Preventive role of Withania somnifera on hyperlipidemia and cardiac oxidative stress in streptozotocin induced type 2 diabetic rats

Purpose: The present study was intended to investigate the preventive role of Withania somnifera (WS) on hyperlipidemia and oxidative stress in the heart of streptozotocin (STZ)-induced type 2 diabetic rats.Methods: Single intraperitoneal injection of STZ (100 mg/kg) was given to 2 days rat pups to induce type 2 diabetes mellitus. Diabetes was confirmed 90 days after the administration of STZ by measuring blood glucose level. WS (200 and 400 mg/kg) was administered orally once a day for 5 weeks after the confirmation of diabetes. Glucose, lactate dehydrogenase (LDH), creatinine kinase (CK), total cholesterol (TCh), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), verylow density lipoprotein cholesterol (VLDL-C) and markers of oxidative stress parameters like lipid peroxidation (LPO), reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT) were evaluated in the heart of type 2 diabetic rats.Results: Oral administration of WS for 5 weeks resulted in a significant (P<0.001) reduction in glucose, LDH, CK, TC, TG, LDL-C, VLDL-C levels with significant elevation of HDL-C levels. On the other hand, WS treated diabetic rats significantly (P<0.01-P<0.001) reduced the elevated levels of LPO, increased levels of antioxidant enzymes (i.e, GSH, GPx, GR, GST, SOD and CAT).Conclusion: These findings propose the role of hyperlipidemia and cardiac oxidative stress in type 2 diabetic rats and suggested protective effect of WS in this animal model.Keywords: Withania somnifera; Hyperlipidemia; Oxidative stress; Streptozotocin; Type 2 diabete

Antidiabetic potential of Moringa oleifera Lam. leaf extract in type 2 diabetic rats, and its mechanism of action

Purpose: To explore the antidiabetic potential of Moringa oleifera leaf extract in type 2 diabetic rats, and the underlying mechanisms.Methods: Streptozotocin (STZ) at a dose of 40 mg/kg was given to high fat diet (HFD)- fed rats to induce type 2 diabetes. M. oleifera leaf extract at doses 100, 200 and 400 mg/kg were given to 3 groups of type 2 diabetic rats. The area under curve (AUC) of glucose and homeostasis model assessment of insulin resistance (HOMA-R) were calculated using appropriate formulas, whereas levels of glucose,insulin, peroxisome proliferator activated receptor-γ (PPARγ, dipeptidyl peptidase-IV (DPP-IV) and inflammatory cytokines (IL-6, IL-1β and TNFα) were assayed using ELISA kits.Results: The leaf extract of M. oleifera significantly reduced the levels of glucose, insulin and cytokines in treated type 2 diabetic groups (p < 0.05). DC group had significantly increased AUC for glucose, whereas the extract-treated groups showed significant  decrease in glucose AUC. There was significant decrease in insulin sensitivity parameters, as indicated by increase in HOMA-R and decrease in PPARγ levels in the DC group (p < 0.05). However, treatment with the M. oleifera extract reversed this trend via marked decrease in HOMA-R level and significant rise in PPARγ level. In contrast, the extract had no effect on DPP-IV concentration in diabetic treated groups (p < 0.05).Conclusion: These results indicate that M. oleifera leaf extract mitigates hyperglycemia in type 2 DM by modulating hyperinsulinemia, PPARγ and inflammatory cytokines. Thus, the extract is a potential source of drug for the management of type 2 DM. Keywords: Moringa oleifera, Diabetes mellitus, Streptozotocin, Peroxisome proliferator activated receptor-γ, Dipeptidyl peptidase I

Sensing properties of sulfonated multi-walled carbon nanotube and graphene nanocomposites with polyaniline

Here, we discuss one of the simplest approaches for chemical functionalization of in-situ prepared polyaniline (Pani) and its nanocomposites with multi-walled carbon nanotubes (MWCNT) and graphene (GN) in chlorosulphonic acid. The effect of polymerization and functionalization was characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) analysis, Field emission scanning electron microscopy (FESEM) and electro-thermal analysis. Results also revealed the presence of π−π interactions between Pani and carbon allotropes leading to the formation of charge-transfer complexes. This strong π−π interaction significantly increased the resultant electrical conductivity, stabilizing them as well. Further, theirs back to back sulphonation in chlorosulphonic acid significantly enhanced the solubility in one way but caused a heavy loss in conductivity conversely. The thermoelectric properties of the as-prepared nanocomposites were investigated as a function of MWCNT and GN contents. It was observed that as-prepared Pani/GN nanocomposites showed a greater electrical conductivity as well as an improved thermal stability in terms of DC electrical conductivity retention under isothermal and cyclic ageing conditions compared with Pani/MWCNT and Pani. Finally these oxidative products were also studied for their sensing response towards amine to detect whether the particular compound is either 1°, 2°, or 3° amine. Keywords: In-situ polymerization, Pani/MWCNT and Pani/GN nanocomposite, Sulphonation, Isothermal and cyclic ageing technique, Amine identificatio

Accelerated Stability Testing of a Clobetasol Propionate-Loaded Nanoemulsion as per ICH Guidelines

The physical and chemical degradation of drugs may result in altered therapeutic efficacy and even toxic effects. Therefore, the objective of this work was to study the stability of clobetasol propionate (CP) in a nanoemulsion. The nanoemulsion formulation containing CP was prepared by the spontaneous emulsification method. For the formulation of the nanoemulsion, Safsol, Tween 20, ethanol, and distilled water were used. The drug was incorporated into an oil phase in 0.05% w/v. The lipophilic nature of the drug led to the O/W nano-emulsion formulation. This was characterized by droplet size, pH, viscosity, conductivity, and refractive index. Stability studies were performed as per ICH guidelines for a period of three months. The shelf life of the nanoemulsion formulation was also determined after performing accelerated stability testing (40°C ± 2°C and 75% ± 5% RH). We also performed an intermediate stability study (30°C ± 2°C / 65% RH ± 5% RH). It was found that the droplet size, conductivity, and refractive index were slightly increased, while the viscosity and pH slightly decreased at all storage conditions during the 3-month period. However, the changes in these parameters were not statistically significant (p≥0.05). The degradation (%) of the optimized nanoemulsion of CP was determined and the shelf life was found to be 2.18 years at room temperature. These studies confirmed that the physical and chemical stability of CP were enhanced in the nanoemulsion formulation

Thymoquinone Ameliorates Doxorubicin-Induced Cardiotoxicity in Swiss Albino Mice by Modulating Oxidative Damage and Cellular Inflammation

Thymoquinone is the active constituent of Nigella sativa, having antioxidant and anti-inflammatory actions. In present study, we have analyzed the effects of thymoquinone on doxorubicin (DOX) induced cardiotoxicity in mice. In this experiment, thirty mice (25–35 gm) were divided into five groups (Groups A, B, C, D, and E) each containing six animals. Normal saline was given to a control group (Group A) for 14 days. Cardiotoxicity was induced by DOX (15 mg/kg, i.p.) in Group B, once on the 13th day of the study, and Groups C and D also received DOX (15 mg/kg, i.p.) and were then treated with thymoquinone (10 and 20 mg/kg, b/w, p.o.), respectively, for 14 days. Group E was given only thymoquione (20 mg/kg b/w, p.o.). A blood serum marker (AST, ALT, CK-MB, and LDH) and oxidative stress marker (LPO, GSH, CAT, SOD, GPx, GR, and GST) were evaluated. Results revealed that serum enzyme marker like aspartate aminotransferase (AST), creatinine kinase-MB (CKMB), and lactate dehydrogenase (LDH) were significantly elevated in Group B as compare to Group A. Similarly, the oxidative stress marker lipid peroxidation (LPO) was also elevated in Group B while the antioxidant enzyme catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase, and glutathione S-transferase (CAT, SOD, GPx, GR, and GST) were also decreased in Group B. The treatment with thymoquinone 10 and 20 mg/kg resulted in a significant decrease in the serum marker and increase in the antioxidant enzymes. In this study, we have found that thymoquinone prevented DOX-induced cardiotoxicity by accelerating heart antioxidant defense mechanisms and down regulating the LPO levels towards normalcy in Groups C and D. The effect of doxorubicin increases the inflammatory cytokine (IL2) in Group B as compared to Group A, and it overcomes by the thymoquinone in Groups C and D. Thus, thymoquinone may have utility as a potential drug for cardiomyopathy