Genome-Wide Identification and Comprehensive Analysis of the GASA Gene Family in Peanuts (Arachis hypogaea L.) under Abiotic Stress.

Peanut (Arachis hypogaea L.) is a globally cultivated crop of significant economic and nutritional importance. The role of gibberellic-acid-stimulated Arabidopsis (GASA) family genes is well established in plant growth, development, and biotic and abiotic stress responses. However, there is a gap in understanding the function of GASA proteins in cultivated peanuts, particularly in response to abiotic stresses such as drought and salinity. Thus, we conducted comprehensive in silico analyses to identify and verify the existence of 40 GASA genes (termed AhGASA) in cultivated peanuts. Subsequently, we conducted biological experiments and performed expression analyses of selected AhGASA genes to elucidate their potential regulatory roles in response to drought and salinity. Phylogenetic analysis revealed that AhGASA genes could be categorized into four distinct subfamilies. Under normal growth conditions, selected AhGASA genes exhibited varying expressions in young peanut seedling leaves, stems, and roots tissues. Notably, our findings indicate that certain AhGASA genes were downregulated under drought stress but upregulated under salt stress. These results suggest that specific AhGASA genes are involved in the regulation of salt or drought stress. Further functional characterization of the upregulated genes under both drought and salt stress will be essential to confirm their regulatory roles in this context. Overall, our findings provide compelling evidence of the involvement of AhGASA genes in the mechanisms of stress tolerance in cultivated peanuts. This study enhances our understanding of the functions of AhGASA genes in response to abiotic stress and lays the groundwork for future investigations into the molecular characterization of AhGASA genes.

Identification of QTLs and allelic effect controlling lignan content in sesame (Sesamum indicum L.) using QTL-seq approach.

Sesame (Sesamum indicum L.), an oilseed crop, is gaining worldwide recognition for its healthy functional ingredients as consumption increases. The content of lignans, known for their antioxidant and anti-inflammatory effects, is a key agronomic trait that determines the industrialization of sesame. However, the study of the genetics and physiology of lignans in sesame is challenging, as they are influenced by multiple genes and environmental factors, therefore, the understanding of gene function and synthetic pathways related to lignan in sesame is still limited. To address these knowledge gaps, we conducted genetic analyses using F7 recombinant inbred line (RIL) populations derived from Goenbaek and Gomazou as low and high lignin content variants, respectively. Using the QTL-seq approach, we identified three loci, qLignan1-1, qLignan6-1, and qLignan11-1, that control lignan content, specifically sesamin and sesamolin. The allelic effect between loci was evaluated using the RIL population. qLignan6-1 had an additive effect that increased lignan content when combined with the other two loci, suggesting that it could be an important factor in gene pyramiding for the development of high-lignan varieties. This study not only highlights the value of sesame lignan, but also provides valuable insights for the development of high-lignan varieties through the use of DNA markers in breeding strategies. Overall, this research contributes to our understanding of the importance of sesame oil and facilitates progress in sesame breeding for improved lignan content.

The Genome of the Korean Island-Originated Perilla citriodora 'Jeju17' Sheds Light on Its Environmental Adaptation and Fatty Acid and Lipid Production Pathways.

Perilla is a key component of Korean food. It contains several plant-specialized metabolites that provide medical benefits. In response to an increased interest in healthy supplement food from the public, people are focusing on the properties of Perilla. Nevertheless, unlike rice and soybeans, there are few studies based on molecular genetics on Perilla, so it is difficult to systematically study the molecular breed. The wild Perilla, Perilla citriodora 'Jeju17', was identified a decade ago on the Korean island of Jeju. Using short-reads, long-reads, and Hi-C, a chromosome-scale genome spanning 676 Mbp, with high contiguity, was assembled. Aligning the 'Jeju17' genome to the 'PC002' Chinese species revealed significant collinearity with respect to the total length. A total of 31,769 coding sequences were predicted, among which 3331 were 'Jeju17'-specific. Gene enrichment of the species-specific gene repertoire highlighted environment adaptation, fatty acid metabolism, and plant-specialized metabolite biosynthesis. Using a homology-based approach, genes involved in fatty acid and lipid triacylglycerol biosynthesis were identified. A total of 22 fatty acid desaturases were found and comprehensively characterized. Expression of the FAD genes in 'Jeju17' was examined at the seed level, and hormone signaling factors were identified. The results showed that the expression of FAD genes in 'Jeju17' at the seed level was high 25 days after flowering, and their responses of hormones and stress were mainly associated with hormone signal transduction and abiotic stress via cis-elements patterns. This study presents a chromosome-level genome assembly of P. citriodora 'Jeju17', the first wild Perilla to be sequenced from the Korean island of Jeju. The analyses provided can be useful in designing ALA-enhanced Perilla genotypes in the future.

Development of an SNP marker set for marker-assisted backcrossing using genotyping-by-sequencing in tetraploid perilla.

High-quality molecular markers are essential for marker-assisted selection to accelerate breeding progress. Compared with diploid species, recently diverged polyploid crop species tend to have highly similar homeologous subgenomes, which is expected to limit the development of broadly applicable locus-specific single-nucleotide polymorphism (SNP) assays. Furthermore, it is particularly challenging to make genome-wide marker sets for species that lack a reference genome. Here, we report the development of a genome-wide set of kompetitive allele specific PCR (KASP) markers for marker-assisted recurrent selection (MARS) in the tetraploid minor crop perilla. To find locus-specific SNP markers across the perilla genome, we used genotyping-by-sequencing (GBS) to construct linkage maps of two F2 populations. The two resulting high-resolution linkage maps comprised 2326 and 2454 SNP markers that spanned a total genetic distance of 2133 cM across 16 linkage groups and 2169 cM across 21 linkage groups, respectively. We then obtained a final genetic map consisting of 22 linkage groups with 1123 common markers from the two genetic maps. We selected 96 genome-wide markers for MARS and confirmed the accuracy of markers in the two F2 populations using a high-throughput Fluidigm system. We confirmed that 91.8% of the SNP genotyping results from the Fluidigm assay were the same as the results obtained through GBS. These results provide a foundation for marker-assisted backcrossing and the development of new varieties of perilla.

Lignan-Rich Sesame (Sesamum indicum L.) Cultivar Exhibits In Vitro Anti-Cholinesterase Activity, Anti-Neurotoxicity in Amyloid-ß Induced SH-SY5Y Cells, and Produces an In Vivo Nootropic Effect in Scopolamine-Induced Memory Impaired Mice.

Alzheimer's disease, a major cause of dementia, is characterized by impaired cholinergic function, increased oxidative stress, and amyloid cascade induction. Sesame lignans have attracted considerable attention owing to their beneficial effects on brain health. This study investigated the neuroprotective potential of lignan-rich sesame cultivars. Among the 10 sesame varieties studied, Milyang 74 (M74) extracts exhibited the highest total lignan content (17.71 mg/g) and in vitro acetylcholinesterase (AChE) inhibitory activity (66.17%, 0.4 mg/mL). M74 extracts were the most effective in improving cell viability and inhibiting reactive oxygen species (ROS) and malondialdehyde (MDA) generation in amyloid-ß25-35 fragment-treated SH-SY5Y cells. Thus, M74 was used to evaluate the nootropic effects of sesame extracts and oil on scopolamine (2 mg/kg)-induced memory impairment in mice compared to the control cultivar (Goenback). Pretreatment with the M74 extract (250 and 500 mg/kg) and oil (1 and 2 mL/kg) effectively improved memory disorder in mice (demonstrated by the passive avoidance test), inhibited AChE, and enhanced acetylcholine (Ach) levels. Moreover, immunohistochemistry and Western blot results showed that the M74 extract and oil reversed the scopolamine-induced increase in APP, BACE-1, and presenilin expression levels in the amyloid cascade and decreased BDNF and NGF expression levels in neuronal regeneration.

Genetic diversity analysis of Korean peanut germplasm using 48 K SNPs 'Axiom_Arachis' Array and its application for cultivar differentiation.

Cultivated peanut (Arachis hypogaea) is one of the important legume oilseed crops. Cultivated peanut has a narrow genetic base. Therefore, it is necessary to widen its genetic base and diversity for additional use. The objective of the present study was to assess the genetic diversity and population structure of 96 peanut genotypes with 9478 high-resolution SNPs identified from a 48 K 'Axiom_Arachis' SNP array. Korean set genotypes were also compared with a mini-core of US genotypes. These sets of genotypes were used for genetic diversity analysis. Model-based structure analysis at K = 2 indicated the presence of two subpopulations in both sets of genotypes. Phylogenetic and PCA analysis clustered these genotypes into two major groups. However, clear genotype distribution was not observed for categories of subspecies, botanical variety, or origin. The analysis also revealed that current Korean genetic resources lacked variability compared to US mini-core genotypes. These results suggest that Korean genetic resources need to be expanded by creating new allele combinations and widening the genetic pool to offer new genetic variations for Korean peanut improvement programs. High-quality SNP data generated in this study could be used for identifying varietal contaminant, QTL, and genes associated with desirable traits by performing mapping, genome-wide association studies.

An Integrated Approach of QTL Mapping and Genome-Wide Association Analysis Identifies Candidate Genes for Phytophthora Blight Resistance in Sesame (Sesamum indicum L.).

Phytophthora blight (PB) caused by Phytophthora nicotianae is a highly destructive disease in sesame (Sesamum indicum L.). In this study, we used linkage mapping and genome-wide association study (GWAS) to identify quantitative trait loci (QTL) and candidate genes associated with PB resistance. The QTL mapping in 90 RILs of the Goenbaek × Osan cross using genotyping-by-sequencing detected significant QTLs for PB resistance on chromosome 10, explaining 12.79%-13.34% of phenotypic variation. Association of this locus to PB resistance was also revealed through bulked segregant analysis in second RIL population (Goenbaek × Milsung cross) comprising 188 RILs. The GWAS of 87 sesame accessions evaluated against three P. nicotianae isolates identified 29 SNPs on chromosome 10 significantly associated with PB resistance. These SNPs were located within a 0.79 Mb region, which co-located with the QTL intervals identified in RIL populations, and hence scanned for identifying candidate genes. This region contained several defense-related candidate R genes, five of which were selected for quantitative expression analysis. One of these genes, SIN_1019016 was found to show significantly higher expression in the resistant parent compared to that in the susceptible parents and selected RILs. Paired-end sequencing of the gene SIN_1019016 in parental cultivars revealed two synonymous SNPs between Goenbaek and Osan in exon 2 of coding DNA sequence. These results suggested SIN_1019016 as one of the candidate gene conferring PB resistance in sesame. The findings from this study will be useful in the marker-assisted selection as well as the functional analysis of PB resistance candidate gene(s) in sesame.

Identification of anthocyanin compositions in black seed coated Korean adzuki bean (Vigna angularis) by NMR and UPLC-Q-Orbitrap-MS/MS and screening for their antioxidant properties using different solvent systems.

The aim of the present research was to investigate the antioxidant properties and anthocyanin profiles in the black seed coated adzuki bean (Vigna angularis, Geomguseul cultivar). The acidic 60% methanol extract (40 µg/mL) contains the highest total phenolic and flavonoid contents (486 ± 3 mg GAE/100 g; 314 ± 10 mg CE/100 g) with potent antioxidant properties (trolox equivalent 1272 ± 26 and 662 ± 24 mg TE/100 g) against ABTS and DPPH radicals compared to other methanol-water ratios (20, 40, 80, and 100%). Ten anthocyanin components were identified in this extract including delphinidin-3,5-O-digalactoside (1), delphinidin-3,5-O-diglucoside (2), delphinidin-3-O-galactoside (3), delphinidin-3-O-glucoside (4), delphinidin-3-O-rutinoside (5), delphinidin-3-O-(p-coumaroyl)glucoside (6), cyanidin-3-O-glucoside (7), petunidin-3-O-galactoside (8), petunidin-3-O-glucoside (9) and petunidin-3-O-(p-coumaroyl)glucoside (10) via NMR spectroscopy and UPLC-Q-Orbitrap-MS/MS analysis. The key anthocyanins 3 and 4 of delphinidin type were isolated by reversed phase C-18 MPLC. Our results indicate that the anthocyanin profiles as well as the high phenolic and flavonoid contents are important factors determining the antioxidant effects of black adzuki bean.

Identification of quantitative trait loci associated with flowering time in perilla using genotyping-by-sequencing.

Understanding the transition to the reproductive period is important for crop breeding. This information can facilitate the production of novel varieties that are better adapted to local environments or changing climatic conditions. Here, we report the development of a high-density linkage map based on genotyping-by-sequencing (GBS) for the genus perilla. Through GBS library construction and Illumina sequencing of an F2 population, a total of 9607 single-nucleotide polymorphism (SNP) markers were developed. The ten-group linkage map of 1309.39 cM contained 2518 markers, with an average marker density of 0.56 cM per linkage group (LG). Using this map, a total of six QTLs were identified. These quantitative trait loci (QTLs) are associated with three traits related to flowering time: days to visible flower bud, days to flowering, and days to maturity. Ortholog analysis conducted with known genes involved in the regulation of flowering time among different crop species identified GI, CO and ELF4 as putative perilla orthologs that are closely linked to the QTL regions associated with flowering time. These results provide a foundation that will be useful for future studies of flowering time in perilla using fine mapping, and marker-assisted selection for the development of new varieties of perilla.

Applications of Panax ginseng leaves-mediated gold nanoparticles in cosmetics relation to antioxidant, moisture retention, and whitening effect on B16BL6 cells.

BACKGROUND: Bioactive compounds in plant extracts are able to reduce metal ions to nanoparticles through the process of green synthesis. Panax ginseng is an oriental medicinal herb and an adaptogen which has been historically used to cure various diseases. In addition, the P. ginseng leaves-mediated gold nanoparticles are the value-added novel materials. Its potential as a cosmetic ingredient is still unexplored. The aim of this study was to evaluate the antioxidant, moisture retention and whitening properties of gold nanoparticles (PgAuNPs) in cosmetic applications. METHODS: Cell-free experiments were performed to evaluate PgAuNP's antioxidant and moisture retention properties and inhibition activity on mushroom tyrosinase. Furthermore, in vitro cell cytotoxicity was evaluated using normal human dermal fibroblast and murine B16BL6 melanoma cells (B16) after treatment with increasing concentrations of PgAuNPs for 24 h, 48 h, and 72 h. Finally, in vitro cell assays on B16 cells were performed to evaluate the whitening effect of PgAuNPs through reduction of cellular melanin content and tyrosinase activity. RESULTS: In vitro DPPH radical scavenging assay results revealed that PgAuNPs exhibited antioxidant activity in a dose-dependent manner. PgAuNPs exhibited moisture retention capacity and effectively inhibited mushroom tyrosinase. In addition, 3-(4,5-dimethyl-thiazol-2yl)-2,5-diphenyl tetrazolium bromide results revealed that PgAuNPs were not toxic to human dermal fibroblast and B16 cells; in addition, they significantly reduced melanin content, tyrosinase activity, and mRNA expression of melanogenesis-associated transcription factor and tyrosinase in B16 cells. CONCLUSION: Our study is the first report to provide evidence supporting that P. ginseng leaves-capped gold nanoparticles could be used as multifunctional ingredients in cosmetics.

Protective effects of perilla oil and alpha linolenic acid on SH-SY5Y neuronal cell death induced by hydrogen peroxide.

BACKGROUND/OBJECTIVE: Oxidative stress plays a key role in neuronal cell damage, which is associated with neurodegenerative disease. The aim of present study was to investigate the neuroprotective effects of perilla oil (PO) and its active component, alpha-linolenic acid (ALA), against hydrogen peroxide (H2O2)-induced oxidative stress in SH-SY5Y neuronal cells. MATERIALS/METHODS: The SH-SY5Y human neuroblastoma cells exposed to 250 µM H2O2 for 24 h were treated with different concentrations of PO (25, 125, 250 and 500 µg/mL) and its major fatty acid, ALA (1, 2.5, 5 and 25 µ/mL). We examined the effects of PO and ALA on H2O2-induced cell viability, lactate dehydrogenase (LDH) release, and nuclear condensation. Moreover, we determined whether PO and ALA regulated the apoptosis-related protein expressions, such as cleaved-poly ADP ribose polymerase (PARP), cleaved caspase-9 and -3, BCL-2 and BAX. RESULTS: Treatment of H2O2 resulted in decreased cell viability, increased LDH release, and increase in the nuclei condensation as indicated by Hoechst 33342 staining. However, PO and ALA treatment significantly attenuated the neuronal cell death, indicating that PO and ALA potently blocked the H2O2-induced neuronal apoptosis. Furthermore, cleaved-PARP, cleaved caspase-9 and -3 activations were significantly decreased in the presence of PO and ALA, and the H2O2-mediated up-regulated BAX/BCL-2 ratio was blocked after treatment with PO and ALA. CONCLUSIONS: PO and its main fatty acid, ALA, exerted the protective activity from neuronal oxidative stress induced by H2O2. They regulated apoptotic pathway in neuronal cell death by alleviation of BAX/BCL-2 ratio, and down-regulation of cleaved-PARP and cleaved caspase-9 and -3. Although further studies are required to verify the protective mechanisms of PO and ALA from neuronal damage, PO and ALA are the promising agent against oxidative stress-induced apoptotic neuronal cell death.

Neuroprotective Effect of Alpha-Linolenic Acid against Aß-Mediated Inflammatory Responses in C6 Glial Cell.

Therapeutic approaches for neurodegeneration, such as Alzheimer's disease (AD), have been widely studied. One of the critical hallmarks of AD is accumulation of amyloid beta (Aß). Aß induces neurotoxicity and releases inflammatory mediators or cytokines through activation of glial cell, and these pathological features are observed in AD patient's brain. The purpose of this study is to investigate the protective effect of alpha-linolenic acid (ALA) on Aß25-35-induced neurotoxicity in C6 glial cells. Exposure of C6 glial cells to 50 µM Aß25-35 caused cell death, overproduction of nitric oxide (NO), and pro-inflammatory cytokines release [interleukin (IL)-6 and tumor necrosis factor-α], while treatment of ALA increased cell viability and markedly attenuated Aß25-35-induced excessive production of NO and those inflammatory cytokines. Inhibitory effect of ALA on generation of NO and cytokines was mediated by down-regulation of inducible nitric oxide synthase and cyclooxygenase-2 protein and mRNA expressions. In addition, ALA treatment inhibited reactive oxygen species generation induced by Aß25-35 through the enhancement of the nuclear factor-erythroid 2-related factor-2 (Nrf-2) protein levels and subsequent induction of heme-oxygenase-1 (HO-1) expression in C6 glial cells dose- and time-dependently. Furthermore, the levels of neprilysin and insulin-degrading enzyme protein expressions, which contribute to degradation of Aß, were also increased by treatment of ALA compared to Aß25-35-treated control group. In conclusion, effects of ALA on Aß degradation were shown to be mediated through inhibition of inflammatory responses and activation of antioxidative system, Nrf-2/HO-1 signaling pathway, in C6 glial cells. Our findings suggest that ALA might have the potential for therapeutics of AD.

The effects of smartphone multitasking on gait and dynamic balance.

[Purpose] This study was performed to analyze the influence of smartphone multitasking on gait and dynamic balance. [Subjects and Methods] The subjects were 19 male and 20 female university students. There were 4 types of gait tasks: General Gait (walking without a task), Task Gait 1 (walking while writing a message), Task Gait 2 (walking while writing a message and listening to music), Task Gait 3 (walking while writing a message and having a conversation). To exclude the learning effect, the order of tasks was randomized. The Zebris FDM-T treadmill system (Zebris Medical GmbH, Germany) was used to measure left and right step length and width, and a 10 m walking test (10MWT) was conducted for gait velocity. In addition, a Timed Up and Go test (TUG) was used to measure dynamic balance. All the tasks were performed 3 times, and the mean of the measured values was analyzed. [Results] There were no statistically significant differences in step length and width. There were statistically significant differences in the 10MWT and TUG tests. [Conclusion] Using a smartphone while walking decreases a person's dynamic balance and walking ability. It is considered that accident rates are higher when using a smartphone.

Alpha-Linolenic Acid from Perilla frutescens var. japonica Oil Protects Aß-Induced Cognitive Impairment through Regulation of APP Processing and Aß Degradation.

Alzheimer's disease (AD) is characterized by progressive cognitive and memory impairment. The major pathological hallmark of AD is the accumulation of amyloid beta (Aß), which is produced from the amyloid precursor protein (APP) through cleavage of ß- and γ-secretase. Recently, dietary plant oil containing ω-3 polyunsaturated fatty acid has become an attractive alternative source to fish oil containing eicosapentaenoic acid or docosahexaenoic acid (DHA). We investigated whether ALA isolated from perilla oil has direct effects on improvement of cognitive ability and molecular mechanisms in APP processing in comparison with DHA. In the present study, ICR mice were treated orally with ALA or DHA (100 mg/kg/day) for 14 days after i.c.v. injection of Aß25-35. Administration of ALA resulted in a prevention of learning and memory deficit in Aß25-35-injected mice compared with the control group, as observed in T-maze, novel object recognition, and Morris water maze tests. ALA supplementation also markedly ameliorated the Aß25-35-induced oxidative stress by inhibition of lipid peroxidation and nitric oxide overproduction in the mouse brain, liver, and kidney, almost down to the levels in DHA-administered group. These effects of ALA on protective mechanisms were related to the regulation of APP processing via promoting nonamyloidogenic pathway such as up-regulation of soluble APP alpha, C-terminal fragment alpha/beta ratio, and A disintegrin and metalloprotease10 protein expressions. Furthermore, ALA inhibited the amyloidogenic pathway through the down-regulation of ß-site APP-cleaving enzyme and presenilin2. ALA also enhanced Aß degradation enzyme, insulin-degrading enzyme. In conclusion, the present study indicated a beneficial effect of ALA in improving the cognitive ability against Aß25-35, and these effects were comparable to those exerted by DHA. Its neuroprotective effects are mediated, in part, by regulation of APP processing and Aß degradation, and thus, ALA might be a potential candidate for prevention or treatment of neurodegenerative diseases such as AD.

The complete chloroplast genome sequence of Perilla citriodora (Makino) Nakai.

Perilla citriodora is a diploid and an aromatic herb species belonging to the family Lamiaceae and widely distributed in East Asia. The complete chloroplast genome sequence of P. citriodora was generated by de novo assembly using whole genome next-generation sequences. The assembled chloroplast genome of P. citriodora was 152 588 bp in length and structurally divided into four distinct regions; large single copy region (83 699 bp), small single copy region (17 537 bp), and a pair of inverted repeat regions (25 676 bp). A total of 115 genes were annotated including 81 protein-coding genes, 30 tRNA genes, and four rRNA genes. Phylogenetic relationship with previously reported chloroplast genomes revealed that P. citriodora is most closely related to P. frutescens, a tetraploid Perilla species.

Changes occurring in nutritional components (phytochemicals and free amino acid) of raw and sprouted seeds of white and black sesame (Sesamum indicum L.) and screening of their antioxidant activities.

The present study is the first to investigate the germination properties regarding phytochemicals, amino acids, total phenolics, and antioxidant capacities of white and black sesame seeds. Nutritional components and antioxidant effects showed considerable differences. Sesamine and sesamolin composition decreased (white: 4.21→1.72, 3.57→1.57 mg/g; black: 2.43→0.58, 1.36→0.45 mg/g) during germination. Moreover, catechin displayed the predominant composition in sprouted seeds with values of 13.50 mg/g (white) and 19.09 (black) mg/g followed by (-)-epicatechin and sinapic acid. Total phenolics increased by approximately 4 times upon germination, i.e., 503.1±27.1→ 2085.0±56.7 (white) and 645.8±31.5→2480.1±49.5 (black), mg GAE/g. Amino acids also remarkably increased in sprouted white (7.04→31.69mg/g) and black (6.55→26.97mg/g) seeds, with individual composition occurring in the following order: asparagine>arginine>tryptophan>leucine>alanine. In particular, arginine and tryptophan exhibited the greatest variations. The antioxidant effects against DPPH radical were stronger in sprouted seeds depending on the phytochemicals. Therefore, sprouted sesame can be utilized as an excellent source for functional foods.

Effects of Vegetable Oils with Different Fatty Acid Compositions on Cognition and Memory Ability in Aß25-35-Induced Alzheimer's Disease Mouse Model.

In this study, we aimed to investigate the protective effect of three kinds of vegetable oils with different fatty acid compositions against cognitive impairment in an Alzheimer's disease (AD) mouse model. After intracerebroventricular injection of amyloid beta25-35 (Aß25-35) into the brain of institute of cancer research mice, olive oil (rich in oleic acid, C18:1), corn oil (rich in linoleic acid, C18:2), and perilla oil (rich in α-linolenic acid [ALA], C18:3) were administered at the oral dose of 500 mg/kg/day for 14 days. The results revealed that Aß25-35 induced learning and memory dysfunction according to the T-maze, novel object recognition, and Morris water maze tests. Among the three vegetable oils, however, the perilla oil group of mice showed marked attenuation of cognitive impairment, that is, a greater number of explorations on a new route/object than on an old route/object in the T-maze and novel object recognition tests. In the Morris water maze test, perilla oil decreased the time to reach the platform and increased the number of crossings over the target quadrant in which the platform was located previously. Furthermore, the beneficial effect of perilla oil supplementation on oxidative stress was reflected in the inhibition of malondialdehyde and nitric oxide (NO) production in Aß25-35-injected mice. We also found that perilla oil downregulated protein expression levels of inducible NO synthase and cyclooxygenase-2 and upregulated brain-derived neurotrophic factor. These findings showed that ALA-rich perilla oil has a potential for prevention or treatment of neurodegenerative diseases such as AD.

Enhanced Absorption Study of Ginsenoside Compound K (20-O-ß-(D-Glucopyranosyl)-20(S)-protopanaxadiol) after Oral Administration of Fermented Red Ginseng Extract (HYFRG™) in Healthy Korean Volunteers and Rats.

To evaluate the pharmacokinetics of compound K after oral administration of HYFRG and RG in humans, an open-label, randomized, single-dose, fasting, and one-period pharmacokinetic study was conducted. After oral administration of a single 3 g dose of HYFRG and RG to 24 healthy Korean males, the mean (±SD) of AUC0-t and C max of compound K from HYFRG were 1466.83 ± 295.89 ng·h/mL and 254.45 ± 51.20 ng/mL, being 115.2- and 80-fold higher than those for RG (12.73 ± 7.83 ng·h/mL and 3.18 ± 1.70 ng/mL), respectively; in case of Sprague Dawley rats the mean (±SD) of AUC0-t and C max of compound K from HYFRG was 58.03 ± 32.53 ng·h/mL and 15.19 ± 10.69 ng/mL, being 6.3- and 6.0-fold higher than those from RG (9.21 ± 7.52 ng·h/mL and 2.55 ± 0.99 ng/mL), respectively. T max of compound K in humans and rats was 2.54 ± 0.92 and 3.33 ± 0.50 h for HYFRG and 9.11 ± 1.45 and 6.75 ± 3.97 hours for RG, respectively. In conclusion, the administration of HYFRG resulted in a higher and faster absorption of compound K in both humans and rats compared to RG.

Perilla frutescens var. japonica and rosmarinic acid improve amyloid-ß25-35 induced impairment of cognition and memory function.

BACKGROUND/OBJECTIVES: The accumulation of amyloid-ß (Aß) in the brain is a hallmark of Alzheimer's disease (AD) and plays a key role in cognitive dysfunction. Perilla frutescens var. japonica extract (PFE) and its major compound, rosmarinic acid (RA), have shown antioxidant and anti-inflammatory activities. We investigated whether administration of PFE and RA contributes to cognitive improvement in an Aß25-35-injected mouse model. MATERIALS/METHODS: Male ICR mice were intracerebroventricularly injected with aggregated Aß25-35 to induce AD. Aß25-35-injected mice were fed PFE (50 mg/kg/day) or RA (0.25 mg/kg/day) for 14 days and examined for learning and memory ability through the T-maze, object recognition, and Morris water maze test. RESULTS: Our present study demonstrated that PFE and RA administration significantly enhanced cognition function and object discrimination, which were impaired by Aß25-35, in the T-maze and object recognition tests, respectively. In addition, oral administration of PFE and RA decreased the time to reach the platform and increased the number of crossings over the removed platform when compared with the Aß25-35-induced control group in the Morris water maze test. Furthermore, PFE and RA significantly decreased the levels of nitric oxide (NO) and malondialdehyde (MDA) in the brain, kidney, and liver. In particular, PFE markedly attenuated oxidative stress by inhibiting production of NO and MDA in the Aß25-35-injected mouse brain. CONCLUSIONS: These results suggest that PFE and its active compound RA have beneficial effects on cognitive improvement and may help prevent AD induced by Aß.

The Neuro-Protective Effect of the Methanolic Extract of Perilla frutescens var. japonicaand Rosmarinic Acid against H2O2-Induced Oxidative Stress in C6 Glial Cells.

Neurodegenerative diseases are often associated with oxidative damage in neuronal cells. This study was conducted to investigate the neuro-protective effect of methanolic (MeOH) extract of Perilla frutescens var. japonica and its one of the major compounds, rosmarinic acid, under oxidative stress induced by hydrogen peroxide (H2O2) in C6 glial cells. Exposure of C6 glial cells to H2O2 enhanced oxidative damage as measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and thiobarbituric acid-reactive substance assays. The MeOH extract and rosmarinic acid prevented oxidative stress by increasing cell viability and inhibiting cellular lipid peroxidation. In addition, the MeOH extract and rosmarinic acid reduced H2O2-induced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the transcriptional level. Moreover, iNOS and COX-2 protein expression was down-regulated in H2O2-indcued C6 glial cells treated with the MeOH extract and rosmarinic acid. These findings suggest that P. frutescens var. japonica and rosmarinic acid could prevent the progression of neurodegenerative diseases through attenuation of neuronal oxidative stress.