin was administered on day 15, and LA was administered for 3 weeks. KEY FINDINGS: Fasting blood sugar (FBS) increased in HFD-fed male, but not female, rats. CS further increased FBS in HFD-fed rats, whereas CS alone did not alter FBS. The homeostatic model assessment-insulin resistance (HOMA-IR) showed results similar to FBS. Serum corticosterone levels markedly increased only in HFD-fed male rats exposed to CS. Pancreas nuclear factor kappa B (NF-κB) levels were higher in HFD-fed male rats exposed to CS than in control rats although there were no sex differences. LA 10 mg/kg significantly reduced FBS, serum insulin, HOMA-IR, and serum corticosterone levels in HFD-fed male rats exposed to CS. LA 10 mg/kg also tended to reduce NF-κB in the pancreas and significantly increased mitochondrial membrane potential (MMP) in the liver. SIGNIFICANCE: Male rats are vulnerable to T2DM induced by CS and HFD, and LA can prevent T2DM in these rats not only by reducing insulin resistance and corticosterone levels but by increasing MMP in the liver.

Codonopsis lanceolata Contributes to Ca2+ Homeostasis by Mediating SOCE and PLC/IP3 Pathways in Vascular Endothelial and Smooth Muscle Cells.

Codonopsis lanceolata has been widely used as an anti-inflammatory and anti-lipogenic agent in traditional medicine. Recently, C. lanceolata was reported to prevent hypertension by improving vascular function. This study evaluated the effects of C. lanceolata and its major component lancemaside A on cytosolic calcium concentration in vascular endothelial cells and vascular smooth muscle cells. Cytosolic calcium concentration was measured using fura-2 AM fluorescence. C. lanceolata or lancemaside A increased the cytosolic calcium concentration by releasing Ca2+ from the endoplasmic reticulum and sarcoplasmic reticulum and by Ca2+ entry into endothelial cells and vascular smooth muscle cells from extracellular sources. The C. lanceolata- and lancemaside A-induced cytosolic calcium concentration increases were significantly inhibited by lanthanum, an inhibitor of non-selective cation channels, in both endothelial cells and vascular smooth muscle cells. Moreover, C. lanceolata and lancemaside A significantly inhibited store-operated Ca2+ entry under pathological extracellular Ca2+ levels. In Ca2+-free extracellular fluid, increases in the cytosolic calcium concentration induced by C. lanceolata or lancemaside A were significantly inhibited by U73122, an inhibitor of phospholipase C, and 2-APB, an inositol 1,4,5-trisphosphate receptor antagonist. In addition, dantrolene treatment, which inhibits Ca2+ release through ryanodine receptor channels, also inhibited C. lanceolata- or lancemaside A-induced increases in the cytosolic calcium concentration through the phospholipase C/inositol 1,4,5-trisphosphate pathway. These results suggest that C. lanceolata and lancemaside A increase the cytosolic calcium concentration through the non-selective cation channels and phospholipase C/inositol 1,4,5-trisphosphate pathways under physiological conditions and inhibit store-operated Ca2+ entry under pathological conditions in endothelial cells and vascular smooth muscle cells. C. lanceolata or lancemaside A can protect endothelial cells and vascular smooth muscle cells by maintaining cytosolic calcium concentration homeostasis, suggesting possible applications for these materials in diets for preventing vascular damage.