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Abstract Studies on the compounds of aromatic oils and their effects on psychophysiological changes in humans are often conducted separately. To obtain better validation, a suitable protocol is needed that can be extrapolated to large-scale olfactory stimulation experiments. Unfortunately, this type of study is still rarely performed. In this situation, we propose a randomized crossover pilot study on olfactory stimulation with aromatic oils in relation to changes in psychophysiological activity by focusing on white musk aromatic oil due to its popularity in the community. Chemical profiling by TDU-GC-MS (thermal desorption gas chromatography/mass spectrometry) was performed to understand the compounds of the aromatic oils presented. To understand the changes in the participants’ impressions and mood states, POMS 2 (Profile of Mood States 2nd Edition) and VAS (Visual analogue scale) were performed in addition to physiological evaluation by using EEG (electroencephalogram), ECG (electrocardiogram) and salivary amylase measurements. The proposed pilot study showed “gorgeous”, “sweet”, and “like” impression toward white musk aromatic oil under VAS evaluation. Mood evaluation under POMS 2 variables such as Fatigue-Inertia (FI), Tension-anxiety (TA) and TMD (total mood disturbance) were significantly decreased under white musk aromatic oil inhalation. Under current protocol, we can also see the changes in autonomic activity and brain activity during olfactory stimulation. This pilot study could be the first step towards a larger sample size experiment on olfactory stimulation. This experiment has been registered to UMIN Clinical Trials Registry with register ID : UMIN000051972 on 24/08/2023.

Abstract Lipidomics and metabolomics communities comprise various informatics tools; however, software programs handling multimodal mass spectrometry (MS) data with structural annotations guided by the Lipidomics Standards Initiative are limited. Here, we provide MS-DIAL 5 for in-depth lipidome structural elucidation through electron-activated dissociation (EAD)-based tandem MS and determining their molecular localization through MS imaging (MSI) data using a species/tissue-specific lipidome database containing the predicted collision-cross section values. With the optimized EAD settings using 14 eV kinetic energy, the program correctly delineated lipid structures for 96.4% of authentic standards, among which 78.0% had the sn-, OH-, and/or C = C positions correctly assigned at concentrations exceeding 1 μM. We showcased our workflow by annotating the sn- and double-bond positions of eye-specific phosphatidylcholines containing very-long-chain polyunsaturated fatty acids (VLC-PUFAs), characterized as PC n-3-VLC-PUFA/FA. Using MSI data from the eye and n-3-VLC-PUFA-supplemented HeLa cells, we identified glycerol 3-phosphate acyltransferase as an enzyme candidate responsible for incorporating n-3 VLC-PUFAs into the sn1 position of phospholipids in mammalian cells, which was confirmed using EAD-MS/MS and recombinant proteins in a cell-free system. Therefore, the MS-DIAL 5 environment, combined with optimized MS data acquisition methods, facilitates a better understanding of lipid structures and their localization, offering insights into lipid biology.

Abstract Sleep plays an important role in human health. Changes in the sleeping environment can affect sleep quality. The present study investigated the effects of natural wood on sleep quality. The interior material was a fully used Cryptomeria japonica wood board (Japanese cedar room), while the particleboard and medium-density fiberboard (MDF) were covered by a vinyl cloth with a woodgrain (resin room). In order to assess sleep quality, the sleep–depth index (SDI) is calculated based on the lengths of sleep stage 3 and the rapid eye movement (REM) stage using electroencephalography (EEG). Before the sleep experiments, the Pittsburgh Sleep Quality Inventory (PSQI) and Morningness–Eveningness Questionnaire (MEQ) were administered to confirm the participants’ usual sleep habits. Thirteen participants were invited to sleep in two different environments. The MEQ before sleep experiments confirmed that eight participants were of the intermediate type and five participants were of the moderate evening type. According to the PSQI, three participants were poor sleepers and ten were good sleepers. The sleep EEG demonstrated that 12 of 13 participants had higher SDI in the Japanese cedarwood room than in the resin room. A Wilcoxon signed-rank test revealed that SDI was significantly prolonged in the Japanese cedarwood room than in the resin room, regardless of the small sample size (n = 13, z = 2.48, p = 0.014, effect size = 0.78). The present study demonstrated that the indoor environment with C. japonica induced a significantly higher SDI compared to that with wood-grain vinyl cloth. This indicates that the interior materials of C. Japonica wood can positively influence the sleep environment.

In the face of increasingly serious environmental pollution, the health of human lung tissues is also facing serious threats. Mogroside ⅡE (M2E) is the main metabolite of sweetening agents mogrosides from the anti-tussive Chinese herbal Siraitia grosvenori. The study elucidated the anti-inflammatory action and molecular mechanism of M2E against acute lung injury (ALI). A lipopolysaccharide (LPS)-induced ALI model was established in mice and MH-S cells were employed to explore the protective mechanism of M2E through the western blotting, co-immunoprecipitation, and quantitative real time-PCR analysis. The results indicated that M2E alleviated LPS-induced lung injury through restraining the activation of secreted phospholipase A2 type IIA (Pla2g2a)-epidermal growth factor receptor (EGFR). The interaction of Pla2g2a and EGFR was identified by co-immunoprecipitation. In addition, M2E protected ALI induced with LPS against inflammatory and damage which were significantly dependent upon the downregulation of AKT and mTOR via the inhibition of Pla2g2a-EGFR. Pla2g2a may represent a potential target for M2E in the improvement of LPS-induced lung injury, which may represent a promising strategy to treat ALI.

Abstract Loquat (Eriobotrya japonica) leaves contain many bioactive components such as ursolic acid (UA) and amygdalin. We investigated the effects of loquat leaf powder and methanol extract in human neuroglioma H4 cells stably expressing the Swedish-type APP695 (APPNL-H4 cells) and C57BL/6 J mice. Surprisingly, the extract greatly enhanced cellular amyloid-beta peptide (Aβ) 42 productions in APPNL-H4 cells. Administration of leaf powder increased Aβ42 levels after 3 months and decreased levels after 12 months compared to control mice. Leaf powder had no effect on working memory after 3 months, but improved working memory after 12 months. Administration of UA decreased Aβ42 and P-tau levels and improved working memory after 12 months, similar to the administration of leave powder for 12 months. Amygdalin enhanced cellular Aβ42 production in APPNL-H4 cells, which was the same as the extract. Three-month administration of amygdalin increased Aβ42 levels slightly but did not significantly increase them, which is similar to the trend observed with the administration of leaf powder for 3 months. UA was likely the main compound contained in loquat leaves responsible for the decrease in intracerebral Aβ42 and P-tau levels. Also, amygdalin might be one of the compounds responsible for the transiently increased intracerebral Aβ42 levels.

Eriobotrya japonica (E. japonica) leaves have been used as an herbal traditional medicine in China and Japan owing to their anti-inflammatory and protective effects against skin conditions and allergy symptoms. These beneficial effects are likely mediated by the various triterpenoids present in E. japonica leaves. However, the efficacy of E. japonica leaves in the treatment of allergic rhinitis has not been evaluated in humans. Therefore, in the present study, a randomized, controlled, double-blind trial was performed on healthy adults of age >20 (n = 27) who were randomly assigned to receive either 2.5 g of placebo or E. japonica leaf supplements once daily for 4 weeks. The Japanese Allergic Rhinitis Quality of Life Standard Questionnaire (JRQLQ), dermatological allergy symptoms, Dermatology Life Quality Index, and skin condition parameters were assessed at baseline and after 4 weeks. Significant differences were observed in the variability of the itchy nose, itchy eyes, and eye symptoms between the E. japonica supplementation and placebo groups after 4 weeks. Arm skin transepidermal water loss was improved only in the E. japonica supplementation group. This study suggests that E. japonica leaves can be used as a functional food ingredient to relieve allergic symptoms.

Numerous health hazards have been connected to advanced glycation end products (AGEs). In this investigation, using reaction models including BSA-fructose, BSA- methylglyoxal (MGO), and BSA-glyoxal (GO), we examined the anti-glycation potential of eight different berry species on AGEs formation. Our results indicate that black chokeberry (Aronia melanocarpa) exhibited the highest inhibitory effects, with IC50 values of 0.35 ± 0.02, 0.45 ± 0.03, and 0.48 ± 0.11 mg/mL, respectively. Furthermore, our findings suggest that black chokeberry inhibits AGE formation by binding to BSA, which alleviates the conformation alteration, prevents protein cross-linking, and traps reactive α-dicarbonyls to form adducts. Notably, three major polyphenols, including cyanidin-3-O-galactoside, cyanidin-3-O-arabinoside, and procyanidin B2 from black chokeberry, showed remarkably inhibitory effect on MGO/GO capture, and new adducts formation was verified through LC-MS/MS analysis. In summary, our research provides a theoretical basis for the use of berries, particularly black chokeberry, as natural functional food components with potential anti-glycation effects.

Abstract Odor environments in living spaces can influence human physiological and psychological states. To elucidate the effect of volatile organic compounds (VOCs) of wood in living spaces on the modulations of cognitive processing, we built two experimental huts to simulate wooden construction living spaces. One hut was made of cedarwood (Cryptomeria japonica), and the other was made of resin. We used cedarwood and resin, because they are often used as construction materials in Japan. In both huts, we measured the participants’ first positivity in the early visual cortex (P1), the third positivity elicited by voluntary attention (P3b), and the automatic occipital negativity to infrequent visual stimuli in event-related potentials (ERPs), while they performed a visual discrimination task. The VOCs in both huts were measured by gas chromatography–mass spectrometry. The concentration of volatile sesquiterpenes was significantly increased in the cedarwood hut. Neither P1 nor P3b was affected by the cedarwood hut. Compared to the resin hut, we observed significantly larger occipital negativities to the infrequent stimuli in the cedarwood hut in the time windows of 280–300 ms at the mid-occipital region. These findings suggest that the increased concentration of volatile sesquiterpenes emitted from cedarwood facilitates the human brain’s response to changes in visual stimuli.

Abstract We examined the association of serum s-adenosylmethionine (SAM), s-adenosylhomocysteine (SAH) (methionine metabolites), and their ratio on the risk of dementia and death in a community-dwelling population of older Japanese individuals. 1371 residents of Hisayama, Japan, aged 65 years or older and without dementia, were followed for a median of 10.2 years (2007–2017). We divided serum SAM, SAH, and SAM/SAH ratio into quartiles. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and their 95% confidence intervals (CIs) of serum SAM, SAH, and SAM/SAH ratio levels on the risk of a composite outcome of all-cause dementia or death, and each outcome. During the follow-up, 635 participants developed all-cause dementia and/or died, of which 379 participants developed dementia and 394 deaths occurred. The multivariable-adjusted HRs of the composite outcome decreased significantly with increasing serum SAM levels (P for trend = 0.01), while they increased significantly with higher serum SAH levels (P for trend = 0.03). Higher serum SAM/SAH ratio levels were significantly associated with a lower risk of the composite outcome (P for trend = 0.002), as well as with lower risk of each outcome. Our findings suggest that the balance of methionine metabolites may closely associate with the risk of dementia and death.

This Special Issue of Molecules gathers eight research papers and two review articles covering the isolation, identification, and biological activity of selected natural products, with the aim of discovering potential candidates that could change society and improve human health [...]

Hericium erinaceus, a mushroom species commonly known as Yamabushitake in Japan, is known to have a stimulatory effect on neurotrophic factors, such as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). Hericenone C, a meroterpenoid with palmitic acid as the fatty acid side chain, is reported to be one such stimulant. However, according to the structure of the compound, the fatty acid side chain seems highly susceptible to lipase decomposition, under in vivo metabolic conditions. To study this phenomenon, hericenone C from the ethanol extract of the fruiting body was subjected to lipase enzyme treatment and observed for changes in the chemical structure. The compound formed after the lipase enzyme digestion was isolated and identified using LC-QTOF-MS combined with 1H-NMR analysis. It was found to be a derivative of hericenone C without its fatty acid side chain and was named deacylhericenone. Interestingly, a comparative investigation of the neuroprotective properties of hericenone C and deacylhericenone showed that the BDNF mRNA expression in human astrocytoma cells (1321N1) and the protection against H2O2-induced oxidative stress was considerably higher in the case of deacylhericenone. These findings suggest that the stronger bioactive form of the hericenone C compound is in fact deacylhericenone.

Abstract Introduction Placenta extract is used as an ingredient in ointments for treating dermatological diseases, skin dryness, and for skin beautification. However, the clinical effects of the equine placenta on humans and the underlying mechanism of action are unclear. This randomized, controlled, double‐blind study aimed to clinically evaluate the effect of oral intake of equine placental extract on human skin quality. Methods Healthy women volunteers between the ages of 30 and 59 years (n = 29) were randomly assigned to receive 220 mg of equine placental extract–placebo orally, once daily for 4 weeks. Skin quality parameters such as skin hydration, skin barrier function (transepidermal water loss [TEWL]), and melanin index were assessed at baseline and after 4 weeks of administration. Results The melanin index was significantly increased in the placebo group, whereas it remained unchanged in the equine placenta group. The pattern of melanin index change was significantly different due to intake or no intake of equine placenta supplements over 4 weeks. No significant difference was found in skin hydration and TEWL between the two groups at 4 weeks of postadministration. It was shown that the intake of the equine placenta was more effective in protecting the skin condition against the change of ultraviolet (UV) sensitively than the change in temperature and humidity. Conclusions Effect of equine placental extract intake was evident on the cheek skin of the equine placenta group where participants were protected from UV‐induced pigmentation. Equine placental extract is useful for decreasing melanin synthesis and melanin content in the human skin and can be used as an effective food supplement to maintain human skin quality.

Nutritional foods are concentrated sources of molecules with a nutritional or physiological effect which contain nutrients. There is a category, “nutricosmetics”, defined as ingestible natural health products that enhance the function and appearance of human skin, nails, and hair. A new variety of Flammulina velutipes (F. velutipes), Oki-Shirayuki 919, was explored to ascertain whether its components have functions of nutricosmetics. We focused on physiological effects for enhancing the human skin condition, such as moisturizing or barrier functions in F. velutipes. A randomized, double-blind, placebo-controlled clinical study was performed between January and March 2022. Among healthy men and women (n = 30) aged 20 to 59 years, the test group (n = 15) took a test product which included F. velutipes dry powder, and the placebo group (n = 15) took a placebo (a similar product in which the F. velutipes dry powder was replaced with plum fruit paste). Since the amount of increase in skin hydration over four weeks in the test group was significantly larger than that in the placebo group, a significant difference between the two groups was observed (p = 0.033). F. velutipe was suggested to have some physiological functions such as improving skin moisture.

This study targets the evaluation of melanin synthesis inhibition activity of the bamboo shoot skin as agro-waste. The total methanolic extract of bamboo peel extract was evaluated for its skin protective effects via measuring its melanin inhibitory activity and its suppression activity on the expression of tyrosinase mRNA levels. Results showed that bamboo peel extract has a good ability for the inhibition of melanin synthesis so further studies were performed for the isolation of its constituents. Twelve compounds have been isolated from the shoot skin of Phyllostachys pubescens. Their structures were elucidated based on extensive spectroscopic methods. The melanin inhibition potential of the isolates was tested with their collagen-production-promoting activity for the determination of active principles. Results showed that Betulinic acid, tachioside, and 1,2-dilinolenin significantly suppressed melanin production per cell compared to control. Triacontanol, tricin, and (+)-lyoniresinol 9′-O-glucoside also tended to decrease melanin production per cell. These findings indicated that the skin of bamboo shoots, a significant agricultural waste, is a useful natural source for further research on its potential for aging problems such hyperpigmentation and cognitive function impairment.

Chemical investigation of the total extract of the Egyptian soft coral Heteroxenia fuscescens, led to the isolation of eight compounds, including two new metabolites, sesquiterpene fusceterpene A (1) and a sterol fuscesterol A (4), along with six known compounds. The structures of 1–8 were elucidated via intensive studies of their 1D, 2D-NMR, and HR-MS analyses, as well as a comparison of their spectral data with those mentioned in the literature. Subsequent comprehensive in-silico-based investigations against almost all viral proteins, including those of the new variants, e.g., Omicron, revealed the most probable target for these isolated compounds, which was found to be Mpro. Additionally, the dynamic modes of interaction of the putatively active compounds were highlighted, depending on 50-ns-long MDS. In conclusion, the structural information provided in the current investigation highlights the antiviral potential of H. fuscescens metabolites with 3β,5α,6β-trihydroxy steroids with different nuclei against SARS-CoV-2, including newly widespread variants.

Hibiscus sabdariffa L. (HS) has a long history of edible and medicinal uses. In this study, the biological activities of the extracts, chromatographic fractions, and hibiscus acid obtained from HS were evaluated for their potential bioactivities. Their ability to promote extracellular matrix synthesis in skin fibroblasts was evaluated by enzyme-linked immunosorbent assays. Their anti-inflammatory activity was evaluated in a nitric oxide (NO)–Griess inflammatory experiment. Furthermore, hibiscus acid was found to have a strong anti-oxidative stress effect through the establishment of an oxidative stress model induced by hydrogen peroxide. Several assays indicated that hibiscus acid treatment can effectively reduce extracellular adenosine triphosphate (ATP) secretion and carbonyl protein production, as well as maintain a high level of reduced/oxidized glutathione (GSH/GSSG) in skin cells, thus providing a possible mechanism by which hibiscus acid can counter antioxidative stress. The present study is the first to explore the reversing skin aging potential and the contributory component of HS.

Averrhoa carambola L. is reported for its anti-obese and anti-diabetic activities. The present study aimed to investigate its aqueous methanol leaf extract (CLL) in vivo anti-obese activity along with the isolation and identification of bioactive compounds and their in vitro α-glucosidase inhibition assessment. CLL improved all obesity complications and exhibited significant activity in an obese rat model. Fourteen compounds, including four flavone glycosides (1–4) and ten dihydrochalcone glycosides (5–12), were isolated and identified using spectroscopic techniques. New compounds identified in planta included (1) apigenin 6-C-(2-deoxy-β-D-galactopyranoside)-7-O-β-D-quinovopyranoside, (8) phloretin 3′-C-(2-O-(E)-cinnamoyl-3-O-β-D-fucopyranosyl-4-O-acetyl)-β-D-fucopyranosyl-6′-O-β-D fucopyranosyl-(1/2)-α-L arabinofuranoside, (11a) phloretin3′-C-(2-O-(E)-p-coumaroyl-3-O-β-D-fucosyl-4-O-acetyl)-β-D-fucosyl-6′-O-(2-O-β-D-fucosyl)-α-L-arabinofuranoside, (11b) phloretin3′-C-(2-O-(Z)-p-coumaroyl-3-O-β-D-fucosyl-4-O-acetyl)-β-D-fucosyl-6′-O-(2-O-β-D-fucosyl)-α-L-arabinofuranoside. Carambolaside M (5), carambolaside Ia (6), carambolaside J (7), carambolaside I (9), carambolaside P (10a), carambolaside O (10b), and carambolaside Q (12), which are reported for the first time from A. carambola L. leaves, whereas luteolin 6-C-α-L-rhamnopyranosyl-(1-2)-β-D-fucopyranoside (2), apigenin 6-C-β-D-galactopyranoside (3), and apigenin 6-C-α-L-rhamnopyranosyl-(1-2)-β-L-fucopyranoside (4) are isolated for the first time from Family. Oxalidaceae. In vitro α-glucosidase inhibitory activity revealed the potential efficacy of flavone glycosides, viz., 1, 2, 3, and 4 as antidiabetic agents. In contrast, dihydrochalcone glycosides (5–11) showed weak activity, except for compound 12, which showed relatively strong activity.

(1) Background: Natural constituents are still a preferred route for counteracting the outbreak of COVID-19. Essentially, flavonoids have been found to be among the most promising molecules identified as coronavirus inhibitors. Recently, a new SARS-CoV-2 B.1.1.529 variant has spread in many countries, which has raised awareness of the role of natural constituents in attempts to contribute to therapeutic protocols. (2) Methods: Using various chromatographic techniques, triterpenes (1–7), phenolics (8–11), and flavonoids (12–17) were isolated from Euphorbia dendroides and computationally screened against the receptor-binding domain (RBD) of the SARS-CoV-2 Omicron variant. As a first step, molecular docking calculations were performed for all investigated compounds. Promising compounds were subjected to molecular dynamics simulations (MD) for 200 ns, in addition to molecular mechanics Poisson–Boltzmann surface area calculations (MM/PBSA) to determine binding energy. (3) Results: MM/PBSA binding energy calculations showed that compound 14 (quercetin-3-O-β-D-glucuronopyranoside) and compound 15 (quercetin-3-O-glucuronide 6″-O-methyl ester) exhibited strong inhibition of Omicron, with ΔGbinding of −41.0 and −32.4 kcal/mol, respectively. Finally, drug likeness evaluations based on Lipinski’s rule of five also showed that the discovered compounds exhibited good oral bioavailability. (4) Conclusions: It is foreseeable that these results provide a novel intellectual contribution in light of the decreasing prevalence of SARS-CoV-2 B.1.1.529 and could be a good addition to the therapeutic protocol.

Background: Sorghum is consumed in Africa, North and South America, India, and other parts of the world, but it is one of several millets in Japan, and its physiological function for Japanese is not well known. In this study, we examined the effect of sorghum on postprandial blood glucose levels in healthy Japanese. Objective: This study aims to investigate the effect of sorghum intake on postprandial blood glucose in healthy adults. Methods: A double-blind crossover study was done on 17 healthy adult men and women recruited from the general population. After an early morning fasting blood glucose test, a placebo or sorghum porridge was administered and blood glucose levels were measured at 30, 60, and 120 minutes after the first washout period. Result: At 60 and 120 minutes after intake, the blood glucose level of people who were administered sorghum porridge was significantly lower than that of those who were administered the placebo. The area under the blood glucose curve was also significantly lower for the test product than for the placebo. Conclusion: Sorghum consumption can suppress the increase in postprandial blood glucose, suggesting that sorghum is useful in preventing the development of diabetes mellitus. [ABSTRACT FROM AUTHOR]

Four new natural compounds named hericenone O (1), hericenone P (2), hericenone Q (3), and hericenone R (4), two of them were reported synthetically (3-4), together with eleven known compounds were isolated from the fruiting bodies of Hericium erinaceus. The chemical structures of the isolated compounds were elucidated by using NMR analysis and mass spectrometry, as well as comparisons with the reported data in the literature. The bioactivity evaluation revealed that hericenone Q showed significant cytotoxic activity against Hep-G2 with IC50 values of 23.89 μM, and against HCT-116 with IC50 values of 65.64 μM. [ABSTRACT FROM AUTHOR]

Introduction: Propolis is a bee product traditionally used for therapy in several diseases. The therapeutic activities of propolis, such as antioxidant, antifungal, antibacterial, and anti-inflammatory, are commonly known. Propolis from the stingless bee (Wallacetrigona insica) showed promising bioactivity essential for the criteria. Objective: The present study focused on an examination of the cytotoxicity effect of secondary metabolites isolated from stingless bee (W. insica) propolis in some cancer cell lines. Methods: The fractionation and isolation of the active compound from stingless bee (W. insica) propolis were done by chromatographic methods and spectroscopic analysis. Results: The prenylated flavonoid named 8,3΄-diisoprenyl kaempferol (broussoflavonol F) showed cytotoxicity to all types of cancer cells (HepG2, MCF-7, HeLa, and HCT116). Among the four cancer-cell lines tested, broussoflavonol F displayed the strongest cytotoxicity effect against HCT116 (IC50 1.66±0.25 μM) and HeLa (IC50 17.10±0.26 μM), compared to 5-FU as a positive standard. It also showed 63.3% of viable cells at 12 μg/ml in CCD841 normal cells. Conclusion: These findings provide scientific evidence that broussoflavonol F from stingless bee (W. insica) propolis might have potential as an anticancer agent. [ABSTRACT FROM AUTHOR]

Four new polyoxygenated cucurbitane triterpene glycosides named kedrojiftene A-D (4-7), were isolated via different chromatographic techniques along with three phenolic compounds (1-3) from the crude extract of Kedrostis gijef. The isolated compounds were elucidated based on 1D, 2D-NMR spectroscopic analyses, HRESIMS and comparison with the related metabolites in literature. In bioassay, the α-glucosidase inhibitory assay for the isolated compounds was carried out and compounds (1-3) showed significant inhibitory activities. [ABSTRACT FROM AUTHOR]