Cranberry proanthocyanidins are cytotoxic to human cancer cells and sensitize platinum-resistant ovarian cancer cells to paraplatin.

Polyphenolic extracts of the principal flavonoid classes present in cranberry were screened in vitro for cytotoxicity against solid tumor cells lines, identifying two fractions composed principally of proanthocyanidins (PACs) with potential anticancer activity. Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight Mass Spectrometry (MALDI-TOF-MS) analysis of the proanthocyanidins (PACs) fractions indicated the presence of A-type PACs with 1-4 linkages containing between 2-8 epicatechin units with a maximum of 1 epigallocatechin unit. PACs exhibited in vitro cytotoxicity against platinum-resistant human ovarian, neuroblastoma and prostate cancer cell lines (IC50 = 79-479 microg/mL) but were non-cytotoxic to lung fibroblast cells (IC50 > 1000 microg/ml). SKOV-3 ovarian cancer cells treated with PACs exhibited classic apoptotic changes. PACs acted synergistically with paraplatin in SKOV-3 cells. Pretreatment of SKOV-3 cells with PACs (106 microg/ml) resulted in a significant reduction of the paraplatin IC50 value. Similarly, in a BrdU incorporation assay, co-treatment of SKOV-3 cells with PACs and paraplatin revealed reduced cell proliferation at lower concentrations than with either individually. In SKOV-3 cell cultures co-treated with PAC-1 and paraplatin, an HPLC analysis indicated differential quantitative presence of various PAC oligomers such as DP-8, -9, -11 and -14 indicating either selective binding or uptake. Cranberry proanthocyanidins exhibit cell-line specific cytotoxicity, induce apoptotic markers and augment cytotoxicity of paraplatin in platinum-resistant SKOV-3 ovarian cancer cells.

Effect of herbo-mineral formulation EHb in experimental anaemia in rodents.

EHb-a herbo-mineral formulations of iron (ferrous form) produced a significantly higher and dose dependent increase in the haemoglobin level, as compared to Fefol (a non-complex-chelated iron preparation). Also, EHb did not produce any overt toxicity or gastric irritation at these dose levels. The results suggest that EHb can be of a better choice in the treatment of anaemia than any other commercially available chelated iron preparations.

Experimental methods for evaluation of psychotropic agents in rodents: II-Antidepressants.

Rodent models of clinical depression are extensively used for the evaluation of putative antidepressants. In the present review, the available experimental methods which can be utilized by most laboratories involved in preclinical screening of antidepressants, have been discussed. The methods have been categorized on the basis of induction of the depressive state or on the assumption that monoamine deficiency leads to depression. These methods have been critically validated in terms of efficacy of standard antidepressants in these tests and, in some cases, by the neurochemical basis of depression, namely, the deficient monoaminergic theory of clinical depression.

Anxiolytic activity of ginkgolic acid conjugates from Indian Ginkgo biloba.

Ginkgolic acid conjugates (GAC) (6-alkylsalicylates, namely n-tridecyl-, n-pentadecyl-, n-heptadecyl-, n-pentadecenyl- and n-heptadecenylsalicylates) isolated from the leaves of Indian Ginkgo biloba Linn., (IGb) were tested for their putative role in anxiety in rats. Elevated plus maze, open-field behaviour, novelty-induced feeding latency and social interaction were the rodent behavioural models used in this study. GAC (0.3 and 0.6 mg/kg, each, p.o.) on single acute administration, showed dose-related changes in the behaviour. GAC (0.6 mg/kg) and DZ augmented open arm entries, the open arm/closed arm entries ratio and increased time spent in the open arm on the elevated plus maze. In the open field, GAC (0.6 mg/kg) and DZ significantly increased ambulation and reduced the immobility time. EGb 761 showed a similar profile. GAC (0.6 mg/kg) and DZ significantly attenuated the increased latency to feed in novel environment. By contrast, EGb 761 and Ginkocer further augmented feeding latency. None of the drugs tested showed any significant effect in the social interaction test. GAC showed consistent and significant anxiolytic activity in all the variables investigated. By contrast, EGb 761 and Ginkocer, which are devoid of GAC, did not evoke significant activity. However, increased rearing and decreased immobility time only in open field behaviour shown by EGb 761 may be due to some antianxiety activity of a lesser degree. Our observations suggest that GAC may be the active constituents of Ginkgo biloba responsible for the anxiolytic activity.

Antioxidant activity of glycowithanolides from Withania somnifera.

Antioxidant activity of active principles of Withania somnifera, consisting of equimolar concentrations of sitoindosides VII-X and withaferin A, was investigated for their effects on rat brain frontal cortical and striatal concentrations of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX). Results were compared with effects induced by deprenyl, an agent with well documented antioxidant activity. Active glycowithanolides of W. somnifera (WSG) (10 and 20 mg/kg, i.p.), administered once daily for 21 days, induced a dose-related increase in SOD, CAT and GPX activity in frontal cortex and striatum, which was statistically significant on days 14 and 21, except with the lower dose of WSG on GPX activity, where the effect was evident only on day 21. The data were comparable to those induced by deprenyl (2 mg/kg/day, i.p.) with respect to SOD, CAT and GPX activities, which were evident by day 14. These findings are consistent with the therapeutic use of W. somnifera as an Ayurvedic rasayana and medhyarasayana. Antioxidant effect of active principles of W. somnifera may explain, at least in part, the reported antistress, immunomodulatory, cognition-facilitating, anti-inflammatory and anti-aging effects produced by them in experimental animals, and in clinical situations.

Effect of Trasina, an Ayurvedic herbal formulation, on pancreatic islet superoxide dismutase activity in hyperglycaemic rats.

Diabetes mellitus was induced in male CF strain rats by streptozotocin (STZ) and hyperglycaemia and superoxide dismutase (SOD) activity of pancreatic islet cells was assessed on days 7, 14, 21 and 28. STZ induced significant hyperglycaemia and a concomitant decrease in islet cell SOD activity. Transina (TR), an Ayurvedic herbal formulation comprising of Withania somnifera, Tinospora cordifolia, Eclipta alba, Ocimum sanctum, Picrorrhiza kurroa and shilajit, had little per se effect on blood sugar concentrations and islet SOD activity in euglycaemic rats, in the doses of 100 and 200 mg/kg, p.o. administered once daily for 28 days. However, these doses of TR induced a dose- related decrease in STZ hyperglycaemia and attenuation of STZ induced decrease in islet SOD activity. The results indicate that the earlier reported anti-hyperglycaemic effect of TR may be due to pancreatic islet free radical scavenging activity, the hyperglycaemic activity of STZ being the consequence of decrease in islet SOD activity leading to the accumulation of degenerative oxidative free radicals in islet beta-cells.