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1.
Antioxidants (Basel) ; 9(1)2019 Dec 21.
Article in English | MEDLINE | ID: mdl-31877697

ABSTRACT

We synthesized the gold nanoparticles (AuNPs) using wedelolactone (WDL) and characterized them using UV-visible spectroscopy, fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopic (SEM), transmission electron microscopic (TEM), energy dispersive X-ray diffraction, and atomic force microscopic (AFM) studies. The electronic spectrum exhibited an absorption peak at 535 nm. The FT-IR results proved that WDL was stabilized on the surface of AuNPs by acting as a capping or reducing agent. The crystalline structure was affirmed by XRD pattern and the spherical shape of WDL-AuNPs was evidenced by SEM, TEM, and AFM. The synthesized WDL-AuNPS were evaluated for anti-diabetic activity in pancreatic RIN-5F cell lines. In vitro results showed that WDL-AuNPs did not only improve the insulin secretion affected by di-(2-ethylhexyl) phthalate (DEHP), but also the cell viability in RIN5F cells. WDL-AuNPs treatment modulates the pro-apoptotic proteins and anti-apoptotic proteins expression to prevent the cells undergoing apoptosis in DEHP-exposed RIN-5F cells. The exposure of DEHP causes an increase in ROS production and lipid peroxidation levels. The free radical scavenging and antioxidant properties of WDL-AuNPs increase the deleterious effect caused by DEHP. On the other side, WDL-AuNPs increase mRNA expressions of insulin-signaling proteins in RIN-5F cells. This study concludes that WDL-AuNPs can be successfully used to regulate the expression of Bcl-2 family proteins, reduce lipid peroxidation, and to improve the secretion of antioxidants and insulin through the GLUT2 pathway in RIN-5F cell lines.

2.
Antioxidants (Basel) ; 8(9)2019 Sep 05.
Article in English | MEDLINE | ID: mdl-31491872

ABSTRACT

In the present study, the authors have attempted to fabricate Polydatin encapsulated Poly [lactic-co-glycolic acid] (POL-PLGA-NPs) to counteract 7,12-dimethyl benzyl anthracene (DMBA) promoted buccal pouch carcinogenesis in experimental animals. The bio-formulated POL-PLGA-NPs were characterized by dynamic light scattering (DLS), Fourier transform infrared (FTIR) spectroscopy, X-ray powder diffraction (XRD) pattern analysis, and transmission electron microscope (TEM). In addition, the nano-chemopreventive potential of POL-PLGA-NPs was assessed by scrutinizing the neoplastic incidence and analyzing the status of lipid peroxidation, antioxidants, phase I, phase II detoxification status, and histopathological changes and in DMBA-treated animals. In golden Syrian hamsters, oral squamous cell carcinoma (OSCC) was generated by painting with 0.5% DMBA in liquid paraffin three times a week for 14 weeks. After 100% tumor formation was observed, high tumor volume, tumor burden, and altered levels of biochemical status were observed in the DMBA-painted hamsters. Intra-gastric administration of varying concentration of POL-PLGA-NPs (7.5, 15, and 30 mg/kg b.wt) to DMBA-treated hamsters assumedly prevents oncological incidences and restores the status of the biochemical markers. It also significantly enhances the apoptotic associated and inhibits the cancer cell proliferative markers expression (p53, Bax, Bcl-2, cleaved caspase 3, cyclin-D1). The present study reveals that POL-PLGA-NPs is a penitential candidate for nano-chemopreventive, anti-lipid peroxidative, and antioxidant potential, and also has a modulating effect on the phase I and Phase II detoxification system, which is associated with reduced cell proliferation and induced apoptosis in experimental oral carcinogenesis.

3.
Microb Pathog ; 135: 103609, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31247255

ABSTRACT

This article reports the utilization of Malus domestica for the synthesis of silver nanoparticles (AgNPs) with cytotoxic activity against the Michigan Cancer Foundation-7 (MCF-7) cell line as well as their antibacterial and radical scavenging potential. The biosynthesized AgNPs were confirmed using various analytical characterization techniques. The cytotoxic effect of Malus domestica-AgNPs (M.d-AgNPs) was studied by MTT assay and scavenging efficacy was assessed by DPPH, nitric oxide radical and phosphomolybdate assays. Furthermore, green synthesized nanoparticles were evaluated for their antibacterial activity against multidrug resistant-clinical isolates. M.d-AgNPs were observed to be almost spherical in shape with an average diameter from 50 to 107.3 nm as assessed by TEM and DLS. M.d-AgNPs revealed the dose-dependent antioxidant activity and antimicrobial activity against multidrug-resistant bacterial strain viz. Enterobacter aerogenes, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia coli. Also, in vitro studies revealed dose-dependent cytotoxic effects of M.d-AgNPs treated MCF-7 cell line. The data strongly suggest that M.d-AgNPs had a potential antioxidant, antimicrobial and cytotoxicity activity.


Subject(s)
Anti-Bacterial Agents/biosynthesis , Anti-Bacterial Agents/pharmacology , Green Chemistry Technology/methods , MCF-7 Cells/drug effects , Malus/metabolism , Metal Nanoparticles/chemistry , Silver/pharmacology , Antineoplastic Agents/pharmacology , Antioxidants/analysis , Biofilms/drug effects , Cost-Benefit Analysis , Drug Resistance, Multiple, Bacterial/drug effects , Drug Stability , Free Radical Scavengers , Green Chemistry Technology/economics , HEK293 Cells/drug effects , Humans , Inhibitory Concentration 50 , Microbial Sensitivity Tests , Particle Size , Phytochemicals/pharmacology , X-Ray Diffraction
4.
Mol Cell Biochem ; 385(1-2): 159-68, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24078031

ABSTRACT

Epidemiological studies have demonstrated that diabetes mellitus is a serious health burden for both governments and healthcare providers. This study was hypothesized to evaluate the antihyperglycemic potential of eugenol by determine the activities of key enzymes of glucose metabolism in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced into male albino Wistar rats by intraperitoneal administration of STZ (40 mg/kg body weight (b.w.)). Eugenol was administered to diabetic rats intragastrically at 2.5, 5, and 10 mg/kg b.w. for 30 days. The dose 10 mg/kg b.w. significantly reduced the levels of blood glucose and glycosylated hemoglobin (HbA1c) and increased plasma insulin level. The altered activities of the key enzymes of carbohydrate metabolism such as hexokinase, pyruvate kinase, glucose-6-phosphate dehydrogenase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, and liver marker enzymes (AST, ALT, and ALP), creatine kinase and blood urea nitrogen in serum and blood of diabetic rats were significantly reverted to near normal levels by the administration of eugenol. Further, eugenol administration to diabetic rats improved body weight and hepatic glycogen content demonstrated the antihyperglycemic potential of eugenol in diabetic rats. The present findings suggest that eugenol can potentially ameliorate key enzymes of glucose metabolism in experimental diabetes, and it is sensible to broaden the scale of use of eugenol in a trial to alleviate the adverse effects of diabetes.


Subject(s)
Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/enzymology , Eugenol/therapeutic use , Glucose/metabolism , Hyperglycemia/drug therapy , Hyperglycemia/enzymology , Animals , Blood Glucose/metabolism , Blood Urea Nitrogen , Body Weight/drug effects , Carbohydrates/urine , Diabetes Mellitus, Experimental/blood , Diabetes Mellitus, Experimental/urine , Drinking Behavior/drug effects , Eugenol/chemistry , Eugenol/pharmacology , Feeding Behavior/drug effects , Fructose-Bisphosphatase/metabolism , Glucose Tolerance Test , Glucose-6-Phosphatase/metabolism , Glucosephosphate Dehydrogenase/metabolism , Glycated Hemoglobin/metabolism , Glycogen/metabolism , Hexokinase/metabolism , Hyperglycemia/blood , Hyperglycemia/urine , Insulin/blood , Kidney/drug effects , Kidney/enzymology , Liver/drug effects , Liver/enzymology , Male , Pancreas/drug effects , Pancreas/metabolism , Pancreas/pathology , Pyruvate Kinase/metabolism , Rats , Streptozocin
5.
Phytomedicine ; 21(3): 225-32, 2014 Feb 15.
Article in English | MEDLINE | ID: mdl-24075211

ABSTRACT

Hyperlipidemia is an associated complication of diabetes and also a major risk factor for cardiovascular diseases. The present study was designed to examine the antihyperlipidemic effect of asiatic acid (AA) in streptozotocin (STZ) induced diabetic rats. Diabetes was induced in male Wistar rats by a single intraperitoneal injection of STZ (40 mg/kg b.w.). Diabetic rats show increased plasma glucose, total cholesterol, triglycerides, free fatty acids, phospholipids, low density lipoprotein, very low density liprotein, atherogenic index and decreased insulin and high density lipoprotein in diabetic rats. The activity of 3-hydroxy 3-methylglutaryl coenzyme A (HMG CoA) reductase increased significantly in contrast to the activities of lipoprotein lipase and lecithin cholesterol acyltransferase. In addition, the molecular docking of AA against HMG CoA reductase involved in cholesterol biosynthesis using Argus software. Diabetic rats were treated with AA shifted all these parameters towards normalcy. AA has shown best ligand binding energy 11.8122 kcal/mol. The antihyperlipidemic effect of AA was compared with glibenclamide; a well-known antihyperglycemic drug. In conclusion, this study indicates that AA showed an antihyperlipidemic effect in addition to its antidiabetic effect in experimental diabetes.


Subject(s)
Acyl Coenzyme A/metabolism , Cholesterol/biosynthesis , Hyperlipidemias/prevention & control , Hypoglycemic Agents/therapeutic use , Hypolipidemic Agents/therapeutic use , Pentacyclic Triterpenes/therapeutic use , Phytotherapy , Animals , Blood Glucose/metabolism , Centella/chemistry , Cholesterol/blood , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/metabolism , Glyburide/pharmacology , Glyburide/therapeutic use , Hydroxymethylglutaryl-CoA-Reductases, NADP-dependent/metabolism , Hyperlipidemias/etiology , Hyperlipidemias/metabolism , Hypoglycemic Agents/pharmacology , Hypolipidemic Agents/pharmacology , Lipid Metabolism/drug effects , Male , Pentacyclic Triterpenes/pharmacology , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Rats , Rats, Wistar , Triglycerides/blood
6.
Environ Toxicol Pharmacol ; 36(2): 472-483, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23792234

ABSTRACT

The present study was to evaluate the protective effects of Rebaudioside A (Reb A) on antioxidant status and lipid profile in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in Wistar rats by a single intraperitoneal administration of STZ (40mg/kg b.w). Diabetic rats showed significantly increased levels of plasma glucose, thiobarbituric acid reactive substances, hydroperoxides and decreased levels of insulin. The activity of enzymatic antioxidants (superoxide dismutase, catalase and glutathione peroxidase) and the levels of non enzymatic antioxidants (vitamin C, vitamin E and reduced glutathione) were decreased in diabetic rats. The levels of total cholesterol (TC), triglycerides (TGs), free fatty acids (FFAs), phospholipids (PLs), low density lipoproteins (LDL-cholesterol) and very low-density lipoproteins (VLDL-cholesterol) in the plasma significantly increased, while plasma high-density lipoproteins (HDL-cholesterol) were significantly decreased in diabetic rats. Oral administration of Reb A (200mg/kg b.w) brought back plasma glucose, insulin, lipid peroxidation products, enzymatic, non-enzymatic antioxidants and lipid profile levels to near normal. The results of the present investigation suggests that Reb A, a natural sweetener exhibits antilipid peroxidative, antihyperlipidemic and antioxidant properties.


Subject(s)
Antioxidants/pharmacology , Diabetes Mellitus, Experimental/drug therapy , Diterpenes, Kaurane/pharmacology , Hypoglycemic Agents/pharmacology , Hypolipidemic Agents/pharmacology , Lipids/blood , Oxidative Stress/drug effects , Administration, Oral , Animals , Antioxidants/administration & dosage , Ascorbic Acid/blood , Biomarkers/blood , Blood Glucose/drug effects , Blood Glucose/metabolism , Catalase/blood , Cholesterol/blood , DNA Damage , Diabetes Mellitus, Experimental/blood , Diabetes Mellitus, Experimental/genetics , Diabetes Mellitus, Experimental/pathology , Diterpenes, Kaurane/administration & dosage , Fatty Acids, Nonesterified/blood , Glutathione/blood , Glutathione Peroxidase/blood , Hypoglycemic Agents/administration & dosage , Hypolipidemic Agents/administration & dosage , Insulin/blood , Kidney/drug effects , Kidney/metabolism , Lipid Peroxidation/drug effects , Lipid Peroxides/blood , Liver/drug effects , Liver/metabolism , Liver/pathology , Male , Phospholipids/blood , Rats , Rats, Wistar , Superoxide Dismutase/blood , Thiobarbituric Acid Reactive Substances/metabolism , Triglycerides/blood , Vitamin E/blood
7.
Phytomedicine ; 20(3-4): 230-6, 2013 Feb 15.
Article in English | MEDLINE | ID: mdl-23102509

ABSTRACT

Asiatic acid (AA), a triterpenoid derivative of Centella asiatica, has shown significant biological effects of antioxidant and anti-inflammatory activities. Aim of this investigation was to evaluate the antihyperglycemic effect of AA on the activities of hepatic enzymes of carbohydrate metabolism in streptozotocin (STZ)-induced diabetic rats. To induce diabetes mellitus, rats were injected with streptozotocin intraperitoneally at a single dose of 40 mg/kg b.w. Diabetic rats showed significant (p<0.05) increased in plasma glucose, glycosylated hemoglobin and significant (p<0.05) decreased in circulating insulin and hemoglobin. The altered activities of key enzymes such as glucose-6-phosphatase and fructose-1,6-bisphosphatase of carbohydrate metabolism significantly (p<0.05) increased whereas hexokinase, pyruvate kinase, glucose-6-phosphate dehydrogenase and glycogen content significantly (p<0.05) decreased in the liver of diabetic rats and also increased activities of aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP). Oral administration of AA (5, 10 and 20 mg/kg b.w.) and glibenclamide (600 µg/kg b.w.) to diabetic rats for 45 days prevented the above alteration and reverted to near normalcy. Protection of body weight loss of diabetic rats by AA was also observed. No significant effect was observed in normal rats treated with AA (20 mg/kg b.w.). In this search, AA found to be potential bioactive compound to regulate the carbohydrate metabolism by modulating the key regulatory enzymes in diabetic rats. These findings merit further research in this field.


Subject(s)
Carbohydrate Metabolism/drug effects , Diabetes Mellitus, Experimental/drug therapy , Pentacyclic Triterpenes/therapeutic use , Animals , Blood Glucose/drug effects , Centella/chemistry , Diabetes Mellitus, Experimental/blood , Diabetes Mellitus, Experimental/enzymology , Drug Evaluation, Preclinical , Glycogen/metabolism , Hemoglobins/metabolism , Insulin/blood , Male , Pentacyclic Triterpenes/pharmacology , Phytotherapy , Plant Extracts , Rats , Rats, Wistar , Triterpenes/pharmacology , Triterpenes/therapeutic use
8.
J. physiol. biochem ; 68(3): 421-431, sept. 2012. ilus
Article in English | IBECS | ID: ibc-122330

ABSTRACT

Rebaudioside A (Reb A), a major constituent of Stevia rebaudiana, was recently proposed as an insulinotropic agent. The aim of this investigation was to evaluate the antihyperglycemic effect of Reb A on the activities of hepatic enzymes of carbohydrate metabolism in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in adult male Albino Wistar rats, weighing 180-200 g, by a single intraperitoneal injection at a dose of STZ (40 mg/kg body weight). Diabetic rats showed significant (P < 0.05) increase in the levels of plasma glucose and glycosylated hemoglobin and significant (P < 0.05) decrease in the levels of plasma insulin and hemoglobin. Activities of gluconeogenic enzymes such as glucose-6-phosphatase and fructose-1,6-bisphosphatase were significantly (P < 0.05) increased while hexokinase and glucose-6-phosphate dehydrogenase were significantly (P < 0.05) decreased in the liver along with glycogen. Oral treatment with Reb A to diabetic rats significantly (P < 0.05) decreased blood glucose and reversed these hepatic carbohydrate metabolizing enzymes in a significant manner. Histopathology changes of pancreas confirmed the protective effects of Reb A in diabetic rats. Thus, the results show that Reb A possesses an antihyperglycemic activity and provide evidence for its traditional usage in the control of diabetes (AU)


Subject(s)
Animals , Rats , Diterpenes/pharmacokinetics , Diabetes Mellitus/physiopathology , Stevia , Hypoglycemic Agents/pharmacokinetics , Plant Extracts/pharmacokinetics , Hyperglycemia/prevention & control , Protective Agents/pharmacokinetics , Disease Models, Animal
9.
J Physiol Biochem ; 68(3): 421-31, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22374587

ABSTRACT

Rebaudioside A (Reb A), a major constituent of Stevia rebaudiana, was recently proposed as an insulinotropic agent. The aim of this investigation was to evaluate the antihyperglycemic effect of Reb A on the activities of hepatic enzymes of carbohydrate metabolism in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in adult male Albino Wistar rats, weighing 180-200 g, by a single intraperitoneal injection at a dose of STZ (40 mg/kg body weight). Diabetic rats showed significant (P<0.05) increase in the levels of plasma glucose and glycosylated hemoglobin and significant (P<0.05) decrease in the levels of plasma insulin and hemoglobin. Activities of gluconeogenic enzymes such as glucose-6-phosphatase and fructose-1,6-bisphosphatase were significantly (P<0.05) increased while hexokinase and glucose-6-phosphate dehydrogenase were significantly (P<0.05) decreased in the liver along with glycogen. Oral treatment with Reb A to diabetic rats significantly (P<0.05) decreased blood glucose and reversed these hepatic carbohydrate metabolizing enzymes in a significant manner. Histopathology changes of pancreas confirmed the protective effects of Reb A in diabetic rats. Thus, the results show that Reb A possesses an antihyperglycemic activity and provide evidence for its traditional usage in the control of diabetes.


Subject(s)
Blood Glucose/metabolism , Diabetes Mellitus, Experimental/metabolism , Diterpenes, Kaurane/pharmacology , Hypoglycemic Agents/pharmacology , Animals , Diabetes Mellitus, Experimental/chemically induced , Diterpenes, Kaurane/therapeutic use , Glucose-6-Phosphatase/metabolism , Glucosephosphate Dehydrogenase/metabolism , Glycogen/metabolism , Hypoglycemic Agents/therapeutic use , Liver/drug effects , Liver/enzymology , Liver/metabolism , Male , Rats , Rats, Wistar , Streptozocin
10.
J Basic Clin Physiol Pharmacol ; 21(4): 369-85, 2010.
Article in English | MEDLINE | ID: mdl-21305852

ABSTRACT

The protective effect of the phenolic compound syringic acid, one of the major benzoic acid derivatives from edible plants and fruits, was evaluated against acetaminophen (APAP)-induced hepatotoxicity in rats. Toxicity was induced in adult male albino Wistar rats by the administration of APAP (750 mg/kg body weight) intraperitoneally. Rats were treated with syringic acid (25, 50, and 100 mg/kg body weight) by the oral route. We assessed the activity of hepatic markers aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, and bilirubin. Lipid peroxidative markers thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides, and a decrease in enzymatic antioxidants superoxide dismutase, catalase, glutathione peroxidase, and non-enzymatic antioxidants vitamin C, vitamin E and reduced glutathione levels. Liver histology also showed convincing evidence regarding their protective nature against fatty changes induced during APAP intoxication. Syringic acid administered at a dose of 50 mg/kg body weight significantly decreased the activities of hepatic and renal function markers to near normal values when compared with the other two doses. The results suggest that syringic acid could afford a significant protective effect against APAP induced hepatic damage in rats.


Subject(s)
Chemical and Drug Induced Liver Injury/prevention & control , Gallic Acid/analogs & derivatives , Liver/drug effects , Protective Agents/pharmacology , Acetaminophen/toxicity , Administration, Oral , Animals , Antioxidants/metabolism , Bilirubin/blood , Bilirubin/metabolism , Chemical and Drug Induced Liver Injury/metabolism , Chemical and Drug Induced Liver Injury/pathology , Dose-Response Relationship, Drug , Gallic Acid/administration & dosage , Gallic Acid/pharmacology , Kidney/drug effects , Kidney/metabolism , Kidney/pathology , Lipid Peroxidation/drug effects , Liver/metabolism , Liver/pathology , Male , Protective Agents/administration & dosage , Rats , Rats, Wistar
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