Effects of Saffron Extract (Affron®) with 100 mg/kg and 200 mg/kg on Hypothalamic-Pituitary-Adrenal Axis and Stress Resilience in Chronic Mild Stress-Induced Depression in Wistar Rats.

Stress-related symptoms are a global concern, impacting millions of individuals, yet effective and safe treatments remain scarce. Although multiple studies have highlighted the stress- alleviating properties of saffron extract, the underlying mechanisms remain unclear. This study employs the unpredictable chronic mild stress (CMS) animal model to investigate the impact of a standardized saffron extract, Affron® (AFN), on hypothalamic-pituitary-adrenal (HPA) axis regulation and neuroplasticity in Wistar rats following repeated oral administration. The research evaluates AFN's effects on various stress-related parameters, including hypothalamic gene expression, stress hormone levels, and the sucrose preference test. In animals subjected to continuous unpredictable CMS, repetitive administration of AFN at doses of 100 mg/kg and 200 mg/kg effectively normalized HPA axis dysregulation and enhanced neuroplasticity. Increased concentrations of AFN demonstrated greater efficacy. Following AFN oral administration, adrenocorticotropic and corticosterone hormone levels exhibited significant or nearly significant reductions in comparison to subjects exposed to stress only. These changes align with the alleviation of stress and the normalization of the HPA axis. These findings elucidate AFN's role in stress mitigation, affirm its health benefits, validate its potential as a treatment for stress-related symptoms, confirm its physiological effectiveness, and emphasize its therapeutic promise.

Yeast Hydrolysate Inhibits Lipid Accumulation via Regulation of Lipid Accumulation-Related Genes in a Drosophila Model of High-Sugar Diet-Induced Obesity.

The increasing frequency of processed food consumption has led to the higher ingestion of sugar, increasing the risk of chronic diseases, such as obesity. Yeast hydrolysates (YHs) inhibit body fat accumulation. However, the action mechanism of YH in relation to high-sugar diet-induced obesity is still unclear. Therefore, this study aimed to evaluate the biological effects of YH on lipid accumulation and verify behavioral changes and carbohydrate metabolic gene regulation in high-sugar diet-fed fruit flies. Adult male flies (Drosophila melanogaster; 2-5 days old) were exposed to 20% sucrose for obesity induction. In high-sugar-fed Drosophila, the effect of YH was compared with that of yeast extract. The effects of YH on body conditions and lipid droplet size were quantified and analyzed. Behavioral factors were evaluated by analyzing circadian rhythm patterns and neurotransmitter content, and a molecular approach was used to analyze the expression of metabolism-related genes. Dietary supplementation with YH did not reduce total sugar content, but significantly decreased the triglyceride (TG) levels in Drosophila. A behavioral analysis showed that the total number of night-time activities increased significantly with YH treatment in a dose-dependent manner. In addition, YH effectively regulated the gene expression of insulin-like peptides related to carbohydrate metabolism as well as genes related to lipogenesis. The TG content was significantly reduced at a YH concentration of 0.5%, confirming that the active compound in YH effectively suppresses fat accumulation. These findings support that YH is a potential anti-obesity food material via regulating carbohydrate metabolism in Drosophila.

Effects of Dendropanax morbiferus Leaf Extract on Sleep Parameters in Invertebrate and Vertebrate Models.

Dendropanax morbiferus is highly valued in traditional medicine and has been used to alleviate the symptoms of numerous diseases owing to its excellent antioxidant activity. This study aimed to evaluate the sleep promotion and related signaling pathways of D. morbiferus extract (DE) via behavioral analysis, molecular biological techniques, and electrophysiological measurements in invertebrate and vertebrate models. In Drosophila, the group treated with 4% DE experienced decreased subjective nighttime movement and sleep bout and increased total sleeping time. Moreover, substantial changes in locomotor activity, including distance moved, velocity, and movement, were confirmed in the 4% DE-treated group. Compared to Drosophila in which insomnia and oxidative stress were induced by exposure to 0.1% caffeine, the DE-treated group improved sleep-related parameters to the level of the normal group. In the Drosophila model, exposure to 4% DE upregulated the expression of gamma-aminobutyric acid (GABA)-related receptors and serotonin receptor (5-HT1A), along with the expression of antioxidant-related factors, glutathione, and catalase. In the pentobarbital-induced sleep test using ICR mice, the duration of sleep was markedly increased by high concentration of DE. In addition, through the electroencephalography analysis of SD-rats, a significant increase in non-rapid-eye-movement sleep and delta waves was confirmed with high concentrations of DE administration. The increase in sleep time and improvement in sleep quality were confirmed to be related to the expression of altered GABA receptors and the enhancement of the contents of the neurotransmitters GABA and serotonin (5-HT) because of high DE administration. High-dose administration of DE also increased the expression of antioxidant-related factors in the brain and significantly decreased malondialdehyde content. Taken together, DE induced improvements in sleep quantity and quality by regulating neurotransmitter content and related receptor expression, along with high antioxidant activity, and may have a therapeutic effect on sleep disorders.

Combined Effects of Ziziphus jujuba, Dimocarpus longan, and Lactuca sativa on Sleep-Related Behaviors through GABAergic Signaling.

We aimed to analyze the increase in the sleep-promoting effects based on the mixed ratio of botanical extracts, Ziziphus jujuba seeds, Dimocarpus longan fruits, and Lactuca sativa leaves, using animal models. Behavioral analyses, including an analysis of the total sleep time of Drosophila melanogaster, were conducted to select the optimal mixed ratio of the three botanical extracts. The effects were verified in a caffeine-induced sleepless model, specific neurotransmitter receptor antagonists, and ICR mice. In D. melanogaster exposed to 2.0% of each extract, group behavior was significantly reduced, and the mixed extracts of Z. jujuba, D. longan, and L. sativa (4:1:1 and 1:4:1) significantly increased the total sleep time with individual fruit flies. In the caffeine-induced insomnia model, mixed extracts (4:1:1 and 1:4:1) led to the highest increase in total sleep time. An analysis of locomotor ability revealed a significant reduction in the mobility percentage in the mixed extract groups (0:0:1, 1:0:1, 1:1:1, 4:1:1, and 1:4:1). The administration of Z. jujuba extract and mixed extracts (4:1:1) significantly increased the expression of GABAA-R, whereas the administration of the mixed extracts (4:1:1) and (1:4:1) significantly increased the expression of GABAB-R1 and GABAB-R2, respectively. D. longan extract and the mixed ratio (1:4:1) reduced the subjective nighttime movement and increased the total sleep time in the presence of flumazenil. An analysis of ICR mice indicated that the administration of mixed extracts (4:1:1) significantly increased sleep duration in a dose-dependent manner. These results indicated that the mixed ratio of Z. jujuba, D. longan, and L. sativa extracts, particularly the mixed ratio of 4:1:1, may have sleep-enhancing effects in fruit flies and mice. The study also identified changes in gene expression related to GABA receptors, indicating the potential mechanism for the observed sleep-promoting effects.