Renoprotective chemical constituents from an edible mushroom, Pleurotus cornucopiae in cisplatin-induced nephrotoxicity.

Pleurotus cornucopiae (Pleurotaceae) is an edible and medicinal mushroom widely distributed in Korea, China, and Japan. The MeOH extract of the fruiting bodies of P. cornucopiae showed renoprotective effects against cisplatin-induced kidney cell damage. Chemical investigation of the MeOH extract led to the isolation and identification of 12 compounds including noransine (1), uridine (2), uracil (3), (3ß, 5α, 6ß, 22E, 24S) -ergosta-7, 22-diene-3, 5, 6, 9-tetrol (4), (22E,24S)-ergosta-7,22-diene-3ß,5α,6ß-triol (5), (22E,24R)-ergosta-8(14),22-diene-3ß,5α,6ß,7α-tetrol (6), cerebroside B (7), (2R) -N- [(1S, 2R, 3E, 7E) -1- [(ß-d-glucopyranosyloxy) methyl] -2-hydroxy-8-methyl-3, 7-heptadecadien-1-yl] -2-hydroxy-heptadecanamide (8), cerebroside D (9), nicotinamide (10), 1,2-bis(hydroxymethyl)-4,5-dimethoxybenzene (11), and benzoic acid (12). Among them, compounds 1 and 11 were isolated as naturally occurring products for the first time, though they were reported as synthetic products in previous papers. All of the compounds (except 8 and 11) abrogated cisplatin-induced LLC-PK1 cell damage in a dose-dependent manner. Of special note, compounds 2, 5, 6, and 12 ameliorated cisplatin-induced nephrotoxicity to 80% of the control value at 10µM. The protective effects of compounds 2, 5, 6, and 12 were mediated via the deactivation of JNK-caspase 3 apoptotic cascade. This study is the first to demonstrate that the chemical constituents of P. cornucopiae display renoprotective effects against anticancer drug-induced damage in kidney cells.

A new cerebroside from the fruiting bodies of Hericium erinaceus and its applicability to cancer treatment.

A new cerebroside, cerebroside E (1) was isolated from the fruiting bodies of Hericium erinaceus (Hericiaceae). The structure of 1 was elucidated by a combination of extensive spectroscopic analyses, including extensive 2D NMR, HR-MS, and chemical reactions. Compound 1 was evaluated for its applicability to medicinal use in several human diseases using cell-based assays. As a result, compound 1 attenuated cisplatin-induced nephrotoxicity in LLC-PK1 cells and exhibited a significant inhibitory effect on angiogenesis in HUVECs. These results collectively reflect the beneficial effects of compound 1 in cancer treatment.

2-Hydroxy-3,4-naphthochalcone (2H-NC) inhibits TNFα-induced tumor invasion through the downregulation of NF-κB-mediated MMP-9 gene expression.

The control of tumor metastasis is important for the successful prevention and treatment of cancer. Emerging evidence indicates that various natural and synthetic chalcones exhibit antimetastatic activity through the inhibition of nuclear factor-κB (NF-κB), although the precise mechanism by which this occurs is currently unclear. In this study, 2-hydroxy-3,4-naphthochalcone (2H-NC) was found to reduce tumor necrosis factor alpha (TNFα)-induced MMP-9 mRNA expression and gelatinolytic enzyme activity. These actions were associated with inhibition of RelA/p65 NF-κB activity. In addition, 2H-NC inhibited TNFα-induced invasion of MDA-MB-231 breast cancer cells, as assessed using a three-dimensional spheroid invasion assay. Taken together, these data demonstrate that 2H-NC prevents TNFα-induced tumor cell invasion through downregulation of NF-κB-mediated MMP-9 gene expression, and thereby identify naphthochalcones as a potentially effective class of molecules to use as a platform for the development of antimetastatic agents.

Chemical constituents of Hericium erinaceum associated with the inhibitory activity against cellular senescence in human umbilical vascular endothelial cells.

Hericium erinaceum is an edible and medicinal mushroom widely used in Korea, Japan, and China. On the search for biologically active compounds supporting the medicinal usage, the MeOH extract of the fruiting bodies of H. erinaceum was investigated for its chemical constituents. Six compounds were isolated and identified as hericenone D (1), (22E,24R)-5α,8α-epidioxyergosta-6,22-dien-3ß-ol (2), erinacerin B (3), hericenone E (4), hericenone F (5) and isohericerin (6) by comparing their spectroscopic data with previously reported values. The inhibitory effects on adriamycin-induced cellular senescence in human dermal fibroblasts (HDFs) and human umbilical vein endothelial cells (HUVECs) of the isolates (1-6) were studied. Among the isolated compounds, ergosterol peroxide (2) reduced senescence associated ß-galactosidase (SA-ß-gal) activity increased in HUVECs treated with adriamycin. According to experimental data obtained, the active compound may inspire the development of a new pharmacologically useful substance to be used in the treatment and prevention of age-related diseases.

The potential of minor ginsenosides isolated from the leaves of Panax ginseng as inhibitors of melanogenesis.

Three minor ginsenosides, namely, ginsenoside Rh6 (1), vina-ginsenoside R4 (2) and vina-ginsenoside R13 (3), were isolated from the leaves of hydroponic Panax ginseng. The chemical structures were determined based on spectroscopic methods, including fast atom bombardment mass spectroscopy (FAB-MS), 1D-nuclear magnetic resonance (NMR), 2D-NMR, and, infrared (IR) spectroscopy. The melanogenic inhibitory activity of compounds 1, 2 and 3 was 23.9%, 27.8% and 35.2%, respectively, at a concentration of 80 µM. Likewise, the three compounds showed inhibitory activity on body pigmentation on a zebrafish model, which is commonly used as a model for biomedical or cosmetic research. These results from in vitro and in vivo systems suggest that the three aforementioned compounds isolated from Panax ginseng may have potential as new skin whitening compounds.

Benzyl alcohol derivatives from the mushroom Hericium erinaceum attenuate LPS-stimulated inflammatory response through the regulation of NF-κB and AP-1 activity.

On the search for anti-inflammatory compounds from natural Korean medicinal sources, a bioassay-guided fractionation and chemical investigation of the MeOH extract from the fruiting bodies of Hericium erinaceum resulted in the isolation and identification of five benzyl alcohol derivatives (1-5). In this study, their anti-inflammatory effects on lipopolysaccharide (LPS)-induced production of pro-inflammatory mediators were examined using RAW 264.7 macrophage cells. The structures of isolates were identified by comparing their spectroscopic data with previously reported values. The analysis of their inhibitory activities on LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production in RAW 264.7 macrophage cells showed that erinacerin B (2) and hericenone E (4) decreased the levels of NO and PGE2 production in a concentration-dependent manner. Next, this study was performed to examine their mechanism of action on the regulation of NO and PGE2 production. Compounds 2 and 4 were found to block the LPS-induced phosphorylation of two major inflammatory transcription factors, NF-κB (p65/p50) and AP-1 (c-Jun and c-Fos). Taken together, these results suggest that down-regulation of LPS-induced NO and PGE2 production by compounds 2 and 4 is mediated through the modulation of NF-κB and AP-1 activation in macrophage cells. These results impact the development of potential health products for preventing and treating inflammatory diseases.

Brazilin inhibits growth and induces apoptosis in human glioblastoma cells.

Brazilin, isolated from the methanol extract of the heart wood of Caesalpinia sappan, sensitizes cancer cells to apoptosis. Glioblastoma multiforme (GBM), which accounts for most cases of central nervous system malignancy, has a very poor prognosis and lacks effective therapeutic interventions. We, therefore, investigated the effects of different concentrations of and different periods of exposure to brazilin on cell proliferation and apoptosis in the glioma U87 cell line. Cell proliferation was investigated by MTT assays and growth curve analysis, apoptosis was assessed by FACS analysis and western blot studies. Brazilin showed dose-dependent inhibition of cell proliferation and induction of apoptosis in glioma cells. It also increased the ratio of cleaved poly-(ADP)-ribose polymerase and decreased the expression of caspase-3 and caspase-7.

Anti-inflammatory cycloartane-type saponins of Astragalus membranaceus.

A new cycloartane-type triterpene glycoside, agroastragaloside V (1) was isolated from the roots of Astragalus membranaceus. The structure was identified as 3-O-ß-(2'-O-acetyl)-D-xylopyranosyl-6-O-ß-D-glucopyranosyl-(24S)-3ß,6α,24α,25-tetrahydroxy- 9,19-cyclolanostane, by means of spectroscopic methods, including HR-FAB/MS, 1D NMR (1H, 13C, DEPT), 2D NMR (gCOSY, gHSQC, gHMBC, NOESY), and IR spectroscopy. Four known cycloartane glycosides, namely, agroastragaloside I (2), agroastragaloside II (3), isoastragaloside II (4) and astragaloside IV (5) were also isolated. All isolated compounds were tested for the ability to inhibit LPS-induced nitric oxide production in RAW264.7 macrophages.

Quality evaluation of Panax ginseng roots using a rapid resolution LC-QTOF/MS-based metabolomics approach.

Korean ginseng (Panax ginseng C.A. Meyer) contains several types of ginsenosides, which are considered the major active medicinal components of ginseng. The types and quantities of ginsenosides found in ginseng may differ, depending on the location of cultivation, making it necessary to establish a reliable method for distinguishing cultivation locations of ginseng roots. P. ginseng roots produced in different regions of Korea, China, and Japan have been unintentionally confused in herbal markets owing to their complicated plant sources. PCA and PLS-DA using RRLC-QTOF/MS data was able to differentiate between ginsengs cultivated in Korea, China, and Japan. The chemical markers accountable for such variations were identified through a PCA loadings plot, tentatively identified by RRLC-QTOF/MS and partially verified by available reference standards. The classification result can be used to identify P. ginseng origin.

Anti-inflammatory lignans from the fruits of Acanthopanax sessiliflorus.

A new lignan, named acanthosessilin A (1), as well as eight known lignan and lignan glycosides 2-9 were isolated from an ethanolic extract of Acanthopanax sessiliflorus fruits. The chemical structures were determined by spectroscopic methods, including HR-EIMS, 1D NMR (1H, 13C, DEPT), 2D NMR (gCOSY, gHSQC, gHMBC, NOESY), and IR spectroscopy. All isolated compounds were tested for the ability to inhibit LPS-induced nitric oxide production in RAW264.7 macrophages.

Evaluation of Agricultural Traits, Phytochemical Contents, and Antioxidant Activities in the Leaves of Amaranth Accessions of Nine Species.

Amaranthus species are widely cultivated as dietary crops and are promising sources of phytochemical compounds with antioxidant properties. To explore Amaranthus as a potential medical resource, 289 accessions (nine species) were cultivated, and their agricultural characteristics, total phenolic content (TPC), rutin contents, and antioxidant activities [2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS)] were studied. Wide variations in agricultural traits, phytochemical contents, and antioxidant activities were observed between the accessions and across species. The effects of agricultural traits were evaluated, and the results indicated that yellow-flowered amaranth genotypes could be important because of their high values of TPC, rutin contents, DPPH, and ABTS. In addition, leaf length, days until 50% flowering, days until 50% heading and days until maturity, showed positive correlations with TPC, rutin contents, DPPH, and ABTS. The whole dataset was subjected to principal component analysis, and distinctive aggregation was observed across the Amaranthus species. In total, 289 accessions were clustered into three groups, and seven genotypes were determined as being good medical resources due to their high phytochemical content and antioxidant activities. Our findings provide important information for the development of new varieties with high phytochemical contents and high levels of antioxidant activity.

Seed Weight and Genotype Influence the Total Oil Content and Fatty Acid Composition of Peanut Seeds.

Peanut, an important oilseed crop cultivated worldwide as a dietary food, is a good food source with health benefits. To explore the potential benefits of peanuts as a food resource, 301 peanut accessions were evaluated to determine the effect of seed weight and genotype on total oil content and fatty acid composition. Total oil was extracted using the Soxhlet method and fatty acids were analyzed by gas chromatography mass spectrometry. Wide variations in the 100-seed weight, total oil content, and fatty acid profile were observed among genotypes and accession types. An effect of seed weight on the fatty acid composition of peanut seeds was observed. Increases in the oleic acid content and decreases in the linoleic acid content occurred in association with increases in the 100-seed weight. Moreover, the 100-seed weight, total oil content, and individual and total fatty acid contents, except arachidic acid, differed significantly (p < 0.001 or 0.05) among the accession types of landrace, cultivar, breeding line, and unknown. The discovery of this high diversity could contribute to further studies of peanut domestication and evolutionary classification. Our findings are important for the selection of peanut seeds with health benefits and development of new varieties of peanut with health benefits.

Investigating the influence of Taekwondo body protectors size on shock absorption.

OBJECTIVE: This study aims to compare and analyze the difference of impact force attenuation according to size and impact location on a Taekwondo body protector. METHODS: Body protectors sized 1 to 5, were impact tested by equipment based on the specifications in the European standard manual (EN 13277-1, 3). The impactor release heights were set to match impact energies of 3 and 15 J. The impactor was made from a 2.5 kg cylindrically cut piece of aluminum. Each body protector was impacted 10 times at the two impact energies and two locations. The differences in performance for each body protector size were compared using a two-way analysis of variance with a significance level of p< 005. The effect sizes were investigated using a partial eta squared value (η2). RESULTS: The significant mean differences between the body protector size and impact area (p< 005) and the average impact time of impact strengths 3 and 15 J were 0.0017 and 0.0012 s, respectively In addition, when an impact strength of 15 J was applied, the maximum resulting impact force exceeded 2000 N for both locations on all sizes. Furthermore, at an impact strength of 3 J size 3 significantly reduced the impact force more than the other sizes; however, size 1 showed the greatest shock absorption at an impact of 15 J. CONCLUSION: The results of this study show that the shock absorption of body protectors does not increase according to size; i.e., a larger body protector does not reduce the impact load more effectively. To improve safety performance, we recommend a maximum impact force of 2000 N or less for all body protectors.

Lactarane sesquiterpenoids from Lactarius subvellereus and their cytotoxicity.

Subvellerolactones B (1), D (2), and E (3), structurally unusual lactarane sesquiterpenoids, were isolated from the fruiting bodies of Lactarius subvellereus together with four known lactarane sesquiterpenes (4-7). The chemical structures and stereochemistries of compounds 1-3 were determined on the basis of spectroscopic analyses, including 1D and 2D NMR experiments and a convenient Mosher ester procedure. Subvellerolactone B (1) exhibited cytotoxicity against the A549, SK-MEL-2, and HCT-15 cell lines with IC50 values of 26.5, 18.3, and 14.2 microM, respectively, and subvellerolactones D (2) and E (3) showed cytotoxicity against the A549 and HCT-15 cell lines (IC50 (2): 25.1 and 17.8 microM, and IC50 (3): 19.6 and 28.7 microM, respectively).

Extraadrenal paragangliomas of the body: imaging features.

OBJECTIVE: This article illustrates the anatomic distribution of the healthy paraganglion system and the imaging and pathologic features of various extraadrenal paragangliomas occurring in the head and neck, chest, and abdomen. CONCLUSION: Although paragangliomas can occur in a variety of anatomic locations, the majority are seen in relatively predictable regions of the body. Extraadrenal paragangliomas have nearly identical imaging features, including a homogeneous or heterogeneous hyperenhancing soft-tissue mass at CT, multiple areas of signal void interspersed with hyperintense foci (salt-and-pepper appearance) within tumor mass at MRI, and an intense tumor blush with enlarged feeding arteries at angiography.

Flavonoids and a Limonoid from the Fruits of Citrus unshiu and Their Biological Activity.

The fruits of Citrus unshiu are one of the most popular and most enjoyed fruits in Korea. As we continue to seek for bioactive metabolites from Korean natural resources, our study on the chemical constituents of the fruits of C. unshiu resulted in the isolation of a new flavonoid glycoside, limocitrunshin 1, along with seven other flavonoids 2-8 and a limonoid 9. All structures were identified by spectroscopic methods, namely 1D and 2D NMR, including HSQC, HMBC, and (1)H-(1)H COSY experiments, HRMS, and other chemical methods. Compounds 3, 5, and 9 are reported to be isolated from this fruit for the first time. The isolated compounds were applied to activity tests to verify their inhibitory effects on inflammation and nephrotoxicity. Compounds 6 and 9 showed the most potent inhibitory activity on renal cell damage and nitric oxide production, respectively. Thus, the fruits of C. unshiu could serve as a valuable natural source of bioactive components with health benefits for potential application in functional foods.

Anti-inflammatory activity of a new cyclic peptide, citrusin XI, isolated from the fruits of Citrus unshiu.

ETHNOPHARMACOLOGICAL RELEVANCE: Citrus unshiu (Rutaceae) is an easy-peeling citrus fruit, which has been used as a traditional Korean medicine for improving skin elasticity, relieving fatigue and cough, and preventing bronchitis, flu, and various cancers. However, its active components associated with anti-inflammation and underlying mechanisms remain unknown. In this study, we investigated the active constituents from the fruits of Citrus unshiu and evaluated the anti-inflammatory activity in order to support the traditional usage of Citrus unshiu. MATERIAL AND METHODS: Repeated column chromatography, together with a semi-preparative HPLC purification was used to separate the bioactive constituent from the EtOAc soluble fraction of the EtOH extract of Citrus unshiu fruits. Anti-inflammatory effects of the isolated compounds on lipopolysaccharide (LPS)-induced production of pro-inflammatory mediators were examined using RAW264.7 macrophage cells. RESULTS: A new cyclic peptide, citrusin XI (1), was isolated and identified from the fruits of Citrus unshiu. The structure of compound 1 was elucidated by spectroscopic analysis, including 1D and 2D nuclear magnetic resonance (NMR) ((1)H, (13)C, COSY, HMQC and HMBC experiments), and high resolution (HR)-mass spectrometry, and its absolute configurations were further confirmed by the Marfey׳s method. Compound 1 decreased NO production in LPS-stimulated RAW264.7 cells in a dose-dependent manner with an IC50 value of 70µM. Compound 1 suppressed NO production by decreasing iNOS expression but COX-2 expression was slightly associated with the reduction by compound 1 in LPS-induced RAW264.7 cells. Furthermore, compound 1 inhibited NF-κB activation by blocking IκBα degradation and NF-κB phosphorylation in LPS-stimulated RAW264.7 cells. CONCLUSIONS: These results indicate that a new cyclic peptide, citrusin XI, from Citrus unshiu fruits has anti-inflammatory properties that inhibit the release of pro-inflammatory mediators. Compound 1 decreases NO production by decreasing iNOS expression and NF-κB activation associated with IκBα degradation and NF-κB phosphorylation in LPS-induced RAW264.7 cells. This is the first study to clarify the underlying mechanism of the anti-inflammatory effect exerted by a pure isolated compound from Citrus unshiu in LPS-stimulated RAW264.7 macrophage cells. The phytochemical, citrusin XI of Citrus unshiu may serve as lead compound in the design of new agents for preventing and treating inflammatory diseases.

A direct protein kinase B-targeted anti-inflammatory activity of cordycepin from artificially cultured fruit body of Cordyceps militaris.

BACKGROUND: Cordyceps militaris is one of well-known medicinal mushrooms with anti-inflammatory, anti-cancer, anti-diabetic, and anti-obesity activities. OBJECTIVE: The objective of the following study is to isolate chemical components from the ethanol extract (Cm-EE) from Cordyceps militaris and to evaluate their anti-inflammatory activities. MATERIALS AND METHODS: Column chromatographic separation was performed and anti-inflammatory roles of these compounds were also examined by using NO production and protein kinase B (AKT) activity assays. RESULTS: From Cm-EE, 13 constituents, including trehalose (1), cordycepin (2), 6-hydroxyethyladenosine (3), nicotinic amide (4), butyric acid (5), ß-dimorphecolic acid (6), α-dimorphecolic acid (7), palmitic acid (8), linoleic acid (9), cordycepeptide A (10), 4-(2-hydroxy-3-((9E,12E)-octadeca-9,12-dienoyloxy)propoxy)-2-(trimethylammonio)butanoate (11), 4-(2-hydroxy-3-(palmitoyloxy)propoxy)-2-(trimethylammonio)butanoate (12), and linoleic acid methyl ester (13) were isolated. Of these components, compound 2 displayed a significant inhibitory effect on NO production in lipopolysaccharide (LPS)-activated RAW264.7 cells. Furthermore, this compound strongly and directly suppressed the kinase activity of AKT, an essential signalling enzyme in LPS-induced NO production, by interacting with its ATP binding site. CONCLUSION: C. militaris could have anti-inflammatory activity mediated by cordycepin-induced suppression of AKT.