Folate/Vitamin B12 Supplementation Combats Oxidative Stress-Associated Carcinogenesis in a Rat Model of Colon Cancer.

Folate and vitamin B12 deficiency is associated with depletion of the major intracellular antioxidant glutathione, and oxidative stress is emerging as an etiological mechanism for colon cancer. Azoxymethane (AOM), a potent carcinogen, induces colon cancer in rats by causing pathophysiological changes and oxidative stress. We investigated the synergistic effect of folate and vitamin B12 supplementation against AOM-induced carcinogenesis and oxidative stress in rat colon. Adult male rats were distributed into four groups: 1) Basal diet only; 2) AOM injection (15 mg/kg once per week in weeks 5 and 6); 3) Folate and vitamin B12 supplemented diet; 4) Folate and B12 diet with AOM injection. After 16 weeks, rats were sacrificed, colon tissue dissected, indicators of oxidative stress were measured, and immunohistochemical and ultrastructural changes were evaluated. AOM-injected rats showed oxidative stress, evident by glutathione depletion, oxidation of cellular proteins, and DNA oxidative damage. AOM increased mucosal levels of antiapoptotic and proapoptotic proteins Bcl2 and Bax and caused ultrastructure changes in colonic cell organelles. Folate and vitamin B12 supplementation decreased the level of oxidative stress and ameliorated the cytotoxic effects of AOM. In this in vivo experimental model of colon cancer, folate and vitamin B12 supplementation combats carcinogen-induced oxidative stress.

Amelioration of azoxymethane induced-carcinogenesis by reducing oxidative stress in rat colon by natural extracts.

BACKGROUND: Azoxymethane (AOM) is a potent carcinogenic agent commonly used to induce colon cancer in rats; the cytotoxicity of AOM is considered to mediate oxidative stress. This study investigated the chemopreventive effect of three natural extracts [pomegranate peel extract (PomPE), papaya peel extract (PapPE) and seaweed extract (SE)] against AOM-induced oxidative stress and carcinogenesis in rat colon. METHODS: Eighty Sprague-Dawley rats (aged 4 weeks) were randomly divided into 8 groups (10 rats/group). Control group was fed a basal diet; AOM-treated group was fed a basal diet and received AOM intraperitonial injections for two weeks at a dose of 15 mg/kg bodyweight, whereas the other six groups were received oral supplementation of PomPE, PapPE or SE, in the presence or absence of AOM injection. All animals were continuously fed ad-libitum until aged 16 weeks, then all rats were sacrificed and the colon tissues were examined microscopically for pathological changes and aberrant crypt foci (ACF) development, genotoxicity (induced micronuclei (MN) cells enumeration), and glutathione and lipid peroxidation. RESULTS: Our results showed that AOM-induced ACF development and pathological changes in the colonic mucosal tissues, increased bone marrow MN cells and oxidative stress (glutathione depletion, lipid peroxidation) in rat colonic cells. The concomitant treatment of AOM with PomPE, PapPE or SE significantly ameliorated the cytotoxic effects of AOM. CONCLUSIONS: The results of this study provide in-vivo evidence that PomPE, PapPE and SE reduced the AOM-induced colon cancer in rats, through their potent anti-oxidant activities.

Sedative activity of methanolic extract of Glochidion multiloculare (Rottler ex Willd) Voigt leaves.

Bangladesh is a good repository of medicinal plants. Traditional healers utilize them for treating many pathological states. Unfortunately, very few of them have been scientifically evaluated to know about the deep inside. The current study here is designed to evaluate the in vivo sedative activity of the leaves of Glochidion multiloculare (Rottler ex Willd) Voigt. With this purpose, the plant leaves were collected and powdered for extraction with methanol. Initially, the plant extract was subjected to brine shrimp lethality bioassay to monitor the presence of bioactive molecules. Later on, different neuropharmacological studies including hole cross, open field, thiopental-sodium induced sleeping time and Elevated-Plus Maze (EPM) tests were conducted to investigate sedative action. In the brine shrimp lethality bioassay, the LC50 value of the extract was found 37.19 µg mL(-1), whereas the standard vincristine sulphate showed the LC50 10.50 µg mL(-1). The moderate toxicity of the extract on brine shrimp indicated the existence of bioactive secondary metabolites in this extract. Besides, the extract decreased the locomotor activity of mice in hole cross, open field and EPM test indicating the CNS depression capability of the plant. Moreover, the extract was very much effective for prolonging the sleeping time (103 min) with quick onset of action (22 min) in comparison to the control group. The efficacy of the plant extract was found closer to the common sedative drug diazepam. Further investigations are required to explore the underlying mechanism of the sedative action and isolate bioactive principles.

Pomegranate (Punica granatum) peel extract efficacy as a dietary antioxidant against azoxymethane-induced colon cancer in rat.

Functional foods include antioxidant nutrients which may protect against many human chronic diseases by combating reactive oxygen species (ROS) generation. The purpose of the present study was to investigate the protective effect of pomegranate peel extract (PPE) on azoxymethane (AOM)-induced colon tumors in rats as an in vivo experimental model. Forty Sprague-Dawley rats (4 weeks old) were randomly divided into 4 groups containing 10 rats per group, and were treated with either AOM, PPE, or PPE plus AOM or injected with 0.9% physiological saline solution as a control. At 8 weeks of age, the rats in the AOM and PPE plus AOM groups were injected with 15 mg AOM/kg body weight, once a week for two weeks. After the last AOM injection, the rats were continuously fed ad-libitum their specific diets for another 6 weeks. At the end of the experiment (i.e. at the age of 4 months), all rats were killed and the colon tissues were examined microscopically for lesions suspected of being preneoplastic lesions or tumors as well as for biochemical measurement of oxidative stress indices. The results revealed a lower incidence of aberrant crypt foci in the PPE plus AOM administered group as compared to the AOM group. In addition, PPE blocked the AOM-induced impairment of biochemical indicators of oxidative stress in the examined colonic tissue homogenates. The results suggest that PPE can partially inhibit the development of colonic premalignant lesions in an AOM-induced colorectal carcinogenesis model, by abrogating oxidative stress and improving the redox status of colonic cells.

An unusual bisnor-clerodane diterpenoid from Polyalthia simiarum.

The stem bark of Polyalthia simiarum has yielded a new bisnor-type clerodane diterpenoid, 2-oxo-14,15-bisnor-3,11E-kolavadien-13-one (1), and three previously known clerodane derivatives, kolavenic acid (2), 16beta-hydroxycleroda-3,13(14)Z-dien-15,16-olide (3), and 16-oxocleroda-3,13(14)E-dien-15-oic acid (4). The structures of these compounds were unambiguously determined by extensive NMR studies as well as by comparison with related compounds. Till now this is the second report of the occurrence of any unusual C-18 clerodane diterpenoid from nature. The crude light petroleum extract and the purified compound 3 demonstrated moderate free radical scavenging activity with IC50 values of 21.5 and 23.5 microg/mL, respectively.

Chemical and biological investigations of Delonix regia (Bojer ex Hook.) Raf.

In this study, five compounds, lupeol (1), epilupeol (2), ß-sitosterol (3), stigmasterol (4) and p-methoxybenzaldehyde (5) were isolated from the petroleum ether and dichloromethane fractions of a methanolic extract of the stem bark of Delonix regia. Antimicrobial screening of the different extracts (15 µg mm-2) was conducted by the disc diffusion method. The zones of inhibition demonstrated by the petroleum ether, carbon tetrachloride and dichloromethane fractions ranged from 9-14 mm, 11-13 mm and 9-20 mm, respectively, compared to kanamycin standard with the zone of inhibition of 20-25 mm. In brine shrimp lethality bioassay, the carbon tetrachloride soluble materials demonstrated the highest toxicity with LC50 of 0.83 µg mL-1, while petroleum ether and dichloromethane soluble partitionates of the methanolic extract revealed LC50 of 14.94 and 3.29 µg mL-1, respectively, in comparison with standard vincristine sulphate with LC50 of 0.812 µg mL-1. This is the first report on compounds separation from D. regia, their antimicrobial activity and cytotoxicity.

A new 7-oxygenated coumarin from Clausena suffruticosa.

A new coumarin, 7-[(2'E,6'E)-7'-carboxy-5'(zeta)-hydroxy-3'-methylocta-2',6'-dienyloxy]-coumarin, was isolated from the leaf of Clausena suffruticosa. Its structure was established by means of spectroscopic data analyses, including mass spectrometry and both 1D and 2D NMR spectroscopy.