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Ginsenoside F2 (GF2) is a protopanaxdiol saponin from Panax ginseng leaves and possesses many potential pharmacological properties. GF2 may prevent obesity by directly binding to the peroxisome proliferator-activated receptor-γ (PPARγ) and inhibiting adipocyte differentiation. However, the mechanism by which GF2 alleviates obesity is unknown. We therefore explored the anti-adipogenesis and anti-obesity effects of GF2 in vitro and in vivo. GF2 inhibited differentiation and reduced the triglyceride (TG) content of 3T3-L1 preadipocytes in the early stage of adipogenesis. Administration of GF2 (50 and 100 mg/kg) to obese mice for 4 weeks reduced the body weight gain, weight of adipose tissues, adipocyte size, and total cholesterol, TG, and AST levels in serum. RNA sequencing and real-time quantitative PCR indicated that GF2 decreased the expression levels of adipokines, including PPARγ, fatty acid synthase, and adiponectin. KEGG enrichment and western blot analyses demonstrated that GF2 accelerated the phosphorylation of AMPK and ACC in vitro and in vivo. Moreover, GF2 promoted the biosynthesis of mitochondria in 3T3-L1 adipocytes and increased the expression of antioxidant enzymes such as SOD and GSH-Px in the liver of obese mice. Therefore, GF2 suppressed adipogenesis and obesity by regulating the expression of adipokines and activating the AMPK pathway. Hence, the findings suggest that GF2 may have potential therapeutic implications to treat obesity.

Vina-ginsenoside R4 (VGN4) is the first example of protopanaxatriol saponin possessing sugar chains located at C-3 and C-20 of aglycone. However, to the best of our knowledge, no report has been published on the neuroprotective effect of VGN4. In the present work, we investigated the neuroprotective effect of VGN4 against 6-hydroxydopamine (6-OHDA)-induced toxicity and its potential mechanism. Pretreatment of PC12 cells with VGN4 attenuated 6-OHDA-induced cell damage and cell apoptosis, which was correlated with the decrease of reactive oxygen species and the increase of antioxidant enzyme activities including superoxide dismutase and catalase. In addition, VGN4 markedly decreased nuclear translation of the nuclear factor-κB and PI3K/Akt/GSK/3β signaling pathway including p85, PDK1, Akt, and GSK-3β. Further studies revealed that PI3K siRNA attenuated the neuroprotective effect of VGN4 on caspase-3 activity. These data indicate that VGN4 might have the potential to be developed as a new neuroprotective functional food.

Six new pentacyclic triterpenoid saponins, centelloside F (1), centelloside G (2), 11-oxo-asiaticoside B (3), 11-oxo-madecassoside (4), 11(β)-methoxy asiaticoside B (5), and 11(β)-methoxy madecassoside (6), along with seven known ones, asiaticoside (7), asiaticoside B (8), madecassoside (9), centellasaponin A (10), isoasiaticoside (11), scheffoleoside A (12), and centelloside E (13), were separated from the 80% MeOH extract of the whole plant of Centella asiatica, which has been used as a medicinal plant and is now commercially available as a diatery supplement in many countries. Compounds 1 and 2, 3 and 4, and 5 and 6 are three pairs of isomers with oleanane- or ursane-type triterpenes as aglycones. The chemical structures of the new triterpene saponins were fully characterized by extensive analysis of their nuclear magnetic resonance and high-resolution electrospray ionization mass spectrometry data. The protective effects of compounds 1-13 on PC12 cells induced by 6-OHDA were screened, and compound 3 displayed the best neuroprotective effect, with 91.75% cell viability at the concentration of 100 μM. Moreover, compound 3 also attenuated cell apoptosis and increased the mRNA expression of antioxidant enzymes, including superoxide dismutase and catalase. Additionally, compound 3 activated the phosphatidylinositol 3-kinase/Akt pathway, including PDK1, Akt, and GSK-3β. These findings suggested that triterpene saponins from C. asiatica were worthy of further biological research to develop new neuroprotective agents.

In this study, the structure and pro-inflammatory activities of water-soluble wheat bran polysaccharides (WBP) were evaluated. WBP were heteropolysaccharides consisting 60.34% arabinoxylan as the main component and 31.80% mannose residues characterized with the instrumental analyses. The result of cellular experiment displayed that WBP had significant pro-inflammatory activities by increasing the concentration of nitric oxide (NO) and up-regulating the inflammatory cytokine expressions of inducible nitric oxide synthase (iNOS), interleukin-1β (IL-1β), cyclooxygenase-2 (COX-2), and tumor necrosis factor-α (TNF-α). WBP mediated macrophages RAW 264.7 pro-inflammatory response through phosphatidylinositol 3 hydroxykinase/protein kinase B (PI3K/Akt) signaling pathway by significantly promoting Akt and phosphoinositide-dependent kinase 1 (PDK1) phosphorylations. Meanwhile, the expression of related phosphorylated proteins JNK and ERK1/2 was significantly up-regulated which suggested that WBP played pro-inflammatory roles by activating mitogen-activated protein kinases (MAPKs) signaling pathway. PRACTICAL APPLICATIONS: In recent years, wheat bran generally has the phenomenon of high yield and low utilization rate. Wheat bran has rich nutritional value and contains a lot of effective biologically active substances. Based on our findings, the water-soluble polysaccharides extracted from wheat bran have significant effects on regulating immunity and can be utilized as sources of natural immune modulators. The research can develop new functions of wheat bran polysaccharides, and improve processing utilization rate and product added value.

Background: The leaves and roots of Panax ginseng are rich in ginsenosides. However, the chemical compositions of the leaves and roots of P. ginseng differ, resulting in different medicinal functions. In recent years, the aerial parts of members of the Panax genus have received great attention from natural product chemists as producers of bioactive ginsenosides. The aim of this study was the isolation and structural elucidation of novel, minor ginsenosides in the leaves of P. ginseng and evaluation of their antiinflammatory activity in vitro. Methods: Various chromatographic techniques were applied to obtain pure individual compounds, and their structures were determined by nuclear magnetic resonance and high-resolution mass spectrometry, as well as chemical methods. The antiinflammatory effect of the new compounds was evaluated on lipopolysaccharide-stimulated RAW 264.7 cells. Results and conclusions: Two novel, minor triterpenoid saponins, ginsenoside LS1 (1) and 5,6-didehydroginsenoside Rg3 (2), were isolated from the leaves of P. ginseng. The isolated compounds 1 and 2 were assayed for their inhibitory effect on nitric oxide production in LPS-stimulated RAW 264.7 cells, and Compound 2 showed a significant inhibitory effect with IC50 of 37.38 μM compared with that of NG-monomethyl-L-arginine (IC50 = 90.76 μM). Moreover, Compound 2 significantly decreased secretion of cytokines such as prostaglandin E2 and tumor necrosis factor-α. In addition, Compound 2 significantly suppressed protein expression of inducible nitric oxide synthase and cyclooxygenase-2. These results suggested that Compound 2 could be used as a valuable candidate for medicinal use or functional food, and the mechanism is warranted for further exploration. Keywords: Antiinflammatory activity, Panax ginseng, Triterpenoid saponins

Two novel cucurbitane glycosides, named as 11-oxomogroside III A1 and 7β-methoxy-mogroside V, along with sixteen known ones were isolated from the fruits of Siraitia grosvenori SWINGLE. The structures of the new compounds were characterized by chemical and extensive spectral methods.

20-Hydroxyl-3-oxolupan-28-oic acid (HOA), a minor component from Mahonia bealei (Fort.) Carr. leaves, has been found to attenuate inflammatory responses. However, the underlying molecular mechanism is still unclear. In this study, we performed a comprehensive transcriptional study to investigate genetic changes. We used RNA sequencing technology to analyses the transcriptional changes in RAW 264.7 cells in a control group, lipopolysaccharide (LPS)-induced group, and HOA-treated group. We identified 1,313 and 388 differentially expressed genes (DEGs) in the control/LPS group and LPS/HOA group, respectively. Gene Ontology (GO) classification revealed that the DEGs were mainly enriched in a series of inflammatory and immune-related processes. The results of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses showed that the DEGs were mainly enriched in inflammatory-related pathways such as the nuclear factor-kappa B (NF-κB) signaling pathway, cytokine-cytokine receptor interaction, chemokine signaling pathway, mitogen-activated protein kinase (MAPK) pathway, and Janus kinase-signal transducer and activator of transcription proteins (JAK-STAT) signaling pathway. The results of qPCR validation revealed that dynamic changes in immune-related mRNAs such as Saa3, Bcl2l1, Mapkapk2, Ccl9, Sdc4, Ddx3x, Socs3, Prdx5, Tlr4, Lif, IL15, Tnfaip3, Tet2, Tgf-β1, and Ccl20, which were significantly upregulated in the LPS group and downregulated in the HOA group. Taken together, these results suggest that HOA may be used as a source of anti-inflammatory agents as well as a dietary complement for health promotion.

Herein, we demonstrate a novel UV-induced decomposable nanocapsule of natural polysaccharide (HA-azo/PDADMAC). The nanocapsules are fabricated based on layer-by-layer co-assembly of anionic azobenzene functionalized hyaluronic acid (HA-azo) and cationic poly diallyl dimethylammonium chloride (PDADMAC). When the nanocapsules are exposed to 365 nm light, ultraviolet photons can trigger the photo-isomerization of azobenzene groups in the framework. The nanocapsules could decompose from large-sized nanocapsules to small fragments. Due to their optimized original size (~180 nm), the nanocapsules can effectively avoid biological barriers, provide a long blood circulation and achieve high tumor accumulation. It can fast eliminate nanocapsules from tumor and release the loaded drugs for chemotherapy after UV-induced dissociation. Besides, HA is an endogenous polysaccharide that shows intrinsic targetability to CD44 receptors on surface of cancer cells. The intracellular experiment shows that the HA-azo/PDADMAC nanocapsules with CD44 targeting ability and UV-controlled intracellular drug release are promising for cancer chemotherapy.

Arabinoxylan (AX) extracted from wheat bran has attracted much attention due to its immunomodulatory activity. However, the molecular mechanisms underlying this activity remain unclear. In this study, we conducted a comprehensive transcriptional study to investigate genetic changes related to AX and identified 2325 differentially expressed genes (DEGs). Gene Ontology classification revealed that the DEGs were mainly enriched in a series of immune-related processes. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that immune-related pathways were significantly enriched in top 20 pathways, including the nuclear factor-kappa B (NF-κB) signaling pathway and the TNF signaling pathway. Validation using quantitative polymerase chain reaction analysis revealed dynamic changes in the mRNA levels of immune-related Cd40, Csf1, Csf2, Fas, IL-1β, IL-6, IL-5, Irf1, and Tnfaip3, which were significantly up-regulated in the AX-treated group. Moreover, AX treatment led to the up-regulation of the nuclear translocation of NF-κB and its upstream target proteins such as PDK1, Akt, IκB-α, and GSK-3β. The dataset compiled from this study provides valuable information for further research on the complex molecular mechanisms associated with AX and the identification of target genes.

Ethnopharmacological relevance A multi-herb Chinese medicinal formula consisting of a variety of medicinal and edible materials has long been consumed as a hot drink and immune enhancer for its efficiency to increase disease resistance in Xinjiang, China. However, no fundamental data has been collected associated with traditional consumption. The present work was designed to evaluate the immunostimulatory role of Xinjiang herbal tea (XMT-WE) in RAW 264.7 macrophages and cyclophosphamide (CTX)-induced immunosuppression mice model. Materials and methods RAW 264.7 cells were treated with various concentrations of XMT-WE. Nitric oxide (NO) levels were determined using Griess reagents, and pro-inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α were investigated with a cytometric bead array kit. The effects on mRNA expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, and TNF-α were investigated. Furthermore, activation of nuclear factor (NF)-κB and AP-1 mitogen-activated protein kinase (MAPK) signaling pathways was investigated. Results Pre-treatment with XMT-WE significantly increased secretion of NO, IL-6, and TNF-α. In addition, XMT-WE markedly increased expression of iNOS, COX-2, and TNF-α as well as AP-1 and NF-κB translocation from the cytoplasm into the nucleus, which was associated with an increase of phosphorylated ERK, JNK, and p38 as well as membrane receptors such as toll-like receptor (TLR) 2 and TLR4. Moreover, XMT-WE promoted the secretion of interleukin-2 (IL-2) and interferon-γ (IFN-γ) in cyclophosphamide (CTX)-induced immunosuppressive mice. Conclusion These results indicated that XMT-WE at 50 µg/ml exerts immunomodulatory activity via TLR2/4-mediated MAPK signaling pathways in RAW 264.7 cells. Furthermore, in vivo experiments revealed that XMT-WE at the dose of 50 and 100 mg/kg strongly stimulated inflammatory cytokines.

Senkyunolide H (SNH) is a phthalide isolated from the rhizome of Ligusticum chuanxiong Hort. that has been reported to have several pharmacological activities, including anti-atherosclerotic, antiproliferative, and cytoprotective effects. In this study, we investigated the neuroprotective effects and potential mechanisms of SNH against 1-methyl-4-phenylpyridinium (MPP+)-induced oxidative stress. We demonstrated that SNH pretreatment significantly attenuated MPP+-induced neurotoxicity and apoptosis in PC12 cells. In addition, SNH attenuated the effect of MPP+ on the expression of the pro-apoptotic factors Bax and caspase-3. Meanwhile, SNH prevented oxidative stress by reducing reactive oxygen species generation, mitochondrial membrane potential loss, cytochrome C release, and malondialdehyde levels while increasing antioxidant enzyme activity (e.g., superoxide dismutase, catalase, and glutathione peroxidase). In addition, SNH inhibited nuclear accumulation of nuclear factor-κB and c-Jun N-terminal kinase and phosphorylation p38 mitogen-activated protein kinases (MAPKs). Overall, this investigation provides novel evidence that SNH exerts neuroprotective effects via the ROS-mediated MAPK pathway and represents a potential preventive or therapeutic agent for neuronal disorders.

A new triterpene diglycoside, tibesaikosaponin V (TKV), was isolated from the methanol extract of the roots of Bupleurum chinense DC. by normal and reversed phase column chromatography. The chemical structure of this new compound was elucidated based on extensive spectroscopic analysis, including 1D and 2D NMR, HR-ESI-MS, and chemical degradation method. Our results indicated that TKV inhibited lipid accumulation and triacylglycerol content occurred without cytotoxicity to 3T3-L1 adipocytes. Furthermore, TKV significantly suppressed the mRNA expression of nuclear transcription factors such as, peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer binding protein α (C/EBPα). These results suggest that TKV shows the ability to inhibit 3T3-L1 preadipocyte differentiation of and may have therapeutic potential for obesity and its associated metabolic disorders.

A heteropolysaccharide (SHP) with a strong immunomodulatory effect on RAW 264.7 cells was prepared from Saccharina japonica. Chemical analysis demonstrated that SHP was primarily composed of mannose, glucuronic acid, glucose, fucose, galactose, xylose and rahmnose with a molar ratio of 1.00:0.85:0.84:0.58:0.30:0.37:0.15. ESI-MS showed that depolymerized SHP produced oligo-glucuronan, oligo-glucuronomannan, sulfated fuco-oligosaccharides and other hetero-oligosaccharides. The in vitro immunomodulatory results showed that SHP could increase NO production and up-regulate the expression of many immune effectors, including iNOS, COX-2 and TNF-α, displaying an apparent immune enhancement activities. Western blot analysis proved that SHP activated the expression levels of many key components involved in NF-κB, MAPK and Akt signaling pathways. Our results together indicated that SHP has the potential to be developed as a novel immunomodulator for activating immune system.

Mahonia bealei (Fort.) Carr., is an economic plant cultivated in Southwest China commonly used in traditional Chinese medicine. In this study, a response surface methodology was used to optimize experimental conditions for the extraction of phenolic compounds from the leaves of Mahonia bealei (Fort.) Carr. The highest extraction ratio of phenolic compounds yielded 39.1 mg gallic acid equivalent/g of dry weight using an ethanol concentration of 30% (v/v) as a solvent and a liquid-to-solid ratio of 21:1 (mL·g-1) for 2 h in 63°C. The crude material was extracted under optimal conditions, enriched, and then purified through a D-101 macroporous adsorption resin, giving a phenolic compound-enriched fraction we named TPMB. Evaluation of its in vitro antioxidant activity suggested that TPMB significantly scavenged the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical, superoxide radical, and hydrogen peroxide in a concentration-dependent manner. In addition, TPMB also exhibited a strong reducing ability and provided protection against oxidative damage induced by oxidative stress in cellular antioxidant activity assays. The results from this study indicate the suitability of the response surface methodology in optimizing the solvent extraction of phenolic compounds from M. bealei. Further research showed that TPMB possesses a strong anti-radical activity and may be an effective oxidation resistance treatment in the medical and food industries.

Background: Wheat is a staple food crop worldwide. Plant height is a key factor in plant architecture as it plays a crucial role in lodging and thus affects yield and quality. Genome-wide studies are mostly applied in crop plants, due to its advanced genotyping technologies, identification of novel loci, and improved statistical approaches. Results: In this study, the population was genotyped by using Illumina iSelect 90K single nucleotide polymorphism (SNP) assay and finally 22,905 high-quality SNPs were used to perform a genome-wide association study (GWAS) for plant architectural traits employing four multi-locus GWAS (ML-GWAS) and three single-locus GWAS (SL-GWAS) models. As a result, 174 and 97 significant SNPs controlling plant architectural traits were detected by four ML-GWAS and three SL-GWAS methods, respectively. Among these SNP makers, 43 SNPs were commonly detected, including seven across multiple environments and thirty-six across multiple methods. Interestingly, five most stable SNPs (Kukri_c34553_89, RAC875_c8121_1490, wsnp_Ex_rep_c66315_64480362, Ku_c5191_340, and tplb0049a09_1302) consistently detected across multiple environments and methods, possibly played a role in modulating plant height and flag leaf length. When comparing ML-GWAS methods, pLARmEB was the most powerful and accountable for the detection of 49 significant SNPs that mostly contributed to plant height (36 SNPs). However, in SL-GWAS the FarmCPU model detected most of the significant SNPs. Moreover, a total of 152 candidate genes were found that are likely to be involved in plant growth and development which may provide insightful information related to plant architectural traits.Conclusion: Altogether, our results reveal 174 and 97 significant SNPs controlling plant architectural traits using four ML-GWAS and three SL-GWAS methods, respectively. The detection of the stable loci across multiple environments and methods, possibly play a role in modulating plant architectural traits in hexaploid wheat, and finally will contribute to the discovery of valuable SNP loci for marker-assisted selection (MAS) in wheat molecular breeding.

Angelica gigas Nakai (AGN) was first processed by ultrafine grinding technology and hot-melt extrusion (HME). The potential antioxidant and anti-inflammatory activities of AGN with a different process were compared, and the effect on the human Kv1.3 potassium channel was detected. The process of ultrafine powderization on AGN significantly increased the total phenolic and flavonoid contents, antioxidant activity, and DNA damage protective effect. On the contrary, AGN solid dispersion (AGN-SD) based on Soluplus® showed the highest inhibitory effect on NO production and the human Kv1.3 channel. In addition, AGN-SD inhibited the production of prostaglandin E2 and intracellular reactive oxygen species and the mRNA expression of inducible nitric oxide synthase, cyclooxygenase-2, interleukin 1β, and interleukin 6. Taken together, these results suggest that ultrafine powderization and solid dispersion formation via HME can significantly improve the biological activities of AGN. The results also suggested that ultrafine powderization and HME may be developed and applied in the pharmaceutical industry.

20(S)-ginsenoside Rh2 (Rh2), a well-known protopanaxadiol-type ginsenoside from Panax ginseng has especially gained attention for its anticancer activities on various types of human cancer cells. However, the molecular mechanism through which Rh2 promotes apoptosis in hepatocellular carcinoma (HePG2) cells is not known at the transcriptome level. Rh2 can specifically inhibit the proliferation of HePG2 in a dose- and time-dependent manner. Moreover, Rh2 can significantly increase the apoptosis which was related with an increase in protein expression levels of caspase-3, caspase-6, and poly (ADP-ribose) polymerase. Comparison of RNA-seq transcriptome profiles from control group and Rh2-treated group yielded a list of 2116 genes whose expression was significantly affected, which includes 971 up-regulated genes and 1145 down-regulated genes. The differentially expressed genes in p53 signaling pathway and DNA replication may have closely relationships to the cells apoptosis caused by Rh2 treatment. The results of qPCR validation showed that dynamic changes in mRNA, such as CDKN1A, CCND2, PMAIP1, GTSE1, and TP73.

Mahonia bealei (Fort.) Carr. is an economically important plant that is widely cultivated in Southwest China. Its leaves are commonly used for tea and contain an abundance of antioxidant compounds. However, methods of the systematic purification of antioxidants from M. bealei are lacking. In this study, antioxidants from this plant were effectively and rapidly enriched. First, antioxidants were screened using online 1,1-diphenyl-2-picryl-hydrazyl radical (DPPH)&ndash, high performance liquid chromatography (HPLC), followed by separation using high-speed countercurrent chromatography with an optical solvent system composed of n-hexane/ethyl acetate/methanol/water (1:5:1:5, v/v/v/v). Three phenolics&mdash, chlorogenic acid (1, 8.3 mg), quercetin-3-O-&beta, d-glucopyranoside (2, 20.5 mg), and isorhamnetin-3-O-&beta, d-glucopyranoside (3, 28.4 mg)&mdash, were obtained from the ethyl acetate-soluble fraction (240 mg) by one-step separation. The chemical structures of the phenolics were characterized by MS and NMR techniques, and the purity of each compound was &gt, 92.0% as determined by HPLC. The isolated compounds were assessed by scavenging activities on DPPH and superoxide radicals as well as cytoprotective assays, all of which showed similar trends regarding the antioxidant capacities of the compounds. Moreover, compounds 1&ndash, 3 significantly attenuated the lipid peroxidation and antioxidant enzyme activities in H2O2-treated RAW264.7 cells. Our study demonstrated the efficiency of a newly developed integrative system for the comprehensive characterization of pure compounds from M. bealei, which will allow their use as reference substances.

Ethnopharmacological relevance Mahonia bealei has a long history of medical use in traditional Chinese medicine for the treatment of inflammatory-associated diseases. Despite numerous phytochemical and pharmacological studies, there is a lack of systematic studies to understand the cellular and molecular mechanisms of the anti-inflammatory activity of this plant. Aim of study This study aimed to evaluate the anti-inflammatory activity of the dichloromethane fraction from M. bealei leaves (MBL-CH). Materials and methods RAW 264.7 cells were pretreated with different concentrations of MBL-CH for 30 min prior to treatment with 1 μg/ml of lipopolysaccharide (LPS). The nuclear factor κB (NF-κB) pathway and subsequent production of inflammatory mediators, such as nitric oxide (NO), prostaglandin E2 (PGE2), and tumour necrosis factor (TNF)-α were investigated. Furthermore, the in vivo mouse model of LPS-induced acute lung injury (ALI) was employed to study the anti-inflammatory effects of MBL-CH. Results Pre-treatment with MBL-CH significantly inhibited the LPS-stimulated secretion of NO, PGE2, and TNF-α into the culture medium, as well as the mRNA levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and TNF-α, which were associated with a reduction in the phosphorylation of IκBα, Akt, and PI3K and inhibition of the transcriptional activity of NF-κB. Furthermore, in vivo experiments revealed that MBL-CH attenuated LPS-stimulated lung inflammation in mice. Conclusion Taken together, our findings indicate that MBL-CH attenuates LPS-stimulated inflammatory responses in macrophages by blocking NF-κB activation through interference with activation of the PI3K/Akt pathway, providing scientific evidence that the plant can be employed in traditional remedies.

Apricot (Prunus armeniaca L.) is an important, nutritionally valuable agricultural crop. A scarcity of transcriptomic and genomic data hinders progress toward understanding the molecular events of apricot embryogenesis, which is the primary determinant of fruit yield and kernel quality. In this study, three cDNA libraries were sequenced using an Illumina/Solexa platform. We obtained 35,928,496, 40,656,940, and 35,970,214 clean reads from endosperm formation (LT-A), embryo development (LT-B), and mature embryo (LT-C) cDNA libraries, respectively. De novo assembly of cDNA sequence data generated 35,614 unigenes with an average length of 973 bp. A total of 29,971 unigenes were matched in Nr, Nt, Swiss-Prot, KEGG, GO, and COG databases. The top matching species in the Nr database was P. persica (88.3% of matched Nr database accessions). A total of 8,327 differentially expressed genes (DEGs) were detected between LT-A and LT-B, of which 3,663 were upregulated and 4,664 were downregulated. Between LT-B and LT-C, 12,673 DEGs were detected, while 13,892 DEGs were uncovered between LT-A and LT-C. This work is the first reported application of next-generation sequencing techniques for transcriptome analysis of apricot embryo development. Besides providing valuable information on apricot embryo development, the comprehensive set of transcript sequences generated in this study may serve as additional molecular resources for the development of apricot functional genomics.

Chemical investigation of the fruits of Phyllanthus emblica led to the isolation of one new aryltetralin-type lignan (1), along with twelve known polyphenols (2–13). Their structures were determined via extensive analyses of spectroscopic data and comparison with the reported literature values. Among them, polyphenols 1, 6, 7, and 10 were isolated from the family Euphorbiaceae for the first time. Furthermore, the chemotaxonomic significance of the isolates was also discussed.

Kernel morphology is one of the major yield traits of wheat, the genetic architecture of which is always important in crop breeding. In this study, we performed a genome-wide association study (GWAS) to appraise the genetic architecture of the kernel traits of 319 wheat accessions using 22,905 single nucleotide polymorphism (SNP) markers from a wheat 90K SNP array. As a result, 111 and 104 significant SNPs for Kernel traits were detected using four multi-locus GWAS models (mrMLM, FASTmrMLM, FASTmrEMMA, and pLARmEB) and three single-locus models (FarmCPU, MLM, and MLMM), respectively. Among the 111 SNPs detected by the multi-locus models, 24 SNPs were simultaneously detected across multiple models, including seven for kernel length, six for kernel width, six for kernels per spike, and five for thousand kernel weight. Interestingly, the five most stable SNPs (RAC875_29540_391, Kukri_07961_503, tplb0034e07_1581, BS00074341_51, and BobWhite_049_3064) were simultaneously detected by at least three multi-locus models. Integrating these newly developed multi-locus GWAS models to unravel the genetic architecture of kernel traits, the mrMLM approach detected the maximum number of SNPs. Furthermore, a total of 41 putative candidate genes were predicted to likely be involved in the genetic architecture underlining kernel traits. These findings can facilitate a better understanding of the complex genetic mechanisms of kernel traits and may lead to the genetic improvement of grain yield in wheat.

The extraction and solvent partition of roots of Incarvillea compacta, a traditional Tibetan folk medicine, and repeated column chromatography and preparative high-performance liquid chromatography for n-butanol fraction yielded four phenylethanoid glycosides, crenatoside (1), 3′′′-O-methylcrenatoside (2), leucoseceptoside A (3), and martynoside (4). The chemical structures were identified on the basis of spectroscopic data analyses including NMR and MS. All compounds were isolated for the first time from the plant. Compound 1 exerted better 1,1-diphenyl-2-picrylhydrazyl free radical scavenging activity. In addition, compounds 1–4 were evaluated for their hepatoprotective activity on carbon tetrachloride (CCl4)-induced liver injury in HepG2 cells. Pretreatment of HepG2 cells with compound 1–4 significantly increased the viability on CCl4-induced cell death. Furthermore, compounds 1–4 also alleviated CCl4-induced hepatotoxicity by enhancement of the antioxidant enzyme activities of superoxide dismutase and reduction of the malondialdehyde content, intracellular ROS as well as NF-κB transactivation. Our results suggest that phenylethanoid glycosides ameliorate CCl4-induced cell injury, and this protection was likely due to antioxidative activity and down-regulation of NF-κB.

Background/Aim: Treatment of human non-small-cell lung cancer (NSCLC) often involves uses of multiple therapeutic strategies with different mechanisms of action. Here we found that resveratrol (RV) enhanced the anti-tumor effects of epidermal growth factor receptor (EGFR) inhibitor erlotinib in NSCLC cells. Methods: Cell viability was measured by MTT assay and clonogenicity assay. Western blot was applied to assess the protein expression levels of target genes. Cell apoptosis was monitored by AnnexinV-FITC assay and sub-G1 population assay. Intracellular ROS were measured by flow cytometric analysis. Cell caspase activities were carried out by fluorometric assays. Results: Exposure of H460, A549, PC-9 and H1975 cells to minimal or non-toxic concentrations of RV and erlotinib synergistically reduced cell viability, colony formation and induced cell apoptosis. Furthermore, RV synergistically enhanced erlotinib-induced apoptosis was involved in ROS production. Additionally, co-treatment with RV and erlotinib repressed the expressions of anti-apoptosis proteins, such as survivin and Mcl-1, whereas promoted p53 and PUMA expression and caspase 3 activity. Moreover, the combination was also more effective at inhibiting the AKT/mTOR/S6 kinase pathway. Subsequently, small interfering RNA (siRNA) depletion of PUMA and overexpression of survivin significantly attenuated NSCLC cells apoptosis induced by the combination of the two drugs. Conclusion: Our findings suggested that RV synergistically enhanced the anti-tumor effects of erlotinib in NSCLC cells were involved in decrease of survivin expression and induction of PUMA expression. In conclusion, based on the observations from our study, we indicated that the combined administration of these two drugs might be considered as a novel therapeutic regimen for treating NSCLC.

Crude polysaccharide obtained from Saccharina japonica using acid hydrolysis and precipitation was separated into sulfated fuco-oligosaccharide (HDF1) and heteropolysaccharide (HDF2). To further explore the bioactive fraction, HDF2 was successfully separated using membrane filtration into HDF2A and HDF2B, which differed in chemical composition and molecular weight. The bioactivity of all the fractions was tested in vitro, including immunomodulatory activity in RAW 264.7 cells and the protective activity in aristolochic acid (AA)-induced NRK-52E cell injury. HDF1 and HDF2B (low-molecular weight sulfated fucans/fuco-oligosaccharides) did not increase the nitric oxide production in RAW 264.7 cells, whereas HDF2 and HDF2A exhibited potential immunomodulatory activity. All the tested compounds showed different degrees of protective activity in AA-induced injury; HDF2A exhibited superior protective activity. Through chemical analysis, HPLC analysis, and IR spectroscopy and MS, it was determined that HDF2A was a galactose-enriched heteropolysaccharide- glucofucogalactan with a distinctive 2:1 ratio of galactose to fucose. In addition, HDF2A also contained a high amount of glucose and minor amounts of mannose, rhamnose, and xylose, with a low content of sulfate. Thus, HDF2A, a complex heterogeneous polysaccharide mixture with a unique monosaccharide composition, could be studied for further structural characterization and pharmaceutical applications.

Citrinin (CIT) is a toxic secondary metabolite produced by fungi belonging to the Penicillium, Aspergillus, and Monascus spp. This toxin has been detected in many agricultural products. In this study, a strain Y3 with the ability to eliminate CIT was screened and identified as Cryptococcus podzolicus, based on the sequence analysis of the internal transcribed spacer region. Neither uptake of CIT by cells nor adsorption by cell wall was involved in CIT elimination by Cryptococcus podzolicus Y3. The extracellular metabolites of Cryptococcus podzolicus Y3 stimulated by CIT or not showed no degradation for CIT. It indicated that CIT elimination was attributed to the degradation of intracellular enzyme(s). The degradation of CIT by C. podzolicus Y3 was dependent on the type of media, yeast concentration, temperature, pH, and initial concentration of CIT. Most of the CIT was degraded by C. podzolicus Y3 in NYDB medium at 42 h but not in PDB medium. The degradation rate of CIT was the highest (94%) when the concentration of C. podzolicus Y3 was 1 × 10⁸ cells/ml. The quantity of CIT degradation was highest at 28°C, and there was no degradation observed at 35°C. The study also showed that acidic condition (pH 4.0) was the most favorable for CIT degradation by C. podzolicus Y3. The degradation rate of CIT increased to 98% as the concentration of CIT was increased to 20 μg/ml. The toxicity of CIT degradation product(s) toward HEK293 was much lower than that of CIT.

Green mold and blue mold caused by Penicillium digitatum and P. italicum respectively, are two main fungal diseases in Citrus reticulata (mandarin oranges) worldwide. They are difficult to prevent for the lack of effective antagonists. This study investigated the efficacy of Yarrowia lipolytica against these diseases in mandarins and the relative defense mechanisms. The results indicated that Y. lipolytica has a great potential to inhibit the infections by P. digitatum and P. italicum in mandarins, while both the decay incidence and lesion diameter decreased in Y. lipolytica treated mandarins, in a dose-dependent manner. Furthermore, Y. lipolytica treatment had no side effects on quality paraments of mandarins. In vitro tests demonstrated that, spore germination and germ tube length of P. digitatum and P. italicum were both inhibited by Y. lipolytica. In addition, Y. lipolytica had a better ability to adapt to the environment, occupy space and utilize nutrients than pathogens, which provided a favorable condition for Y. lipolytica to colonize wounds and surfaces of mandarins. This research also showed that, Y. lipolytica induced higher activities of polyphenol oxidase (PPO), peroxidase (POD), catalase (CAT), phenylalanine ammonia lyase (PAL), and increased the contents of flavonoid compounds and total phenols, which activated the defense mechanisms of mandarins. These results suggested that Y. lipolytica is a promising antagonistic yeast to control green mold and blue mold in mandarins.

Oxidative stress has been considered as a major cause of cell damage in various neurodegenerative disorders. One of the reasonable strategies for delaying the disease's progression is to prevent reactive oxygen species (ROS) mediated cellular injury by dietary or pharmaceutical augmentation of free radical scavengers. Isocampneoside II (ICD) is an active phenylethanoid glycoside isolated from the medicinal hardwood genus Paulownia. This study was designed to explore free radical scavenging potential of ICD in different in vitro systems and its protective role in hydrogen peroxide (H₂O₂)-induced oxidative stress and apoptotic death in cultured rat pheochromocytoma (PC12) cells. The results showed ICD eliminated approximately 80.75% superoxide radical at the concentration of 0.1mg/ml and inhibited metal chelating by 22.07% at 8 mg/ml. Additionally, ICD showed a strong ability on reducing power and provided protection against oxidative protein damage induced by hydroxyl radicals. Pretreatment of PC12 cells with ICD prior to H₂O₂ exposure elevated cell viability, enhanced activity of superoxide dismutase and catalase, and decreased levels of malondialdehyde and intracellular ROS. Furthermore, ICD inhibited cell apoptosis and Bax/Bcl-2 ratio induced by H₂O₂. These findings suggested ICD may be considered as a potential antioxidant agent and should encourage for further research in neurodegenerative diseases.

A novel peptidomics approach was used to discover cold-induced peptides in loquat fruit. Twenty unique peptides derived from 18 proproteins were identified, and they were involved in sugar signalling, protein metabolism and stress response. The quantitative analysis revealed 7 peptides with more than 2-fold upregulation, especially a 4.96-fold increase detected in the phytosulfokine (PSK) peptide. To further evaluate effects of PSK1 on fruit chilling tolerance, weight loss, firmness and internal browning were investigated in PSK1-treated loquat fruit at 0°C. By contrast, these chilling injury symptoms were effectively reduced by PSK1. PSK1 markedly delayed decreases of ATP content and energy charge. The PSK1-treated fruit exhibited significantly lower activities of cell-wall degrading enzymes and transcripts of genes related to lignin synthesis. Our results demonstrated that PSK1 improves chilling tolerance of loquat fruit by maintaining high energy status and cell integrity. Peptidomics analysis provides a promising tool to discover some key peptides.

Chloranthalactone B (CTB), a lindenane-type sesquiterpenoid, was obtained from the Chinese medicinal herb Sarcandra glabra, which is frequently used as a remedy for inflammatory diseases. However, the anti-inflammatory mechanisms of CTB have not been fully elucidated. In this study, we investigated the molecular mechanisms underlying these effects in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. CTB strongly inhibited the production of nitric oxide and pro-inflammatory mediators such as prostaglandin E2, tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and IL-6 in RAW264.7 cells stimulated with LPS. A reverse-transcription polymerase chain reaction assay and Western blot further confirmed that CTB inhibited the expression of inducible nitric oxide synthase, cyclooxygenase-2, TNF-α, and IL-1β at the transcriptional level, and decreased the luciferase activities of activator protein (AP)-1 reporter promoters. These data suggest that inhibition occurred at the transcriptional level. In addition, CTB blocked the activation of p38 mitogen-activated protein kinase (MAPK) but not c-Jun N-terminal kinase or extracellular signal-regulated kinase 1/2. Furthermore, CTB suppressed the phosphorylation of MKK3/6 by targeting the binding sites via formation of hydrogen bonds. Our findings clearly show that CTB inhibits the production of inflammatory mediators by inhibiting the AP-1 and p38 MAPK pathways. Therefore, CTB could potentially be used as an anti-inflammatory agent.

A new cycloartane-type triterpene glycoside, namely soulieoside M (1), and one known compound, beesioside I (2), were isolated from the ethanolic extract of the rhizomes of Souliea vaginata. Their structures were determined spectroscopically and compared with previously reported spectral data. Compounds 1 and 2 were evaluated for their cytotoxic activities against three human cancer cell lines.

Antioxidant and nitric oxide (NO) production inhibitory activities of various extracts from scouring rush (Equisetum hyemale L.) were investigated. Antioxidant assays including DPPH free radical scavenging activity, reducing power assay, metal-chelating assay, superoxide radical scavenging assay, and nitrite scavenging ability, and assays to determine total phenolic and flavonoid contents were performed. The inhibition of NO production was measured in lipopolysaccharides (LPS)-induced RAW 264.7 macrophages, and reverse transcription (RT)-PCR was used to analyse the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) in RAW 264.7 macrophages. Overall, all extracts showed high phenolic content and strong DPPH radical scavenging ability. Methanol extract exhibited stronger metal-chelating activity and NO production inhibitory activity compared with other extracts. The expression of iNOS and COX-2 was obviously augmented in response to LPS. Taken together, scouring rush could be used as a suitable natural antioxidant and a source of anti-inflammatory agent.

This study was carried out to analyze the nutritional composition, mineral content and antioxidant activity of Kalopanax pictus leaves. K. pictus leaves are high in carbohydrates (60.37%) and crude protein content (27.05%) on a dry weight basis with low content of fatty acids (1.45%). Hyperoside ( 1 ), 3,5-di-O-caffeoyl quinic acid ( 2 ), methyl 3,5-dicaffeoyl quinate ( 3 ), and 3-O-feruloylquinic acid ( 4 ) were isolated and purified from this plant as well. In all the chemical assays used, compound 3 exerted better 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity, reducing power ability, and was a potent inhibitor of hydrogen peroxide (H 2 O 2 )-induced human embryonic kidney 293 (HEK 293) cell death and lipid peroxidation, whereas compound 4 presented as a powerful radical scavenger against superoxide radicals. Our results suggest that the chemical components of K. pictus leaves possess good antioxidant capacities and this species might have potential applications in the food and medical industries.

Two diarylheptanoids, 1,7-bis-(3,4-dihydroxyphenyl)-heptane-3-one-5-O-β-d-xylopyranoside (I) and 1,7-bis-(3,4-dihydroxyphenyl)-heptane-5-O-β-d-xylopyranoside (II), were isolated from the bark of Alnus hirsuta. Compounds I and II exhibited strong antioxidative activity against 1,1-diphenyl-2-picrylhydrazyl radicals, with IC50 values of 8.36 ± 0.54 and 8.67 ± 1.46 μM, respectively. In addition, we demonstrated that compounds I and II inhibited the production of nitric oxide and reactive oxygen species and the expression of proinflammatory molecules such as inducible nitric oxide synthase and cyclooxygenase-2 in lipopolysaccharide-induced macrophages. According to our results, the two diarylheptanoids isolated from the bark of A. hirsuta exhibited significant antioxidative activity and anti-inflammatory effects and may be useful in the pharmaceutical industry for alleviating oxidative stress.

Alnus hirsuta is a deciduous, broad-leaved tree that thrives in damp locations, and the bark of the Alnus species has been used in traditional oriental medicine as a remedy for hemorrhage, fever, diarrhea, and alcoholism. Two diarylheptanoids, 1,7-bis-(3,4-dihydroxyphenyl)-heptane-3-one-5-O-β-D-xylopyranoside (Compound I) and 1,7-bis-(3,4-dihydroxyphenyl)-heptane-5-O-β-D-xylopyranoside (Compound II), were isolated from the stem bark of A. hirsuta. In the present study, the investigations of two diarylheptanoids on insulin signaling were performed in insulin-responsive human hepatocarcinoma (HepG2) cells co-treated with high glucose. As the results, the insulin metabolic effect of glucose uptake was inhibited by high glucose. However, treatment of Compound I enhanced the glucose uptake ability in HepG2 cells, whereas, Compound II did not affect glucose incorporation noticeably. In addition, we demonstrated that treatment of HepG2 cells with Compound I improved the mRNA expression level of insulin receptor (IR) and insulin receptor substrate-1 (IRS-1).

Kalopanax pictus is a deciduous tree used in traditional medicine. The leaves have been consumed as a vegetable in Korea. In this study, we examined the antioxidant and anti-inflammatory capacity of the extracts from K. pictus leaves in vitro using hydroxyl radical scavenging assay, DNA nicking assay, metal chelating assay, reducing power assay, DPPH free radical scavenging assay, and nitric oxide inhibition assay. The effect of the hot water extract was stronger than that of the methanolic and ethanolic extracts in all of the assays. Moreover, the total phenolic contents in the extracts were measured by spectrophotometry. Meanwhile, a regression analysis revealed a correlation coefficient between the content of phenolics and antioxidant activity. Overall, our data suggest that K. pictus leaves possess significant antioxidant properties.

The role of NEFL in NSCLC remains largely unknown. Immunohistochemistry was performed to investigate the expression of NEFL in 108 lung cancer specimens. NEFL expression was associated with decreased lymph node metastases and favorable prognosis. Furthermore, real-time PCR and Western blot were used to investigate the expression of the NEFL gene in NSCLC cell lines. Subsequently, lentivirus-mediated RNA interference and overexpression were used to demonstrate that knocked-down of NEFL enhanced the invasion and migration of A549 and H460 NSCLC cells, whereas NEFL overexpression resulted in a suppression of the invasion and migration of GLC-82 and L78 cells in vitro. In addition, bisulfite sequence PCR assay demonstrated that NEFL downregulation was associated with promoter methylation, and NEFL expression was restored after treatment with 5-Aza-dC. Finally, we demonstrated that NEFL inhibited the NF-κB pathway, thereby suppressing the expression of uPA and decreasing NSCLC invasiveness and migration. Our studies suggest that NEFL methylation is a novel mechanism for NSCLC invasion and metastasis and that NEFL may represent a candidate biomarker for recurrence and survival in patients with NSCLC.

A Chinese patient with severe hypertriglyceridemia was found to have similar clinical features to that of malignant hyperlipemia in infancy. DNA sequence analysis of the apoC-II gene from the patient’s parents revealed a novel heterozygous mutation of T → A substitution at position −190 base in the apoC-II promoter. We speculated that the patient was a homozygote of the same mutation that resulted in the deficiency of apoC-II. In vitro expression studies showed T → A substitution in the apoC-II promoter leads to a decrease by approximately 20% in transcriptional activity compared with its counterpart that inserted the normal promoter. These results suggested that T → A substitution at position −190 in the apoC-II gene promoter only partly affected transcriptional activity of the apoC-II promoter, leading to decrease of apoC-II expression in quantity.

The role of the adventitia in vascular function and vascular lesion formation has been largely ignored. This article introduces the hypothesis that the activation of the adventitia, specifically the fibroblasts, contributes to the formation of intimal atherosclerotic lesions. The evidence for this hypothesis includes: (a) the early proliferative changes seen in fibroblasts found in the adventitia; (b) the increase and the alteration of extracellular matrix deposition in the adventitia; (c) fibroblast differentiation into myofibroblasts and migration into the intima; and (d) fibroblast synthesis and release of cytokines that have potent effects on neighboring smooth muscle and endothelial cells prior to intimal lesion formation. In conclusion, the activation of adventitial fibroblasts is a key regulator of vascular function and structure from the "outside-in" and contributes to the development of atherosclerotic lesions. The outer location of the adventitia makes it a suitable location for drug delivery and gene therapy aimed at preventing and treating atherosclerosis.

A patient with severe hypertriglyceridemia and recurrent pancreatitis was found to have significantly decreased lipoprotein lipase (LPL) activity and normal apolipoprotein C-II concentration in post-heparin plasma. DNA analysis of the LPL gene revealed two mutations, one of which was a novel homozygous G-->C substitution, resulting in the conversion of a translation initiation codon methionine to isoleucine (LPL-1). The second was the previously reported heterozygous substitution of glutamic acid at residue 242 with lysine (LPL-242). In vitro expression of both mutations separately or in combination demonstrated that LPL-1 had approximately 3% protein mass and 2% activity, whereas LPL-242 had undetectable activity but normal mass. The combined mutation LPL-1-242 exhibited similar changes as for LPL-1, with markedly reduced mass, and for LPL-242, with undetectable activity. These results suggest that the homozygous initiator codon mutation rather than the heterozygous LPL-242 alteration was mainly responsible for the patient phenotypes.

Oxidative stress-mediated cellular injury has been considered as a major cause of neurodegenerative diseases including Alzheimer and Parkinson diseases. The scavenging of reactive oxygen species (ROS) mediated by antioxidants may be a potential strategy for retarding the disease's progression. Macranthoin G (MCG), isolated from Eucommia ulmoides, is a derivative from chlorogenic acid methyl ester and caffeic acid. This study is aimed to investigate the protective role of MCG against the cytotoxicity induced by hydrogen peroxide (H2O2) and to elucidate potential protective mechanisms in rat pheochromocytoma (PC12) cells. The results showed that the treatment of PC12 cells with MCG prior to H2O2 exposure effectively increased the cell viability, and stabilized the mitochondria membrane potential (MMP); furthermore, it enhanced the antioxidant enzyme activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) and the levels of intracellular glutathione (GSH); it also decreased the malondialdehyde (MDA) content, intracellular ROS, caspase-3 activation, as well as cell apoptosis. In addition, the MCG treatment minimized the cell injury by H2O2 via down-regulation of the NF-κB pathway as well as activation of phosphorylation of IκBα, p38, and the extracellular signal-regulated kinase (ERK). These results showed that that MCG is promising as a potential therapeutic agent for neurodegenerative diseases induced by oxidative damage and should be encouraged for further research.

Objective: To explore the mechanism of multi-infarct dementia (MID) treated with the principle of Yijing Tishen (YJTS, reinforcing Kidney-essence and refreshing mental activities).Methods: MID rat models were established successfully with injecting sterile and naturally dried blood clots of the homologous rat into common carotid artery and screened by the first jumping-off latency of diving-platform reflex, based on which, the effect of YJTS in learning and memorizing, monoamine neurotransmitters content in brain tissue, malondialdehyde (MDA) content and Superoxide dismutase (SOD) activity in serum and brain tissue, and brain morphosis of multi-infarct rats were observed.Results: Obvious malfunction of learning and memorizing was found in MID rat models, and there were also significant decreasing of monoamine neurotransmitters content in partial brain zones, decreasing of SOD activity in brain and increasing of MDA content in serum and brain. YJTS could obviously improve learning and memorizing, raise SOD activity and monoamine neurotransmitters content in brain tissue, lower MDA content in serum and brain of MID rat models, protect brain morphosis of multi-infarct rats.Conclusion: YJTS might treat MID by restraining lipid peroxidation, improving monoamine neurotransmitters content in partial brain zones and decreasing ischemic damage of brain tissue.

Loquat (Eriobotrya japonica Lindl.) is an important non-climacteric fruit and rich in essential nutrients such as minerals and carotenoids. During fruit development and ripening, thousands of the differentially expressed genes (DEGs) from various metabolic pathways cause a series of physiological and biochemical changes. To better understand the underlying mechanism of fruit development, the Solexa/Illumina RNA-seq high-throughput sequencing was used to evaluate the global changes of gene transcription levels. More than 51,610,234 high quality reads from ten runs of fruit development were sequenced and assembled into 48,838 unigenes. Among 3256 DEGs, 2304 unigenes could be annotated to the Gene Ontology database. These DEGs were distributed into 119 pathways described in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. A large number of DEGs were involved in carbohydrate metabolism, hormone signaling, and cell-wall degradation. The real-time reverse transcription (qRT)-PCR analyses revealed that several genes related to cell expansion, auxin signaling and ethylene response were differentially expressed during fruit development. Other members of transcription factor families were also identified. There were 952 DEGs considered as novel genes with no annotation in any databases. These unigenes will serve as an invaluable genetic resource for loquat molecular breeding and postharvest storage.

Methyl 3,5-dicaffeoyl quinate (MDQ) is a flavonoid glucoside found in several plants that scavenges 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radicals and peroxynitrite, and inhibits the formation of cholesteryl ester hydroperoxide during the copper ion-induced oxidation of blood plasma in rats. In this study, MDQ inhibited proliferation and induced apoptosis in HT-29 cells in a dose-dependent manner as detected by 1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT), trypan blue exclusion, and flow cytometric assays. Western blot analysis showed that apoptosis was dependent on caspase-3 activity. PARP cleavage and the cytosolic release of cytochrome c from mitochondria increased significantly. In addition, these events were accompanied by a collapse in the mitochondrial membrane potential and a decreased Bcl-2/Bax ratio. Furthermore, the MDQ-induced G(0)/G(1) arrest was correlated with an increase in p27 and a decrease in cyclin D1 and p53. MDQ also inhibited the phosphorylation of PI3K/Akt and ERK; significantly reduced NF-κB; and in general displayed a significant anti-proliferative effect via a cell cycle arrest and apoptotic induction in HT-29 cells. These results suggest that MDQ has therapeutic potential against human colon carcinoma.

Four new megastigmane glycosides, named gusanlungionosides A-D (1-4), together with 10 known compounds (5-14), were isolated from the stems of Arcangelisia gusanlung. The structures and absolute configurations of 1-4 were elucidated by comprehensive analysis of their NMR and CD data. Compounds 1-4 exhibited strong inhibitory effects not only on the mushroom tyrosinase activity in vitro but also on melanogenesis in cells.

Mahonia bealei (Fort.) Carr. (Berberidaceae) leaves have been widely used as a tea leaf beverage south of the Qinling Mountains of China. In this study, the antioxidant and antiproliferative properties of M. bealei leaves were investigated. Our data showed that the water extract of M. bealei leaves (WML) exhibited extremely high antioxidant properties, which were demonstrated by its ability to scavenge 50% of 1,1-diphenyll-2-2-pricylhydrazyl (DPPH) free radicals at 60.46 μg/ml, and it eliminated approximately 71.19% of superoxide radicals at 500 μg/ml. In addition, the WML showed strong reducing abilities and provided protection against oxidative protein damage induced by hydroxyl radicals. Cellular proliferation and the induction of apoptosis were also examined by cellular proliferation assay, flow cytometry, and mRNA expression analysis. These results demonstrate that WML significantly inhibited the growth of human colon cancer (HT-29) cells in a concentration-dependent manner, and it gradually increased the proportion of apoptotic cells and reduced the expression of the survivin gene. The bioactivity-guided study of WML resulted in the isolation and identification of berberine, a known isoquinoline alkaloid. Berberine exhibited strong antiproliferative activity on HT-29 cells, with IC 50 values of 36.54 μM, suggesting it is, in part, responsible of the anticancer activity of WML.

Duchesnea indica (Rosaceae family) is herb used extensively in traditional Chinese medicine. In this study we investigated its protective activity against hydrogen peroxide (H 2 O 2 )-induced cytotoxicity in human skin fibroblast (CCD-986Sk) cells and 12- O -tetradecanoylphorbol-13-acetate (TPA)-induced H 2 O 2 in the skin of hairless mice. Pretreatment of CCD-986Sk cells with methanolic extract of D. indica (DIM) improved the cell viability, enhanced activity of catalase, and decreased the leakage of lactate dehydrogenase (LDH) and the levels of malondialdehyde (MDA) and intracellular reactive oxygen species (ROS) in H 2 O 2 injured cells. Furthermore, DIM inhibited cell apoptosis and Bax expression induced by H 2 O 2 . In addition, the level of H 2 O 2 stimulated by TPA was decreased by DIM in the skin of hairless mice. These results suggest that DIM offers protection against oxidative stress in vitro and in vivo , and this ability suggests potential use for protection against oxidation-induced skin damage.

Kalopanax pictus is a deciduous tree used in traditional medicine; its leaves are also consumed as a vegetable. In this study, the ethyl acetate fraction of K. pictus leaves (EFK) was tested in vitro for anticancer activity against four cell lines: human colon cancer (HT-29) cells, human stomach cancer (NCI-N87) cells, human breast cancer (MDA-MB231) cells, and mouse melanoma (B16F1) cells. Results indicated that EFK showed the most potent tumor selective growth inhibitory activity against HT-29 cells with less cytotoxic effect on normal cell lines. Cytotoxicity of EFK on HT-29 cells was associated mainly with cell chromatin condensation, DNA fragmentation, and loss of membrane phospholipid asymmetry with appearance of G2/M phase arrest. Cell death induced by EFK displayed features characteristic of apoptosis, and was associated with generation of reactive oxygen species (ROS) and increase of Bax/Bcl-2 ratio. These findings suggest that K. pictus leaves have anticancer properties and may be valuable for application in pharmaceutical industry.

For the first time, a pale amorphous coumarin derivative, 5-methoxyl aesculetin (MOA), was isolated from the dried bark of Fraxinus rhynchophylla Hance (Oleaceae). MOA modulates cytokine expression in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages, but the precise mechanisms are still not fully understood. We determined the effects of MOA on the production of inflammatory mediators and pro-inflammatory cytokines in the LPS-induced inflammatory responses of RAW 264.7 macrophages. MOA significantly inhibited the LPS-induced production of nitric oxide (NO), prostaglandin E₂ (PGE₂), tumor necrosis factor-α (TNF-α), interleukin-6, and interleukin-1β. It also effectively attenuated inducible nitric oxide (NO) synthase, cyclooxygenase-2, and TNF-α mRNA expression and significantly decreased the levels of intracellular reactive oxygen species. It inhibited phosphorylation of the extracellular signal-regulated kinase (ERK1/2), thus blocking nuclear translocation of activation protein (AP)-1. In a molecular docking study, MOA was shown to target the binding site of ERK via the formation of three hydrogen bonds with two residues of the kinase, which is sufficient for the inhibition of ERK. These results suggest that the anti-inflammatory effects of MOA in RAW 264.7 macrophages derive from its ability to block both the activation of mitogen-activated protein kinases (MAPKs) and one of their downstream transcription factors, activator protein-1 (AP-1). Our observations support the need for further research into MOA as a promising therapeutic agent in inflammatory diseases.