Sleep-Enhancing Effect of Water Extract from Jujube (Zizyphus jujuba Mill.) Seeds Fermented by Lactobacillus brevis L32.

Although Ziziphus jujuba Mill (jujube) is used in folk medicine for hypnotic sedative, anxiolytic, and many other purposes, to date, only a few studies have revealed its sleep-promoting effects and related mechanisms. Currently, drugs used for the treatment of sleep disorders have various side effects, so it is essential to develop safe natural materials. Therefore, we evaluated the sleep-enhancing activity and mechanism of action of an aqueous extract of jujube seeds (ZW) fermented with Lactobacillus brevis L-32 in rodent models. The starch contained in ZW was removed by enzymatic degradation and fermented with L. brevis to obtain a fermented product (ZW-FM) with a high γ-aminobutyric acid (GABA) content. To evaluate the sleep-promoting effect of ZW-FM, pentobarbital-induced sleep tests were performed on ICR mice, and electroencephalography analysis was undertaken in Sprague Dawley rats. Additionally, the awakening relief effects of ZW-FM were confirmed in a caffeine-induced insomnia model. Finally, the mechanism of sleep enhancement by ZW-FM was analyzed using GABA receptor type A (GABAA) antagonists. The ZW-FM-treated groups (100 and 150 mg/kg) showed increased sleep time, especially the δ-wave time during non-rapid eye movement (NREM) sleep. In addition, the 150 mg/kg ZW-FM treatment group showed decreased sleep latency and increased sleep time in the insomnia model. In particular, NREM sleep time was increased and REM sleep time, which was increased by caffeine treatment, was decreased by ZW-FM treatment. ZW-FM-induced sleep increase was inhibited by the GABAA receptor antagonists picrotoxin, bicuculline, and flumazenil, confirming that the increase was the result of a GABAergic mechanism. These results strongly suggest that the increased GABA in water extract from jujube seeds fermented by L. brevis acts as a sleep-promoting compound and that the sleep-promoting activity is related to GABAA receptor binding.

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.

An Anthocyanin-Enriched Extract from Vaccinium uliginosum Improves Signs of Skin Aging in UVB-Induced Photodamage.

Accumulating evidence indicates that botanical extracts affect skin biophysical parameters, such as hydration, transepidermal water loss (TEWL), melanin index, erythema index, and wrinkle development. Vaccinium uliginosum extract contains a high level of anthocyanins as antioxidant and is ideal for use in dietary skin care products. Here, we assessed the photoprotective effects of dietary V. uliginosum extract in ultraviolet B (UVB)-irradiated hairless mice. Quantitative analysis of anthocyanin composition in the ethanol-extracted V. uliginosum sample was performed using high-performance liquid chromatography (HPLC). Skin parameter analysis and hematoxylin and eosin (H&E) staining were conducted on skin samples from UVB-irradiated hairless mice to evaluate the effects of V. uliginosum extract on skin conditions. In addition, skin mRNA and protein expression were assessed to characterize the molecular mechanisms underlying the effects of the anthocyanin-enriched extract on skin appearance and condition. Administration of the ethanol-extracted V. uliginosum sample caused significant changes in skin water-holding capacity, TEWL, wrinkle-related parameters, and epidermal thickness in UVB-irradiated hairless mice. In addition, oral administration of V. uliginosum attenuated the gene expression of matrix metalloproteinase (MMP) and increased levels of tissue inhibitor of metalloproteinase (TIMP) and antioxidant-related genes. Further, V. uliginosum administration downregulated inflammatory cytokine levels and UVB-induced phosphorylation of extracellular signaling regulated kinase (ERK), as well as Jun N-terminal kinase (JNK) and p38 protein levels. Oral administration of anthocyanin-enriched V. uliginosum extract can improve the appearance and condition of the skin following UV irradiation.

Photoprotective Effect of Dietary Galacto-Oligosaccharide (GOS) in Hairless Mice via Regulation of the MAPK Signaling Pathway.

This study investigated the suppression of photoaging by galacto-oligosaccharide (GOS) ingestion following exposure to ultraviolet (UV) radiation. To investigate its photoprotective effects, GOS along with collagen tripeptide (CTP) as a positive control was orally administered to hairless mice under UVB exposure for 8 weeks. The water holding capacity, transepidermal water loss (TEWL), and wrinkle parameters were measured. Additionally, quantitative reverse-transcription polymerase chain reaction and Western blotting were used to determine mRNA expression and protein levels, respectively. The GOS or CTP orally-administered group showed a decreased water holding capacity and increased TEWL compared to those of the control group, which was exposed to UVB (CON) only. In addition, the wrinkle area and mean wrinkle length in the GOS and CTP groups significantly decreased. Skin aging-related genes, matrix metalloproteinase, had significantly different expression levels in the CTP and GOS groups. Additionally, the tissue inhibitor of metalloproteinases and collagen type I gene expression in the CTP and GOS groups significantly increased. Oral administration of GOS and CTP significantly lowered the tissue cytokine (interleukin-6 and -12, and tumor necrosis factor-α) levels. There was a significant difference in UVB-induced phosphorylation of JNK, p38, and ERK between the GOS group and the CON group. Our findings indicate that GOS intake can suppress skin damage caused by UV light and has a UV photoprotective effect.