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Two new berkeley meroterpenoids (1 and 2), along with seven known compounds (3‒9) were isolated from a fungus, Penicillium sp. SSW03M2 GY derived from a sediment at Seosan bay, South Korea. Chemical structures of the isolated compounds were elucidated on the basis of 1D, 2D NMR, HRESIMS, and optical rotation. All the isolated compounds, 1 showed anti-virulence activity by significantly inhibiting α-toxin (Hla) secreted by methicillin-resistant Staphylococcus aureus without its growth inhibition.

A new α-pyrone analog, arthrifuranone A (1) was isolated from an EtOAc-extract of Arthrinium pseudosinense culture medium. The isolation workflow was guided by a Molecular Networking-based dereplication strategy. The chemical structure of the new compound was elucidated using MS and NMR spectroscopic techniques, and the absolute configuration was established by the Mosher's method and gauge-including atomic orbital NMR chemical shift calculations, followed by DP4 + analysis. The isolated compound was evaluated for its estrogenic activity using the MCF-7 estrogen responsive human breast cancer cells. Compound 1 showed estrogenic activity by increasing the proliferation of MCF-7 cells at the concentration of 3.125 μM via phosphorylation of estrogen receptor-α.

Fourteen azaphilone-type polyketides (1-14), including nine new ones (1-6 and 8-10), were isolated from cultures of Vitex rotundifolia-associated Penicillium sp. JVF17, and their structures were determined by spectroscopic analysis together with computational methods and chemical reactions. Neuroprotective effects of the isolated compounds were evaluated against glutamate-induced neurotoxicity. Treatment with compounds 3, 6, 7, and 11-14 increased cell viabilities of hippocampal neuronal cells damaged by glutamate, with compound 12 being the most potent. Compound 12 markedly decreased intracellular Ca2+ and nuclear condensation levels. Mechanistically, molecular markers of apoptosis induced by treatment with glutamate, i.e., phosphorylation of MAPKs and elevated Bax/Bcl-2 expression ratio, were significantly lowered by compound 12. The azaphilones with an isoquinoline core structure were more active than those with pyranoquinones, but N-substitution decreased the activity. This study, including the structure-activity relationship, indicates that the azaphilone scaffold is a promising lead toward the development of novel neuroprotective agents.

Six new β-resorcylic acid derivatives (1–5 and 7) were isolated from a halophyte-associated fungus, Colletotrichum gloeosporioides JS0419, together with four previously reported β-resorcylic acid lactones (RALs). The relative and absolute stereochemistry of 1 was completely established by a combination of spectroscopic data and chemical reactions. The structures of the isolated compounds were elucidated by analysis of HRMS and NMR data. Notably, compounds 1–3 had a β-resorcylic acid harboring a long unesterified aliphatic side chain, whereas the long aliphatic chains were esterified to form macrolactones in 4–9. Among the isolated compounds, monocillin I and radicicol showed potent antifungal activities against Cryptococcus neoformans, comparable to clinically available antifungal agents and radicicol showed weak antifungal activity against Candida albicans. These findings provide insight into the chemical diversity of fungal RAL-type compounds and their pharmacological potential.

A new phenolic glucoside, (7E,9E)-3-hydroxyavenalumic acid-3-O-[6'-O-(E)-caffeoyl]-β-d-glucopyranoside (1), and three new acetylated flavone glycosides, acacetin-7-O-[β-d-glucopyranosyl(1″″→2″)-4‴-O-acetyl-α-l-rhamnopyranosyl(1‴→6″)]-β-d-glucopyranoside (3), acacetin-7-O-[6″″-O-acetyl-β-d-glucopyranosyl(1″″→2″)-3‴-O-acetyl-α-l-rhamnopyranosyl(1‴→6″)]-β-d-glucopyranoside (5), and acacetin-7-O-[3″″,6″″-di-O-acetyl-β-d-glucopyranosyl(1″″→2″)-4‴-O-acetyl-α-l-rhamnopyranosyl(1‴→6″)]-β-d-glucopyranoside (7), as well as 34 known compounds (2, 4, 6, and 8-38) were isolated from the aerial parts of Elsholtzia ciliata. The chemical structures of the new compounds were determined by spectroscopic/spectrometric data interpretation using NMR and HRESIMS. The neuroprotective effect of the isolated compounds was evaluated by a cell viability assay on HT22 murine hippocampal neuronal cells. Among them, 23 compounds, including new substances 1 and 3, exhibited neuroprotective effects against glutamate-induced HT22 cell death. In particular, compounds 2, 16, 17, 20, 22, 28, 29, and 31 presented potent neuroprotective effects with EC50 values of 1.5-8.3 μM.

Atherosclerosis is a widespread and chronic progressive arterial disease that has been regarded as one of the major causes of death worldwide. It is caused by the deposition of cholesterol, fats, and other substances in the tunica intima which leads to narrowing of the blood vessels, loss of elasticity, and arterial wall thickening, thus causing difficulty in blood flow. Natural products have been used as one of the most important strategies for the treatment and prevention of cardiovascular diseases for a long time. In recent decades, as interests in natural products including medicinal herbs have increased, many studies regarding natural compounds that are effective against atherosclerosis have been conducted. The purpose of this review is to provide a brief over-view of the natural compounds that have been used for the treatment and prevention of atherosclerosis, and their mechanisms of action based on recent research.

Cinnamoyl-containing nonribosomal peptides (CCNPs) form a unique family of actinobacterial secondary metabolites and display various biological activities. A new CCNP named epoxinnamide (1) was discovered from intertidal mudflat-derived Streptomyces sp. OID44. The structure of 1 was determined by the analysis of one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) data along with a mass spectrum. The absolute configuration of 1 was assigned by the combination of advanced Marfey’s method, 3JHH and rotating-frame overhauser effect spectroscopy (ROESY) analysis, DP4 calculation, and genomic analysis. The putative biosynthetic pathway of epoxinnamide (1) was identified through the whole-genome sequencing of Streptomyces sp. OID44. In particular, the thioesterase domain in the nonribosomal peptide synthetase (NRPS) biosynthetic gene cluster was proposed as a bifunctional enzyme, which catalyzes both epimerization and macrocyclization. Epoxinnamide (1) induced quinone reductase (QR) activity in murine Hepa-1c1c7 cells by 1.6-fold at 5 μM. It also exhibited effective antiangiogenesis activity in human umbilical vein endothelial cells (IC50 = 13.4 μM).

Two new isochromanone derivatives, (3S,4S)-3,8-dihydroxy-6-methoxy-3,4,5-trimethylisochroman-1-one (1) and methyl (S)-8-hydroxy-6-methoxy-5-methyl-4a-(3-oxobutan-2-yl)benzoate (2), together with six known compounds (3‒8) were isolated from the cultures of an endophytic fungus Phoma sp. PF2 obtained from Artemisia princeps. The chemical structures of the isolated compounds were elucidated by interpretation of spectroscopic data (1D, 2D NMR, HRESIMS, and CD) and calculation of ECD. All the isolated compounds (1‒8) showed moderate inhibitory activities on nitric oxide levels in lipopolysaccharide-induced RAW264.7 machrophage cells.

Menopause, caused by decreases in estrogen production, results in symptoms such as facial flushing, vaginal atrophy, and osteoporosis. Although hormone replacement therapy is utilized to treat menopausal symptoms, it is associated with a risk of breast cancer development. We aimed to evaluate the estrogenic activities of Spartina anglica (SA) and its compounds and identify potential candidates for the treatment of estrogen reduction without the risk of breast cancer. We evaluated the estrogenic and anti-proliferative effects of extracts of SA and its compounds in MCF-7 breast cancer cells. We performed an uterotrophic assay using an immature female rat model. Among extracts of SA, belowground part (SA-bg-E50) had potent estrogenic activity. In the immature female rat model, the administration of SA-bg-E50 increased uterine weight compared with that in the normal group. Among the compounds isolated from SA, 1,3-di-O-trans-feruloyl-(-)-quinic acid (1) had significant estrogenic activity and induced phosphorylation at serine residues of estrogen receptor (ER)α. All extracts and compounds from SA did not increase MCF-7 cell proliferation. Compound 1 is expected to act as an ERα ligand and have estrogenic effects, without side effects, such as breast cancer development.

Three unusual polyketides with a 5/6/10-fused ring system, named colletotrichalactones A-Ca (1-3a), were isolated from cultures of the endophytic fungus, Colletotrichum sp. JS-0361, which was isolated from a leaf of Morus alba. Their structures, including their absolute stereochemistries, were completely established using extensive spectroscopic methods together with a chemical reaction utilizing competing enantioselective acylation coupled with LC/MS. Compounds possessing this ring skeleton were previously reported in three studies. Our rigorous chemical investigation revealed the complete configuration of this skeleton, which agreed with the results for glabramycin B with this ring skeleton established by computational chemistry and enantioselective synthesis in previous reports. 1 and 2 had unstable aldehyde groups that were easily converted to acetal groups in the presence of solvents. Meanwhile, compound 3a, with terminal acetal functionality, was deduced to be an artefact originating from compound 3 with a terminal aldehyde group. Compounds 1 and 3a displayed moderate-to-potent cytotoxic activities against MCF7 cells with IC50s of 35.06 and 25.20 µM, respectively.

Background Lespedeza cuneata G.Don (LCE), which belongs to the genus Lespedeza (Leguminosae), is a traditional oriental medicine known to prevent diabetes and cardiovascular diseases. However, no scientific studies about the effectiveness of LCE, their responsible bioactive constituents, and its mechanisms against endothelial dysfunction have been performed. Purpose This study was performed to investigate the role of LCE and its chemical components in ameliorating endothelial dysfunction. Methods The production of nitric oxide (NO) was evaluated after LCE treatment in HUVECs. Cell viability was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reagent. Western blot analysis was performed to determine the protein expression of endothelial nitric oxide synthase (eNOS) and protein kinase B (PKB, also known as Akt) in human umbilical vein endothelial cells (HUVECs). Results Pretreatment with L-NAME and LY294002 significantly decreased the LCE-induced NO production, as well as eNOS and Akt phosphorylation. β-Sitosterol and β-Sitosterol 6′-linolenoyl-3-O-β-D-glucopyranoside are the bioactive constituents increase NO production as well as eNOS phosphorylation. Conclusion Our findings suggest that LCE increase NO production via eNOS phosphorylation of PI3K/Akt signaling pathway.

Inflammation is a vital process that maintains tissue homeostasis. However, it is widely known that uncontrolled inflammation can contribute to the development of various diseases. This study aimed to discover anti-inflammatory metabolites from Penicillium bialowiezense. Seven spiroditerpenoids, including two new compounds, breviones P and Q (1 and 2), were isolated and characterized by various spectroscopic and spectrometric methods. All isolated compounds were initially tested for their inhibitory effects against lipopolysaccharide-induced nitric oxide (NO) production in RAW 264.7 macrophages. Of these, brevione A (3) exhibited this activity with a half-maximal inhibitory concentration value of 9.5 μM. Further mechanistic studies demonstrated that 3 could suppress the expression of pro-inflammatory cytokines and mediators, such as NO, prostaglandin E2, interleukin (IL)-1β, tumor necrosis factor-α, IL-6, and IL-12 by inhibiting the activation of nuclear factor-kappa B and c-Jun N-terminal kinase.

Graphical abstract, Porcine epidemic diarrhea virus (PEDV) causes severe diarrhea and high fatality of piglets, influencing the swine industry. Japanese horse chestnut (seed of Aesculus turbinata) contains many saponin mixtures, called escins, and has been used for a long time as a traditional medicinal plant. Structure-activity relationship (SAR) studies on escins have revealed that acylations at C-21 and C-22 with angeloyl or tigloyl groups were important for their cytotoxic effects. However, the strong cytotoxicity of escins makes them hard to utilize for other diseases and to develop as nutraceuticals. In this research, we investigated whether escin derivatives 1–7 (including new compounds 2, 3, 5 and 6), without the angeloyl or tigloyl groups and with modified glycosidic linkages by hydrolysis, have PEDV inhibitory effects with less cytotoxicity. Compounds 1–7 had no cytotoxicity at 20 μM on VERO cells, while compounds 8–10 showed strong cytotoxicity at similar concentrations on PEDV. Our results suggest that escin derivatives showed strong inhibitory activities on PEDV replication with lowered cytotoxicity. These studies propose a method to utilize Japanese horse chestnut for treating PEDV and to increase the diversity of its bioactive compounds.

Endophytes, important plant-associated mycobionts, have attracted a great deal of attention because of their bioactive secondary metabolites. Even though halophytes have been reported to overcome salt stress via associations with their endophytes, few studies have investigated the metabolites produced by the endophytes from halophytes. In this study, a dark septate endophytic fungal strain (JS0464), identified as Gaeumannomyces sp. by ITS sequencing, was isolated from the rhizome of a halophyte, Phragmites communis, in Suncheon bay, South Korea. This strain was cultured on a large scale and extracted with ethyl acetate. Chemical investigations of extracts of JS0464 led to the isolation of two glycosylated dialkylresorcinol derivatives (1-2), an anthraquinone derivative (3) and eight known compounds (4-11), which were identified by spectroscopic analyses incorporating one-dimensional/2D NMR and MS. Nine compounds showed significant nitric oxide reduction activity in lipopolysaccharide-stimulated microglia BV-2 cells, seven of which did not impair cell viability. The results suggest that endophytes from the halophytes could be potential resources for bioactive natural products.

Cordyceps bassiana is one of Cordyceps species with anti-oxidative, anti-cancer, anti-inflammatory, anti-diabetic, anti-obesity, anti-angiogenic, and anti-nociceptive activities. This mushroom has recently demonstrated to have an ability to reduce 2,4-dinitrofluorobenzene- induced atopic dermatitis symptoms in NC/Nga mice. In this study, we further examined phytochemical properties of this mushroom by column chromatography and HPLC analysis. By chromatographic separation and spectroscopic analysis, 8 compounds, such as 1,9-dimethylguanine (1), adenosine (2), uridine (3), nicotinamide (4), 3-methyluracil (5), 1,7-dimethylxanthine (6), nudifloric acid (7), and mannitol (8) were identified from 6 different fractions and 4 more subfractions. Through evaluation of their anti-inflammatory activities using reporter gene assay and mRNA analysis, compound 1 was found to block luciferase activity induced by NF-кB and AP-1, suppress the mRNA levels of cyclooxygenase (COX)-2 and tumor necrosis factor (TNF)-a. Therefore, our data strongly suggests that compound 1 acts as one of major principles in Cordyceps bassiana with anti-inflammatory and anti-atopic dermatitis activities.

Six new isochroman derivatives (annulohypoxylomans A–C, 1–3; annulohypoxylomanols A and B, 6 and 7; and annulohypoxyloside, 8), an isocoumarin (annulohypoxylomarin A, 4), and an azaphilone derivative (xylariphilone, 5) were isolated from an ethyl acetate extract derived from cultures of the endophytic fungus JS540 found in the leaves of Zizania caduciflora. The JS540 strain was identified as Annulohypoxylon truncatum. The structures of the isolated compounds were elucidated by one- and two-dimensional nuclear magnetic resonance and mass spectrometry and by comparison with related compounds from the literature. The anti-inflammatory activities of the isolated compounds were evaluated in lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells. Xylariphilone (5) exhibited significant inhibitory effects on LPS-induced interleukin (IL)-6, IL-12 p40, and tumor necrosis factor (TNF)-α production with IC50 values of 5.3, 19.4, and 37.6 μM, respectively.

Chemical investigation of the ethyl acetate extract of an endophytic fungus, Alternaria brassicae JS959 derived from a halophyte, Vitex rotundifolia, led to the isolation of a new chromone, (2'S)-2-(2-acetoxypropyl)-7-hydroxy-5-methylchromone (1), along with sixteen known compounds: a chromone (2), twelve benzopyranones (3-14) and three perylenequinones (15-17). The chemical structures of the isolated compounds were identified by extensive spectroscopic data analysis including 1D, 2D NMR, HRESIMS, and optical rotation. Of these compounds, 1 and 2 showed inhibitory activity on Cu2+‒induced low density lipoprotein (LDL) and high density lipoprotein (HDL) oxidation in human blood plasma. The results suggest that metabolites of endophytic microbes could provide the basis for developing treatments for heart disease.

Two sesquiterpenoids, annulohpoxylotol A and B, were isolated along with five sterols from an ethyl acetate extract of cultures of the endophytic fungus Annulohypoxylon truncatum growing on leaves of Zizania caduciflora. The structures of the isolated compounds were established using one-dimensional (1D) and two-dimensional (2D)-NMR and mass spectrometry. The nuclear factor-kappa B (NF-κB) inhibitory activities of the isolated compounds stimulated with tumor necrosis factor-alpha (TNF-α) were measured using a luciferase reporter system. Annulohpoxylotol A (1) significantly inhibited NF-κB activation in a dose-dependent manner, with an IC50 of 7.11 μM, whereas annulohpoxylotol B (2) and ergone (7) moderately inhibited NF-κB transcriptional activity, with IC50 values of 19.24 and 17.51 μM, respectively.

Colletotrichum sp. is a widely distributed fungal genus, which is mainly known to cause anthracnose on cereals, legumes, fruit trees, and vegetables. Even though many of the Colletotrichum sp. are plant pathogens, a variety of secondary metabolites with diverse bioactivities have been reported to be produced by this fungus. At least 109 secondary metabolites from the fungus Colletotrichum have been reported to date. They mostly include nitrogen-containing metabolites, sterols, terpenes, pyrones, phenolics, and fatty acids. Herein, the authors review the structurally interesting secondary metabolites produced by Colletotrichum and their biological activities.

The fungal strain Alternaria alternata JS0515 was isolated from Vitex rotundifolia (beach vitex). Twelve secondary metabolites, including one new altenusin derivative (1), were isolated. The isolated metabolites included seven known altenusin derivatives (2–8), two isochromanones (9, 10), one perylenequinone (11), and one benzocycloalkanone (12). Their structures were determined via 1D and 2D nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry (MS), and computational electronic circular dichroism (ECD) analysis. Compounds 3 and 11 increased pyruvate dehydrogenase (PDH) activity in AD-293 human embryonic kidney cells and significantly inhibited PDH phosphorylation. The IC50 values of 3 and 11 were 32.58 and 27.82 μM, respectively.

The rapid increase of Methicillin-resistant Staphylococcus aureus (MRSA) infections and the cross-resistance of MRSA to other antibiotics create an urgent demand for new therapeutic agents. Antimicrobial peptides (AMPs) are one of the most promising options for next-generation antibiotics. In this study, novel peptides were designed based on antimicrobial peptide fragments derived from Aristicluthys nobilia interferon-I to promote anti-MRSA activity and decrease adverse effects. Design strategies included substitutions of charged or hydrophobic amino acid residues for noncharged polar residues to promote amphipathicity. Two designed peptides, P5 (YIRKIRRFFKKLKKILKK-NH2) and P9 (SYERKINRHFKTLKKNLKKK-NH2), showed potent antimicrobial activities against both sensitive Staphylococcus aureus clinical isolates and MRSA strains without significant hemolysis or cytotoxicity to human hemocytes and renal epithelial cells. Scanning Electronic Microscopy (SEM) and qRT-PCR were employed to investigate the effects of P5 and P9 on S. aureus biofilm formation, morphology, and virulence-related gene expression. P5 and P9 significantly inhibited the biofilm and destroyed the cell membrane integrity, in addition to down-regulating several virulence factor genes and biofilm formation-related genes including spa, hld, and sdrC. P5 and P9 could be promising candidate antibacterial agents for the treatment of MRSA infections.

Apios americana is an important food crop producing edible tubers with high nutritional and medicinal values and is widely cultivated in many countries. Despite its usefulness, research on its secondary metabolites and biological activities has been limited. In the present study, a new coumaronochromone, (2 R,3 S)-3,7,4'-trihydroxy-5-methoxycoumaronochromone (1), and two new isoflavone glucosides, 7,2',4'-trihydroxy-5-methoxyisoflavone-4'- O-β-d-glucopyranoside (3) and 5,7,4'-trihydroxyisoflavone-7- O-β-d-gentiotrioside (5), were isolated from the tubers of A. americana via chromatographic separation. Seventeen known compounds (2, 4, and 6-20) were also obtained from this plant part. The chemical structures of 1, 3, and 5 were determined by the interpretation of spectroscopic data. The absolute structure of the new compound 1 was established from experimental and calculated electronic circular dichroism spectra. This is the first study to determine the absolute configuration of a 3-hydroxycoumaronochromone derivative. The potential anti-inflammatory activity of the 20 isolates obtained was evaluated by measuring their inhibitory effects on nitric oxide production in lipopolysaccharide-stimulated RAW 264.7 macrophages. Among the isolates, seven compounds (1, 3, 6-8, 15, and 20) showed substantial inhibition of nitric oxide production in RAW 264.7 cells, with the most active being compound 1 (IC

Colletotrichum sp. JS-0367 was isolated from Morus alba (mulberry), identified, and cultured on a large scale for chemical investigation. One new anthraquinone (1) and three known anthraquinones (2-4) were isolated and identified using spectroscopic methods including 1D/2D-NMR and HRESIMS. Although the neuroprotective effects of some anthraquinones have been reported, the biological activities of the four anthraquinones isolated in this study have not been reported. Therefore, the neuroprotective effects of these compounds were determined against murine hippocampal HT22 cell death induced by glutamate. Compound 4, evariquinone, showed strong protective effects against HT22 cell death induced by glutamate by the inhibition of intracellular ROS accumulation and Ca2+ influx triggered by glutamate. Immunoblot analysis revealed that compound 4 reduced the phosphorylation of MAPKs (JNK, ERK1/2, and p38) induced by glutamate. Furthermore, compound 4 strongly attenuated glutamate-mediated apoptotic cell death.

Sparassis crispa (Wulf.) belonging to the family of Sparassidaceae, has been widely used as an edible mushroom due to its unique flavor and functions to improve health. In this study, the compounds isolated from the extract of this mushroom were simultaneously quantified by the developed HPLC-DAD method and evaluated for the inhibitory activities on the production of the LPS-stimulated cytokines (IL-12p40, IL-6, and TNF-α) in bone marrow-derived dendritic cells (BMDCs). The contents of this compounds were 0.1928 ± 0.0118, 4.4137 ± 0.0240, 0.5237 ± 0.0005, 2.7303 ± 0.0206 mg/g for sparoside A (1), methyl 2,4-dihydroxy-3-methoxy-6-methylbenzoate (2), sparalide A (3), and 5′-deoxy-5′-methylthioadenosine (4), respectively, which demonstrated that they are the major constituents of this mushroom. Thus, our results were found that the sparoside A (1), 5-hydroxy-7-methoxyphthalide (6), 5-methoxy-7-hydroxyphthalide (7), nicotinamide (10), and adenosine (11) inhibit LPS-stimualted cytokine production, compound 6 is the most potent inhibitory activities on the production of IL-12p40, IL-6, and TNF-α with IC50 values of 0.19, 0.18, and 0.91 μM, respectively.

Kyoung Mee Kim,1,2 Hyun Kyung Lim,1,2 Sang Hee Shim,1,2 Joohee Jung1,2 1College of Pharmacy, 2Innovative Drug Center, Duksung Women’s University, Seoul, Republic of Korea Abstract: Chrysin is a flavone that is found in several plants and in honeycomb and possesses various biological activities. However, its low solubility means it has poor bioavailability, which must be resolved to enable its pharmaceutical applications. In the present study, chrysin was incorporated into methoxy poly(ethylene glycol)-β-polycaprolactone nanoparticles (chrysin-NPs) using the oil-in-water technique in order to overcome problems associated with chrysin. The properties of chrysin-NPs were analyzed, and their anticancer effects were investigated in vitro and in vivo. Chrysin-NPs were 77nm sized (as determined by dynamic laser light scattering) and showed a monodisperse distribution. The zeta potential of chrysin-NPs was –2.22mV, and they were spherically shaped by cryo-transmission electron microscopy (cryo-TEM). The loading efficiency of chrysin-NPs was 46.96%. Chrysin-NPs retained the cytotoxicity of chrysin in A549 cells. The therapeutic efficacies of chrysin-NPs were compared with those of chrysin in an A549-derived xenograft mouse model. Chrysin-NPs were intravenously injected at a 10 times lower dosage than chrysin 3 times per week (q2d×3/week). However, free chrysin was orally administrated 5 times per week (q1d×5/week). Chrysin-NP-treated group showed significant tumor growth delay, which was similar to that of chrysin-treated group, despite the considerably lower total dosage. These results suggest that the injectable chrysin-NPs enhance therapeutic efficacy in vivo and offer a beneficial formulation for chemotherapy. Keywords: chrysin, nanoparticle, chemotherapeutic efficacy, non-small-cell lung cancer, in vivo model

Background Bacterial biofilms exhibit reduced sensitivity to conventional antibiotics and host defence systems and contribute to the persistence of chronic bacterial infections. Hypothesis The antibiofilm approach using plant alkaloids provides an alternative to antibiotic strategies. Study design In this study, the antibiofilm activities of various plant alkaloids were investigated against enterohemorrhagic Escherichia coli O157:H7 and Pseudomonas aeruginosa. In the subsequent investigation, the effects of five norharmane derivatives were investigated. Result Harmaline significantly inhibited biofilm formation by E. coli O157:H7, P. aeruginosa PAO1, P. aeruginosa PA14, and Klebsiella oxytoca, and norharmane (β-carboline) was found to have antibiofilm activity. It was also found that functional groups at the C-1 and C-7 positions of norharmane could play important roles in its antibiofilm activity. Confocal and electron microscopic observations confirmed biofilm inhibition by harmaline and norharmane, and both reduced fimbriae production and swarming and swimming motilities. Furthermore, harmaline and norharmane attenuated the virulence of E. coli O157:H7 in a Caenorhabditis elegans nematode model. Conclusion These findings strongly suggest that harmaline and norharmane could have potential use in antibiofilm strategy against persistent bacterial infections.

Cisplatin-induced nephrotoxicity is a serious adverse effect that limits the use of cisplatin in cancer patients. In the present study, we investigated the protective effect of lanostane triterpenoids (1–10) isolated from the ethanolic extract of Poria cocos Wolf against cisplatin-induced cell death in LLC-PK1 kidney tubular epithelial cells. Treatment of cisplatin induced significant cell death, which was suppressed by treatment with dehydroeburicoic acid monoacetate (1) and 3β-acetoxylanosta-7,9(11),24-trien-21-oic acid (9). Compound 1 exhibited the highest efficacy among the tested compounds and was thus subjected to further mechanistic studies. The increase in the percentage of apoptotic cells induced by cisplatin reduced by 4.3% after co-treatment of cells with compound 1 (50 and 100 μM). Furthermore, phosphorylation of the mitogen-activated protein kinases JNK, ERK, and p38, and caspase-3, which characterize oxidative stress-mediated apoptosis, increased significantly after treatment with cisplatin, and decreased after treatment with compound 1. These results indicate that the renoprotective effects of compound 1 may be mediated by its anti-apoptotic activity.

A novel ergosterol conjunction-type alkaloid, hericirine ( 1 ), was isolated from the dried fruiting bodies of Hericium erinaceum . The overall framework of 1 was isolated, and combined with hericerin and ergosterol. Its structure was elucidated based on spectroscopic analysis using 1D and 2D NMR, IR and HRESIMS techniques. We found that hericirine significantly inhibited protein expression of iNOS and COX-2 and reduced NO, PGE 2 , TNF-α, IL-6 and IL-1β production in RAW264.7 cells exposed to LPS.

In this study, 23 oleanane-type triterpenoid saponins were isolated from a methanol extract of the roots of Pulsatilla koreana. The NF-κB inhibitory activity of the isolated compounds was measured in TNFα-treated HepG2 cells using a luciferase reporter system. Compounds 19–23 inhibited TNFα-stimulated NF-κB activation in a dose-dependent manner, with IC50 values ranging from 0.75–8.30 μM. Compounds 19 and 20 also inhibited the TNFα-induced expression of iNOS and ICAM-1 mRNA. Moreover, effect of the isolated compounds on PPARs transcriptional activity was assessed. Compounds 7–11 and 19–23 activated PPARs the transcriptional activity significantly in a dose-dependent manner, with EC50 values ranging from 0.9–10.8 μM. These results suggest the presence of potent anti-inflammatory components in P. koreana, and will facilitate the development of novel anti-inflammatory agents.

Endophytes have been recognized as a source for structurally novel and biologically active secondary metabolites. Among the host plants for endophytes, some medicinal plants that produce pharmaceuticals have been reported to carry endophytes, which could also produce bioactive secondary metabolites. In this study, the medicinal plant Aconitum carmichaeli was selected as a potential source for endophytes. An endophytic microorganism, Aureobasidium pullulans AJF1, harbored in the flower of Aconitum carmichaeli, was cultured on a large scale and extracted with an organic solvent. Extensive chemical investigation of the extracts resulted in isolation of three lipid type compounds (1&ndash, 3), which were identified to be (3R,5R)-3,5-dihydroxydecanoic acid (1), (3R,5R)-3-(((3R,5R)-3,5-dihydroxydecanoyl)oxy)-5-hydroxydecanoic acid (2), and (3R,5R)-3-(((3R,5R)-5-(((3R,5R)-3,5-dihydroxydecanoyl)oxy)-3-hydroxydecanoyl)oxy)-5-hydroxydecanoic acid (3) by chemical methods in combination with spectral analysis. Compounds 2 and 3 had new structures. Absolute configurations of the isolated compounds (1&ndash, 3) were established using modified Mosher&rsquo, s method together with analysis of NMR data for their acetonide derivatives. All the isolates (1&ndash, 3) were evaluated for antibiotic activities against Escherichia coli, Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, and their cytotoxicities against MCF-7 cancer cells. Unfortunately, they showed low antibiotic activities and cytotoxic activities.

Cinnamomum cassia (Lauraceae) has long been used as one of the most frequently used traditional oriental medicines for the treatment of gastritis, diabetes, blood circulation disturbance and inflammatory diseases. Cinnamomulactone (1), a new butyrolactone was isolated from the twigs of C. cassia together with nine known compounds, coumarin (2), trans-cinnamic acid (3), cinnamaldehyde (4), 2-hydroxycinnamaldehyde (5), 2-methoxycinnamaldehyde (6), 2-hydroxy-cinnamyl alcohol (7), benzoic acid (8), (+)-syringaresinol (9) and phenethyl (E)-3-[4-methoxyphenyl]-2-propenoate (10). The planar structure of 1 was elucidated on the basis of spectroscopic data analysis and its configurations were determined by coupling constant (3 J HH) analysis and a comparison with specific rotation data of related compounds on the literatures. The structures of known compounds were confirmed by the comparison of their spectroscopic data to the reported values. Compound 10 was isolated for the first time from this plant. Compounds 1, 2, 4, and 9 showed inhibitory activity against matrix metalloproteinases (MMPs) gene expression. Among them, compound 1 has been revealed to suppress the gene expression of MMP-3 and interleukin (IL)-1β as well as MMP-1 in tumor necrosis factor (TNF)-α stimulated rheumatoid arthritis synovial fibroblasts.

Ethnopharmacological relevance Salvia plebeia R. Br. is an edible plant widely spread in many countries. It has been used as a traditional medicine to treat common cold, flu, cough, hepatitis, hemorrhoids, etc. The purpose of the study is to explicate antiviral compounds responsible for its traditional use for the common cold or flu. Materials and methods The methanolic extract of the aerial parts of S. plebeia was extracted with CHCl3, EtOAc, and n-BuOH, successively. The EtOAc and CHCl3 fractions were subjected to a successive of chromatographic method, which led to the isolation of fourteen compounds. Inhibition activities of the isolated compounds were evaluated against influenza A (H1N1) neuraminidase. Results Chemical investigation of the methanolic extracts of S. plebeia resulted in the isolation of two novel benzoylated monoterpene glycosides, named as plebeiosides A (1) and B (2), together with twelve known compounds including four flavonoids (4–5, 7, 10), two sesquiterpenoids (8, 12), four phenolics (9–10, 13–14), a steroid (6), and a triterpenoid (3). Their chemical structures were elucidated based on spectroscopic data and absolute stereochemistries of 1 and 2 were determined by comparison of optical rotations of their hydrolysates with literature values. Compounds 5, 7, 9, and 11 exhibited potent enzymatic inhibition against H1N1 neuraminidase (IC50 values ranging from 11.18±1.73 to 19.83±2.28 μM). Furthermore, two flavonoids (5 and 7) and one rosmarinic acid methyl ester (9) reduced cytopathic effects of the H1N1 virus during replication. Conclusions The antiviral activities of the flavonoids and phenolics isolated from the extracts of S. plebeia supported the traditional application of this medicine on common cold or flu. In this study, benzoylated monoterpene glycosides were first found to exist in this species. Moreover, the present study suggested potential of three compounds (5, 7, and 9) to be new lead structures for the development of new neuraminidase inhibitors in the future.

Three new neo-clerodane diterpenoids, barbatellarines C–E (1–3), were isolated from the CHCl3-soluble fraction of the aerial part of Scutellaria barbata. Their chemical structures were elucidated by detailed analysis of NMR and MS data. Compounds 1 and 2 were C(13) epimers, which was confirmed by an NOE difference experiment and the NOESY spectrum. The relative configuration was determined on the basis of the 1H-NMR J-value and NOE data, while the absolute configuration of the previously isolated analogue, barbatellarine B (4), as a representative member of the group, was assigned by CD analysis.

Barceloneic acid C, a new polyketide from an endophytic fungus Phoma sp. JS752 and its antibacterial activities

Two polyketide metabolites, nhatrangins A (1) and B (2), were isolated from a Vietnamese collection of Lyngbya majuscula. These compounds are related to the aplysiatoxin series of metabolites, which have also been isolated from this species of marine cyanobacterium. The use of 900 MHz cryoprobe NMR allowed the elucidation of the 2D structure of 1 from approximately 0.3 mg of compound. LC-MS analysis was utilized to direct the isolation of additional material as well as the isolation of 2. Conformational analysis was completed using J-based coupling constant analysis and selective NOE experiments.

Crude water extracts of 13 traditional Korean medicinal ingredients used for leiomyomal treatment were prepared and used to treat human uterine normal myometrial and leiomyomal cell cultures. All the ingredients inhibited proliferation and altered the morphology of both myometrial and leiomyomal cells. Among the 13 ingredients, n-hexane-, chloroform-, and ethylacetate-soluble fractions were extracted from seven ingredients that potently inhibited cell proliferation in their water extract form. Among these, the ethylacetate-fraction of Phlomis umbrosa and Spatholobus suberectus, and the chloroform-fraction of Curcuma zedoaria and S. suberectus inhibited leiomyomal cell proliferation significantly compared to myometrial cell proliferation. Similarly, immunohistochemical analysis showed the inhibition of transforming growth factor-beta receptor 2 in leiomyomal tissue after treatment with the fractions of the ingredients. Moreover, the chloroform-fraction of C. zedoaria was subfractionated by open column chromatography. Two of the eight subfractions (fractions 6 and 7) potently inhibited cell proliferation in leiomyoma compared to myometrium. Further study will be performed with the goal of isolating specific compounds from two effective subfractions of C. zedoaria, ethylacetate-fraction of P. umbrosa, and the ethylacetate and chloroform-fractions of S. suberectus. The present study may be helpful in developing an alternative remedy to leiomyoma with minimal side-effects compared to the current treatments.

To identify the active substance in the male silkworm pupae that strengthens men's vitality, the vasorelaxation activity was determined by measuring the vascular endothelial nitric oxide (eNO) produced in calf pulmonary artery endothelial (CPAE) cells treated with extracts from the pupae. Dried silkworm male pupae were extracted with ethanol and suspended in water, then partitioned with hexane, chloroform, ethylacetate, and butanol, sequentially. Among these fractions, the aqueous fraction had maximal NO production (156.87 μM/200 μl well, 10 mg/ml) and minimal cytotoxicity (IC 50 362.3 mg/ml). The vasorelaxation substances (VAS) from the aqueous fraction were isolated by a combination of gel filtration and anion-exchange chromatography on DEAE Sephadex A-25 and reverse phase-HPLC. Their chemical structures were determined on the basis of their spectroscopic parameters of EI-MS, MALDI-TOF MS, 1 H and 13 C NMR, 1 H- 1 H COSY, and GC–MS spectral data. The active substance was subsequently identified as a dimethyladenosine and dimethyladenosine-5′- l -arabinose that has phosphodiesterase (PDE) inhibition activity. This compound was shown to inhibit PDE4 activity in a dose-dependent manner. Also, it inhibited the PDE5 activity of cyclic-GMP-specific PDE5 enzyme. These results imply that dimethyladenosine may be a lead compound for the development and improvement of vasculogenic impotence drugs through phosphodiesterase inhibition and NO production in endothelial cells.

Six new (erinarols A-F, 1-6) and five known (7-11) ergostane-type sterol fatty acid esters were isolated from the methanol extract of the dried fruiting bodies of Hericium erinaceum. Their chemical structures were elucidated using chemical and physical methods as well as through comparison of NMR and mass spectral data with those reported previously. This is the first comprehensive investigation on ergostane-type sterol fatty acid esters from H. erinaceum. The isolated compounds were evaluated for their PPAR transactivational effects using a luciferase reporter system. Compounds 1 and 2 significantly activated the transcriptional activity of PPARs in a dose-dependent manner, with EC50 values of 8.2 and 6.4 μM, respectively. Moreover, compounds 1 and 2 also activated PPARα and PPARγ transcriptional activity, with stimulation from 1.3- to 3.9-fold at 20 μM concentrations.

A new triterpenoid saponin, together with five known saponins, were isolated from the nonpolar n-hexane fraction of the leaves of Aralia elata. The structure of the new saponin, durupcoside C, was elucidated as hederagenin 3-O-beta-D-glucopyranosyl(1--3)-beta-D-glucopyranosyl(1--3)-alpha-L-arabinopyranoside on the basis of spectroscopic analysis. The known saponins were characterized as 3-O-alpha-L-rhamnopyranosyl(1--2)-alpha-L-arabinopyranosyl hederagenin 28-O-beta-D-xylopyranosyl(1--6)-beta-D-glucopyranosyl ester, hederagenin 3-O-beta-D-glucopyranosyl(1--3)-alpha-L-rhamnopyranosyl(1--2)-alpha-L-arabinopyranoside, oleanolic acid 3-O-beta-D-glucopyranosyl(1--3)-alpha-L-rhamnopyranosyl(1--2)-alpha-L-arabinopyranoside, hederagenin 3-O-alpha-L-rhamnopyranosyl(1--2)-alpha-L-arabinopyranoside (alpha-hederin), and hederagenin 3-O-beta-D-glucopyranosyl(1--3)-alpha-L-arabinopyranoside (collinsonidin). In addition, two known lipids, Arisaema glyceride 3 and ceramide mixtures were also isolated and characterized. Collinsonidin and two known lipids were isolated for the first time from this plant.

Four new lanostane-type triterpenes were isolated from the MeOH extract of the fruiting bodies of Ganoderma applanatum. Their structures were established as 3beta,7beta,20,23xi-tetrahydroxy-11,15-dioxolanosta-8-en-26-oic acid (1), 7beta,20,23xi-trihydroxy-3,11,15-trioxolanosta-8-en-26-oic acid (2), 7beta,23xi-dihydroxy-3,11,15-trioxolanosta-8,20E(22)-dien-26-oic acid (3), and 7beta-hydroxy-3,11,15,23-tetraoxolanosta-8,20E(22)-dien-26-oic acid methyl ester (4), respectively, by extensive spectroscopic analyses.

Five new phenolic glycosides, 2-beta-D-glucopyranosyloxy-5-hydroxyphenylacetic acid methyl ester (4), 4-hydroxy-2-[3-hydroxy-3-methylbutyl]-5-methylphenyl beta-D-glucopyranoside (5), 4-hydroxy-2-[(E)-4-hydroxy-3-methyl-2-butenyl]-5-methylphenyl beta-D-glucopyranoside (7), 4-hydroxy-2-[(2E,6Z)-8-beta-D-glucopyranosyloxy-3,7-dimethylocta-2,6-dien-1-yl]-5-methylphenyl beta-D-glucopyranoside (8), and 2,7-dimethyl-1,4-dihydronaphthalene-5,8-diol 5-O-beta-D-xylopyranosyl(1--6)-beta-D-glucopyranoside (10), were isolated from the whole plants of Pyrola japonica (Pyrolaceae), together with androsin, (-)-syringaresinol glucoside, homoarbutin, pirolatin, hyperin, monotropein and chimaphilin.

Five compounds of terpenoids and coumarins were isolated from the non-polar fraction of Artemisia apiacea by open column chromatography. Their structures were elucidated as alpha-amyrin (1), beta-amyrin (2), beta-sitosterol (3), 5,6,7-trimethoxycoumarin (4) and 6-methoxy-7,8-methylenedioxycoumarin (5) by chemical and spectroscopic analysis. This is the first report of the isolation of alpha-amyrin, beta-amyrin, 5,6,7-trimethoxycoumarin and 6-methoxy-7,8-methylenedioxycoumarin from this plant.

Aconitum jaluense Komar. (Ranunculaceae) is one of the Aconitum plants growing in Korean peninsula. An investigation of the alkaloidal constituents of this species led to the isolation of seven C19-norditerpenoid and a C20-diterpenoid alkaloid. Three of them have been identified as neoline, mesaconitine, and hypaconitine, which were isolated from this plant collected from Mt. Bultasan in the north part. The other five alkaloids were determined as lipomesaconitine, lipohypaconitine, 15alpha-hydroxyneoline, hokbusine A, and napelline, which have not been found in this plant. Structures of those alkaloids were determined on the basis of their spectral data. It is of interest to note that a comparison of the present work and the previous report showed some differences in the alkaloidal contents.