Suppression of 12-O-tetradecanoylphorbol-13-acetate-induced ornithine decarboxylase activity by resveratrol derivatives

As demonstrated previously, resveratrol (3,4',5-trihydroxy-trans-stilbene) inhibits 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ornithine decarboxylase (ODC), the key rate limiting enzyme in mammalian polyamine synthesis. Using human bladder epithelial carcinoma HTB-24 cells in culture where resveratrol inhibits induction with an IC50 of 8.8 µM, we now report potential metabolites demonstrate greater activity [tetrabutylammonium (E)-4-(3,5-dihydroxystyryl)phenyl sulfate (IC50 1.2 µM), resveratrol tripotassium 3,5,4'-trisulfate (IC50 1.8 µM), resveratrol tripotassium 3,4'-disulfate (IC50 1.8 µM), and resveratrol tripotassium 3,5-disulfate (IC50 2.3 µM)]. Based on RT-PCR studies, ODC inhibition occurs at the transcriptional level, but this was not due to direct inhibition of protein kinase C (e.g., resveratrol IC50, 79 µM; resveratrol tripotassium 3,5-disulfate IC50, 49 µM). Additional work is underway to more fully investigate this potentially important observation. [This work was supported by program project P01 CA48112 awarded by the National Cancer Institute. SL acknowledges Indo-US Science and Technology Forum (IUSSTF), New Delhi for a Research Fellowship]

Novel Marine Phenazines as Potential Cancer Chemopreventive and Anti-Inflammatory Agents

Two new (1 and 2) and one known phenazine derivative (lavanducyanin, 3) were isolated and identified from the fermentation broth of a marine-derived Streptomyces sp. (strain CNS284). In mammalian cell culture studies, compounds 1, 2 and 3 inhibited TNF-α-induced NFκB activity (IC50 values of 4.1, 24.2, and 16.3 μM, respectively) and LPS-induced nitric oxide production (IC50 values of >48.6, 15.1, and 8.0 μM, respectively). PGE2 production was blocked with greater efficacy (IC50 values of 7.5, 0.89, and 0.63 μM, respectively), possibly due to inhibition of cyclooxygenases in addition to the expression of COX-2. Treatment of cultured HL-60 cells led to dose-dependent accumulation in the subG1 compartment of the cell cycle, as a result of apoptosis. These data provide greater insight on the biological potential of phenazine derivatives, and some guidance on how various substituents may alter potential anti-inflammatory and anti-cancer effects

Cancer chemoprevention activity of labdane diterpenes from rhizomes of Hedychium coronarium

Hedychium coronarium J. Koenig, Zingiberaceae, is a medicinal plant popularly used to treat inflammatory conditions in different countries. Three labdane diterpenes [isocoronarin D (1), methoxycoronarin D (2), ethoxycoronarin D (3)] and benzoyl eugenol (4) were isolated from rhizomes and their chemopreventive potential was evaluated using in vitro assays, namely the inhibition of NF-κB, COX-1 and -2, the induction of antioxidant response element (ARE), and the inhibition of cell proliferation. Diterpene 1 activated ARE (EC50 57.6 ± 2.4 µM), while 2, 3 and 4 significantly inhibited NF-κB (IC50 of 7.3 ± 0.3, 3.2 ± 0.3 and 32.5 ± 4.9 µM, respectively). In addition, 2 and 3 selectively inhibited COX-1 (IC50 values of 0.9 ± 0.0 and 3.8 ± 0.0 µM, respectively). These data support the potential chemopreventive activity of constituents from H. coronarium rhizomes

Heliotropiumides A and B, new phenolamides with N-carbamoyl putrescine moiety from Heliotropium foertherianum collected in Hawaii and their biological activities

Two new compounds heliotropiumides A (1) and B (2), phenolamides each with an uncommon carbamoyl putrescine moiety, were isolated from the seeds of a naturalized Hawaiian higher plant, Heliotropium foertherianum Diane & Hilger in the borage family, which is widely used for the treatment of ciguatera fish poisoning. The structures of compounds 1 and 2 were characterized based on MS spectroscopic and NMR analysis, and DP4+ calculations. The absolute configuration (AC) of compound 1 was determined by comparison of its optical rotation with those reported in literature. Compound 2 showed inhibition against NF-κB with an IC50 value of 36 μM.Fil: Cai, You-Sheng. University of Hawaii at Hilo; Estados Unidos. Wuhan University; ChinaFil: Sarotti, Ariel Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; ArgentinaFil: Gündisch, Daniela. University of Hawaii at Hilo; Estados UnidosFil: Kondratyuk, Tamara P.. University of Hawaii at Hilo; Estados UnidosFil: Pezzuto, John. Long Island University; Estados Unidos. University of Hawaii Cancer Center; Estados UnidosFil: Turkson, James. University of Hawaii Cancer Center; Estados UnidosFil: Cao, Shugeng. University of Hawaii at Hilo; Estados Unido

Potential anti-inflammatory, antioxidant and antimicrobial activities of Sambucus australis

Context: Sambucus australis Cham. & Schltdl. (Adoxaceae) is used in Brazilian folk medicine to treat inflammatory disorders. Objective: To evaluate the in vitro anti-inflammatory, antioxidant and antimicrobial properties of S. australis. Materials and methods: The anti-inflammatory activity of ethanol extracts of the leaf and bark of S. australis (1–100 μg/mL) were studied in lipopolysaccharide/interferon γ stimulated murine macrophages RAW 264.7 cells (24 h incubation) by investigating the release of nitric oxide (NO) and tumour necrosis factor-alpha (TNF-α) and in the TNF-α-induced nuclear factor kappa (NF-κB) assay. Minimum inhibitory concentration (MIC) was determined by the microdilution test (24 h incubation). Antioxidant activity was determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP) and the NO scavenging assays. Chemical composition was assessed by LC-MS/MS. Results: Antioxidant activities in the DPPH (IC50 43.5 and 66.2 μg/mL), FRAP (IC50 312.6 and 568.3 μg/mL) and NO radical scavenging assays (IC50 285.0 and 972.6 μg/mL) were observed in the leaf and bark ethanol extracts, respectively. Solely the leaf extract showed significant inhibition of NO and TNF-α production in RAW264.7 cells at concentrations of 2 and 100 μg/mL, respectively, and suppression of TNF-α inhibition of NF-κB by 12.8 and 20.4% at concentrations of 50 and 100 μg/mL, respectively. The extract also exhibited antibacterial activity against Salmonella typhimurium (MIC 250 μg/mL) and Klebsiella pneumoniae (MIC 250 μg/mL). LC-MS/MS revealed the presence of chlorogenic acid and rutin as major compounds. Discussion and conclusion: The results indicate that the ethanol leaf extract of S. australis exhibit prominent anti-inflammatory effects

NF-κB inhibitors, unique γ-pyranol-γ-lactams with sulfide and sulfoxide moieties from Hawaiian plant Lycopodiella cernua derived fungus Paraphaeosphaeria neglecta FT462

Abstract LC-UV/MS-based metabolomic analysis of the Hawaiian endophytic fungus Paraphaeosphaeria neglecta FT462 led to the identification of four unique mercaptolactated γ-pyranol–γ-lactams, paraphaeosphaerides E–H (1–4) together with one γ-lactone (5) and the methyl ester of compound 2 (11). The structures of the new compounds (1–5 and 11) were elucidated through the analysis of HRMS and NMR spectroscopic data. The absolute configuration was determined by chemical reactions with sodium borohydride, hydrogen peroxide, α-methoxy-α-(trifluoromethyl)phenylacetyl chlorides (Mosher reagents), and DP4 + NMR calculations. All the compounds were tested against STAT3, A2780 and A2780cisR cancer cell lines, E. coli JW2496, and NF-κB. Compounds 1 and 3 strongly inhibited NF-κB with IC50 values of 7.1 and 1.5 μM, respectively