Sang Hee Shim

Sterols from Hericium erinaceum and their inhibition of TNF-α and NO production in lipopolysaccharide-induced RAW 264.7 cells.

Erinarols G-J and 10 known ergostane-type sterols were isolated from a methanol extract of the dried fruiting bodies of Hericium erinaceum. Their chemical structures were elucidated using extensive spectroscopic analyses including 1D and 2D NMR experiments and HR-ESI-MS analysis, as well as through comparison with previously reported data. Anti-inflammatory effects of the isolated compounds were evaluated in terms of inhibition of tumor necrosis factor α (TNF-α) and nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated murine RAW264.7 macrophage cells. The results showed that erinarols H and J, as well as 2 of the ergostane-type sterols exhibited inhibitory activity against TNF-α secretion, with inhibition values ranging from 33.7% to 43.3% at 10 μM. Erinarols J and three ergostane-type sterols exhibited significant inhibitory effects against NO production, with inhibition values ranging from 38.4% to 71.5% at 10 μM.

Sterol fatty acid esters from the mushroom Hericium erinaceum and their PPAR transactivational effects.

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.

Protective effect of lanostane triterpenoids from the sclerotia of Poria cocos Wolf against cisplatin-induced apoptosis in LLC-PK1 cells

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 100μM). 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.

Antiviral activities of compounds from aerial parts of Salvia plebeia R. Br

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±2.28μM). 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.

Erinacene D, a new aromatic compound from Hericium erinaceum

The Journal of Antibiotics (2014) 67, 727–729; doi:10.1038/ja.2014.57; published online 7 May 2014Fruiting bodies of Hericium erinaceum (Hericiaceae) are known as atraditional edible mushroom. The main constituents of H. erinaceum,which include polysaccharides, aromatic compounds and fatty acids,have been investigated previously, and their bioactive effects are wellknown.

New Aromatic Compounds from the Fruiting Body of Sparassis crispa (Wulf.) and Their Inhibitory Activities on Proprotein Convertase Subtilisin/Kexin Type 9 mRNA Expression

Successive chromatography of EtOAc-soluble extracts of the fruiting body of Sparassis crispa (Wulf.) resulted in isolation of four new aromatic compounds, sparoside A (1) and sparalides A-C (3-5), two new naturally occurring compounds, 2 and 6, and eight known compounds, 7-14. The chemical structures were determined by interpretation of nuclear magnetic resonance and mass spectrometry spectroscopic data. Extract, solvent-soluble fractions of the extract, and all of the pure compounds isolated from the fractions were subjected to the mRNA expression assay for proprotein convertase subtilisin/kexin type 9 (PCSK9). Among them, sparoside A (1), hanabiratakelide A (8), adenosine (11), and 5α,6α-epoxy-(22E,24R)-ergosta-8(14),22-diene-3β,7β-diol (14) exhibited potent inhibitory activities on PCSK9 mRNA expression, with IC50 values of 20.07, 7.18, 18.46, and 8.23 μM, respectively (berberine, positive control, IC50 = 8.04 μM), suggesting that compounds 1, 8, 11, and 14 are suitable for use in supplements to the statins for hyperlipidemia treatments.

Chemical Constituents Identified from Fruit Body of Cordyceps bassiana and Their Anti-Inflammatory Activity.

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-κB and AP-1, suppress the mRNA levels of cyclooxygenase (COX)-2 and tumor necrosis factor (TNF)-α. 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.

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

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

Three new secoiridoid glycosides from the rhizomes and roots of Gentiana scabra and their anti-inflammatory activities

Three new (1–3) and 17 known (4–20) iridoid and secoiridoid glycosides were isolated from a methanol extract of the rhizomes and roots of Gentiana scabra. Their chemical structures were elucidated from 1D and 2D NMR, IR absorption, and HR-ESI-MS spectra, as well as comparisons of these data with reported values. The effects of the isolated compounds on lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells were investigated. Compounds 6, 10 and 20 exhibited significant inhibitory effects on LPS-induced IL-12 p40 and IL-6 production with IC50 values of 1.62–14.29 μM. Compound 10 also showed a strong inhibitory effect on the LPS-stimulated production of TNF-α with an IC50 value of 10.45 μM.

Secondary Metabolites Produced by an Endophytic Fungus Pestalotiopsis sydowiana and Their 20S Proteasome Inhibitory Activities

Fungal endophytes have attracted attention due to their functional diversity. Secondary metabolites produced by Pestalotiopsis sydowiana from a halophyte, Phragmites communis Trinus, were investigated. Eleven compounds, including four penicillide derivatives (1–4) and seven α-pyrone analogues (5–10) were isolated from cultures of P. sydowiana. The compounds were identified based on spectroscopic data. The inhibitory activities against the 20S proteasome were evaluated. Compounds 1–3, 5, and 9–10 showed modest proteasome inhibition activities, while compound 8 showed strong activity with an IC50 of 1.2 ± 0.3 μM. This is the first study on the secondary metabolites produced by P. sydowiana and their proteasome inhibitory activities. The endophytic fungus P. sydowiana might be a good resource for proteasome inhibitors.