Kazunori Sasaki

Background/Objective: Sea buckthorn contains an exceptionally rich profile of bioactive nutrients and metabolites, with established systemic therapeutic benefits across diverse pathological models. However, comprehensive data bridging these systemic outcomes with specific tissue responses are still lacking. This descriptive transcriptomic study establishes a predictive framework to guide the future application of sea buckthorn and its isolated derivatives in targeted preventive and therapeutic strategies. Methods: We utilized a 3D spheroid culture of normal human amniotic epithelial stem cells (hAESCs) to evaluate the bioactivity effects of sea buckthorn juice (SBJ) treatment. Results: Microarray analysis validated spheroid structural growth by revealing the upregulation of key upstream markers of proliferation. This SBJ-induced proliferation was supported by a coordinated upregulation of mitochondrial machinery, including oxidative phosphorylation, mitochondrial RNA processing, the TCA cycle, and mitochondrial membrane organization. Cell type signature analysis revealed that treated cells acquired highly proliferative and active extracellular matrix (ECM) remodeling traits. Furthermore, tissue database mapping showed that the cells shared strong transcriptional similarity with human embryo and Wharton’s jelly proliferative states. Muscle-type signatures, including cardiomyocyte, myoblast, and smooth muscle lineages, were consistently enriched. Conclusions: Overall, these findings provide a transcriptomic signature-based predictive model for the biological effects of SBJ. Based on gene ontology and tissue-specific enrichment profiles, our data offer hypothesis-generating predictions suggesting a potential role for SBJ in supporting cellular regeneration via stem cell proliferation. Furthermore, tissue-specific analysis indicates a putative capacity to modulate smooth muscle integrity, inferred from transcriptomic similarities with muscle-type gene signatures. While pure extracted compounds demonstrate beneficial effects, evaluating the whole SBJ matrix provides a broader understanding of its full, unique profile of bioactive properties. These in vitro findings highlight the potential value of the complete juice matrix, forming a predictive baseline for future in vivo and clinical evaluations.

The Japanese population has the world’s longest life expectancy but faces the challenge of extending the healthy life expectancy without developing chronic diseases. Therefore, the effectiveness of products derived from olives used in the Mediterranean diet as a potential dietary solution has attracted attention. This study examined the effects of desert olive tree pearls (DOTPs), which contain 162 times more polyphenol hydroxytyrosol than olive oil, on the cognitive function of middle-aged and older adults using the Cognitrax test. Participants (aged 51–82 years) were assigned to the DOTP intake (n = 36) or placebo group (n = 36) in a randomized, double-blind, placebo-controlled, parallel-group study. The participants received 3 g of DOTPs or placebo in olive oil twice daily for 12 weeks. Among cognitive domains, complex attention had a significant time × group interaction effect (p = 0.049) between the DOTP and placebo groups. The simple main effect for this item was significantly different (p < 0.001 and p = 0.572, respectively). Time effects were significant (p < 0.05) for the psychomotor speed, reaction time, cognitive flexibility, processing speed, and executive function domains. Therefore, DOTPs have the potential to alleviate cognitive problems faced by middle-aged and older adults in Japan.

Carnosic acid (CA) is a phenolic diterpene widely distributed in herbal plants, rosemary and sage. Although its medicinal properties, such as antioxidant, antimicrobial, and neuroprotective effects, have been well-documented, its relevant biochemical processes and molecular targets have not been fully explored yet. In the present study, we conducted an untargeted whole-genome transcriptomics analysis to investigate CA-induced early biological and molecular events in human amniotic epithelial stem cells (hAESCs) with the aim of exploring its multiple tissue-specific functionalities and potential molecular targets. We found that seven days of CA treatment in hAESCs could induce mesoderm-lineage-specific differentiation. Tissue enrichment analysis revealed that CA significantly enriched lateral plate mesoderm-originated cardiovascular and adipose tissues. Further tissue-specific PPI analysis and kinase and transcription factor enrichment analyses identified potential upstream regulators and molecular targets of CA in a tissue-specific manner. Gene ontology enrichment analyses revealed the metabolic, antioxidant, and antifibrotic activities of CA. Altogether, our comprehensive whole-genome transcriptomics analyses offer a thorough understanding of the possible underlying molecular mechanism of CA.

In recent years, perinatal stem cells, such as human amniotic epithelial cells (hAECs), have attracted increasing interest as a novel tool of stem cell-based high-throughput drug screening. In the present study, we investigated the bioactivities of squalene (SQ) derived from ethanol extract (99.5%) of a microalgae Aurantiochytrium Sp. (EEA-SQ) in hAECs using whole-genome DNA microarray analysis. Tissue enrichment analysis showed that the brain was the most significantly enriched tissue by the differentially expressed genes (DEGs) between EEA-SQ-treated and control hAECs. Further gene set enrichment analysis and tissue-specific functional analysis revealed biological functions related to nervous system development, neurogenesis, and neurotransmitter modulation. Several adipose tissue-specific genes and functions were also enriched. Gene-disease association analysis showed nervous system-, metabolic-, and immune-related diseases were enriched. Altogether, our study suggests the potential health benefits of microalgae-derived SQ and we would further encourage investigation in EEA-SQ and its derivatives as potential therapeutics for nervous system- and metabolism-related diseases.

We previously performed a 4 week interventional trial that suggested that continuous intake of rosemary extract improves the mood states, fatigue, and cognitive function of working generation healthy adult Japanese men. However, the severity of depression in participants in our previous study was relatively mild. Therefore, in the present study, a post-hoc analysis of our previous study was conducted, limited to participants whose total mood disturbance (TMD) scores, which indicate greater mood disturbance, were above the median at baseline, to evaluate whether rosemary extract was effective for individuals with poor mental health. Following the intervention, the scores of TMD and “Confusion-Bewilderment” were significantly decreased (both p < 0.05), and scores of “Vigor-Activity” were significantly increased in the rosemary group (n = 8) compared with those in the control group (n = 13; p < 0.01). When comparing the scores from pre- and post-intervention, significant improvements in “Tension-Anxiety”, “Vigor-Activity”, “Fatigue on awakening”, “Daytime sleepiness”, and “Psychomotor speed” were observed in the rosemary group only (all p < 0.05). Based on these results, it was expected that rosemary extracts were effective for improving the mental energy and sleep quality of work-age men with poor mental health.

Hyperuricemia is defined as a disease with high uric acid (UA) levels in the blood and a strong risk factor for gout. Urolithin A (UroA) is a main microbial metabolite derived from ellagic acid (EA), which occurs in strawberries and pomegranates. In this study, we evaluated antihyperuricemic effect of UroA in both cultured hepatocytes and hyperuricemic model mice. In cultured hepatocytes, UroA significantly and dose-dependently reduced UA production. In model mice with purine bodies-induced hyperuricemia, oral administration of UroA significantly inhibited the increase in plasma UA levels and hepatic xanthine oxidase (XO) activity. In addition, DNA microarray results exhibited that UroA, as well as allopurinol, a strong XO inhibitor, induced downregulation of the expression of genes associated with hepatic purine metabolism. Thus, hypouricemic effect of UroA could be, at least partly, attributed to inhibition of purine metabolism and UA production by suppressing XO activity in the liver. These results indicate UroA possesses a potent antihyperuricemic effect and it could be a potential candidate for a molecule capable of preventing and improving hyperuricemia and gout.

Lippia citriodora ethanolic extract (VEE) and verbascoside (Vs), a phenypropanoid glycoside, have been demonstrated to exert relaxant and anxiolytic properties. However, the molecular mechanisms behind their effects are still unclear. In this work, we studied the effects and action mechanisms of VEE and Vs in vivo and in vitro, on human neurotypic SH-SY5Y cells.TST was conducted on mice treated orally with VEE (25, 50 and 100 mg/Kg), Vs (2.5 and 5 mg/Kg), Bupropion (20 mg/Kg) and Milli-Q water. Higher dose of VEE-treated mice showed an increase of immobility time compared to control groups, indicating an induction of relaxation. This effect was found to be induced by regulation of genes playing key roles in calcium homeostasis (calcium channels), cyclic AMP (cAMP) production and energy metabolism. On the other hand, low doses of VEE and Vs showed an antidepressant-like effect and was confirmed by serotonin, noradrenalin, dopamine and BDNF expressions. Finally, VEE and Vsenhancedcell viability, mitochondrial activity and calcium uptake in vitro confirming in vivo findings. Our results showed induction of relaxation and antidepressant-like effects depending on the administered dose of VEE and Vs, through modulation of cAMP and calcium.

Mood disorder accounts for 13 % of global disease burden. And while therapeutic agents are available, usually orally administered, most have unwanted side effects, and thus making the inhalation of essential oils (EOs) an attractive alternative therapy. Rosmarinus officinalis EO (ROEO), Mediterranean ROEO reported to improve cognition, mood, and memory, the effect on stress of which has not yet been determined. Here, the anti-stress effect of ROEO on stress was evaluated in vivo and in vitro. Six-week-old male ICR mice were made to inhale ROEO and subjected to tail suspension test (TST). To determine the neuronal differentiation effect of ROEO in vitro, induction of ROEO-treated PC12 cells differentiation was observed. Intracellular acetylcholine and choline, as well as the Gap43 gene expression levels were also determined. Inhalation of ROEO significantly decreased the immobility time of ICR mice and serum corticosterone level, accompanied by increased brain dopamine level. Determination of the underlying mechanism in vitro revealed a PC12 differentiation-induction effect through the modulation of intracellular acetylcholine, choline, and Gap43 gene expression levels. ROEO activates the stress response system through the NGF pathway and the hypothalamus-pituitary-adrenal axis, promoting dopamine production and secretion. The effect of ROEO may be attributed to its bioactive components, specifically to α-pinene, one of its major compounds that has anxiolytic property. The results of this study suggest that ROEO inhalation has therapeutic potential against stress-related psychiatric disorders.