Effect of myricetin on cognitive impairments in the transgenic Drosophila model of Parkinson’s Disease

Parkinson’s Disease (PD) is a progressive neurodegenerative disorder involving the loss of dopaminergic neurons. Despite the availability of many drugs to ease the life of PD patients, there is no permanent cure until now. Now-a-days, there has been a considerable attention towards the use of herbal products to treat PD patients worldwide due to less side effects. In this context, here we investigated myricetin, a common plant derived flavonoid, on the cognitive impairments exhibited by the transgenic Drosophila expressing human ?-synuclein in the neurons. The PD flies were allowed to feed on the diet having 10, 20 and 40 ?M of myricetin for 24 days and then assayed for cognitive impairments. The exposure of myricetin showed a dose dependent significant delay in the cognitive impairments. Molecular docking studies showed the positive interaction between myricetin and ?-synuclein. The results suggest a protective effect of myricetin against the cognitive impairments.

16α-Hydroxycholic Acid: In Vivo Microbial Transformation Product of Cholic Acid.

Aims: This study describes the transformation of cholic acid to hydroxylated cholic acid metabolites that could not be easily synthesized. Study Design: The transformation was catalyzed by thermophilic Geobacillus stearothermophilus comb. nov., isolated from oil contaminated soil in Kuwait. Cholic acid, as the sole source of carbon, was added to G. stearothermophilus cells in phosphate buffer pH 7 and shaken at 65ºC for 5 days. Methodology: The cholic acid transformation products were extracted with ethyl acetate, purified on preparative TLC plates and their molecular structures were established from their spectral data. Results: The bacterium could selectively oxidize hydroxyl-groups at C3 and C7 while leaving the C12-hydroxyl-group unoxidized, in cholic acid. Five commonly found metabolites of cholic acid and a novel transformation product, 16α-hydroxycholic acid, were identified. Conclusion: Our results indicate that G. stearothermophilus can hydroxylate/oxidize a steroid nucleus at various ring positions, and has a unique ability for hydroxylation at C16α in cholic acid.

Antidiuretic and antidiarrhoeal activities of polar and non-polar extract of Brassica oleracea.

Diuretic activities of both polar and non-polar extract of leaves of Brassica oleracea were investigated on male white rabbits and male Sprague-Dawley rats. Anti diarrheal activity of the same extract was investigated on male and female swiss albino mice. Both polar and non-polar extract exhibited anti diuretic activities on both rats and rabbits. Polar and Non-polar extract also showed anti diarrheal activity on male and female mice. Anti diarrheal activity affects both latent period and number of stools.

Chromosomal aberration and micronucleus studies of two topoisomerase (II) targeting anthracyclines.

Anthracycline antibiotics are widely used in cancer chemotherapy. Doxorubicin and Idarubicin, topoisomerase-targeting anthracyclines, were examined for their effect on chromosomal aberration and micronucleus induction in cultured human lymphocytes employing lymphocyte transformation test and cytokinesis-blocked micronucleus (CBMN) assay. A statistically significant dose-dependent increase in micronucleus frequency (p < 0.001) in binucleated cells was seen as well as a significant increase in chromosomal aberration frequency was also observed for both the drugs. A variety of aberrations were scored including terminal deletions, breaks, gaps, exchanges, fragment formation, ends rejoining, interstitial deletions etc. Nuclear division index was also calculated and showed a cell cycle delay towards higher doses. A number of necrotic and apoptotic cells were also observed at higher concentrations. This confirms the two drugs to be clastogenic and aneugenic.

Possible modulating action of plant infusion of Ocimum sanctum L. on chromosomal aberrations and sister chromatid exchanges induced by chlormadinone acetate in human lymphocytes in vitro.

Chlormadinone acetate (CMA) is a synthetic progesterone analogue. It has its usage in oral contraceptives formulations and also for estrous synchronization of animals. The aim of the present study is to study the anti- genotoxic activity of the plant infusion against the CMA induced genotoxic damage on cultured human lymphocytes, using chromosomal aberrations and sister chromatid exchanges (SCFs) as parameters. For chromosomal aberration analysis, the treatment of 40 microM of CMA was associated with 4.33% abnormal metaphases. The treatment of 40 microM of CMA, separately with 1.075 x 10(-4), 2.125 x 10(-4) and 3.15 x 10(-4) gm l(-1) of plant infusion results in the reduction of the number of abnormal metaphases i.e. 2.67%, 2.00% and 1.67% respectively. For sister chromatid exchange analysis, the frequency of sister chromatid exchange per cell (SCE(S)/Cell) for the treatment of 40 microM of CMA was 6.43. The treatment of 40 microM of CMA, separately with 1.075 x 10(-4), 2.125 x 10(-4) and 3.15 x 10(-4) gm l(-1) of plant infusion results in the significant reduction of the frequency of SCE(S)/Cell i.e. 3.76, 3.01 and 2.94, respectively, as compared to the CMA (40 microM) treatment alone (6.43). The used dosages of plant infusion did not increase chromosomal aberrations and sister chromatid exchanges at significant level as compared to the untreated. The results of the present study suggest that the plant infusion per se does not have genotoxic potential, but can modulate the genotoxicity of chlormadinone acetate in human lymphocytes in vitro.

Protective role of nordihydroguaiaretic acid (NDGA) against the genotoxic damage induced by ethynodiol diacetate in human lymphocytes in vitro.

Antioxidants and plant products are reported to reduce the genotoxic damage of steroids. In our present study we have tested different dosages of nordihydroguaiaretic acid (NDGA) against the genotoxic damage induced by ethynodiol diacetate in the presence of S9 mix. Treatments with nordihydroguaiaretic acid (NDGA) results in the reduction of the genotoxic damage. A significant decrease was observed at all the tested doses of NDGA in sister chromatic exchanges of number of abnormal cells. The results suggest a protective role of NDGA against the genotoxic damage.

Protective role of allicin and L-ascorbic acid against the genotoxic damage induced by chlormadinone acetate in cultured human lymphocytes.

In our present study, different doses of allicin and L-ascorbic acid were tested against the genotoxic damage induced by chlormadinone acetate (CMA; 40 microM) using chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs) as the parameters. Treatment with allicin and L-ascorbic acid resulted in reduction of CAs and SCEs. The results suggested a protective role of allicin and L-ascorbic acid against CMA induced genotoxic damage.

Antigenotoxic effect of allicin against methyl methanesulphonate induced genotoxic damage.

Allicin, one of the sulfur compounds especially thiosulphonates of garlic (Allium sativum), possesses antioxidant and thioldisulphide exchange activity and is also shown to cause a variety of actions potentially useful for human health. In this investigation we determined its antigenotoxic potential using chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs) induced by methyl methanesulphonate (MMS) as genotoxic end points both in the presence as well as absence of rat liver microsomal activation system (S9 mix) in cultured human lymphocytes. We tested the effect of 5, 10 and 20 microM of allicin on the damage exerted by 60 microM of MMS. The levels of CAs and SCEs were lowered suggesting an antigenotoxic role of allicin against genotoxic damage both in the presence as well as absence of metabolic activation.

Evaluation of genotoxic potential of norethynodrel in human lymphocytes in vitro.

The genotoxicity study of a synthetic progestin norethynodrel, was carried out on human lymphocytes chromosomes using sister chromatid exchanges (SCEs), replication index (RI) and chromosomal aberrations (CAs) as parameters. The study was carried out in the presence and absence of metabolic activation (S9 mix). Norethynodrel was studied at three different concentrations (20, 40 and 60 microg/ml of peripheral blood lymphocyte culture) and was found non-genotoxic in the absence of metabolic activation. But in the presence of S9 mix norethynodrel increased SCE (p<0.03) and CA (p<0.005) frequencies and inhibits lymphocyte proliferation (p<0.03) at 60 microg/ml. The results suggest a genotoxic and cytotoxic effect of norethynodrel in human lymphocytes in vitro in the presence of S9 mix.

In vivo induction of sister chromatid exchanges (SCEs) and chromosomal aberrations (CAs) by lynestrenol.

Genotoxicity study of synthetic progestin lynestrenol, was carried out on mouse bone marrow cells using sister chromatid exchanges (SCEs) and chromosomal aberrations (CAs) as parameters. Lynestrenol was studied at three different doses (6.87, 13.75 and 27.50 mg/kg body wt.). SCE and CA increased significantly as compared to normal control when treated with lynestrenol at 13.75 and 27.50 mg/kg body wt. The present results suggest that lynestrenol has both a genotoxic and cytotoxic effects in mouse bone marrow cells.

Induction of chromosomal aberrations and sister chromatid exchanges by chlormadinone acetate in human lymphocytes: a possible role of reactive oxygen species.

Genotoxicity study of a synthetic progestin chlormadinone acetate (CMA) was carried out in human lymphocytes using chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs) as parameter. Effect of CMA was studied at 10, 20, 30 and 40 microM. CMA was genotoxic at 30 and 40 microM. With a view to study the possible mechanism of genotoxicity of CMA, superoxide dismutase (SOD) and catalase (CAT) were used separately and in combination along with the CMA (40 microM) at different doses. SOD treatment increased CAs and SCEs at both the doses. CAT treatment decreased the frequencies of CAs and SCEs in both, separately and in combination with SOD, suggesting a possible role of reactive oxygen species for the genotoxic damage.

Antigenotoxic effect of allicin against SCEs induced by methyl methanesulphonate in cultured mammalian cells.

Allicin, one of the sulphur compounds of garlic (Allium sativum), possesses antioxidant and thiol disulphide exchange activity and is also shown to cause a variety of activities potentially useful for human health. In this investigation, the effect of 1,5,10 and 20 microM of allicin was determined for inhibiting the rate of SCE induced by 60 microM of MMS. Cultured human lymphocytes from two female donors were used for the experiment. The levels of SCEs were lowered by allicin suggesting its antigenotoxic activity in mammalian cells in vitro.