Anti-inflammatory Cerebrosides from Cultivated Cordyceps militaris

Cordyceps militaris (bei-chong-chaw, northern worm grass) is a precious and edible entomopathogenic fungus, which is widely used in traditional Chinese medicine (TCM) as a general booster for the nervous system, metabolism, and immunity. Saccharides, nucleosides, mannitol, and sterols were isolated from this fungus. The biological activity of <i>C. militaris</i> was attributed to the saccharide and nucleoside contents. In this study, the aqueous methanolic fraction of <i>C. militaris</i> fruiting bodies exhibited a significant anti-inflammatory activity. Bioactivity-guided fractionation of the active fraction led to the isolation of eight compounds, including one new and two known cerebrosides (ceramide derivatives), two nucleosides, and three sterols. Cordycerebroside A (<b>1</b>), the new cerebroside, along with soyacerebroside I (<b>2</b>) and glucocerebroside (<b>3</b>) inhibited the accumulation of pro-inflammatory iNOS protein and reduced the expression of COX-2 protein in LPS-stimulated RAW264.7 macrophages. This is the first study on the isolation of cerebrosides with anti-inflammatory activity from this TCM

Zoanthamine-Type Alkaloids from the Zoanthid <i>Zoanthus kuroshio</i> Collected in Taiwan and Their Effects on Inflammation

<i>Zoanthus kuroshio</i> is a colorful zoanthid with a fluorescent pink oral disc and brown tentacles, which dominates certain parts of the Taiwanese and Japanese coasts. This sea anemone is a rich source of biologically active alkaloids. In the current investigation, two novel halogenated zoanthamines [5α-iodozoanthenamine (<b>1</b>) and 11β-chloro-11-deoxykuroshine A (<b>2</b>)], along with four new zoanthamines [18-<i>epi-</i>kuroshine A (<b>3</b>), 7α-hydroxykuroshine E (<b>4</b>), 5α-methoxykuroshine E (<b>5</b>), and 18-<i>epi</i>-kuroshine E (<b>6</b>)], and six known compounds were isolated from <i>Z. kuroshio</i>. Compounds <b>1</b> and <b>2</b> are the first examples of halogenated zoanthamine-type alkaloids isolated from nature. Compounds <b>3</b> and <b>6</b> are the first zoanthamine stereoisomers with a <i>cis</i>-junction of the A/B rings. All isolated compounds were evaluated for their anti-inflammatory activities by measuring their effects on superoxide anion generation and elastase release by human neutrophils in response to fMLP

Isodesacetyluvaricin, an Annonaceous Acetogenin, Specifically Inhibits Gene Expression of Cyclooxygenase-2

Cyclooxygenase-2 (COX-2) is an inducible isoform of the enzyme responsible for the synthesis of several inflammatory mediators. In a search for phytochemicals with anti-inflammatory activity, the COX-2 inhibitory activity of 15 typical Annonaceous acetogenins was examined. Isodesacetyluvaricin (<b>1</b>), from the Formosan tropical fruit tree <i>Annona glabra</i>, exhibited the most potent activity. Reverse transcription PCR was used to test the effect of <b>1</b> on epidermal growth factor-stimulated expression of COX-2 in cultures of A431 human epidermoid carcinoma cells. Three hours after exposure to <b>1</b> (5 μM), A431 cells had barely detectable levels of COX-2 mRNA. A corresponding but smaller decline in the COX-2 protein appeared on using Western blots. Lipopolysaccharide-stimulated expression of COX-2 in Raw 264.7 mouse leukemic monocyte–macrophages showed a similar decrease. Luciferase assays revealed that cells exposed to <b>1</b> had reduced activities of two COX-2 promoter-transcription factors: cAMP response element-binding factor and nuclear factor of activated T-cells. Compound <b>1</b> did not affect cell proliferation, as measured by a colorimetric assay, or intracellular store-operated calcium influx, as determined by fluorescence imaging. Thus, <b>1</b> may serve as a lead compound for targeting inflammatory diseases as well as angiogenesis and cancer metastasis

Cytotoxic Lanostanoids from <i>Poria cocos</i>

Six new and 16 known lanostanoids were isolated from the sclerotia of <i>Poria cocos</i>. The structures of the new isolates were elucidated to be 16α-hydroxy-3-oxo-24-methyllanosta-5,7,9(11),24(31)-tetraen-21-oic acid (<b>1</b>), 3β,16α,29-trihydroxy-24-methyllanosta-7,9(11),24(31)-trien-21-oic acid (<b>2</b>), 3β,16α,30-trihydroxy-24-methyllanosta-7,9(11),24(31)-trien-21-oic acid (<b>3</b>), 3β-acetoxy-16α,24β-dihydroxylanosta-7,9(11),25-trien-21-oic acid (<b>4</b>), 3β,16α-dihydroxy-7-oxo-24-methyllanosta-8,24(31)-dien-21-oic acid (<b>5</b>), and 3α,16α-dihydroxy-7-oxo-24-methyllanosta-8,24(31)-dien-21-oic acid (<b>6</b>), based on extensive spectroscopic analyses. The absolute configuration of <b>4</b> was determined using Mosher’s method. The antiproliferative activity of the isolated compounds (except <b>3</b> and <b>4</b>) was evaluated against four leukemic cell lines (Molt 4, CCRF-CEM, HL 60, and K562). Dehydropachymic acid (<b>9</b>), dehydroeburicoic acid (<b>12</b>), pachymic acid (<b>14</b>), and lanosta-7,9(11),24-trien-21-oic acid (<b>20</b>) exhibited an antiproliferative effect on the CCRF-CEM cancer cell line with IC₅₀ values of 2.7, 6.3, 4.9, and 13.1 μM, respectively. Both dehydropachymic acid (<b>9</b>) and dehydroeburicoic acid (<b>12</b>) showed antiproliferative effects against Molt 4 (IC₅₀ 13.8 and 14.3 μM) and HL 60 (IC₅₀ 7.3 and 6.0 μM) leukemic cell lines. Primary computational analysis using a chemical global positioning system for natural products (ChemGPS-NP) on the active lanostanoids from <i>P. cocos</i> suggested that targets other than topoisomerases may be involved in the antiproliferative activity

Bioactive 6<i>S</i>‑Styryllactone Constituents of <i>Polyalthia parviflora</i>

Parvistones A–E (<b>1</b>–<b>5</b>), five new styryllactones possessing a rare α,β-lactone moiety and a 6<i>S</i> configuration, were isolated from a methanolic extract of <i>Polyalthia parviflora</i> leaves. The structures and the absolute configuration of the isolates were elucidated using NMR spectroscopy, specific rotation, circular dichroism, and X-ray single-crystal analysis. Compounds <b>8</b>, <b>9</b>, <b>11</b>, and <b>12</b> were isolated for the first time. The results were supported by comparing the data measured to those of 6<i>R</i>-styryllactones. Moreover, a plausible biogenetic pathway of the isolated compounds was proposed. The structure–activity relationship of the compounds in an in vitro anti-inflammatory assay revealed the 6<i>S</i>-styryllactones to be more potent than the 6<i>R</i> derivatives. However, the effect was opposite regarding their cytotoxic activity. In addition, 6<i>S</i>-styrylpyrones isolated showed more potent anti-inflammatory and cytotoxic activity when compared to the 1<i>S</i>-phenylpyranopyrones obtained

Bioactive 6<i>S</i>‑Styryllactone Constituents of <i>Polyalthia parviflora</i>

Parvistones A–E (<b>1</b>–<b>5</b>), five new styryllactones possessing a rare α,β-lactone moiety and a 6<i>S</i> configuration, were isolated from a methanolic extract of <i>Polyalthia parviflora</i> leaves. The structures and the absolute configuration of the isolates were elucidated using NMR spectroscopy, specific rotation, circular dichroism, and X-ray single-crystal analysis. Compounds <b>8</b>, <b>9</b>, <b>11</b>, and <b>12</b> were isolated for the first time. The results were supported by comparing the data measured to those of 6<i>R</i>-styryllactones. Moreover, a plausible biogenetic pathway of the isolated compounds was proposed. The structure–activity relationship of the compounds in an in vitro anti-inflammatory assay revealed the 6<i>S</i>-styryllactones to be more potent than the 6<i>R</i> derivatives. However, the effect was opposite regarding their cytotoxic activity. In addition, 6<i>S</i>-styrylpyrones isolated showed more potent anti-inflammatory and cytotoxic activity when compared to the 1<i>S</i>-phenylpyranopyrones obtained