N-Feruloyl Serotonin Attenuates Neuronal Oxidative Stress and Apoptosis in Aß25-35-Treated Human Neuroblastoma SH-SY5Y Cells.

Amyloid-beta (Aß) aggregation and deposition have been identified as a critical feature in the pathology of Alzheimer's disease (AD), with a series of functional alterations including neuronal oxidative stress and apoptosis. N-feruloyl serotonin (FS) is a plant-derived component that exerts antioxidant activity. This study investigated the protective effects of FS on Aß25-35-treated neuronal damage by regulation of oxidative stress and apoptosis in human neuroblastoma SH-SY5Y cells. The radical scavenging activities increased with the concentration of FS, exhibiting in vitro antioxidant activity. The Aß25-35-treated SH-SY5Y cells exerted neuronal cell injury by decreased cell viability and elevated reactive oxygen species, but that was recovered by FS treatment. In addition, treatment of FS increased anti-apoptotic factor B-cell lymphoma protein 2 (Bcl-2) and decreased the pro-apoptotic factor Bcl-2-associated X protein. The FS attenuated Aß-stimulated neuronal apoptosis by regulations of mitogen-activated protein kinase signaling pathways. Moreover, activated CREB-BDNF signaling was observed by the treatment of FS in Aß25-35-induced SH-SY5Y cells. These results demonstrate that FS shows potential neuroprotective effects on Aß25-35-induced neuronal damage by attenuation of oxidative stress and apoptosis, and suggest that FS may be considered a promising candidate for the treatment of AD.

Extracts of Perilla frutescens var. Acuta (Odash.) Kudo Leaves Have Antitumor Effects on Breast Cancer Cells by Suppressing YAP Activity.

Yes-associated protein (YAP)/WW domain-containing transcription factor (TAZ) is critical for cell proliferation, survival, and self-renewal. It has been shown to play a crucial oncogenic role in many different types of tumors. In this study, we investigated the antitumor effect of the extracts of Perilla frutescens var. acuta (Odash.) Kudo leaves (PLE) on Hippo-YAP/TAZ signaling. PLE induced the phosphorylation of YAP/TAZ, thereby inhibiting their activity. In addition, the treatment suppresses YAP/TAZ transcriptional activity via the dissociation of the YAP/TAZ-TEAD complex. To elucidate the molecular mechanism of PLE in the regulation of YAP activity, we treated WT and cell lines with gene knockout (KO) for Hippo pathway components with PLE. The inhibitory effects of PLE on YAP-TEAD target genes were significantly attenuated in LATS1/2 KO cells. Moreover, we found the antitumor effect of PLE on MDA-MB-231 and BT549, both of which are triple-negative breast cancer (TNBC) cell lines. PLE reduced the viability of TNBC cells in a dose-dependent manner and induced cell apoptosis. Further, PLE inhibited the migration ability in MDA-MB-231 cells. This ability was weakened in YAP and TEAD-activated clones suggesting that the inhibition of migration by PLE is mainly achieved by regulating YAP activity. Taken together, the results of this study indicate that PLE suppressed cell growth and increased the apoptosis of breast cancer (BC) cells via inactivation of YAP activity in a LATS1/2-dependent manner.

Isolation and identification of phytochemicals and biological activities of Hericium ernaceus and their contents in Hericium strains using HPLC/UV analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Hericium ernaceus has been traditionally used for the treatment of dyspepsia, gastric ulcer and enervation in traditional Chinese medicine for a long time. AIM OF THE STUDY: To examine the effect of Hericium strains on their ability to inhibit LPS and interferon-γ induced NO production in cell culture and the bioassay correlation of hericenone C, D, F, isolated from H. ernaceus. MATERIALS AND METHODS: Hericenone C, D, F were isolated from H. ernaceus by open column chromatography and identified on the basis of spectroscopic analyses including (1)H NMR, (13)C NMR and MS. The amounts of hericenone C, D, and F in Hericium strains were determined by HPLC/UV analysis. In order to investigate the anti-inflammatory effect of Hericium strains extracts, RAW 264.7 cells were treated with 200µg/mL of Hericium strains extracts for 48h. Cell growth was assessed by MTT assay. RESULTS: Phytochemical constituents were isolated from H. ernaceus by open column chromatography. Their structures were elucidated as hericenones C, D, and F on the basis of spectroscopic analyses including (1)H NMR, (13)C NMR and MS. The amounts of hericenones C, D, and F in Hericium strains were determined by HPLC/UV analysis. Hericenones C, D, and F contents were highest in Norugungdenglee-2 (8.289±0.593mg/g), KFRI-1453 (4.657±0.462mg/g), and KFRI-1093 (5.408±0.420mg/g) strains, respectively. All Hericium strains extracts tested inhibited the lipopolysaccharide- and interferon-γ-induced inflammatory activity of RAW264.7 cells. The strain KFRI-1093 about 39.6% reduced NO generation with compared to control. CONCLUSION: We believe that the anti-inflammatory effect of KFRI-1093 was due to hericenone F content. Our results contribute towards validation of the traditional use, natural drugs and health supplements. And also, the developed simple, accurate and rapid LC method can be used determinate the content of hericenones from other Hericium strains.

Heat-Killed Enterococcus faecalis EF-2001 Ameliorates Atopic Dermatitis in a Murine Model.

Recent reports have shown the immunomodulatory effect of heat-killed lactic acid bacteria. Atopic dermatitis (AD) is an allergic skin disease, caused by immune dysregulation among other factors. The aim of this study was to assess the effect of heat-killed Enterococcus faecalis EF-2001 (EF-2001) on AD. We established an in vivo AD model by repeated local exposure of Dermatophagoides farinae extract (DFE; house dust mite extract) and 2,4-dinitrochlorobenzene (DNCB) to the ears of mice. After oral administration of EF-2001 for four weeks, the epidermal and dermal ear thickness, mast cell infiltration, and serum immunoglobulin levels were measured. In addition, the gene expression levels of pathogenic cytokines in the ears, lymph nodes, and splenocytes were assayed. EF-2001 attenuated AD symptoms based on the ear thickness, histopathological analysis, and serum immunoglobulin levels. Moreover, EF-2001 decreased the DFE/DNCB-induced expression of various pathogenic cytokines in the ears, lymph nodes, and splenocytes. These results suggest that EF-2001 has therapeutic potential in the treatment of AD owing to its immunomodulatory effects.

A comparison of antioxidant activity of Korean White and Red Ginsengs on H2O2-induced oxidative stress in HepG2 hepatoma cells.

The aim of this study was to determine and compare the preventive effect of Korean White Ginseng and Red Ginseng on oxidative stress in H2O2-treated HepG2 cells. The roots of ginseng were extracted with 70% methanol and partitioned with butanol to obtain saponin fractions, which have been known as bioactive constituents of ginseng. 2',7'-Dichlorofluorescein diacetate (DCF-DA) assay and malondialdehyde (MDA) content were measured for evaluating intracellular reactive oxygen species (ROS) generation. Also, mRNA expressions and activities of antioxidant enzymes were analyzed to determine the antioxidant activity of saponin or non-saponin fractions of ginsengs. According to DCF-DA assay, H2O2-induced MDA release and ROS generation were significantly reduced by treatment with saponin fractions of white and red ginseng roots. Also, saponin fractions increased effectively intracellular antioxidant enzyme activities including catalase, glutathione peroxidase and superoxide dismutase in H2O2- treated HepG2 hepatoma cells. In general, red ginseng was more effective than white ginseng for reducing oxidative stress. These results indicate that administration of red ginseng may certainly contribute relatively stronger than white ginseng to prevent from damaging liver function by oxidative stress.

Inhibited apoptosis of C(2)C(1)2 myoblasts by a Eupatorium chinense var. simplicifolium root extract.

We investigated the effects of a Eupatorium chinense var. simplicifolium (EUC) root extract on muscle disorders and explored the underlying mechanism for oxidative stress-induced C(2)C(12) myoblast damage. An EUC pre-treatment reduced the decreased cell viability after an H2O2 treatment. The heat shock protein (HSP) 70 level increased, and the phosphorylation of Jun amino-terminal kinases (JNKs) decreased in the EUC-pre-treated C(2)C(12) myoblasts. The results of the present study demonstrate the potential benefit of a herbal medicine in treating oxidative stress-related muscle disorders.

Anethum graveloens flower extracts inhibited a lipopolysaccharide-induced inflammatory response by blocking iNOS expression and NF-κB activity in macrophages.

Inflammation is a system used by a host to defend against the presence of bacteria, viruses, or yeasts. Toll-like receptors (TLRs) in the plasma membranes of macrophages are activated when they recognize the molecular structure of a virus or bacterium. Lipopolysaccharide (LPS), an outer cell-wall component of Gram-negative bacteria, initiates an inflammatory process via TLR4. We investigated the effect of the extract of Anethum graveloens flowers (AGFs) on LPS-mediated inflammation in RAW 264.7 cells. The extract markedly suppressed nitric oxide generation in a concentration-dependent manner in LPS-stimulated RAW 264.7 cells. It inhibited inducible nitric oxide synthase (iNOS) and the mRNA expression of cytokines such as interleukin-1 beta and interleukin-6 in LPS-stimulated RAW 264.7 cells. It also inhibited iNOS protein levels in LPS-stimulated RAW 264.7 cells. In addition, AGF decreased the LPS-induced phosphorylation of mitogen-activated protein kinases in LPS-stimulated RAW 264.7 cells. AGF inhibited the phosphorylation of Akt, an upstream molecule of the nuclear factor kappa B (NF-κB) pathway, and thus inhibited NF-κB activity in LPS-stimulated RAW 264.7 cells. These results suggest that AGF exerts an anti-inflammatory effect in LPS-stimulated RAW 264.7 cells by inhibiting iNOS expression and blocking the NF-κB pathway.

The antidiabetic effect of ginsenoside Rb2 via activation of AMPK.

Ginsenosides, which are active compounds found in ginseng (Panax ginseng), are used as antidiabetic treatments. The aim of this study was to determine whether Rb2, a type of ginsenoside, regulates hepatic gluconeogenesis through AMP-activated protein kinase (AMPK) and the orphan nuclear receptor small heterodimer partner (SHP) in hyperlipidemic conditions used as an in vitro model of type 2 diabetes. Considering these results, we concluded that Rb2 may inhibit palmitate-induced gluconeogenesis via AMPK-induced SHP by relieving ER stress, a cause of gluconeogenesis.

Enhanced production of asiaticoside from hairy root cultures of Centella asiatica (L.) Urban elicited by methyl jasmonate.

Transformed root ("hairy root") cultures have been shown to be a good model for the study of many secondary metabolites. However, economically important compounds such as asiaticoside and madecassoside are produced in insignificant amounts in the root of Centella asiatica (L.) Urban. To overcome this problem, C. asiatica was transformed using Agrobacterium rhizogenes strain R1000 that harbors pCAMBIA1302 encoding the hygromycin phosphotransferase (hpt) and green fluorescence protein (mgfp5) genes and the hairy culture was coupled with elicitation technique. Hairy roots were obtained at a frequency of up to 14.1% from a tissue junction between the leaf and petiole. Abundant hairy roots were observed when co-cultivation of the plant with A. rhizogenes was done for 7 days (36.1%). Transformation was confirmed by PCR and Southern blot analyses. Five weeks after inoculation, no asiaticoside was detected in the hairy root samples. However, when 0.1 mM methyl jasmonate (MJ) was applied as an elicitor to the culture medium for 3 weeks, a large quantity of asiaticoside was generated (7.12 mg/g, dry wt). In the case of gene expression, 12 h after MJ treatment the expression of the CabAS (C. asiatica putative beta-amyrin synthase) gene in the hairy roots is significantly different from that of the control and this level of transcripts was maintained for 14 days. Our results showed that production of C. asiatica hairy roots could be optimized and the resulting cultures could be elicited with MJ treatment for enhanced production of asiaticoside.