Arachis hypogaea L.; peanut; groundnut; resveratrol; stilbenoids; arachidin; antioxidant; anti-inflammation.

A potent antioxidant, resveratrol (3,4',5-trihydroxystilbene), was extracted using 80% methanol from peanut roots (Arachis hypogaea L.), isolated with a solid-phase extraction column, purified by a semipreparative HPLC, and identified with 1H NMR and MS. The highest and lowest resveratrol contents in the peanut roots of 2000 fall and 2001 spring crops were 1.330 and 0.130 mg/g and 0.063 and 0.015 mg/g, respectively. When the dehydrated peanut root powders of spring and fall crops were combined and cooked with pork-fat patties (1%, w/w) and the separated oils were stored at 60 degrees C for conjugated diene hydroperoxide (CDHP) determination, CDHP contents of the control oils increased after 3 days of storage, whereas the contents in the peanut root-treated oils of spring and fall crops did not increase after 9 and 15 days of storage, respectively. It is of merit to find that peanut roots, usually left in the field as agricultural waste, contain resveratrol and bear potent antioxidative activity.

The molecular mechanisms for the anti-inflammatory activity of phenanthroindolizidine alkaloids were examined in an in vitro system mimicking acute inflammation by studying the suppression of lipopolysaccharide (LPS)/interferon-␥ (IFN␥)-induced nitric oxide production in RAW264.7 cells. Two of the phenanthroindolizidine alkaloids, NSTP0G01 (tylophorine) and NSTP0G07 (ficuseptine-A), exhibited potent suppression of nitric oxide production and did not show significant cytotoxicity to the LPS/IFN␥-stimulated RAW264.7 cells, in contrast to their respective cytotoxic effects on cancer cells. Tylophorine was studied further to investigate the responsible mechanisms. It was found to inhibit the induced protein levels of tumor necrosis factor-␣, inducible nitric-oxide synthase (iNOS), and cyclooxygenase (COX)-II. It also inhibited the activation of murine iNOS and COX-II promoter activity. However, of the two common responsive elements of iNOS and COX-II promoters, nuclear factor-B (NF-B) and adaptor protein (AP)1, only AP1 activation was inhibited by tylophorine in the LPS/IFN␥-stimulated RAW264.7 cells. Further studies showed that the tylophorine enhanced the phosphorylation of Akt and thus decreased the expression and phosphorylation levels of c-Jun protein, thereby causing the subsequent inhibition of AP1 activity. Furthermore, the tylophorine was able to block mitogen-activated protein/extracellular signal-regulated kinase kinase 1 activity and its downstream signaling activation of NF-B and AP1. Thus, NSTP0G01 exerts its anti-inflammatory effects by inhibiting expression of the proinflammatory factors and related signaling pathways.Phenanthroindolizidine alkaloids are a small group of compounds well known for their profound cytotoxic activity (Pettit et al., 1984;Abe et al., 1998;Staerk et al., 2000Staerk et al., , 2002 and thus have been exploited as potential therapeutic leads for anticancer agents (Staerk et al., 2002). These alkaloids were also shown to have anti-inflammatory, antiasthmatic, and antianaphylactic properties with consequences of altered immunological status in vivo (Gopalakrishnan et al., 1979(Gopalakrishnan et al., , 1980Raina and Raina, 1980;Ganguly and Sainis, 2001;Staerk et al., 2002). Although adenyl cyclase was stimulated in asthmatic patients' peripheral leukocytes treated with tylophorine (Raina and Raina, 1980), the molecular mechanisms of actions of these phenanthroindolizidine alkaloids for aforementioned functions are not clear as yet. Moreover, the analysis and knowledge of the structure-activity relationships of the phenanthroindolizidine alkaloids with their biological function are also scarce.Inflammation is a central feature of many pathological conditions and is mediated by a variety of soluble factors and cellular signaling events. For example, NF-B-dependent gene expression plays an important role in inflammatory responses and increases the expression of genes encoding cytokines and receptors involved in proinflammatory enzymes such as iNOS and COX-II (Giuliani et al....

Idiopathic pulmonary fibrosis (IPF) is a lethal, chronic, progressive disease characterized by formation of scar tissue within the lungs. Because it is a disease of unknown etiology, it is difficult to diagnose, to predict disease course and to devise treatment strategies. Recent evidence suggests that activated macrophages play key roles in the pathology of IPF. Therefore, imaging probes that specifically recognize these pools of activated immune cells could provide valuable information about how these cells contribute to the pathobiology of the disease. Here we demonstrate that cysteine cathepsin-targeted imaging probes can be used to monitor the contribution of macrophages to fibrotic disease progression in the bleomycin-induced murine model of pulmonary fibrosis. Furthermore, we show that the probes highlight regions of macrophage involvement in fibrosis in human biopsy tissues from IPF patients. Finally, we present first-in-human results demonstrating non-invasive imaging of active cathepsins in fibrotic lesions of patients with IPF. Together, our findings validate small molecule cysteine cathepsin probes for clinical PET imaging and suggest that they have the potential to be used to generate mechanistically-informative molecular information regarding cellular drivers of IPF disease severity and progression.

This work was designed to study the safety, biodistribution, and radiation dosimetry of a gastrin-releasing peptide receptor (GRPR)– targeting, 68Ga-labeled bombesin (BBN) peptide derivative PET tracer, NOTA-Aca-BBN(7–14) (denoted as 68Ga-BBN) in healthy volunteers and to assess the level of receptor expression in glioma patients. Methods Four healthy volunteers (2 male and 2 female) underwent whole-body PET/CT at multiple time points after a bolus injection of 68Ga-BBN (111 ± 148 MBq). Regions of interest were drawn manually over major organs, and time–activity curves were obtained. Dosimetry was calculated using the OLINDA/EXM software. Twelve patients with glioma diagnosed by contrast-enhanced MRI underwent PET/CT at 30–45 min after 68Ga-BBN injection. Within 1 wk afterward, the tumor was surgically removed and immunohistochemical staining of tumor samples against GRPR was performed and correlated with the PET/CT results. Results 68Ga-BBN was well tolerated in all healthy volunteers, with no adverse symptoms being noticed or reported. 68Ga-BBN cleared rapidly from the circulation and was excreted mainly through the kidneys and urinary tract. The total effective dose equivalent and effective dose were 0.0335 ± 0.0079 and 0.0276 ± 0.0066 mSv/MBq, respectively. In glioma patients, all MRI-identified lesions showed high signal intensity on 68Ga-BBN PET/CT. SUVmax and SUVmean were 2.08 ± 0.58 and 1.32 ± 0.37, respectively. With normal brain tissue as background, tumor-to-background ratios were 24.0 ± 8.85 and 13.4 ± 4.54 based on SUVmax and SUVmean, respectively. The immunohistochemical staining confirmed a positive correlation between SUV and GRPR expression level (r2 = 0.71, P < 0.001). Conclusion 68Ga-BBN is a PET tracer with favorable pharmacokinetics and a favorable dosimetry profile. It has the potential to evaluate GRPR expression in glioma patients and guide GRPR-targeted therapy of glioma.

Purification of CHCl3 and EtOAc solubles of the MeOH extract of Cephalanceropsis gracilis afforded seven new indole alkaloids, cephalinones A (1), B (2), C (3), and D (4) and cephalandoles A (5), B (6), and C (7), besides eight known compounds. The structures of the new compounds were determined by spectroscopic analysis. All 15 indole alkaloids were evaluated for their cytotoxic effects on MCF-7, NCI-H460, and SF-268 cell lines by the MTT method. Only cephalinone-F (6) showed significant cytotoxicity.

The total synthesis of alkaloids phenanthroindolizidine 1a, tylophorine 1b, and phenanthroquinolizidine 1c, has been achieved in 46%, 49%, and 42% overall yield, respectively, starting from the corresponding phenanthrene-9-carboxaldehyde. Compound exhibited potent inhibition activity in three human cancer cell lines, with IC(50) values ranging from 104 to 130 nM. The structure-activity relations of these alkaloids and some of their synthetic intermediates against the three cell lines were also described.

A newly modified sonochemical approach was demonstrated to synthesize stable Au suspensions. The formation of Au nanoparticles with diameters of ∼20 nm was accomplished through the ultrasonic irradiation of aqueous HAuCl 4 solutions containing trisodium citrate at 4 °C. The efficient generation in gold particles only occurred when the sufficient citrate concentrations (1.9, 2.9, and 3.9 mM) were reached. At low citrate concentrations ranging from 0.49 to 1.5 mM, large aggregates of coalesced Au particles were observed as sonication time increased. It is proposed that citrate could transform as the reducing radicals, 1,2,3-tricarboxy-2-propyl radicals, for the AuCl 4reduction and might also act as the stabilizer during particles formation.