Hyowon Lee

BACKGROUND: Chrysanthemum morifolium has long been utilized in traditional medicine for its antioxidant and sedative properties, yet its potential in sleep regulation and neuroprotection against oxidative stress remains underexplored. This study investigates the antioxidant and sleep‐enhancing effects of C. morifolium extract (CE) in HT22 hippocampal neuronal cells and animal models, focusing on its bioactive component, luteolin‐7‐glucoside (L‐7‐G) and the underlying molecular mechanisms. RESULTS: CE exhibited potent antioxidant activity, significantly reducing reactive oxygen species and malondialdehyde levels while improving cell survival under oxidative stress. It upregulated antioxidant enzyme expression and activated the Nrf2/HO‐1 pathway, effects linked to L‐7‐G. In pentobarbital‐induced sleep models, CE increased sleep duration by up to 1.41‐fold compared to controls, with L‐7‐G showing similar efficacy. Electroencephalography revealed enhanced δ‐wave activity and prolonged non‐rapid eye movement (NREM) sleep with CE treatment. In a caffeine‐induced insomnia model, CE reduced wake time, restored NREM sleep, and counteracted sleep disturbances by enhancing δ‐wave activity. Mechanistic analysis showed CE upregulated GABA _A and 5‐HT _1A receptor expression, with its sleep‐promoting effects partially mediated through GABA _A receptor interactions. CONCLUSION: CE, particularly through L‐7‐G, exhibits significant potential as a natural agent for reducing oxidative stress and enhancing sleep quality, offering a promising avenue for managing sleep disorders. © 2025 The Author(s). Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Fenugreek seed extract rich in trigonelline, protodioscin, and 4-hydroxy- l -isoleucine alleviates menopause-related sleep disturbances in OVX mice by modulating GABAergic, melatoninergic, and adenosinergic pathways.

Jujube seed extract (JSE), rich in polyphenols and flavonoids, exhibits neuroprotective and sleep-enhancing properties.In vitro, JSE protected HT22 cells against oxidative stress by activating the Nrf2/HO-1 pathway and upregulatingantioxidant enzymes. In vivo, JSE increased non-REM sleep and delta wave activity in pentobarbital- and caffeine-induced sleep models. Spinosin contributed to these effects. Long-term JSE administration upregulated GABAA, GABAB, and 5-HT1A receptors in brain tissue. These findings suggest that JSE offers dual benefits in mitigating oxidativestress and promoting sleep through antioxidant defense and neurotransmitter modulation, supporting its potential as a natural therapeutic agent.

Current Topics in Lactic Acid Bacteria and Probiotics, 한국유산균프로바이오틱스학회 학술지

BACKGROUND: Sleep is essential for overall health and wellbeing. This study investigated the sleep‐promoting effects of fermented pea protein hydrolysate (PPF) with increased gamma‐aminobutyric acid (GABA) content produced by Lactobacillus brevis SYLB 0016. The effects of PPF on sleep duration and structure were assessed in pentobarbital‐induced ICR mice and Sprague Dawley (SD) rats using electroencephalogram (EEG) analysis.RESULTS: Hydrolysis of pea protein with Alcalase, Protana Prime, and Protana UBoost increased the amino nitrogen content, degree of hydrolysis and glutamate content to 160.51 mmol L⁻¹. Fermentation by Lactobacillus brevis SYLB 0016 increased the GABA content from 3.16 to 90.35 mmol L⁻¹. PPF significantly increased sleep duration (56.3 min) compared to the normal control (30.6 min) in pentobarbital‐induced sleep tests. Non‐rapid eye movement (NREM) sleep time increased with a significant rise in δ‐waves activity following administration of 150 mg kg⁻¹ of PPF. In caffeine‐induced insomnia, both low‐ and high‐dose PPF significantly increased sleep duration. Three weeks of oral PPF administration elevated GABA_A and GABA_B receptor expression, with GABA_A receptor protein levels showing a significant change. Co‐administration of flumazenil with PPF reduced sleep time, indicating the involvement of the GABA_A receptor benzodiazepine site in PPF's sleep‐enhancing effects.CONCLUSION: In conclusion, PPF with enhanced GABA content improves NREM sleep by increasing δ waves activity. As a hypoallergenic compound, PPF holds potential as a supplement to ameliorate sleep disorders. © 2025 Society of Chemical Industry.

This study characterized the sleep activity, sleep mechanism, and active peptides of whey protein hydrolysates selected through behavioral analysis of fruit-flies (Drosophila melanogaster). Sleep-inducing whey protein (WP) hydrolysate was selected through fruit fly behavior analysis, and sleep activity was measured using a pentobarbital model and electroencephalographic analysis. The mechanism of action was confirmed using a γ-aminobutyric acid (GABA) receptor antagonist, and the active peptide was identified using liquid chromatography-mass spectroscopy. Whey protein hydrolysate, prepared using Alcalase and Prozyme (WP-AP), increased sleep time in a dose-dependent manner. WP-AP significantly increased not only sleep time but also slow-wave sleep and showed an insomnia-alleviating effect in a caffeine-induced insomnia mouse model. In addition, the gene and protein expression levels of GABA sub-type A (GABA_A) receptors increased in the brains of mice orally administered with WP-AP. Through peptide analysis, the mixture of DIQK, VPPF peptide, and GABA contained in WP-AP was estimated to exhibit sleep activity, and due to its high content, DIQK was speculated to be the main sleep -inducing ingredient. These results indicate that WP-AP has the potential to be used as a new ingredient to improve sleep quality.

Many cell culture experiments are performed under light to evaluate the photodynamic or photosensitizing efficacy of various agents. In this study, the modulation of photosensitizing responses and phototoxicity under cell culture conditions by different medium components was investigated. The significant levels of reactive oxygen species (ROS) generated from DMEM, RPMI 1640, and MEM were observed under the irradiation of fluorescent light (FL) and white and blue LEDs, indicating that these media have their own photosensitizing properties; DMEM showed the most potent property. Phenol red-free DMEM (Pf-D) exhibited a stronger photosensitizing property than normal DMEM by 1.31 and 1.25 times under FL and blue LEDs, respectively; phenol red and riboflavin-free DMEM (PRbf-D) did not show any photosensitizing properties. The inhibitory effect on light transmission was more pronounced in DMEM than in RPMI, and the interference effect on green LED light was greatest at 57.8 and 27.4%, respectively; the effect disappeared in Pf-D. The media containing riboflavin induced strong phototoxicity in HaCaT keratinocytes by generating H₂O₂ under light irradiation, which was quenched by sodium pyruvate in the media. The presence of serum in the media was also reduced the phototoxicity; H₂O₂ levels in the media decreased serum content dependently. The phototoxicity of erythrosine B and protoporphyrin IX under FL was more sensitively pronounced in PRbf-D than in DMEM. The present results indicate that several medium components, including riboflavin, phenol red, sodium pyruvate, and serum, could modulate photosensitizing responses in a cell culture system by inducing photosensitizing activation and by interfering with irradiation efficacy and ROS generation.

In this study, we investigated the effects of whey protein hydrolysate (WPH) fermented with Lactobacillus brevis on sleep behavior and GABAergic mechanisms in rodent models. Fermentation converted the glutamate in WPH to high (3.15 ± 0.21 mg/mL) levels of γ-aminobutyric acid (GABA). Fermented WPH (WP-SF) enhanced sleep duration in mice by increasing GABA content in the brain. The increase in sleep duration induced by WP-SF resulted from an increase in delta wave activity during non-rapid eye movement sleep, and its sleep-promoting effect in a caffeine-induced insomnia model was characterized by an increase in delta waves. WP-SF increased GABAergic receptors at both mRNA and protein levels. Cotreatment with GABA_A receptor antagonists abolished the sleep-promoting effects of WP-SF, indicating that WP-SF shares binding sites with antagonists on GABA_A receptors. Collectively, WP-SF effectively increased sleep duration by enhancing delta wave activity through GABAergic activation; thus, it is suggested as a functional food-grade ingredient for promoting sleep.