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.

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.

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.

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.

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.

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.

Analysis of yield of eleutherosides B and E in Acanthopanax divaricatus and A. koreanum grown with varying cultivation methods.

An analysis of the yield of eleutherosides B and E in Acanthopanax divaricatus and A. koreanum was performed using high performance liquid chromatography to evaluate production by different cultivation methods. In A. divaricatus and A. koreanum, the total content of eleutherosides B and E was 2.466-7.360 mg/g varying by plant section, 3.886-11.506 mg/g by pinching site, 3.655-10.083 mg/g by planting time, and 3.652-10.108 mg/g by fertilizer ratio. Thus the total content of eleutherosides B and E in A. divaricatus and A. koreanum differed depending on cultivation methods. These results present useful information for high eleutheroside content applications in A. divaricatus and A. koreanum. This information can affect selection of plant section and cultivation methods for nutraceutical, pharmaceutical, and cosmeceutical material development.

Identification, characterisation, and quantification of phenolic compounds in the antioxidant activity-containing fraction from the seeds of Korean perilla (Perilla frutescens) cultivars.

The present research was the first to investigate phenolic compound profiles and antioxidant properties in the seeds of various perilla (Perilla frutescens) cultivars. The 80% methanol extract (50 µg/ml) of this species showed potent antioxidant activities against 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) radicals. Phenolic compounds were characterised by nuclear magnetic resonance (NMR) spectroscopy, and ultra performance liquid chromatography with photodiode array detector and electrospray ionisation/mass (UPLC-PDA-ESI/MS) analysis. Nine compounds were elucidated as caffeic acid-3-O-glucoside (1), caffeic acid (2), luteolin-7-O-glucoside (3), apigenin-7-O-glucoside (4), rosmarinic acid-3-O-glucoside (5), rosmarinic acid (6), luteolin (7), apigenin (8), and chrysoeriol (9). The individual and total phenolic contents were remarkably different, especially rosmarinic acid-3-O-glucoside (5) and rosmarinic acid (6) which were the predominant compounds (>95%) in all perilla cultivars. Additionally, Yeupsil cultivar exhibited the highest phenolic content (5029.0 µg/g) and antioxidant activity, whereas the lowest was shown by Dasil (2138.7 µg/g). Therefore, these results suggest that antioxidant effects of perilla seeds are correlated with phenolic contents.

Isolation and identification of phenolic compounds from the seeds of Perilla frutescens (L.) and their inhibitory activities against α-glucosidase and aldose reductase.

Five phenolic compounds were isolated from the seeds of Perilla (Perilla frutescens L.) using gradient solvent fractionation, silica gel column chromatography, and preparative high-performance liquid chromatography (HPLC). Their chemical structures were identified as caffeic acid-3-O-glucoside (1), rosmarinic acid-3-O-glucoside (2), rosmarinic acid (3), luteolin (4), and apigenin (5) using NMR spectroscopy and HPLC-ESI/MS analysis. Among them, luteolin (4) inhibited α-glucosidase (EC 3.2.1.20) with IC(50) value of 45.4µM. The inhibition kinetic analysed by Dixon plot indicate that luteolin is a noncompetitive inhibitor, and the inhibition constant K(I) was calculated at 45.0µM. Moreover, rosmarinic acid (3) and luteolin (4) inhibited recombinant human aldose reductase (EC 1.1.1.21) with IC(50) values of 11.2 and 0.6µM, respectively. Notably, the inhibition kinetic of luteolin (4) follows a hyperbolic dependence on aldose reductase inhibition by Dixon plot. Thus, inhibition kinetic indicates that luteolin (4) is a mixed-type inhibitor.