Ping Chung Kuo

Isolation of a Natural Antioxidant, Dehydrozingerone from Zingiber officinale and Synthesis of Its Analogues for Recognition of Effective Antioxidant and Antityrosinase Agents

In the present study, the antioxidative and inhibitory activity of Zingiber officinale Rosc. rhizomes-derived materials (on mushroom tyrosinase) were evaluated. The bioactive components of Z. officinale rhizomes were characterized by spectroscopic analysis as zingerone and dehydrozingerone, which exhibited potent antioxidant and tyrosinase inhibition activities. A series of substituted dehydrozingerones [(E)-4-phenyl-3-buten-2-ones] were prepared in admirable yields by the reaction of appropriate benzaldehydes with acetone and the products were evaluated in terms of variation in the dehydrozingerone structure. The synthetic analogues were examined for their antioxidant and antityrosinase activities to probe the most potent analogue. Compound 26 inhibited Fe2+-induced lipid peroxidation in rat brain homogenate with an IC50 = 6.3±0.4 μM. In the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical quencher assay, compounds 2, 7, 17, 26, 28, and 29 showed radical scavenging activity equal to or higher than those of the standard antioxidants, like a-tocopherol and ascorbic acid. Compound 27 displayed superior inhibition of tyrosinase activity relative to other examined analogues. Compounds 2, 17, and 26 exhibited non-competitive inhibition against oxidation of 3,4-dihydroxyphenylalanine (L-DOPA). From the present study, it was observed that both number and position of hydroxyl groups on aromatic ring and a double bond between C-3 and C-4 played a critical role in exerting the antioxidant and antityrosinase activity.

Anti-inflammatory principles from Cordyceps sinensis.

In order to explore the anti-inflammatory principles of the mycelia of Cordyceps sinensis, the crude extract and partially purified fractions were examined for their inhibition of superoxide anion generation and elastase release. Further chemical investigation of the bioactive fractions has resulted in the identification of 50 compounds, including five constituents, cordysinins A-E (1-5), reported from a natural source for the first time. In addition, compounds were examined for their anti-inflammatory activity. 1-(5-Hydroxymethyl-2-furyl)-β-carboline displayed the most significant inhibition of superoxide anion generation and elastase release with IC50 values of 0.45±0.15 and 1.68±0.32 μM, respectively.

Synthesis, in vitro anti-inflammatory and cytotoxic evaluation, and mechanism of action studies of 1-benzoyl-β-carboline and 1-benzoyl-3-carboxy-β-carboline derivatives

In the present study, various 1-substituted and 1,3-disubstituted β-carboline derivatives were synthesized by a modified single-step Pictet-Spengler reaction. The compounds were examined for cytotoxicity and anti-inflammatory activity, as measured by the inhibition of prostaglandin E(2) (PGE(2)) production and nitric oxide (NO) production. While only two compounds (28 and 31) showed marginal cytotoxicity against four human cancer cell lines, most of the tested compounds exhibited potent inhibitory activity of both NO and PGE(2) production. Moreover, compounds 6 and 16 significantly reduced the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2), suggesting that β-carboline analogs can inhibit NO and PGE(2) production at the translational level. In addition, several of the β-carboline derivatives (1, 2, 4-8, 11, 13, 22, 25, 27, 31, and 41-43) displayed significant inhibitory activity of superoxide anion (O(2)(·-)) generation or elastase release compared to the reference compound, with 6 being the most potent. N-Formyl-L-methionyl-phenylalanine (FMLP)-induced phosphorylation of c-JunN-terminal kinase (JNK) and protein kinase B (AKT) were also inhibited by 6, suggesting that it suppresses human neutrophil functions by inhibiting the activation of JNK and AKT signaling pathways. Therefore, the synthetic 1-benzoyl-3-carboxy β-carboline analogs may have great potential to be developed as anti-inflammatory agents.

β-carboline alkaloids from Stellaria dichotoma var. lanceolata and their anti-inflammatory activity.

The present investigation on the chemical constituents of the roots of Stellaria dichotoma var. lanceolata has resulted in the isolation of 21 β-carboline alkaloids, including 13 new compounds, dichotomides III-XIV (1-12) and dichotomine E (13), and eight known compounds. The structures of the new compounds were established on the basis of spectroscopic data analysis. Among these isolated alkaloids, five compounds were examined for their anti-inflammatory potential for the inhibition of NO production in LPS-treated RAW 264.7 cells. All compounds tested exhibited significant inhibition of NO production, with IC(50) values in the range of 11.3 to 19.3 μM.

Anti-inflammatory Diterpenoids from Croton tonkinensis

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

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

Background The aim of this study was to determine the molecular mechanisms of physalin F, an effective purified extract of Physalis angulata L. (Solanacae), in renal carcinoma A498 cells. Methodology/Principal Findings 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 c 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 N-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. Conclusion 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.

Constituents of the Roots of Clausena lansium and Their Potential Anti-inflammatory Activity

Eight new carbazole alkaloids, claulamines C (1), D (2), and E (5) and clausenalines B-F (3, 4, 6-8), four new coumarins, clausemarins A-D (9-12), and 43 known compounds were isolated from the roots of Clausena lansium. The structures of the new compounds were established on the basis of 2D-NMR spectroscopic analysis, and their absolute configurations were established from their ECD spectra. The configuration of wampetin was revised as E using a NOESY experiment. Most of the isolated compounds were evaluated for their potential anti-inflammatory activity. The results showed that compounds 9, 13-18, and 20-22 exhibited strong inhibition of superoxide anion generation with IC50 values ranging from 1.9 to 8.4 μM, while compounds 18, 19, and 21 inhibited elastase release with IC50 values in the range from 2.0 to 6.9 μM.

Flavonoids and ent-labdane diterpenoids from Andrographis paniculata and their antiplatelet aggregatory and vasorelaxing effects

Two new flavones, designated as andropaniculosin A (1) and andropaniculoside A (2), and 30 known compounds were isolated as a result of detailed chemical examination on the whole plants of Andrographis paniculata. Their structures have been elucidated mainly by 1D and 2D NMR, and MS spectroscopic methods. Among them, four flavonoids showed potent inhibition of collagen, arachidonic acid, thrombin, and platelet activation factor induced platelet aggregation. Furthermore, a diterpenoid demonstrated moderate vasorelaxing effect in isolated rat thoracic aorta.

Anti-Platelet Aggregation and Vasorelaxing Effects of the Constituents of the Rhizomes of Zingiber officinale

In the present study, the chemical investigation of the bioactive fractions of the rhizomes of Zingiber officinale has resulted in the identification of twenty-nine compounds including one new compound, O-methyldehydrogingerol (1). Some of the isolates were subjected into the evaluation of their antiplatelet aggregation and vasorelaxing bioactivities. Among the tested compounds, [6]-gingerol (13) and [6]-shogaol (17) exhibited potent anti-platelet aggregation bioactivity. In addition, [10]-gingerol (15) inhibited the Ca2+-dependent contractions in high K+ medium. According to the results in the present research, the bioactivity of ginger could be related to the anti-platelet aggregation and vasorelaxing mechanism.

Chemical constituents from Lobelia chinensis and their anti-virus and anti-inflammatory bioactivities

In total, forty six compounds, including the novel compound lobechine (1), were characterized from the methanol extracts of Lobelia chinensis. The chemical structures of known metabolites were identified by comparing their spectroscopic and physical data with compounds reported in the literature. The structure of lobechine (1) was comprehensively established with the aid of 1D and 2D NMR spectroscopic analyses. In addition, selected isolates were screened for their inhibition of HSV-1 replication, superoxide anion generation, and elastase release. Among the tested compounds, scoparone (10) exhibited significant inhibition of superoxide anion generation with IC50 of 6.14 ± 1.97 μM and lobechine (1) exhibited moderate inhibition of elastase release with IC50 of 25.01 ± 6.95 μM, respectively.