Synthesis and characterisation of arsenic nanoparticles and its interaction with DNA and cytotoxic potential on breast cancer cells.

Therapeutic applications of arsenic trioxide (ATO) are limited due to their severe adverse effects. However, nanoparticles of ATO might possess inimitable biologic effects based on their structure and size which differ from their parent molecules. Based on this conception, AsNPs were synthesized from ATO and comparatively analysed for their interaction mechanism with DNA using spectroscopic & electrochemical techniques. Finally, anti-proliferative activity was assessed against different breast cancer cells (MDA-MB-231 & MCF-7) and normal non-cancerous cells (HEK-293). The DNA interaction study revealed that AsNPs and ATO exhibit binding constant values in the order of 106 which indicates strong binding interaction. Binding of AsNPs did not disturb the structural integrity of DNA, on the other hand an opposing effect was observed with ATO through biophysical techniques. Further, in vitro study, confirms cytotoxicity of ATO and AsNPs against different cells, however at particular concentration ATO exhibits more cytotoxicity than that of AsNPs. Furthermore, cytotoxicity was confirmed through acridine orange and comet assay. In conclusion, AsNPs are safer than ATO with comparable efficacy and might be a suitable candidate for the development of novel therapeutic agent against breast cancer and other solid tumours.

In vitro biocompatibility and proliferative effects of polar and non-polar extracts of cucurbita ficifolia on human mesenchymal stem cells.

Cucurbita ficifolia (C. ficifolia) has been traditionally known for its medicinal properties as an antioxidant, anti-diabetic and anti-inflammatory agent. However, there has been an enduring attention towards the identification of unique method, to isolate the natural components for therapeutic applications. Our study focuses on different polar and non-polar solvents (methanol, hexane and chloroform) to extract the bioactive components from C. ficifolia (pumpkin) and to study the biocompatibility and cytotoxicity effects on human bone marrow-mesenchymal stem cells (hBM-MSCs). The extracts were screened for their effects on cytotoxicity, cell proliferation and cell cycle on the hBM-MSCs cell line. The assays demonstrated that the chloroform extract was highly biocompatible, with less cytotoxic effect, and enhanced the cell proliferation. The methanol extract did not exhibit significant cytotoxicity when compare to the control. Concordantly, the cell cycle analysis confirmed that chloroform extract enhances the proliferation at lower concentrations. On the other hand, hexane extract showed high level of cytotoxicity with apoptotic and necrotic changes in hBM-MSCs. Collectively, our data revealed that chloroform is a good candidate to extract the bioactive components from C. ficifolia. Furthermore, our results suggest that specific gravity and density of the solvent might play a crucial role in the extraction process, which warrants further investigations.

Protective Effect of Carvacrol on Oxidative Stress and Cellular DNA Damage Induced by UVB Irradiation in Human Peripheral Lymphocytes.

Exposure to ultraviolet B (UVB; 280-320 nm) radiation induces the formation of reactive oxygen species (ROS) in the biological system. In this study, we examined the protective effect of carvacrol on UVB-induced lipid peroxidation and oxidative DNA damage with reference to alterations in cellular an-tioxidant status in human lymphocytes. A series of in vitro assays (hydroxyl radical, superoxide, nitric oxide, DPPH (2,2-Diphenyl-1-picryl hydrazyl), and ABTS (2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging assays) demonstrate antioxidant property of carvacrol in our study. UVB exposure significantly increased thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (LHPs), % tail DNA and tail moment; decreased % cell viability and antioxidant status in UVB-irradiated lymphocytes. Treatment with carvacrol 30 min prior to UVB-exposure resulted in a significant decline of TBARS, LHP, % tail DNA, and tail moment and increased % cell viability as carvacrol concentration increased. UVB irradiated lymphocytes with carvacrol alone (at 10 µg/mL) gave no significant change in cell viability, TBARS, LHP, % tail DNA, and tail moment when compared with normal lymphocytes. On the basis of our results, we conclude that carvacrol, a dietary antioxidant, mediates its protective effect through modulation of UVB-induced ROS.

Carvacrol ameliorates the PPAR-A and cytochrome P450 expression on D-galactosamine induced hepatotoxicity rats.

BACKGROUND: Carvacrol (2-methyl-5-(1-methylethyl)-phenol) is a predominant monoterpenic phenol which occurs in many essential oils of the family Labiatae including Origanum, Satureja, Thymbra, Thymus, and Corydothymus species. It is well known for its anti-inflammatory, antioxidant and antitumor activities. The present study investigates the influence of carvacrol on CYP2E1 and PPAR-α on D-Galactosamine (D-GalN)-induced hepatotoxic rats. MATERIALS AND METHODS: The mRNA and protein expression levels of CYP2E1 and PPAR-α have been assayed by semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and western blot analysis. RESULT: The result demonstrated that the mRNA and protein expressions of CYP2E1(p=0.012; p=0.015) significantly up-regulated while the mRNA and protein expressions of PPAR-α (p=0.026; p=0.03) significantly down-regulated on D-galactosamine induced hepatotoxic rats and treatment with carvacrol significantly suppressed the mRNA and protein (CYP2E1, p=0.010; p=0.011) (PPAR-α, p=0.033; p=0.037) expressions of these genes. CONCLUSION: Thus, the present results have shown that carvacrol has the hepatoprotective effect and also alleviates liver damage associated with GalN induced hepatotoxic rats by down-regulating the CYP2E1 and up-regulating the PPAR-α expression.

Carvacrol suppresses the expression of inflammatory marker genes in D-galactosamine-hepatotoxic rats.

OBJECTIVE: To unravel the mechanism of anti-inflammatory activity of carvacrol in D-galactosamine (D-GalN)-induced hepatotoxic rats. METHODS: The mRNA and protein expression levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and nuclear factor kappa-B (NF-κB) were assayed by semi-quantitative reverse transcriptase polymerase chain reaction (RTPCR) and western blot analysis. RESULTS: We found that the mRNA and protein expressions of TNF-α, IL-6, iNOS, COX-2 and NF-κB were significantly up-regulated in D-galactosamine induced hepatotoxic rats and treatment with carvacrol significantly down-regulated the expressions of these genes showing the mechanism behind the anti-inflammatory activity of carvacrol. CONCLUSIONS: All above results reveal that the carvacrol well known anti-inflammatory activities in D-galactosamine induced hepatotoxic rats.

Pharmacological effect of carvacrol on D: -galactosamine-induced mitochondrial enzymes and DNA damage by single-cell gel electrophoresis.

The present study aimed at investigating the effect of carvacrol on hepatic mitochondrial enzyme activities and DNA damage in D: -galactosamine (D: -GalN)-induced hepatotoxicity in male albino Wistar rats. The activities of hepatic mitochondrial enzymes such as isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, NADPH dehydrogenase and cytochrome c oxidase significantly decreased in D: -GalN-hepatotoxic rats, and administration of carvacrol brought these parameters towards normality. In D: -GalN-hepatotoxic rats, the hepatic mitochondrial concentration of thiobarbituric acid reactive substances significantly increased, and administration of carvacrol significantly reduced them towards normality. Furthermore, the activities of enzymatic antioxidants such as superoxide dismutase and glutathione peroxidase and the levels of non-enzymatic antioxidants such as vitamin C, vitamin E and reduced glutathione decreased significantly in the liver mitochondria. Administration of carvacrol returned the enzymatic and non-enzymatic antioxidants towards normality. D: -GalN-hepatotoxic rats had increased DNA damage, which administration of carvacrol significantly decreased. These results suggest that carvacrol has liver mitochondrial antioxidant properties and possesses a defensive effect against mitochondrial enzymes and DNA damage in D: -GalN-induced rats.

Effects of Melothria maderaspatana leaf extract on antioxidant status in sham-operated and uninephrectomized DOCA-salt hypertensive rats.

The present study was designed to investigate the antihypertensive and antioxidant effect of Melothria maderaspatana leaf extract (MME) on sham-operated and DOCA-salt (deoxycorticosterone acetate) induced hypertensive rats. Administration of DOCA-salt significantly increased the systolic (from 127 to 212 mm Hg) and diastolic (from 91 to 174 mm Hg) blood pressure compared to sham-operated control rats, while treatment with MME significantly reduced the systolic (from 212 to 135 mm Hg) and diastolic (from 174 to 96 mm Hg) blood pressure compared to hypertensive control. In DOCA-salt rats, the plasma and tissue concentration of thiobarbituric acid reactive substances (TBARS) and lipid hydroperoxide (LOOH) significantly increased and administration of MME significantly reduced these parameters towards the levels in sham-operated control. In hypertensive rats, activities of the enzymatic antioxidants such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) and levels of non-enzymatic antioxidants such as vitamin C, vitamin E and reduced glutathione (GSH) decreased significantly in the plasma and tissues. Administration of MME returned the enzymatic and non-enzymatic antioxidants towards sham-operated control. MME shows both antihypertensive and antioxidant properties in DOCA-salt hypertensive rats and, among the three different doses tested, 200 mg/kg caused the maximum effect.

Effect of carvacrol on hepatic marker enzymes and antioxidant status in D-galactosamine-induced hepatotoxicity in rats.

Carvacrol (2-methyl-5-(1-methylethyl)-phenol) is a predominant monoterpenic phenol which occurs in many essential oils of the family Labiatae including Origanum, Satureja, Thymbra, Thymus, and Corydothymus species. This study was designed to investigate the hepatoprotective and antioxidant properties of carvacrol on D-galactosamine (D-GalN)-induced hepatotoxicity and oxidative damage in male albino Wistar rats. D-GalN hepatotoxic rats exhibited elevation in the activities of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, and lipidperoxidative markers such as thiobarbituric acid reactive substances (TBARS) and lipid hydroperoxides. Activities of enzymatic antioxidants (superoxide dismutase, catalase, and glutathione peroxidase) and the levels of non-enzymatic antioxidants (vitamin C, vitamin E, and reduced glutathione) in the plasma, erythrocytes, liver, and kidney decreased in the hepatotoxic rats. Oral administration of carvacrol for 21 days brought these parameters towards normal. The biochemical observations were supported by histological studies of rat liver and kidney tissues. These results suggest that carvacrol could afford a significant hepatoprotective and antioxidant effect against D-GalN-induced rats.

Antihyperlipidemic effect of carvacrol on D-galactosamine-induced hepatotoxic rats.

Carvacrol (2-methyl-5-(1-methylethyl)-phenol) is a predominant monoterpenic phenol occuring in many essential oils of the family Labiatae including, Origanum, Satureja, Thymbra, Thymus, and Corydothymus species. The present study was designed to investigate the effect of carvacrol on D-galactosamine (D-GalN)-induced hepatotoxicity in rats. D-GalN-hepatotoxic rats exhibited elevation in the serum bilirubin level and the activities of the hepatic marker enzymes aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and gamma glutamyl transpeptidase. In the plasma, increased levels of very low density lipoprotein cholesterol and low density lipoprotein cholesterol and decreased high density lipoprotein cholesterol were observed. Further, an increase in the levels of total cholesterol, phospholipids, triglycerides, and free fatty acids in the plasma and tissues of liver and kidney were observed in hepatotoxic rats. The administration of carvacrol for 21 days prevented and improved these parameters toward normalcy. The results suggest that carvacrol affords a significant hepatoprotective and hypolipidemic effect against D-GalN-induced-rats.