Honokiol Dimers and Magnolol Derivatives with New Carbon Skeletons from the Roots of <i>Magnolia officinalis</i> and Their Inhibitory Effects on Superoxide Anion Generation and Elastase Release

<div><p>Two honokiol dimers, houpulins A and B (<b>1</b> and <b>2</b>), and two magnolol derivatives, houpulins C and D (<b>3</b> and <b>4</b>), were isolated and characterized from an ethanol extract obtained from the roots of <i>Magnolia officinalis</i>. The chemical structures were determined based on spectroscopic and physicochemical analyses, which included 1D and 2D NMR, as well as mass spectrometry data. These four oligomers possess new carbon skeletons postulated to be biosynthesized from the coupling of three or four C₆-C₃ subunits. In addition, the new oligomers were evaluated for inhibition of superoxide anion generation and elastase release, and houpulin B (<b>2</b>) was identified as a new anti-inflammatory lead compound.</p></div

[Ca²⁺]_i to return to half of the peak value (<i>t</i>_1/2) by compound 2.

<p>[Ca²⁺]_i to return to half of the peak value (<i>t</i>_1/2) by compound 2.</p

Compound 2 did not alter activation of ERK, p38 MAPK, JNK, and Akt.

<p>Compound 2 did not alter activation of ERK, p38 MAPK, JNK, and Akt.</p

Plausible biosynthetic pathway to 1 and 2.

<p>Plausible biosynthetic pathway to 1 and 2.</p

Inhibitory effects of <b>1</b>–<b>4</b> on superoxide anion generation and elastase release by human neutrophils in response to FMLP/CB.

a<p>Concentration necessary for 50% inhibition. Results are presented as the mean ± S.D. (n = 3).</p>***<p>P<0.001 compared with the control value.</p>b<p>Alone induced superoxide generation by human neutrophils.</p>c<p>Sorafenib, a tyrosine kinase inhibitor, was used as a positive control.</p

Anti-inflammatory Diterpenoids from <i>Croton tonkinensis</i>

Phytochemical investigation of the methanolic extract of <i>Croton tonkinensis</i> afforded two known kauranes (<b>1</b>, <b>2</b>), eight new <i>ent</i>-kauranes (<b>3</b>–<b>10</b>), and 16 known <i>ent</i>-kaurane-type diterpenoids (<b>12</b>–<b>27</b>). In addition, 30 known compounds were identified by comparison of their physical and spectroscopic data with reported data. Among the isolated compounds, <i>ent</i>-18-acetoxykaur-16-en-15-one (<b>20</b>) displayed the most significant inhibition of superoxide anion generation and elastase release

Chemical Constituents and Anti-inflammatory Principles from the Fruits of <i>Forsythia suspensa</i>

Fifty compounds were isolated from the fruits of <i>Forsythia suspensa</i>, including 13 new compounds characterized as eight new diterpenoids (<b>1</b>–<b>8</b>), three new lignans (<b>9</b>–<b>11</b>), a new iridoid (<b>12</b>), and a new triterpenoid (<b>13</b>). Their structures were established on the basis of spectroscopic and spectrometric analysis. Most of the isolated compounds were examined for their anti-inflammatory activity in vitro. The results showed that several compounds displayed significant inhibition of fMLP/CB-induced superoxide anion generation and elastase release, with IC₅₀ values ranging from 0.6 ± 0.1 to 8.6 ± 0.8 μg/mL and from 0.8 ± 0.3 to 7.3 ± 1.1 μg/mL, respectively

Physalin F Induces Cell Apoptosis in Human Renal Carcinoma Cells by Targeting NF-kappaB and Generating Reactive Oxygen Species

<div><h3>Background</h3><p>The aim of this study was to determine the molecular mechanisms of physalin F, an effective purified extract of <em>Physalis angulata</em> L. (Solanacae), in renal carcinoma A498 cells.</p> <h3>Methodology/Principal Findings</h3><p>Physalin F was observed to significantly induce cytotoxicity of three human renal carcinoma A498, ACHN, and UO-31 cells in a concentration-dependent manner; this was especially potent in A498 cells. The physalin F-induced cell apoptosis of A498 cells was characterized by MTT assay, nuclear DNA fragmentation and chromatin condensation. Using flow cytometry analysis, physalin F induced A498 cell apoptosis as demonstrated by the accumulation of the sub-G1 phase in a concentration- and time-dependent manner. Moreover, physalin F-mediated accumulation of reactive oxygen species (ROS) caused Bcl-2 family proteins, Bcl-2, and Bcl-xL degradation, which led to disruption of mitochondrial membrane potential and release of cytochrome <em>c</em> from the mitochondria into the cytosol. These effects were associated with induction of caspase-3 and caspase-9 activity, which led to poly(ADP-ribose) polymerase cleavage. However, the antioxidant <em>N</em>-acetyl-_L-cysteine (NAC) and glutathione (GSH) resulted in the inhibition of these events and reversed physalin F-induced cell apoptosis. In addition, physalin F suppressed NF-κB activity and nuclear translocation of p65 and p50, which was reversed by NAC and GSH.</p> <h3>Conclusion</h3><p>Physalin F induced cell apoptosis through the ROS-mediated mitochondrial pathway and suppressed NF-κB activation in human renal cancer A498 cells. Thus, physalin F appears to be a promising anti-cancer agent worthy of further clinical development.</p> </div

Effect of physalin F on NF-κB.

<p>A498 cells were incubated in the absence or presence of physalin F (10 µg/mL) for indicated time and detection the expression of phospho-IκBα and IκBα (A). (B) The nuclear and cytosol extract were prepared as indicated in Methods and Materials and were analyzed by Western blotting for the detection of specific protein, as indicated (p-p65, p65, p50, GAPDH, and nucleolin). (C) cells were exposed to physalin F (10 µg/mL) for 6 hr and nuclear extracts were incubated with a hot NF-κB probe (lane 2–4) or cold probe (lane 1, indicate “cold”) and demonstrate the specificity of the bands obtained on EMSA. The data are representative of three independent experiments. P indicates positive nuclear extract. ** <i>P</i><0.01 compared with the control group. (D) Effect of ROS scavengers on physalin F-inhibited NF-κB nuclear translocation in A498 cells. Cells were pretreated with NAC (10 mM) and GSH (3 mM) for 0.5 hr and then treated with 10 µg/mL of physalin F for 6 hr. The nuclear extract were prepared as indicated in Methods and Materials. The levels of p65 and p50 were detected by Western blotting.</p

γ- and δ‑Lactams from the Leaves of <i>Clausena lansium</i>

Eight new clausenamides, including three γ-lactams (<b>1</b>–<b>3</b>), four δ-lactams (<b>4</b>–<b>7</b>), and an amide (<b>8</b>), and seven known lactams, including compounds <b>9</b>–<b>11</b>, which were purified from natural sources for the first time, were characterized from the leaves of <i>Clausena lansium</i>. Their structures were elucidated using spectroscopic methods, and the absolute configurations were determined using electronic circular dichroism and single-crystal X-ray diffraction analyses with Cu Kα radiation. Compound <b>2</b> (50 μM) protected 22.24% of cortical neurons against Aβ_25–35-induced cell death