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Callus suspension techniques have been considered attractive for improving bioactive metabolite productivity; methyl jasmonate (MeJA) is a widely used elicitor for stimulating synthetic pathways. In this study, a multivariate analysis-based metabolomics approach was employed to investigate the primary and specialized metabolites in the leaves, unelicited calli, and 100 or 200 μM MeJA elicited calli of Damnacanthus major. Rubiadin, a powerful anthraquinone with various therapeutic properties, was only identified in D. major calli, accumulating in a MeJA elicitation concentration-dependent manner. Callus cultures also contained high levels of amino acids, sugars, and phenolic compounds, indicating energy metabolism and metabolic adaptation responses for proliferation and stabilization. Regarding MeJA application, elicited calli contained higher amounts of quinic acid, kaempferol, and glucose with lower amounts of sucrose and raffinose than those in the unelicited control, which were closely related to protective mechanisms against MeJA. Moreover, excessive elicitation increased the asparagine, fructose, and raffinose levels and decreased the glucose and sucrose levels, which was ascribed to increased activation of the aminoacyl-tRNA biosynthesis pathway and wider utilization of glucose than of fructose after sucrose degradation. These results will be useful for optimizing plant cell culture techniques to achieve high production rates for valuable specialized metabolites. [ABSTRACT FROM AUTHOR]

In Jeju-native Citrus, flavonoids are the main contributors to the various types of biological activity, such as antioxidant, antitumor, and anti-inflammatory activity. Thus, we developed simultaneous quantification methods for the analysis of ten bioactive flavonoids in Jeju Citrus fruits (Dangyuja, Gamja, Jigak, Sadugam, and Soyuja) harvested at six different time points using a high-performance liquid chromatography–diode array detector (HPLC-DAD). Separation was performed using a flow rate of 0.8 mL/min, a column temperature of 40 °C, a mobile phase buffer of 0.5% acetic acid, and a detection wavelength of 278 nm. The established analytical method showed good linearity (R2 ≥ 0.9997), precision (inter-day < 0.599%, intra-day < 0.055%), and accuracy (recoveries 92.30–108.80%). The HPLC–DAD method was subsequently applied to analyze flavonoids in Citrus samples. Overall, the quantification results indicated that the compositions and content of flavonoids differed for each Citrus species. The harvesting period also influenced the changes in flavonoid content within each Citrus species. The analytical results with chemometrics revealed that higher flavonoid levels in early-harvested Citrus were derived from the improved fruit size and reduced flavonoid synthesis during maturation. This study provides a practical and reliable method for the analysis of ten flavonoids that can be further utilized in the quality assessment of Jeju Citrus. [ABSTRACT FROM AUTHOR]

Current research highlights the use of natural products or phytochemicals as drugs and functional additives to treat obesity with few side effects. Sargassum horneri (SH) and Ulva australis (UA) are marine waste resources on Jeju Island, Republic of Korea. In this study, we analyzed their antioxidant and anti-obesity efficacies to confirm their potential as functional additives. We prepared SH and UA extracts using 80% ethanol and observed that free radical scavenging activity and total phenol content were high in SH extracts, and total flavonoid content was elevated in UA extracts. Additionally, 3T3-L1 cells were treated with SH and UA extracts, and the ability of the extracts to inhibit adipocyte differentiation was examined using Oil Red O staining and analysis of neutral fat content. We confirmed that the mRNA expression of the C/EBPα, PPARγ, and SREBP1c genes that act on adipocyte differentiation, and of FAS, a fatty acid synthase, was suppressed. Experiments in a mouse model of obesity showed that 12-week administration of a high-fat diet with 1% extract added to drinking water resulted in lower weight gain compared to the high-fat diet alone. These results suggest that SH and UA extracts have antioxidant properties and are effective in obesity prevention. Therefore, the two marine waste resources are potential functional additive candidates for preventing obesity. [ABSTRACT FROM AUTHOR]

Green mandarins are widely consumed unripe as mandarin oranges (Citrus unshiu Marcov.), which exhibit anti-inflammatory and anti-wrinkle effects by inhibiting the production of inflammatory cytokines and matrix metalloproteinase. A randomized, double-blind, placebo-controlled clinical study was performed to verify the skin improvement efficacy and safety of green mandarin extract (PTE). For the standardization of PTE, narirutin was set as a marker compound, and PTE with a constant narirutin content was prepared for the study. After randomizing subjects with periorbital wrinkles, they were orally administered PTE (300 mg/day) or a placebo for 12 weeks. Periorbital wrinkles were measured using PRIMOSCR SF. Skin elasticity, moisture content, transepidermal water loss, and gloss were also measured. In the study results, the depth, volume, and skin roughness of the periorbital wrinkles were significantly improved compared to the control group (p = 0.011, 0.009, and 0.004, respectively). The survey confirmed that the skin condition improved after PTE consumption for 12 weeks. No adverse reactions associated with PTE were observed during the study period. Thus, the results demonstrate that PTE effectively improves UV-induced skin wrinkles. Therefore, it is considered that PTE has sufficient value as a functional food ingredient that can prevent skin aging. [ABSTRACT FROM AUTHOR]

Bananas, one of the most widely consumed fruits worldwide, are a rich source of valuable phytochemicals. In this study, the antioxidant and the anticancer potential of banana flesh was investigated. Of the four kinds of banana flesh extracts, the hexane extract (HE) had the highest total polyphenol content (2.54 ± 0.60 mg GAE/g) and total flavonoid content (1.69 ± 0.34 mg RE/g), followed by the chloroform fraction, total ethanol extract, and ethanol fraction. HE was found to exert a strong radical scavenging activity on 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH•) and 2,2′‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonicacid) (ABTS•) free radicals. According to the IC50 values in various cancer cell lines, HE was found to possess the greatest cell growth inhibitory potential in human pancreatic cancer PANC‐1 cells and human triple‐negative breast cancer MDA‐MB‐231 cells. HE induced apoptosis in PANC‐1 and MDA‐MB‐231 cells, as evidenced by the appearance of condensation of chromatin, proteolytic activation of caspase‐3 and 7, and increase in the level of the cleaved form of poly (ADP‐ribose) polymerase protein. Gas chromatography mass spectrometry (GC‐MS) analysis of HE identified several anticancer compounds including palmitic acid, linoleic acid, oleic acid, campesterol, stigmasterol, and γ‐sitosterol, supporting the anticancer potential of HE. Our investigation provides a rationale for the use of banana flesh to minimize the risk of cancer‐like diseases. [ABSTRACT FROM AUTHOR]

Cysteine-rich angiogenic inducer 61 (CYR61) is an extracellular matrix-associated protein involved in survival, tumorigenesis, and drug resistance. Therefore, we examined the effects of flavones against CYR61-overexpressing human gastric adenocarcinoma AGS (AGS-cyr61) cells, which show remarkable resistance to 5-fluorouracil (5-FU), adriamycin (ADR), tamoxifen (TAM), paclitaxel (PAC), and docetaxel (DOC). Among the tested flavones, quercetin had the lowest 50% inhibitory concentration (IC50) and significantly reduced the viability of AGS-cyr61 cells compared with AGS cells. Quercetin: (1) reduced multidrug resistance-associated protein 1 and nuclear factor (NF)-kappa B p65 subunit levels; (2) reversed multidrug resistance (MDR); (3) inhibited colony formation and induced caspase-dependent apoptosis; and (4) suppressed migration and down-regulated epithelial–mesenchymal transition-related proteins in AGS-cyr61. Moreover, AGS-cyr61 cells treated with quercetin concentrations close to the IC50 and simultaneously treated with 5-FU or ADR in the sub-lethal range showed strong synergism between quercetin and these two drugs. These findings indicate that CYR61 is a potential regulator of drug resistance and that quercetin may be a novel agent for improving the efficacy of anticancer drugs in AGS-cyr61 cells. [ABSTRACT FROM AUTHOR]

Activation of signal transducer and activator of transcription 3 (STAT3) is well known to play a major role in the cell growth, survival, proliferation, metastasis, and angiogenesis of various cancer cells. Most of the citrus species offer large quantities of phytochemicals that have beneficial effects attributed to their chemical components. Our study was carried out to evaluate the anticancer effects of the pericarp of Iyokan (Citrus iyo Hort. ex Tanaka), locally known as yeagam in Korea, through modulation of the STAT3 signaling pathway in both tumor cells and a nude mice model. The effect of supercritical extracts of yeagam peel (SEYG) on STAT3 activation, associated protein kinases, STAT3-regulated gene products, cellular proliferation, and apoptosis was examined. The in vivo effect of SEYG on the growth of DU145 human prostate xenograft tumors in athymic nu/nu male mice was also investigated. We found SEYG exerted substantial inhibitory effect on STAT3 activation in human prostate cancer DU145 cells as compared to other tumor cells analyzed. SEYG inhibited proliferation and downregulated the expression of various STAT3-regulated gene products such as bcl-2, bcl-xL, survivin, IAP-1/2, cyclin D1, cyclin E, COX-2, VEGF, and MMP-9. This correlated with an increase in apoptosis as indicated by an increase in the expression of p53 and p21 proteins, the sub-G1 arrest, and caspase-3-induced PARP cleavage. When administered intraperitoneally, SEYG reduced the growth of DU145 human prostate xenograft tumors through downmodulation of STAT3 activation in athymic nu/nu male mice. Overall, these results suggest that SEYG extract has the potential source of STAT3 inhibitors that may have a potential in chemoprevention of human prostate cancer cells. [ABSTRACT FROM AUTHOR]

Magnolia flower buds are a source of herbal medicines with various active compounds. In this study, differences in the distribution and abundance of major essential oils, phenolic acids, and primary metabolites between white flower buds of Magnolia heptapeta and violet flower buds of Magnolia denudata var. purpurascens were characterised. A multivariate analysis revealed clear separation between the white and violet flower buds with respect to primary and secondary metabolites closely related to metabolic systems. White flower buds contained large amounts of monoterpene hydrocarbons (MH), phenolic acids, aromatic amino acids, and monosaccharides, related to the production of isoprenes, as MH precursors, and the activity of MH synthase. However, concentrations of β-myrcene, a major MH compound, were higher in violet flower buds than in white flower buds, possibly due to higher threonine levels and low acidic conditions induced by comparatively low levels of some organic acids. Moreover, levels of stress-related metabolites, such as oxygenated monoterpenes, proline, and glutamic acid, were higher in violet flower buds than in white flower buds. Our results support the feasibility of metabolic profiling for the identification of phytochemical differences and improve our understanding of the correlated biological pathways for primary and secondary metabolites. [ABSTRACT FROM AUTHOR]