Antioxidant activities and phenolic contents of the methanol extracts of the stems of Acokanthera oppositifolia and Adenia gummifera

Abstract Background Acokanthera oppositifolia Lam (family: Apocynaceae) is a shrub or small tree with white latex, and the leaves of this plant are used in the form of a snuff to treat headaches and in infusions for abdominal pains and convulsions and septicaemia. Adenia gummifera Harv of the family Passifloraceae is a distinctive woody climber whose infusions are used as emetics and are said to help with some forms of depression. Lipid peroxidation has gained more importance today because of its involvement in pathogenesis of many diseases. Free radicals are the main agents in lipid peroxidation. Antioxidants thus play an important role of protecting the human body against damage by the free radicals. Plants containing phenolic compounds have been reported to possess strong antioxidant properties. Methods The antioxidant activities and phenolic contents of the methanol extracts of the stems of Acokanthera oppositifolia and Adenia gummifera were evaluated using in vitro standard procedures. Spectrophotometry was the basis for the determinations of total phenol, total flavonoids, flavonols, and proanthocyanidins. Tannins, quercetin and catechin equivalents were used for these parameters. The antioxidant activities of the stem extract of Acokanthera oppositifolia were determined by the 2,2'-azinobis-3- ethylbenzothiazoline-6-sulfonic acid (ABTS), 1,1-Diphenyl-2-picrylhydrazyl (DPPH), and ferrous reducing antioxidant property (FRAP) methods. Results The results from this study showed that the antioxidant activities of the stem extract of Acokanthera oppositifolia as determined by the 1,1-Diphenyl-2-picrylhydrazyl (DPPH), and ferrous reducing antioxidant property (FRAP) methods, were higher than that of Adenia gummifera. The levels of total phenols and flavonols for A. oppositifolia were also higher. On the other hand, the stem extract of Adenia gummifera had higher level of total flavonoids and proanthocyanidins than that of Acokanthera oppositifolia. The 2, 2'-azinobis-3- ethylbenzothiazoline-6-sulfonic acid (ABTS) activities of the 2 plant extracts were similar and comparable to that of BHT. Conclusion Thus, the present results indicate clearly that the extracts of Acokanthera oppositifolia and Adenia gummifera possess antioxidant properties and could serve as free radical inhibitors or scavengers, acting possibly as primary antioxidants. This study has to some extent validated the medicinal potential of the stems of Acokanthera oppositifolia and Adenia gummifera.</p

Randomized phase II study with two gemcitabine- and docetaxel-based combinations as first-line chemotherapy for metastatic non-small cell lung cancer

<p>Abstract</p> <p>Background</p> <p>Docetaxel and gemcitabine combinations have proven active for the treatment of non-small cell lung cancer (NSCLC). The aim of the present study was to evaluate and compare two treatment schedules, one based on our own preclinical data and the other selected from the literature.</p> <p>Methods</p> <p>Patients with stage IV NSCLC and at least one bidimensionally-measurable lesion were eligible. Adequate bone marrow reserve, normal hepatic and renal function, and an ECOG performance status of 0 to 2 were required. No prior chemotherapy was permitted. Patients were randomized to arm A (docetaxel 70 mg/m²on day 1 and gemcitabine 900 mg/m²on days 3–8, every 3 weeks) or B (gemcitabine 900 mg/m2 on days 1 and 8, and docetaxel 70 mg/m2 on day 8, every 3 weeks).</p> <p>Results</p> <p>The objective response rate was 20% (95% CI:10.0–35.9) and 18% (95% CI:8.6–33.9) in arms A and B, respectively. Disease control rates were very similar (54% in arm A and 53% in arm B). No differences were noted in median survival (32 vs. 33 weeks) or 1-year survival (33% vs. 35%). Toxicity was mild in both treatment arms.</p> <p>Conclusion</p> <p>Our results highlighted acceptable activity and survival outcomes for both experimental and empirical schedules as first-line treatment of NSCLC, suggesting the potential usefulness of drug sequencing based on preclinical models.</p> <p>Trial registration number</p> <p>IOR 162 02</p

Docetaxel and gemcitabine activity in NSCLC cell lines and in primary cultures from human lung cancer

The activity of the following drugs was investigated in two established NSCLC cell lines: docetaxel, gemcitabine, vinorelbine, paclitaxel, doxorubicin (0.01, 0.1, 1 μg ml−1), cisplatin, ifosfamide (1, 2, 3 μg ml−1) and carboplatin (2, 4, 6 μg ml−1). The cytotoxic activity was evaluated by the sulphorhodamine B assay. The two most active drugs, docetaxel and gemcitabine, used singly and in association, were investigated as a function of treatment schedule. The sequence docetaxel→gemcitabine produced only a weak synergistic interaction in RAL but a strong synergism in CAEP cells. The synergistic interaction increased in both cell lines after a 48-h washout between the drug administrations. Flow cytometric analysis showed that in docetaxel→gemcitabine sequence, docetaxel produced a block in G2/M phase and, after 48 h, provided gemcitabine with a large fraction of recovered synchronized cells in the G1/S boundary, which is the specific target phase for gemcitabine. Conversely, simultaneous treatment induced an antagonistic effect in both cell lines, and the sequential scheme gemcitabine→docetaxel produced a weak synergistic effect only in RAL cells. Moreover, the synergistic interaction disappeared when washout periods of 24 or 48 h between two drug administrations were adopted. The synergistic activity of docetaxel→ 48-h washout→gemcitabine was confirmed in 11 of 14 primary cultures, which represents an important means of validating experimental results before translating them into clinical practice. © 1999 Cancer Research Campaig

Famine food of vegetal origin consumed in the Netherlands during World War II

Background: Periods of extreme food shortages during war force people to eat food that they normally do not consider edible. The last time that countries in Western Europe experienced severe scarcities was during World War II. The so-called Dutch famine or Hunger Winter (1944-1945) made at least 25,000 victims. The Dutch government took action by opening soup kitchens and providing information on wild plants and other famine food sources in "wartime cookbooks." The Dutch wartime diet has never been examined from an ethnobotanical perspective. Methods: We interviewed 78 elderly Dutch citizens to verify what they remembered of the consumption of vegetal and fungal famine food during World War II by them and their close surroundings. We asked whether they experienced any adverse effects from consuming famine food plants and how they knew they were edible. We identified plant species mentioned during interviews by their local Dutch names and illustrated field guides and floras. We hypothesized that people living in rural areas consumed more wild species than urban people. A Welch t test was performed to verify whether the number of wild and cultivated species differed between urban and rural citizens. Results: A total number of 38 emergency food species (14 cultivated and 21 wild plants, three wild fungi) were mentioned during interviews. Sugar beets, tulip bulbs, and potato peels were most frequently consumed. Regularly eaten wild species were common nettle, blackberry, and beechnuts. Almost one third of our interviewees explicitly described to have experienced extreme hunger during the war. People from rural areas listed significantly more wild species than urban people. The number of cultivated species consumed by both groups was similar. Negative effects were limited to sore throats and stomachache from the consumption of sugar beets and tulip bulbs. Knowledge on the edibility of famine food was obtained largely by oral transmission; few people remembered the written recipes in wartime cookbooks. Conclusion: This research shows that 71years after the Second World War, knowledge on famine food species, once crucial for people's survival, is still present in the Dutch society. The information on famine food sources supplied by several institutions was not distributed widely. For the necessary revival of famine food knowledge during the 1940s, people needed to consult a small group of elders. Presumed toxicity was a major reason given by our participants to explain why they did not collect wild plants or mushrooms during the war

Fenretinide is active in osteosarcoma in vitro by down-regulation of caveolin-1 expression.

We show for the first time that fenretinide is active against human osteosarcoma in vitro, at concentrations identical to or lower than those detectable in patient\u2019s plasma during chemopreventive clinical trials for breast cancer or head and neck carcinoma. Results show for the first time that caveolin-1 may be a novel molecular target for fenretinide therapeutic activity in this tumor, where its protein expression is downregulated by the drug

AKT come bersaglio molecolare dell'attivit\ue0 di fenretinide nel glioblastoma umano

Il glioblastoma multiforme rappresenta la forma pi\uf9 maligna dei tumori cerebrali. La prognosi \ue8 fatale con un tempo medio di sopravvivenza non superiore ai 12 mesi. Studi recenti hanno identificato nell'attivazione della chinasi Akt/PKB un ruolo importante nella tumorigenesi, crescita ed aumento del grado di malignit\ue0 in questo tumore. La chinasi Akt/PKB inibisce il processo apoptotico attraverso l'inattivazione di BAD e dei fattori di trascrizione forkhead; inoltre, essa \ue8 coinvolta nella progressione del ciclo cellulare tramite regolazione diretta della Ciclina D1. Akt/PKB pu\uf2 quindi rappresentare un nuovo importante bersaglio nella strategia terapeutica del glioblastoma umano. La Fenretinide o N-(4-idrossifenil) retinamide \ue8 un derivato sintetico dell' acido retinoico, possiede bassa epatotossicit\ue0 ed ha una buona tollerabilit\ue0 in vivo. Interessante la sua composizione altamente lipofila che le permette di attraversare la barriera emato-encefalica. Numerosi studi hanno dimostrato la capacit\ue0 di questo farmaco di indurre apoptosi in vitro e di poter esercitare effetti chemiopreventivi e terapeutici. Il meccanismo molecolare d'azione non \ue8 stato ancora del tutto chiarito. Fenretinide ha dimostrato di poter agire con meccanismi dipendenti e indipendenti dai recettori per i retinoidi e di indurre apoptosi tramite attivazione della cascata delle caspasi via ceramide e specie reattive dell'ossigeno. In leucemie, linfoblastomi, neuroblastomi e carcinomi mammari in vitro l'attivit\ue0 antiproliferativa del farmaco \ue8 associata ad una riduzione dell'espressione di Ciclina D1 e Cdk4. Entrambe queste molecole sono coinvolte nella tumorigenesi del glioblastoma e rappresentano bersagli molecolari del sistema Akt/PKB. Dati di letteratura indicano che Fenretinide inibisce la proliferazione in glioblastomi umani in vitro, con induzione di apoptosi mediata dalla caspasi 3. Qui sono riportati i risultati di uno studio teso alla individuazione dell\u2019eventuale ruolo di AKT nel meccanismo molecolare dell\u2019azione esercitata da Fenretinide nel glioblastoma umano. L'analisi \ue8 stata condotta in vitro in due linee cellulari di glioblastoma umano (CRS-A2 e A-172), esprimenti ciascuna alti livelli di Akt/PKB. E' stata valutata l'attivit\ue0 antiproliferativa di Fenretinide, non nota prima in queste linee tumorali, e confermata l'induzione di apoptosi, tramite attivazione della caspasi 3. In parallelo, mediante Western blotting, \ue8 stata condotta una analisi di espressione delle principali proteine coinvolte nel pathway di Akt/PKB. I risultati dimostrano inibizione della crescita indotta da Fenretinide, in entrambe le linee cellulari; il processo apoptotico viene attivato dal farmaco nella linea CRS-A2, con un meccanismo caspasi-3 dipendente. In parallelo all'inibizione della proliferazione cellulare si osservano una down-regolazione del complesso Ciclina D1/Cdk4, della p21CIP1 e di Akt/PKB: in questo caso, con una riduzione sia dei livelli basali di Akt, che della sua forma fosforilata. La chinasi Akt/PKB, di cui \ue8 noto il ruolo nel sostenere il fenotipo tumorale, quando costitutivamente attivata, si dimostra quindi bersaglio molecolare innovativo dell\u2019azione di Fenretinide nel glioblastoma umano, aprendo la strada a nuove prospettive terapeutiche

Mitochondrial DNA D-loop as a new target of Saporin 6 nuclease activity

The single-chain ribosome-inactivating proteins (RIPs) from plant origin, including Saporin 6 from the seeds of Saponaria officinalis, are ribotoxins known to act as N-glycosidases which depurinate the conserved alpha sarcin loop of large rRNAs. As a consequence, the eukaryotic ribosomes become inactivated, thereby arresting the protein synthesis at the elongation step. RIPs are currently under study as antiviral and antiproliferative agents. Additional in vitro activities of RIPs against either RNA or DNA have been recently described. A specific nuclease activity on plasmidic DNA was demonstrated by either purified or bacterial-recombinant molecules. We report here that human mitochondrial DNA (mtDNA) is a new specific target of Saporin 6 nuclease activity. A unique site of cleavage has been identified and mapped within the most variable part of the D-loop region of the covalently closed circular mtDNA molecule