A rare olive compound oleacein functions as a TrkB agonist and mitigates neuroinflammation both in vitro and in vivo.

BACKGROUND: Neuroinflammation is widely acknowledged as a characteristic feature of almost all neurological disorders and specifically in depression- and anxiety-like disorders. In recent years, there has been significant attention on natural compounds with potent anti-inflammatory effects due to their potential in mitigating neuroinflammation and neuroplasticity. METHODS: In the present study, we aimed to evaluate the neuroprotective effects of oleacein (OC), a rare secoiridoid derivative found in extra virgin olive oil. Our goal was to explore the BDNF/TrkB neurotrophic activity of OC and subsequently assess its potential for modulating neuroinflammatory response using human neuroblastoma cells (SH-SY5Y cells) and an in vivo model of depression induced by lipopolysaccharide (LPS)-mediated inflammation. RESULTS: In SH-SY5Y cells, OC exhibited a significant dose-dependent increase in BDNF expression. This enhancement was absent when cells were co-treated with inhibitors of BDNF's receptor TrkB, as well as downstream molecules PI3K and MEK. Whole-transcriptomics analysis revealed that OC upregulated cell cycle-related genes under normal conditions, while downregulating inflammation-associated genes in LPS-induced conditions. Furthermore, surface plasmon resonance (SPR) assays demonstrated that OC exhibited a stronger and more stable binding affinity to TrkB compared to the positive control, 7,8-dihydroxyflavone. Importantly, bioluminescence imaging revealed that a single oral dose of OC significantly increased BDNF expression in the brains of Bdnf-IRES-AkaLuc mice. Furthermore, oral administration of OC at a dosage of 10 mg/kg body weight for 10 days significantly reduced immobility time in the tail suspension test compared to the LPS-treated group. RT-qPCR analysis revealed that OC significantly decreased the expression of pro-inflammatory cytokines Tnfα, Il6, and Il1ß, while simultaneously enhancing Bdnf expression, as well as both pro and mature BDNF protein levels in mice hippocampus. These changes were comparable to those induced by the positive control antidepressant drug fluoxetine. Additionally, microarray analysis of mouse brains confirmed that OC could counteract LPS-induced inflammatory biological events. CONCLUSION: Altogether, our study represents the first report on the potential antineuroinflammatory and antidepressant properties of OC via modulation of BDNF/TrkB neurotrophic activity. This finding underscores the potential of OC as a natural therapeutic agent for depression- and anxiety-related disorders.

Comparative Analysis of Olive-Derived Phenolic Compounds' Pro-Melanogenesis Effects on B16F10 Cells and Epidermal Human Melanocytes.

Olive leaf contains plenty of phenolic compounds, among which oleuropein (OP) is the main component and belongs to the group of secoiridoids. Additionally, phenolic compounds such as oleocanthal (OL) and oleacein (OC), which share a structural similarity with OP and two aldehyde groups, are also present in olive leaves. These compounds have been studied for several health benefits, such as anti-cancer and antioxidant effects. However, their impact on the skin remains unknown. Therefore, this study aims to compare the effects of these three compounds on melanogenesis using B16F10 cells and human epidermal cells. Thousands of gene expressions were measured by global gene expression profiling with B16F10 cells. We found that glutaraldehyde compounds derived from olive leaves have a potential effect on the activation of the melanogenesis pathway and inducing differentiation in B16F10 cells. Accordingly, the pro-melanogenesis effect was investigated by means of melanin quantification, mRNA, and protein expression using human epidermal melanocytes (HEM). This study suggests that secoiridoid and its derivates have an impact on skin protection by promoting melanin production in both human and mouse cell lines.

A comparative transcriptomics analysis reveals ethylene glycol derivatives of squalene ameliorate excessive lipogenesis and inflammatory response in 3T3-L1 preadipocytes.

Squalene (SQ) is a natural compound with anti-inflammatory, anti-cancer, and anti-oxidant effects, but due to its low solubility, its biological properties have been greatly underestimated. This study aims to explore the differences in gene expression patterns of four newly synthesized amphipathic ethylene glycol (EG) derivatives of SQ by whole-genome transcriptomics analysis using DNA microarray to examine the mRNA expression profile of adipocytes differentiated from 3T3-L1 cells treated with SQ and its EG derivatives. Enrichment analyses of the transcriptional data showed that compared with SQ, its EG derivatives exerted different, in most cases desirable, biological responses. EG derivatives showed increased enrichment of mitochondrial functions, lipid and glucose metabolism, and inflammatory response. Mono-, di-, and tetra-SQ showed higher enrichment of the cellular component-ribosome. Histological staining showed EG derivatives prevented excessive lipid accumulation. Additionally, mitochondrial transcription factors showed upregulation in tetra-SQ-treated cells. Notably, EG derivatives showed better anti-inflammatory effects. Further, gene-disease association analysis predicted substantial improvement in the bioactivities of SQ derivatives in metabolic diseases. Cluster analyses revealed di- and tetra-SQ had more functional similarities than others, reflected in their scanning electron microscopy images; both di- and tetra-SQ self-organized into similar sizes and shapes of vesicles, subsequently improving their cation binding activities. Protein-protein interaction networks further revealed that cation binding activity might explain a major part, if not all, of the differences observed in functional analyses. Altogether, the addition of EG derivatives may improve the biological responses of SQ and thus may enhance its health-promoting potential.

Comprehensive Transcriptome Profiling of Antioxidant Activities by Glutathione in Human HepG2 Cells.

Glutathione (GSH) has long been recognised for its antioxidant and detoxifying effects on the liver. The hepatoprotective effect of GSH involves the activation of antioxidative systems such as NRF2; however, details of the mechanisms remain limited. A comparative analysis of the biological events regulated by GSH under physiological and oxidative stress conditions has also not been reported. In this study, DNA microarray analysis was performed with four experiment arms including Control, GSH, hydrogen peroxide (HP), and GSH + HP treatment groups. The GSH-treated group exhibited a significant upregulation of genes clustered in cell proliferation, growth, and differentiation, particularly those related to MAPK, when compared with the Control group. Additionally, liver functions such as alcohol and cholesterol metabolic processes were significantly upregulated. On the other hand, in the HP-induced oxidative stress condition, GSH (GSH + HP group) demonstrated a significant activation of cell proliferation, cell cycle, and various signalling pathways (including TGFß, MAPK, PI3K/AKT, and HIF-1) in comparison to the HP group. Furthermore, several disease-related pathways, such as chemical carcinogenesis-reactive oxygen species and fibrosis, were significantly downregulated in the GSH + HP group compared to the HP group. Collectively, our study provides a comprehensive analysis of the effects of GSH under both physiological and oxidative stress conditions. Our study provides essential insights to direct the utilisation of GSH as a supplement in the management of conditions associated with oxidative stress.

Keratin Microspheres as Promising Tool for Targeting Follicular Growth.

Skin is the body barrier that constrains the infiltration of particles and exogenous aggression, in which the hair follicle plays an important role. Recent studies have shown that small particles can penetrate the skin barrier and reach the hair follicle, making them a potential avenue for delivering hair growth-related substances. Interestingly, keratin-based microspheres are widely used as drug delivery carriers in various fields. In this current study, we pursue the effect of newly synthesized 3D spherical keratin particles on inducing hair growth in C57BL/6 male mice and in human hair follicle dermal papilla cells. The microspheres were created from partially sulfonated, water-soluble keratin. The keratin microspheres swelled in water to form spherical gels, which were used for further experiments. Following topical application for a period of 20 days, we observed a regrowth of hair in the previously depleted area on the dorsal part of the mice in the keratin microsphere group. This observation was accompanied by the regulation of hair-growth-related pathways as well as changes in markers associated with epidermal cells, keratin, and collagen. Interestingly, microsphere keratin treatment enhanced the cell proliferation and the expression of hair growth markers in dermal papilla cells. Based on our data, we propose that 3D spherical keratin has the potential to specifically target hair follicle growth and can be employed as a carrier for promoting hair growth-related agents.

Antiobesity and Hypolipidemic Potential of Nitraria retusa Extract in Overweight/Obese Women: A Randomized, Double-Blind, Placebo-Controlled Pilot Study.

This study aimed to assess the efficacy of Nitraria retusa extract (NRE) in reducing weight, body mass index (BMI), body fat composition (BF), and anthropometric parameters among overweight/obese women, comparing the results with those of a placebo group. Overweight/obese individuals participated in a 12-week, double-blind, randomized, placebo-controlled trial. Body weight, BMI, body composition, and anthropometric parameters were assessed. Additionally, lipid profile and safety evaluation parameters were evaluated. Compared to the placebo group, the NRE group exhibited a mean weight loss difference of 2.27 kg (p < 0.001) at the trial's conclusion. Interestingly, the most significant weight reduction, amounting to 3.34 kg ± 0.93, was observed in younger participants with a BMI > 30.0. Similarly, BMI and BF% significantly decreased in the NRE group, contrary to the placebo group (p = 0.008 and p = 0.005, respectively). The percentage of body water (BW) (p = 0.006) as well as the ratio of LBM/BF (p = 0.039) showed a significant increase after the NRE intervention compared to the placebo. After age adjustment, all variables, except LBM/BF, retained statistical significance. Additionally, all anthropometric parameters were significantly reduced only in the NRE group. Most importantly, a significant reduction in Triglyceride (TG) levels in the NRE group was revealed, in contrast to the placebo group (p = 0.011), and the significance was still observed after age adjustment (p = 0.016). No side effects or adverse changes in kidney and liver function tests were observed in both groups. In conclusion, NRE demonstrated potent antiobesity effects, suggesting that NRE supplementation may represent an effective alternative for treating obesity compared to antiobesity synthetic drugs.

Modulation of mitochondrial activity by sugarcane (Saccharum officinarum L.) top extract and its bioactive polyphenols: a comprehensive transcriptomics analysis in C2C12 myotubes and HepG2 hepatocytes.

Age-related mitochondrial dysfunction leads to defects in cellular energy metabolism and oxidative stress defense systems, which can contribute to tissue damage and disease development. Among the key regulators responsible for mitochondrial quality control, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) is an important target for mitochondrial dysfunction. We have previously reported that bioactive polyphenols extracted from sugarcane top (ST) ethanol extract (STEE) could activate neuronal energy metabolism and increase astrocyte PGC-1α transcript levels. However, their potential impact on the mitochondria activity in muscle and liver cells has not yet been investigated. To address this gap, our current study examined the effects of STEE and its polyphenols on cultured myotubes and hepatocytes in vitro. Rhodamine 123 assay revealed that the treatment with STEE and its polyphenols resulted in an increase in mitochondrial membrane potential in C2C12 myotubes. Furthermore, a comprehensive examination of gene expression patterns through transcriptome-wide microarray analysis indicated that STEE altered gene expressions related to mitochondrial functions, fatty acid metabolism, inflammatory cytokines, mitogen-activated protein kinase (MAPK) signaling, and cAMP signaling in both C2C12 myotubes and HepG2 hepatocytes. Additionally, protein-protein interaction analysis identified the PGC-1α interactive-transcription factors-targeted regulatory network of the genes regulated by STEE, and the quantitative polymerase chain reaction results confirmed that STEE and its polyphenols upregulated the transcript levels of PGC-1α in both C2C12 and HepG2 cells. These findings collectively suggest the potential beneficial effects of STEE on muscle and liver tissues and offer novel insights into the potential nutraceutical applications of this material.

Transcriptomics and biochemical evidence of trigonelline ameliorating learning and memory decline in the senescence-accelerated mouse prone 8 (SAMP8) model by suppressing proinflammatory cytokines and elevating neurotransmitter release.

In recent years, exploring natural compounds with functional properties to ameliorate aging-associated cognitive decline has become a research priority to ensure healthy aging. In the present study, we investigated the effects of Trigonelline (TG), a plant alkaloid, on memory and spatial learning in 16-week-old senescence-accelerated mouse model SAMP8 using an integrated approach for cognitive and molecular biology aspects. After 30 days of oral administration of TG at the dose of 5 mg/kg/day, the mice were trained in Morris Water Maze task. TG-treated SAMP8 mice exhibited significant improvement in the parameters of escape latency, distance moved, and annulus crossing index. Next, we performed a whole-genome transcriptome profiling of the mouse hippocampus using microarrays. Gene ontology analyses showed that a wide range of biological processes, including nervous system development, mitochondrial function, ATP synthesis, and several signaling pathways related to inflammation, autophagy, and neurotransmitter release, were significantly enriched in TG-treated SAMP8 compared to nontreated. Further, a nonlinear dimensionality reduction technique, Uniform Manifold Approximation and Projection (UMAP), was applied to identify clusters of functions that revealed TG primarily regulated pathways related to inflammation, followed by those involved in neurotransmitter release. In addition, a protein-protein interaction network analysis indicated that TG may exert its biological effects through negatively modulating Traf6-mediated NF-κB activation. Finally, ELISA test showed that TG treatment significantly decreased proinflammatory cytokines- TNFα and IL6 and increased neurotransmitters- dopamine, noradrenaline, and serotonin in mouse hippocampus. Altogether, our integrated bio-cognitive approach highlights the potential of TG in alleviating age-related memory and spatial impairment.

Evaluation of Cognitive and Physical Function Among Older Adults by Their Physical Activity: A Cross-Sectional Kasama Study, Japan.

BACKGROUND: The amyloid-ß1-42 (Aß42) level is a biomarker that is widely used to evaluate individual cognitive dysfunction early in neurodegenerative diseases, as well as differentiate between normal cognitive function, mild cognitive impairment, Alzheimer's disease, and vascular cognitive impairment. OBJECTIVE: Our cross-sectional study evaluated the association between daily exercise and physical and cognitive function and Aß42 levels among a subsample of 325 older adults from the Kasama Study. METHODS: Participants (age: 74.5 [range 65-90] years) were classified into three exercise groups: the dual-task (DEG, n = 128), single-task (SEG, n = 122), and non-exercise (NEG, n = 75) groups. The main outcomes were the plasma Aß42 levels and the scores of the five cognitive (5-COG) tests and five cognition-related physical function (5-PHYS) tests. RESULTS: The Aß42 levels and 5-COG and 5-PHYS scores were higher in the SEG and DEG than in the NEG. The Aß42 levels were higher in the DEG than in the NEG (p = 0.008). CONCLUSIONS: Physical activities such as regular exercise may benefit older adults, improving their cognitive and physical function.

Microarray meta-analysis reveals comprehensive effects of 3,4,5-tricaffeolyquinic acid in cell differentiation and signaling.

Caffeoylquinic acids (CQA) are polyphenolic compounds found in fruits, vegetables, coffee, and spices that have exhibited several beneficial activities, including antioxidant, antibacterial, neuroprotective, anti-inflammatory, anticancer, antiviral, antidiabetic, and cardiovascular effects. A derivative, TCQA (3,4,5-Tri-O-caffeoylquinic acid), has also shown both neurogenic and pigment differentiation potential. A transcriptomic-based meta-analysis was conducted to explore potential biochemical processes and molecular targets of TCQA. This approach involved integrating data from various cell and tissue types, including human amniotic stem cells, human neural stem cells, human dermal papilla cells, and the brain cortex of aging model mice. It offered a comprehensive perspective on the significant gene regulations in response to TCQA treatment. The objective was to uncover the mechanism and novel targets of TCQA, facilitating a further understanding of its functions. New areas of interest found were TCQA's effect on adipogenesis, heart, and muscle tissue development. In addition, significantly enhanced biological activities found through meta-analysis included cell cycle, VEGFA-VEGFR2 pathway, and BMP signaling. Overall, a comprehensive functional and visual analysis using available biological databases uncovered the multi-target potential of this natural compound.

Hematinic Potential of Olive Leaf Extract: Evidence from an In Vivo Study in Mice and a Pilot Study in Healthy Human Volunteers.

Natural resources have recently received considerable attention as complementary or alternative hematinic agents. In this regard, olive leaf extract, which is rich in bioactive phenolic compounds, has been reported to induce erythroid differentiation in human hematopoietic stem cells. Therefore, in the present study, we aimed to explore the potential hematinic properties of aqueous olive leaf extract (WOL) in vivo. After 24 days of administering WOL to healthy mice orally, red blood cell (RBC), hematocrit, reticulocyte, and reticulocyte hemoglobin content (CHr) showed a significant increase. Additionally, WOL promoted plasma iron levels and the expression of splenic ferroportin (Fpn), an iron transporter. Additionally, a single-arm pilot study involving a limited number of healthy volunteers was conducted to assess WOL's feasibility, compliance, and potential benefits. Following an 8-week intervention with WOL, RBC count and hemoglobin level were significantly increased. Notably, there were no significant changes in the safety measures related to liver and kidney functions. Furthermore, we identified oleuropein and oleuroside as the active components in WOL to induce erythroid differentiation in the K562 cell line. Altogether, our study presents evidence of the hematinic potential of WOL in the in vivo studies, opening up exciting possibilities for future applications in preventing or treating anemia.

Self-stabilizing performance of γ-oryzanol in oil-in-water emulsions and solid dispersions.

The surface activity of γ-oryzanol was evaluated by the pendant drop method (PDM), and its self-stabilizing properties were investigated by high-pressure homogenization (HPH) and solvent displacement method (SDM). Emulsions prepared by HPH were highly unstable due to the poor surface-active character of γ-oryzanol as identified by the PDM. In contrast, solid dispersions fabricated by SDM had comparable particle size to those prepared using Tween 80 (T80) as surfactant, and were stable up to 30 days of storage at 4 °C. The self-stabilizing properties of γ-oryzanol were attributed to the mechanism of spontaneous particle formation in SDM and to the ability of γ-oryzanol molecules to prevent particles aggregation by electrostatic repulsion. The outcome of this study indicates the potential of encapsulating selected bioactive compounds, such as γ-oryzanol, in stable colloidal systems by SDM without adding emulsifier(s), regardless of their surface-active character.

RSK4 confers paclitaxel resistance to ovarian cancer cells, which is resensitized by its inhibitor BI-D1870.

Many ovarian cancers initially respond well to chemotherapy, but often become drug-resistant after several years. Therefore, analysis of drug resistance mechanisms and overcoming resistance are urgently needed. Paclitaxel is one of the first-choice and widely-used drugs for ovarian cancer, but like most drugs, drug resistance is observed in subsequent use. RSK4 is known as a tumor-suppressor, however, it has increasingly been reported to lead to drug resistance. Here, we found that RSK4 expression was elevated in paclitaxel-resistant ovarian cancer cells using DNA microarray, quantitative real-time PCR, and western blotting analysis. We examined the contribution of RSK4 to paclitaxel resistance and found that paclitaxel sensitivity was restored by RSK inhibitor co-treatment. We analyzed the mechanism by which resistance is developed when RSK4 level is elevated, and accelerated phosphorylation of the downstream translation factor eIF4B was discovered. In the Kaplan-Meier plot, the overall survival time was longer with RSK4 high, supporting its role as a tumor suppressor, as in previous findings, but the tendency was reversed when focusing on paclitaxel treatment. In addition, RSK4 levels were higher in non-responders than in responders in the ROC plotter. Finally, external expression of RSK4 in ovarian cancer cells increased the cell viability under paclitaxel treatment. These findings suggest that RSK4 may contribute to paclitaxel resistance, and that co-treatment with RSK4 inhibitors is effective treatment of paclitaxel-resistant ovarian cancer in which RSK4 is elevated.

Investigation into Molecular Brain Aging in Senescence-Accelerated Mouse (SAM) Model Employing Whole Transcriptomic Analysis in Search of Potential Molecular Targets for Therapeutic Interventions.

With the progression of an aging society, cognitive aging has emerged as a pressing concern necessitating attention. The senescence-accelerated mouse-prone 8 (SAMP8) model has proven instrumental in investigating the early stages of cognitive aging. Through an extensive examination of molecular changes in the brain cortex, utilizing integrated whole-genome transcriptomics, our principal aim was to uncover potential molecular targets with therapeutic applications and relevance to drug screening. Our investigation encompassed four distinct conditions, comparing the same strain at different time points (1 year vs. 16 weeks) and the same time point across different strains (SAMP8 vs. SAMR1), namely: physiological aging, accelerated aging, early events in accelerated aging, and late events in accelerated aging. Focusing on key functional alterations associated with aging in the brain, including neurogenesis, synapse dynamics, neurometabolism, and neuroinflammation, we identified candidate genes linked to these processes. Furthermore, employing protein-protein interaction (PPI) analysis, we identified pivotal hub genes involved in interactions within these functional domains. Additionally, gene-set perturbation analysis allowed us to uncover potential upstream genes or transcription factors that exhibited activation or inhibition across the four conditions. In summary, our comprehensive analysis of the SAMP8 mouse brain through whole-genome transcriptomics not only deepens our understanding of age-related changes but also lays the groundwork for a predictive model to facilitate drug screening for cognitive aging.

Exploring the Effects of Short-Term Daily Intake of Nitraria retusa Tea on Lipid Profile: A Pre-Post, Uncontrolled Pilot Study in Both Healthy and Overweight/Obese Adults.

In the present study, we aimed to explore the feasibility, compliance, and potential benefits of Nitraria retusa extract (NRE) intervention in both healthy (BMI ≤ 24.9 Kg/m2) and overweight/obese adults (BMI > 25 Kg/m2). A total of 98 participants, including 37 healthy individuals and 61 overweight/obese adults, were randomly assigned to either a low-dose (500 mg/day) or a high-dose (2000 mg/day) NRE intervention group. Plasma lipid biomarkers, liver and kidney functions, general hematology, and blood glucose levels were measured at the baseline and 10 days after intervention. While the lipid profile of the healthy participants did not show any statistically significant changes, the obese participants in the high-dose group experienced a significant decrease in triglyceride levels (within-group difference p value = 0.004) and an increase in HDL levels (within-group p value < 0.001). No significant differences were observed in other parameters, indicating that NRE at the given doses was safe. Furthermore, the study had impressive compliance and acceptability, with over 90% of participants completing the intervention and diligently following the study protocol. This pilot study represents the first investigation into the feasibility, acceptability, and potential benefits of NRE intervention on lipid profiles in human volunteers.

Effects of Desert Olive Tree Pearls Containing High Hydroxytyrosol Concentrations on the Cognitive Functions of Middle-Aged and Older Adults.

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.

A Rare Olive Compound Oleacein Improves Lipid and Glucose Metabolism, and Inflammatory Functions: A Comprehensive Whole-Genome Transcriptomics Analysis in Adipocytes Differentiated from Healthy and Diabetic Adipose Stem Cells.

Oleacein (OLE), a rare natural compound found in unfiltered extra virgin olive oil, has been shown to have anti-inflammatory and anti-obesity properties. However, little is known regarding the mechanisms by which OLE influences metabolic processes linked to disease targets, particularly in the context of lipid metabolism. In the present study, we conducted whole-genome DNA microarray analyses in adipocytes differentiated from human adipose-derived stem cells (hASCs) and diabetic hASCs (d-hASCs) to examine the effects of OLE on modulating metabolic pathways. We found that OLE significantly inhibited lipid formation in adipocytes differentiated from both sources. In addition, microarray analysis demonstrated that OLE treatment could significantly downregulate lipid-metabolism-related genes and modulate glucose metabolism in both adipocyte groups. Transcription factor enrichment and protein-protein interaction (PPI) analyses identified potential regulatory gene targets. We also found that OLE treatment enhanced the anti-inflammatory properties in adipocytes. Our study findings suggest that OLE exhibits potential benefits in improving lipid and glucose metabolism, thus holding promise for its application in the management of metabolic disorders.

A Descriptive Whole-Genome Transcriptomics Study in a Stem Cell-Based Tool Predicts Multiple Tissue-Specific Beneficial Potential and Molecular Targets of Carnosic Acid.

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.

Solid acid-catalyzed one-step synthesis of oleacein from oleuropein.

In this study, we developed a new synthetic strategy to convert secoiridoid glucosides into unique dialdehydic compounds using solid acid catalysts. Specifically, we succeeded in the direct synthesis of oleacein, a rare component of extra-virgin olive oil, from oleuropein, which is abundant in olive leaves. Whereas the conventional total synthesis of oleacein from lyxose requires more than 10 steps, these solid acid catalysts enabled the one-step synthesis of oleacein from oleuropein. A key step in this synthesis was the selective hydrolysis of methyl ester. Density functional theory calculations at the B3LYP/631+G (d) level of theory revealed the formation of a tetrahedral intermediate bonded to one H2O molecule. These solid acid catalysts were easily recovered and reused at least five times by simple cleaning. Importantly, this synthetic procedure was not only applicable to other secoiridoid glucosides, but could also be employed for the corresponding scale-up reaction using oleuropein extracted from olive leaves as the starting material.

Botryococcus terribilis Ethanol Extract Exerts Anti-inflammatory Effects on Murine RAW264 Cells.

The present study aimed to evaluate the effects of Botryococcus terribilis ethanol extract (BTEE) on lipopolysaccharide (LPS)-induced inflammation in RAW264 cells. BTEE significantly attenuated LPS-induced nitric oxide production and inflammatory cytokines release, including Ccl2, Cox2, and Il6. On the other hand, several anti-inflammatory mediators, such as Pgc1ß and Socs1, were increased in BTEE-treated cells. Further, we performed an untargeted whole-genome microarray analysis to explore the anti-inflammatory molecular mechanism of BTEE. Enrichment analysis showed BTEE significantly downregulated 'response to stimulus', 'locomotion', and 'immune system response' and upregulated 'cell cycle' gene ontologies in both 6- and 17-h post-LPS stimulation conditions. Pathway analysis revealed BTEE could downregulate the expressions of chemokines of the CC and CXC subfamily, and cytokines of the TNF family, TGFß family, IL1-like, and class I helical. PPI analysis showed AXL receptor tyrosine kinase (Axl), a receptor tyrosine kinase from the TAM family, and its upstream transcription factors were downregulated in both conditions. Node neighborhood analysis showed several Axl coexpressed genes were also downregulated. Further, kinase enrichment and chemical perturbation analyses supported Axl inhibition in BTEE-treated conditions. Altogether, these findings suggest anti-inflammatory effects of BTEE that are mediated via the suppression of pro-inflammatory cytokines and predict its potential as an Axl inhibitor.