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1.
Toxicol Mech Methods ; 32(2): 123-131, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34433383

ABSTRACT

Semecarpus anacardium Linn. (Family: Anacardiaceae), commonly known marking nuts has been used in various traditional system of medicines for various ailments (such as antiatherogenic, antiinflammatory, antimicrobial, hypoglycemic, anticarcinogenic etc) since ancient times.Based on the wide pharmacological activities of this plant, the present study was aimed to explore the antioxidant and antihyperlipidemic potential in high fat diet fed rats using catechol derivatives I-IV and biflavonoid isolated from seeds of Semecarpus anacardium. Oral administration of catechol derivatives I-IV and biflavonoid at a concentration of 50 mg/kg b.wt to high fat diet fed rats for a period of 30 days significantly decreased the lipid profiles, body weight gain and organ weight when compared to untreated hypercholesterolemic rats. However, biflavonoid treated hypercholesterolemic rats showed more pronounced effects in all the parameters tested when compared to all catechol derivatives (I-IV) treated hypercholesterolemic rats. The effect produced by biflavonoid on various parameters was comparable to that of simvastastin- a standard drug. In vitro antioxidant activities were also conducted using these five compounds in which biflavonoid showed more significant antioxidant potential at a concentration of 1000 µg/ml when compared to catechol derivatives (I-IV). The pronounced antioxidant potential of biflavonoid might have contributed to the hypolipidemic action in hypercholesterolemic rats and improved oil red O staining of thoracic aorta has also supported the parameters investigated. Further, the molecular mechanism of cholesterol lowering potential of this drug is needed.


Subject(s)
Antioxidants , Biflavonoids , Catechols , Hypolipidemic Agents , Semecarpus , Animals , Antioxidants/pharmacology , Biflavonoids/pharmacology , Catechols/pharmacology , Hypercholesterolemia/drug therapy , Hypolipidemic Agents/therapeutic use , Plant Extracts/therapeutic use , Rats , Seeds/chemistry , Semecarpus/chemistry
2.
Toxicol Rep ; 5: 231-239, 2018.
Article in English | MEDLINE | ID: mdl-29854594

ABSTRACT

The present study was aimed at evaluating the acute and subacute toxicity of catechol derivatives (I-IV, isolated from Semecarpus anacardium nuts) in Wistar Albino rats. In acute study (14 days), catechol derivatives I-IV 800 mg/kg caused no behavioral adverse effects and mortality. Fifty percent (LD50) of mortality was observed in catechol derivatives I-III (1600 mg/kg b.wt) and catechol derivative IV (1250 mg/kg b.wt). In subacute study, daily oral administration of catechol derivatives I-IV (300 mg/kg b.wt) for 30 days did not result in death or significant changes in the body weight and organ weight, In hematological and some biochemical analysis showed few beneficial effects particularly in catechol derivatives I and IV treated rats that is transient rise in WBC count and HDL cholesterol and decrease in LDL, plasma and tissue lipid profile. These results indicate the impact of catechol derivatives in boosting the immune system and reducing cardiovascular risk factors and thereby they possess cardio protective and immunopotentiating effect. Further, histopathological examination of liver and kidney showed normal architecture that suggests no morphological disturbances. Based on the results obtained, it may be concluded that the catechol derivatives are potentially toxic but therapeutically effective.

3.
Phytomedicine ; 21(6): 793-9, 2014 May 15.
Article in English | MEDLINE | ID: mdl-24629597

ABSTRACT

The present study was designed to evaluate the antihyperglycemic potential of tangeretin on the activities of key enzymes of carbohydrate and glycogen metabolism in control and streptozotocin induced diabetic rats. The daily oral administration of tangeretin (100mg/kg body weight) to diabetic rats for 30 days resulted in a significant reduction in the levels of plasma glucose, glycosylated hemoglobin (HbA1c) and increase in the levels of insulin and hemoglobin. The altered activities of the key enzymes of carbohydrate metabolism such as hexokinase, pyruvate kinase, lactate dehydrogenase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, glucose-6-phosphate dehydrogenase, glycogen synthase and glycogen phosphorylase in liver of diabetic rats were significantly reverted to near normal levels by the administration of tangeretin. Further, tangeretin administration to diabetic rats improved hepatic glycogen content suggesting the antihyperglycemic potential of tangeretin in diabetic rats. The effect produced by tangeretin on various parameters was comparable to that of glibenclamide - a standard oral hypoglycemic drug. Thus, these results show that tangeretin modulates the activities of hepatic enzymes via enhanced secretion of insulin and decreases the blood glucose in streptozotocin induced diabetic rats by its antioxidant potential.


Subject(s)
Blood Glucose/metabolism , Citrus/chemistry , Diabetes Mellitus, Experimental/drug therapy , Flavones/therapeutic use , Hypoglycemic Agents/therapeutic use , Liver/drug effects , Phytotherapy , Animals , Antioxidants/pharmacology , Antioxidants/therapeutic use , Diabetes Mellitus, Experimental/blood , Diabetes Mellitus, Experimental/enzymology , Flavones/pharmacology , Glycated Hemoglobin/metabolism , Glycogen/blood , Hypoglycemic Agents/pharmacology , Insulin/metabolism , Insulin Secretion , Liver/enzymology , Male , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Rats, Wistar
4.
Asian Pac J Trop Med ; 6(12): 925-33, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24144022

ABSTRACT

OBJECTIVE: To investigate the bioactive constituents of Shemamruthaa (SM), a herbal combination and its therapeutic effects on the mitochondrial functions with reference to lipid peroxidation (LPO), antioxidant status, citric acid cycle enzymes and electron transport chain enzymes in mammary tissues of 7,12-dimethylbenz(a)-anthracene (DMBA) induced mammary carcinoma in rat model. METHODS: Adult female Sprague-Dawley rats were used for the study and were divided into four groups. Group I served as control and Group II rats were induced mammary carcinoma by administration of DMBA (25 mg/kg b.w.) orally. The normal and cancer-induced rats (Group III) were treated with SM (400 mg/kg b.w./day) orally by gastric incubation for 14 days. Group IV rats served as SM-treated control animals. RESULTS: Cancer-induced rats showed a considerably increased level of LPO with concomitant decreased levels of antioxidants, citric acid cycle enzymes, electron transport chain enzymes and cytochrome contents in the mammary tissue. Treatment with SM brought back the aforementioned biochemical parameters to near normal. CONCLUSIONS: From the results, it can be inferred that Shemamruthaa possesses significant anticancer effect through its role in attenuation of LPO, prevention of membrane damage and restoring membrane integrity.


Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/therapeutic use , Mammary Neoplasms, Experimental/drug therapy , Plant Extracts/chemistry , Plant Extracts/therapeutic use , 9,10-Dimethyl-1,2-benzanthracene/toxicity , Animals , Antineoplastic Agents/pharmacology , Female , Hibiscus/chemistry , Mammary Glands, Animal/chemistry , Mammary Neoplasms, Experimental/chemically induced , Mammary Neoplasms, Experimental/pathology , Phyllanthus/chemistry , Plant Extracts/pharmacology , Rats , Rats, Sprague-Dawley
5.
Mol Cell Biochem ; 380(1-2): 43-55, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23625195

ABSTRACT

The present study was designed to examine the antihyperlipidaemic potential of iridoid glucoside isolated from Vitex negundo leaves in STZ-induced diabetic rats. The levels of cholesterol (TC), triglycerides, lipoproteins, free fatty acids, phospholipids, fatty acid composition, proinflammatory cytokines, muscle glycogen content, and glucose transporter 4 (GLUT4) expression were estimated in control and diabetic rats. Oral administration of iridoid glucoside at a dose of 50 mg/kg body weight per day to STZ-induced diabetic rats for a period of 30 days resulted in a significant reduction in plasma and tissue (liver and kidney) cholesterol, triglycerides, free fatty acids, and phospholipids. In addition, the decreased plasma levels of high-density lipoprotein-cholesterol and increased plasma levels of low density lipoprotein- and very low density lipoprotein-cholesterol in diabetic rats were restored to near normal levels following treatment with iridoid glucoside. The fatty acid composition of the liver and kidney was analyzed by gas chromatography. The altered fatty acid composition in the liver and kidney of diabetic rats was also restored upon treatment with iridoid glucoside. Moreover, the elevated plasma levels of proinflammatory cytokines and decreased levels of muscle glycogen and GLUT4 expression in the skeletal muscle of diabetic rats were reinstated to their normal levels via enhanced secretion of insulin from the remnant ß cells of pancreas by the administration of iridoid glucoside. The effect produced by iridoid glucoside on various parameters was comparable with that of glibenclamide, a well-known antihyperglycemic drug.


Subject(s)
Cytokines/blood , Diabetes Mellitus, Experimental/prevention & control , Fatty Acids/metabolism , Glucose Transporter Type 4/biosynthesis , Iridoid Glucosides/pharmacology , Lipids/blood , Muscle, Skeletal/drug effects , Animals , Blotting, Western , Cholesterol/blood , Cholesterol/metabolism , Diabetes Mellitus, Experimental/blood , Diabetes Mellitus, Experimental/metabolism , Enzyme-Linked Immunosorbent Assay , Fatty Acids/blood , Glyburide/administration & dosage , Glyburide/pharmacology , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/pharmacology , Inflammation Mediators/blood , Iridoid Glucosides/administration & dosage , Kidney/drug effects , Liver/drug effects , Liver/metabolism , Male , Muscle, Skeletal/metabolism , Pancreas/drug effects , Pancreas/pathology , Rats , Rats, Wistar , Triglycerides/blood , Triglycerides/metabolism
6.
Phytomedicine ; 20(7): 577-84, 2013 May 15.
Article in English | MEDLINE | ID: mdl-23453307

ABSTRACT

The study was undertaken to evaluate the antidiabetic effect of green tea extract on carbohydrate metabolic key enzymes in control and streptozotocin high fat diet -induced diabetic rats. The daily oral treatment of green tea extract (300 mg/kg body weight) to diabetic rats for 30 days resulted in a significant reduction in the levels of plasma glucose, glycosylated hemoglobin (HbA1c) and increase in the levels of insulin and hemoglobin. The altered activities of the key enzymes of carbohydrate metabolism such as hexokinase, pyruvate kinase, lactate dehydrogenase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, glucose-6-phosphate dehydrogenase, glycogen synthase and glycogen phosphorylase in liver of diabetic rats were significantly reverted to near normal levels by the administration of green tea extract. Further, green tea extract administration to diabetic rats improved muscle and hepatic glycogen content suggesting the antihyperglycemic potential of green tea extract in diabetic rats. The obtained results were compared with metformin, a standard oral hypoglycemic drug. Thus, this study indicates that the administration of green tea extract to diabetic rats resulted in alterations in the metabolism of glucose with subsequent reduction in plasma glucose levels.


Subject(s)
Diabetes Mellitus, Experimental/enzymology , Diet, High-Fat/adverse effects , Enzymes/metabolism , Glucose/metabolism , Liver/metabolism , Plant Extracts/pharmacology , Tea , Animals , Blood Glucose/metabolism , Body Weight/drug effects , Carbohydrate Metabolism/drug effects , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/etiology , Dose-Response Relationship, Drug , Eating/drug effects , Glycated Hemoglobin/metabolism , Glycogen/metabolism , Hypoglycemic Agents/pharmacology , Insulin/metabolism , Liver/drug effects , Liver/enzymology , Male , Muscle, Skeletal/drug effects , Muscle, Skeletal/metabolism , Plant Extracts/analysis , Plant Extracts/chemistry , Rats , Rats, Wistar , Streptozocin , Tea/chemistry
7.
Eur J Pharmacol ; 698(1-3): 489-98, 2013 Jan 05.
Article in English | MEDLINE | ID: mdl-23110815

ABSTRACT

Hyperlipidemia is an associated complication of diabetes mellitus. The association of hyperglycemia with an alteration of lipid parameters presents a major risk for cardiovascular complications in diabetes. The present study was designed to examine the antihyperlipidemic effect of 20-OH ecdysone on lipid profile and tissue fatty acid changes in streptozotocin induced diabetic rats. The levels of blood glucose, cholesterol, triglycerides, free fatty acids, phospholipids, low density lipoprotein, very low density lipoprotein, high density lipoprotein, lipoprotein lipase, lecithin cholesterol acyl transferase, 3-hydroxy 3-methylglutaryl coenzyme A reductase and fatty acid composition were estimated in plasma, liver and kidneys of control and experimental groups of rats. Oral administration of 20-OH ecdysone at a dose of 5mg/kg bodyweight per day to STZ-induced diabetic rats for a period of 30 days resulted in a significant reduction in fasting blood glucose, cholesterol, triglycerides, free fatty acids, phospholipids, low density lipoprotein, very low density lipoprotein, 3-hydroxy 3-methylglutaryl coenzyme A reductase and elevation of high density lipoprotein, lipoprotein lipase and lecithin cholesterol acyl transferasein comparison with diabetic untreated rats. Moreover, administration of 20-OH ecdysone to diabetic rats also decreased the concentrations of fatty acids, viz., palmitic, stearic (16:1) and oleic acid (18:1), whereas linolenic (18:3) and arachidonic acid (20:4) were elevated. The antihyperlipidemic effect of 20-OH ecdysone was compared with glibenclamide a well-known antihyperglycemic drug. The result of the present study indicates that 20-OH ecdysone showed an antihyperlipidemic effect in addition to its antidiabetic effect in experimental diabetes.


Subject(s)
Diabetes Mellitus, Experimental/drug therapy , Ecdysterone/pharmacology , Fatty Acids/metabolism , Lipids/blood , Animals , Blood Glucose/metabolism , Diabetes Mellitus, Experimental/blood , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Experimental/pathology , Ecdysterone/therapeutic use , Fatty Acids/chemistry , Kidney/drug effects , Kidney/metabolism , Lipoprotein Lipase/blood , Liver/drug effects , Liver/metabolism , Male , Pancreas/drug effects , Pancreas/metabolism , Pancreas/pathology , Phosphatidylcholine-Sterol O-Acyltransferase/blood , Rats , Rats, Wistar
8.
Phytomedicine ; 19(8-9): 725-9, 2012 Jun 15.
Article in English | MEDLINE | ID: mdl-22484004

ABSTRACT

The aim of the present investigation was to evaluate the anti-diabetic activity of 20-OH-ecdysone on glucose metabolic key enzymes in control and streptozotocin induced diabetic rats. On oral administration of 20-OH-ecdysone at a dose of 5mg/kg body weight per day to diabetic rats for 30 days resulted in a significant decrease in the levels of plasma glucose, glycosylated hemoglobin (HbA1c) and an increase in the levels of insulin and hemoglobin. Administration of 20-OH-ecdysone showed significant increase in the levels of glycolytic enzyme (hexokinase) and hepatic shunt enzyme (glucose-6-phosphate dehydrogenase) whereas significant decrease in the levels of gluconeogenic enzymes (glucose-6-phosphatase and fructose-1,6-bisphosphatase) in diabetic treated rats. Furthermore, protection against body weight loss of diabetic animals also observed. This study indicates that the administration of 20-OH-ecdysone to diabetic rats resulted in alterations in the metabolism of glucose with subsequent reduction in plasma glucose levels. A comparison was made between the action of 20-OH-ecdysone and antidiabetic drug-glibenclamide. The effects produced by the 20-OH-ecdysone were comparable to that of glibenclamide.


Subject(s)
Carbohydrate Metabolism/drug effects , Diabetes Mellitus, Experimental/metabolism , Ecdysterone/pharmacology , Administration, Oral , Animals , Blood Glucose/metabolism , Body Weight/drug effects , Diabetes Mellitus, Experimental/drug therapy , Drinking/drug effects , Eating/drug effects , Enzymes/metabolism , Fructose-Bisphosphatase/metabolism , Glucose-6-Phosphatase/metabolism , Glucosephosphate Dehydrogenase/metabolism , Glycated Hemoglobin/metabolism , Glycogen/metabolism , Hexokinase/metabolism , Hypoglycemic Agents/pharmacology , Rats , Streptozocin , Vitex/chemistry
9.
Eur J Pharmacol ; 674(2-3): 460-7, 2012 Jan 15.
Article in English | MEDLINE | ID: mdl-22094064

ABSTRACT

Vitex negundo is a medicinal plant used to treat many ailments. An active compound of iridoid glucoside was isolated from V. negundo leaves and its efficacy was investigated in streptozotocin induced diabetic rats with special reference to carbohydrate metabolizing enzymes. The optimum dose of iridoid glucoside was determined by oral glucose tolerance test. The effects of iridoid glucoside were compared with glibenclamide Administration of iridoid glucoside (50mg/kg body weight) to diabetic rats for 30 days resulted in significant reduction in the levels of plasma glucose, glycosylated hemoglobin and increase in the levels of insulin and hemoglobin. Administration of iridoid glucoside showed a significant increase in the levels of glycolytic enzymes and glycogen content and decrease in the levels of gluconeogenic enzymes in the liver of diabetic treated rats. Further, iridoid glucoside showed antihyperlipidemic activity as evidenced by significant reduction in serum total cholesterol, triglyceride, low density lipoprotein and very low density lipoprotein coupled together with elevation of high density lipoprotein in diabetic rats. A significant decrease was observed in the activities of aspartate aminotransferase, alanine aminotransferase and decrease in the levels of serum urea and creatinine in diabetic treated rats when compared to diabetic untreated rats. Treatment of iridoid glucoside alleviated body weight loss in diabetic rats. The effect produced by iridoid glucoside on various parameters was comparable to that of glibenclamide. These results indicate that iridoid glucoside possess antihyperlipidemic effect in addition to its antidiabetic effect.


Subject(s)
Carbohydrate Metabolism/drug effects , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/enzymology , Iridoid Glucosides/pharmacology , Animals , Blood Glucose/metabolism , Body Weight/drug effects , Creatinine/blood , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Experimental/physiopathology , Drinking/drug effects , Glucose Tolerance Test , Glycated Hemoglobin/metabolism , Insulin/blood , Iridoid Glucosides/therapeutic use , Liver/drug effects , Liver/enzymology , Liver/metabolism , Male , Rats , Rats, Wistar , Transaminases/blood , Urea/blood
10.
Phytomedicine ; 19(3-4): 211-6, 2012 Feb 15.
Article in English | MEDLINE | ID: mdl-22112721

ABSTRACT

The aim of present study was to isolate an iridoid glucoside from the leaves of Vitex negundo and evaluates its effects on dearrangement in plasma and tissues glycoprotein components in streptozotocin-induced diabetic rats. The levels of blood glucose, plasma and tissues glycoproteins such as hexose, hexosamine, fucose and sialic acid were significantly increased whereas plasma insulin levels were significantly decreased in diabetic rats. On oral administration of iridoid glucoside at a concentration of 50 mg/kg b.w. once daily to diabetic rats for the period of 30 days, reversed the above-mentioned hyperglycemia-induced biochemical changes to near normal levels. The anti-hyperglycemic effect of iridoid glucoside was comparable with glibenclamide, a known hypoglycemic drug. Based on the results obtained from the present study, it may be concluded that iridoid glucoside possesses significant productive effect on glycoprotein metabolism in addition to its antidiabetic effect.


Subject(s)
Diabetes Mellitus, Experimental/drug therapy , Glycoproteins/blood , Hypoglycemic Agents/pharmacology , Iridoid Glucosides/pharmacology , Plant Leaves/chemistry , Vitex/chemistry , Administration, Oral , Animals , Blood Glucose/chemistry , Diabetes Mellitus, Experimental/blood , Fucose/chemistry , Glyburide/pharmacology , Glycoproteins/analysis , Glycoproteins/chemistry , Hexosamines/chemistry , Hypoglycemic Agents/chemistry , Insulin/blood , Insulin/chemistry , Iridoid Glucosides/administration & dosage , Iridoid Glucosides/isolation & purification , Male , N-Acetylneuraminic Acid/chemistry , Rats , Rats, Wistar
11.
J Diet Suppl ; 8(2): 144-57, 2011 Jun.
Article in English | MEDLINE | ID: mdl-22432686

ABSTRACT

Extra cellular matrix (ECM) and basement membrane (BM) are important layers that regulate cell structure, cell migration, and cellular proliferation. Degradation of both ECM and BM mediated by proteases favors the tumor invasion and promotes angiogenesis. Female Sprague-Dawley rats weighing 180 ± 10 g were categorized into 6 groups. Group-1 animals served as vehicle control. Group-2 to Group-4 animals were administered with 7,12-dimethylbenz(a)anthracene (25 mg/rat dissolved in olive oil, orally) on day 1 of experimental period to induce mammary carcinoma. (After 90 days, mammary carcinoma was confirmed by histopathological examination). Group-3 and Group-4 rats were subsequently treated with Semecarpus anacardium nut milk extract (SA) and Kalpaamruthaa (KA), respectively. Group-5 and Group-6 animals served as drug control for SA and KA, respectively. Pro-angiogenic factors like proteases, cyclooxygenase-2, and vascular endothelial growth factor were elevated in tumor-bearing animals and decreased in SA- and KA-supplemented rats. Increased levels of these angiogenic factors in tumor-bearing rats indicate the progression of mammary tumor. The decreased levels of these angiogenic in SA- and KA-treated rats may be due to the ameliorative effect of phenolic compounds such as flavonoids, tannins, and other compounds present in the drug.


Subject(s)
Angiogenesis Inhibitors/therapeutic use , Breast Neoplasms/drug therapy , Mammary Neoplasms, Experimental/drug therapy , Phyllanthus emblica , Phytotherapy , Plant Extracts/therapeutic use , Semecarpus , 9,10-Dimethyl-1,2-benzanthracene , Angiogenesis Inhibitors/pharmacology , Animals , Breast Neoplasms/metabolism , Cyclooxygenase 2 Inhibitors/pharmacology , Cyclooxygenase 2 Inhibitors/therapeutic use , Female , Mammary Neoplasms, Experimental/metabolism , Nuts , Peptide Hydrolases/metabolism , Plant Extracts/pharmacology , Polyphenols/pharmacology , Polyphenols/therapeutic use , Rats , Rats, Sprague-Dawley , Vascular Endothelial Growth Factor A/metabolism
12.
Endocrine ; 38(1): 11-7, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20960096

ABSTRACT

Alterations in lipid metabolism and lipoprotein disturbances have played an important role in increasing the risk of cardiovascular mortality and morbidity in diabetes. A drug that has hypoglycemic activity can be used for the treatment of hyperlipidemia also. The present study was carried out to evaluate the hypolipidemic activity of Semecarpus anacardium. Male Wister rats weighing 250-270 g were injected with Streptozotocin at a dose of 50 mg/kg body weight and administered with S. anacardium (300 mg/kg body weight) and Metformin (500 mg/kg body weight) for 21 days. Control and drug control groups were also included in the study. After the experimental duration, serum was collected, liver and kidney were excised and used for the analysis of lipid and lipid metabolizing enzymes. The results of the study revealed that S. anacardium administration was able to decrease the levels of LDL, cholesterol, VLDL, TG, phospholipid and free fatty acid and increase the HDL levels and favorably modulate the lipid metabolizing enzymes in the liver and kidney. These results show that S. anacardium exerts hypolipidemic activity in diabetic rats.


Subject(s)
Diabetes Mellitus, Experimental/metabolism , Hyperlipidemias/drug therapy , Hyperlipidemias/metabolism , Lipid Metabolism/drug effects , Plant Preparations/pharmacology , Semecarpus , Animals , Diabetes Mellitus, Experimental/complications , Enzyme Activation/drug effects , Hyperlipidemias/etiology , Lipase/metabolism , Lipids/blood , Male , Rats , Rats, Wistar , Sterol Esterase/metabolism
13.
Breast Cancer Res Treat ; 114(2): 377-84, 2009 Mar.
Article in English | MEDLINE | ID: mdl-18427979

ABSTRACT

BACKGROUND: Tamoxifen (TAM) a non-steroidal antiestrogen, is widely used in adjuvant therapy for all stages of breast carcinomas and in chemoprevention of high-risk group. TAM also has estrogenic activity on liver and endometrium causing severe oxidative stress with various biochemical derangements. Coenzyme Q(10), Riboflavin and Niacin (CoRN) are well-known potent antioxidants and protective agents against many diseases including cancer. In this context, this study was undertaken to find if co-administration of TAM along with CoRN could alleviate the sole TAM-induced biochemical derangements in postmenopausal women with breast cancer. METHOD: The vitamin supplementation with TAM was given for a period of 90 days. Blood samples were collected at the base line, 45th and 90th day during the course of treatment. Various blood chemistry profiles were assessed in 78 untreated, sole TAM treated and combinatorial treated group along with 46 age- and sex-matched controls. RESULTS: A statistically significant alteration in various blood chemistry parameters, such as serum total bilirubin (S. BIL), serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), gamma glutamyl transpeptidase (gamma-GT), uric acid (UA), lipoprotein lipase (LPL), lecithin: cholesterol acyl transferases (LCAT), potassium, calcium and Na(+), K(+)-ATPase in sole TAM-treated group, was favorably reverted back to near normal levels on combinatorial therapy with CoRN. CONCLUSION: TAM on co-administration with CoRN has a favorable impact on various blood chemistry profiles. However, large scale randomized studies over a longer time span are required to ascertain the safety and efficacy of co-administrating antioxidants with conventional chemotherapy.


Subject(s)
Antineoplastic Agents, Hormonal/therapeutic use , Breast Neoplasms/blood , Breast Neoplasms/drug therapy , Niacin/administration & dosage , Riboflavin/administration & dosage , Tamoxifen/therapeutic use , Ubiquinone/analogs & derivatives , Adult , Aged , Blood Chemical Analysis , Dietary Supplements , Electron Transport Chain Complex Proteins/metabolism , Female , Humans , Lipids/analysis , Middle Aged , Postmenopause , Ubiquinone/administration & dosage , Vitamin B Complex/administration & dosage
14.
Biofactors ; 32(1-4): 151-9, 2008.
Article in English | MEDLINE | ID: mdl-19096111

ABSTRACT

Tamoxifen, a non-steroidal anti-estrogen is now widely used and has led to an increase in both disease-free and overall survival of women after primary surgery. Tamoxifen therapy is found to cause hypertriglyceridemia by reducing activity of lipolytic enzymes on triglycerides, and thereby increasing the risk of cardiovascular disease. Angiogenesis promotes local tumour progression and invasion and enables tumour cell dissemination and metastasis formation. Our study has found that co-administration of Coenzyme Q10 (100 mg) along with tamoxifen (10 mg, twice a day) to breast cancer patients reduced the level of angiogenesis markers and lipid levels.


Subject(s)
Angiogenesis Inhibitors/therapeutic use , Breast Neoplasms/drug therapy , Hypolipidemic Agents/therapeutic use , Tamoxifen/therapeutic use , Ubiquinone/analogs & derivatives , Adult , Aged , Carcinoembryonic Antigen/blood , Cytokines/blood , Female , Humans , Lipids/blood , Matrix Metalloproteinases/metabolism , Middle Aged , Mucin-1/blood , Tamoxifen/administration & dosage , Ubiquinone/therapeutic use
15.
Br J Nutr ; 100(6): 1179-82, 2008 Dec.
Article in English | MEDLINE | ID: mdl-18377693

ABSTRACT

In the present study, eighty-four breast cancer patients were randomized to receive a daily supplement of 100 mg co-enzyme Q10, 10 mg riboflavin and 50 mg niacin (CoRN), one dosage per d along with 10 mg tamoxifen twice per d. A significant increase in poly(ADP-ribose) polymerase levels and disappearance of RASSF1A DNA methylation patterns were found in patients treated with supplement therapy along with tamoxifen compared to untreated breast cancer patients and tamoxifen alone-treated patients. An increase in DNA repair enzymes and disappearance of DNA methylation patterns attributes to reduction in tumour burden and may suggest good prognosis and efficacy of the treatment.


Subject(s)
Breast Neoplasms/drug therapy , DNA Methylation/drug effects , DNA Repair Enzymes/drug effects , Dietary Supplements , Tamoxifen/therapeutic use , Adult , Aged , Antineoplastic Agents, Hormonal/therapeutic use , Breast Neoplasms/genetics , DNA Repair Enzymes/metabolism , DNA, Neoplasm/genetics , Female , Humans , Middle Aged , Niacin/therapeutic use , Poly(ADP-ribose) Polymerases/metabolism , Riboflavin/therapeutic use , Single-Blind Method , Ubiquinone/analogs & derivatives , Ubiquinone/therapeutic use
16.
Vascul Pharmacol ; 48(4-6): 191-201, 2008.
Article in English | MEDLINE | ID: mdl-18407793

ABSTRACT

Tumour angiogenesis is a complex mechanism consisting of multi-step events including secretion or activation of angiogenic factors by tumour cells, activation of proteolytic enzymes, proliferation, migration and differentiation of endothelial cells. Both primary and metastatic tumours in the breast are dependent on angiogenesis. In the present study, 84 breast cancer patients were randomized to receive a daily supplement of CoQ(10) 100 mg, riboflavin 10 mg and niacin 50 mg (CoRN), one dosage per day along with tamoxifen (TAM) 10 mg twice a day. Serum pro-angiogenic levels were elevated in untreated breast cancer patients (Group II) and their levels were found to be reduced in breast cancer patients undergoing TAM therapy for more than 1 year (Group III). When these group III breast cancer patients were supplemented with CoRN for 45 days (Group IV) and 90 days (Group V) along with TAM, a further significant reduction in pro-angiogenic marker levels were observed. Supplementing CoRN to breast cancer patients has found to decrease the levels of pro-angiogenic factors and increase the levels of anti-angiogenic factors. A reduction in pro-angiogenic marker levels attributes to reduction in tumour burden and may suggest good prognosis and efficacy of the treatment, and might even offer protection from cancer metastases and recurrence.


Subject(s)
Angiogenesis Inhibitors/therapeutic use , Antineoplastic Agents, Hormonal/therapeutic use , Antioxidants/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Neovascularization, Pathologic/drug therapy , Niacin/therapeutic use , Riboflavin/therapeutic use , Tamoxifen/therapeutic use , Ubiquinone/analogs & derivatives , Vitamins/therapeutic use , Adult , Aged , Biomarkers/metabolism , Data Interpretation, Statistical , Elastin/metabolism , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunoblotting , Matrix Metalloproteinases/metabolism , Middle Aged , Neovascularization, Pathologic/metabolism , Neovascularization, Pathologic/pathology , Reverse Transcriptase Polymerase Chain Reaction , Tissue Inhibitor of Metalloproteinase-1/biosynthesis , Tissue Inhibitor of Metalloproteinase-2/biosynthesis , Ubiquinone/therapeutic use , Urokinase-Type Plasminogen Activator/biosynthesis
17.
Chem Biol Interact ; 173(1): 43-58, 2008 May 09.
Article in English | MEDLINE | ID: mdl-18358458

ABSTRACT

Chronic myeloid leukemia (CML) is a clonal disorder characterized by proliferation of hematopoietic cells that possess the BCR-ABL fusion gene resulting in the production of a 210 kDa chimeric tyrosine kinase protein. CML, when left untreated, progresses to a blast phase during which the disease turns aggressive and shows poor response to known treatment regimens. We have studied a Siddha herbal agent, Semecarpus anacardium Linn. nut milk extract (SA) for its antileukemic activity and its effect on the changes in energy metabolism in leukemic mice. Leukemia was induced in BALB/c mice by tail vein injection of BCR-ABL(+) 12B1 murine leukemia cell line. This resulted in an aggressive leukemia, similar to CML in blast crisis, myeloid subtype, confirmed by histopathological study and RT-PCR for the p210 mRNA in the peripheral blood, spleen and liver. Leukemia-bearing mice showed a significant increase in lipid peroxides, glycolytic enzymes, a decrease in gluconeogenic enzymes and significant decrease in the activities of TCA cycle and respiratory chain enzymes as compared to control animals. SA treatment was compared with standard drug imatinib mesylate. SA administration to leukemic animals resulted in clearance of the leukemic cells from the bone marrow and internal organs on histopathological examination and this was confirmed by RT-PCR for the p210 mRNA. Treatment with SA significantly reversed the changes seen in the levels of the lipid peroxides, the glycolytic enzymes, the gluconeogenic enzymes and the mitochondrial enzymes. These effects are probably due to the flavonoids, polyphenols and other compounds present in SA which result in total regression of leukemia and correction of the alterations in energy metabolism. Study of animals treated with SA alone did not reveal any adverse effects. On the basis of the observed results, SA can be considered as a readily accessible, promising and novel antileukemic chemotherapeutic agent.


Subject(s)
Energy Metabolism/drug effects , Leukemia, Experimental/physiopathology , Plant Extracts/pharmacology , Semecarpus/chemistry , Animals , Base Sequence , Body Weight/drug effects , Bone Marrow/drug effects , Bone Marrow/pathology , DNA Primers , Female , Fusion Proteins, bcr-abl/genetics , Lipid Peroxides/metabolism , Liver/drug effects , Liver/pathology , Mice , Mice, Inbred BALB C , Microscopy, Electron, Transmission , RNA, Messenger/genetics , Spleen/drug effects , Spleen/pathology
18.
Cancer Chemother Pharmacol ; 61(6): 933-41, 2008 May.
Article in English | MEDLINE | ID: mdl-17668211

ABSTRACT

BACKGROUND: Reactive oxygen species (ROS) such as superoxide anion, hydrogen peroxide (H(2)O(2)), hydroxyl radical have been implicated in pathogenesis of various diseases including cancer and metastasis. Tamoxifen (TAM) is a non-steroidal anti-estrogen drug most widely used as an adjuvant hormonal therapy in breast cancer. TAM also has estrogenic activity on liver and endometrium causing severe oxidative stress and hypertriglycerdemia. Coenzyme Q(10) (CoQ(10)), Niacin and Riboflavin are well-known potent antioxidants and protective agents against many diseases including cancer. In this context, this study was undertaken to find if co-administration of CoQ(10), Niacin and Riboflavin along with TAM could augment the antioxidant (AO) status in postmenopausal women with breast cancer. METHODS: The vitamin supplementation with Tamoxifen was given for a period of 90 days. Blood samples were collected at the base line, 45th and 90th day during the course of treatment. Plasma lipids, lipid peroxides and various circulating enzymatic and non-enzymatic antioxidants were estimated in 78 untreated, sole TAM treated and combinatorial treated group along with 46 age- and sex-matched controls. RESULTS: Enhanced oxidative stress as evidenced by increased lipids and lipid peroxides with decreased AO levels in untreated breast cancer patients was observed. Adjuvant TAM-treated group had a limited impact on the increased oxidative stress with decreased AO status. Severe hypertriglycerdemia was observed in TAM-treated group when compared to untreated and control subjects. Combinatorial therapy (CT) of CoQ(10), Niacin and Riboflavin along with TAM decreased the oxidative stress and increased the AO status. CONCLUSION: The antioxidant defense system is compromised in breast cancer patients. There is a shift in the oxidant / antioxidant balance in favor of lipid peroxidation (LPO), which could lead to tumour promotion observed in the disease. CT of CoQ(10), Niacin and Riboflavin along with TAM significantly increased the AO status, while decreasing lipid and lipid peroxides. The results suggest the necessity of therapeutic co-administration of antioxidants along with conventional drug to such patients. However, due to limited number of cases included in this study, more studies may be required to substantiate the results and arrive at a definitive conclusion, in terms of safety and efficacy of adding an AO therapy in treatment of breast cancer.


Subject(s)
Antineoplastic Agents, Hormonal/therapeutic use , Antioxidants/metabolism , Breast Neoplasms/metabolism , Niacin/metabolism , Riboflavin/metabolism , Tamoxifen/therapeutic use , Ubiquinone/analogs & derivatives , Adult , Aged , Breast Neoplasms/drug therapy , Enzymes/blood , Enzymes/metabolism , Female , Humans , Lipid Peroxidation/drug effects , Lipids/blood , Middle Aged , Oxidative Stress/drug effects , Thiobarbituric Acid Reactive Substances/metabolism , Ubiquinone/metabolism
19.
Chem Biol Interact ; 168(3): 193-202, 2007 Jul 20.
Article in English | MEDLINE | ID: mdl-17588554

ABSTRACT

BACKGROUND: Rheumatoid arthritis (RA) is a prevalent and debilitating disease that affects the joints. Infiltration of blood-derived cells in the affected joints upon activation generate reactive oxygen/nitrogen species, resulting in an oxidative stress. One approach to counteract this oxidative stress is the use of antioxidants as therapeutic agents. OBJECTIVES: Kalpaamruthaa (KA), a modified indigenous Siddha preparation constituting Semecarpus anacardium nut milk extract (SA), Emblica officinalis (EO) and honey was evaluated for its synergistic antioxidant potential in adjuvant induced arthritic rats than sole SA treatment. MATERIALS AND METHODS: Levels/activities of reactive oxygen species (ROS)/reactive nitrogen species (RNS), myeloperoxidase, lipid peroxide and enzymic and non-enzymic antioxidants were determined in control, arthritis induced, SA and KA treated (150 mg/kg b.wt.) animals. RESULTS AND CONCLUSION: The levels/activities of ROS/RNS, myeloperoxidase and lipid peroxide were increased significantly (p<0.05) and the activities of enzymic and non-enzymic antioxidants were in turn decreased in arthritic rats, whereas these changes were reverted to near normal levels upon SA and KA treatment. KA showed an enhanced antioxidant potential than sole treatment of SA in adjuvant induced arthritic rats. KA via enhancing the antioxidant status in adjuvant induced arthritic rats than sole SA treatment proves to be an important therapeutic modality in the management of RA and thereby instituting the role of oxidative stress in the clinical manifestation of the disease RA. The profound antioxidant efficacy of KA than SA alone might be due to the synergistic action of the polyphenols such as flavonoids, tannins and other compounds such as vitamin C and hydroxycinnamates present in KA.


Subject(s)
Antioxidants/metabolism , Arthritis/chemically induced , Arthritis/drug therapy , Disease Models, Animal , Freund's Adjuvant/adverse effects , Medicine, Ayurvedic , Plant Extracts/therapeutic use , Animals , Inflammation/chemically induced , Inflammation/drug therapy , Lipid Peroxidation/drug effects , Male , Peroxidase/metabolism , Plant Extracts/pharmacology , Rats , Rats, Wistar , Reactive Oxygen Species/metabolism , Synovial Membrane/drug effects , Synovial Membrane/enzymology
20.
Cell Biol Int ; 31(10): 1198-206, 2007 Oct.
Article in English | MEDLINE | ID: mdl-17572113

ABSTRACT

There is an increasing interest in identifying potent cancer-preventive and therapeutic agents against breast cancer. A great number of reports have in recent years dealt with anticancer characteristics of Semecarpus anacardium nut extract (SA). The majority of these studies has been targeted on the protective effect rendered to the living system rather than the preventive effect on cancer cells. SA was tested for its inhibitory effect on human breast cancer cells (T47D). Cytotoxicity analyses suggested that these cells had become apoptotic. SA was discovered to induce rapid Ca(2+) mobilization from intracellular stores of T47D cell line, and its cytotoxicity against T47D was well correlated with altered mitochondrial transmembrane potential. At the molecular level, these changes are accompanied by decrease in bcl(2) and increase in bax, cytochrome c, caspases and PARP cleavage, and ultimately by internucleosomal DNA fragmentation. Taken together, our results provide unprecedented evidence that SA triggers apoptotic signals in T47D cells.


Subject(s)
Apoptosis/drug effects , Breast Neoplasms/pathology , Nuts/chemistry , Phytotherapy , Plant Extracts/pharmacology , Semecarpus/chemistry , Breast Neoplasms/metabolism , Calcium/metabolism , Caspases/metabolism , Colony-Forming Units Assay , Cytochromes c/metabolism , Humans , Membrane Potential, Mitochondrial/drug effects , Nitric Oxide Synthase/metabolism , Poly(ADP-ribose) Polymerases/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , Tumor Cells, Cultured , bcl-2 Homologous Antagonist-Killer Protein , bcl-2-Associated X Protein/metabolism
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