Chandramohan Govindasamy

Galangin, a dietary flavonoid, improves antioxidant status and reduces hyperglycemia-mediated oxidative stress in streptozotocin-induced diabetic rats

ABSTRACT Objective: To examine the effect of galangin on hyperglycemia-mediated oxidative stress in streptozotocin (STZ)-induced diabetic rats. Methods: Diabetes was induced by intraperitoneal administration of low-dose STZ (40 mg/kg body weight (BW)) into male albino Wistar rats. Galangin (8 mg/kg BW) or glibenclamide (600 µg/kg BW) was given orally, once daily for 45 days to normal and STZ-induced diabetic rats. Results: Diabetic rats showed significantly increased levels of plasma glucose, thiobarbituric acid reactive substances, lipid hydroperoxides, and conjugated dienes. The levels of insulin and non-enzymatic antioxidants (vitamin C, vitamin E, reduced glutathione) and the activity of enzymatic antioxidants (superoxide dismutase, catalase, glutathione peroxidase, and glutathione-S-transferase (GST)) were decreased significantly in diabetic control rats. These altered plasma glucose, insulin, lipid peroxidation products, enzymatic and non-enzymatic antioxidants ions were reverted to near-normal level after the administration of galangin and glibenclamide. Conclusion: The present study shows that galangin decreased oxidative stress and increased antioxidant status in diabetic rats, which may be due to its antidiabetic and antioxidant potential.

Influence of 3-hydroxymethyl xylitol, a novel antidiabetic compound isolated from Casearia esculenta (Roxb.) root, on glycoprotein components in streptozotocin-diabetic rats.

Casearia esculenta root (Roxb.) is widely used in traditional system of medicine to treat diabetes in India. An active compound, 3-hydroxymethyl xylitol (3-HMX), has been isolated, and its optimum dose has been determined in a short duration study and patented. In addition, the long-term effect of 3-HMX in type 2 diabetic rats on antihyperglycemic, antioxidants, antihyperlipidemic, and protein metabolism and kidney marker enzymes was investigated, and its effect was shown previously. In this study, we investigated the effect of 3-HMX on plasma and tissue glycoproteins in streptozotocin-diabetic rats. Animals were divided into five groups viz., control group, 3-HMX (40 mg/kg of body weight) treated group, diabetic group, diabetic+3-HMX (40 mg/kg of body weight), and diabetic+glibenclamide (600 μg/kg of body weight). 3-HMX was administered orally at a dose of 40 mg/kg of body weight for 45 days. The study shows significant increases in the level of sialic acid except kidney and elevated levels of hexose, hexosamine, and fucose in the liver and kidney of diabetic rats, and the treatment with 3-HMX and glibenclamide showed reversal of these parameters toward normalcy. Thus, the study indicates that 3-HMX possesses a significant beneficial effect on glycoprotein components.

Galangin, a natural flavonoid reduces mitochondrial oxidative damage in streptozotocin-induced diabetic rats

ABSTRACT Objective: We designed this study to observe the effect of galangin on damaged mitochondria in the liver of diabetic rats. Methods: Male albino Wistar rats were made diabetic by injecting streptozotocin (STZ) intraperitoneally (40 mg kg−1 body weight (BW)). Galangin (8 mg kg−1 BW) or glibenclamide (600 µg kg−1 BW) was given orally daily once for 45 days to both healthy and diabetic rats. Results: Diabetic rats showed significant (P < 0.05) increase in liver mitochondrial oxidant [Thiobarbituric acid reactive substance (TBARS)] level and a significant decrease in enzymatic [superoxide dismutase (SOD), glutathione peroxidase (GPx)] and non-enzymatic (reduced glutathione (GSH)) antioxidant levels when compared with healthy rats. The mitochondrial enzymes isocitrate dehydrogenase (ICDH), alpha-ketoglutarate dehydrogenase (α-KGDH), succinate dehydrogenase (SDH) and malate dehydrogenase (MDH) and mitochondrial respiratory chain enzymes NADH-dehydrogenase and Cytochrome c-oxidase were decreased significantly (P < 0.05) in diabetic rats when compared with healthy rats. A natural flavonoid galangin administered to hyperglycemia-induced rats resulted in the following findings as compared to hyperglycemia-induced control rats: the oxidant levels decreased significantly (P < 0.05); the enzymatic and non-enzymatic antioxidant levels increased significantly (P < 0.05) and the function of mitochondrial enzymes and the mitochondrial respiratory chain enzymes increased significantly (P < 0.05). Conclusion: From the results, we conclude that galangin could maintain liver mitochondrial function in diabetic rats.

Binary functional porous multi mineral–substituted apatite nanoparticles for reducing osteosarcoma colonization and enhancing osteoblast cell proliferation

We investigated the use of combined nanoparticles in bone replacement for patients with bone cancer. Bismuth (Bi) is known to have antitumor effects, and the inclusion of Bi in bioactive mineral (M)-substituted hydroxyapatite (M-HAP) may provide anti-cancer properties implant resources. A series of Bi-substituted M-HAP (Bi-M-HAP) nanoparticles with various Bi concentrations was synthesized via the ultrasound irradiation method. The nanoparticles were examined using physicochemical strategies. The cell-substance interface of the nanoparticles was observed in vitro with human osteosarcoma cells and cell multiplication was measured at 1, 3, and 7days of incubation and in vivo in rats after 3weeks of implantation. The nanoparticles promoted osseous proliferation, improved mechanical strength, and repressed the development of cancerous cells. Overall, Bi-M-HAP nanoparticles show promise for treatment of bone cancer and advance the field of embedded biomaterials.

Galangin, a dietary flavonoid, ameliorates hyperglycaemia and lipid abnormalities in rats with streptozotocin-induced hyperglycaemia

Abstract Context: Galangin, a natural flavonoid, is found in honey and Alpinia officinarum Hance (Zingiberaceae). Galangin has antiviral, antimicrobial, antidiabetic and anticancer properties, without side effects. The effects of galangin on hyperglycaemia and lipid abnormalities are not known. Objective: To elucidate the effectiveness of galangin on hyperglycaemia-associated complications and lipid changes in rats with streptozotocin (STZ)-induced hyperglycaemia. Materials and methods: Diabetes was induced in adult Wistar rats by administering 40 mg/kg of STZ. In our previous study, galangin had no toxicity at concentrations up to 320 mg/kg. Therefore three doses of galangin (4, 8 or 16 mg/kg BW) or glibenclamide (600 µg/kg BW) were administered daily to diabetic rats orally for 45 days. Results: Diabetic rats showed a significant (p < 0.05) increased levels of plasma glucose (281.10 mg/dL) and decreased levels of insulin (6.01 μU/mL). Additionally, diabetic rats showed a significant (p < 0.05) increased levels of plasma lipid profiles such as total cholesterol (149.05 mg/dL), triglycerides (143.28 mg/dL), free fatty acids (139.37 mg/dL), phospholipids (127.53 mg/dL), plasma low-density lipoprotein-cholesterol (98.72 mg/dL), plasma very low-density lipoprotein-cholesterol (28.65 mg/dL), and significant (p < 0.05) decreased in plasma high-density lipoprotein-cholesterol (21.68 mg/dL). When galangin was administered to the hyperglycaemic rats, plasma glucose and insulin levels and lipid profiles reverted to levels similar to those in healthy control rats. Discussion and conclusions: Administration of galangin reduced hyperlipidaemia related to the risk of diabetic complications and could be beneficial for diabetic hyperlipidaemic patients. Further work detailing its mechanism-of-action for improving hyperglycaemic-associated lipid abnormalities is needed.

Human CD3+ T-Cells with the Anti-ERBB2 Chimeric Antigen Receptor Exhibit Efficient Targeting and Induce Apoptosis in ERBB2 Overexpressing Breast Cancer Cells

Breast cancer is a common malignancy among women. The innate and adaptive immune responses failed to be activated owing to immune modulation in the tumour microenvironment. Decades of scientific study links the overexpression of human epidermal growth factor receptor 2 (ERBB2) antigen with aggressive tumours. The Chimeric Antigen Receptor (CAR) coding for specific tumour-associated antigens could initiate intrinsic T-cell signalling, inducing T-cell activation, and cytotoxic activity without the need for major histocompatibility complex recognition. This renders CAR as a potentially universal immunotherapeutic option. Herein, we aimed to establish CAR in CD3+ T-cells, isolated from human peripheral blood mononucleated cells that could subsequently target and induce apoptosis in the ERBB2 overexpressing human breast cancer cell line, SKBR3. Constructed CAR was inserted into a lentiviral plasmid containing a green fluorescent protein tag and produced as lentiviral particles that were used to transduce activated T-cells. Transduced CAR-T cells were then primed with SKBR3 cells to evaluate their functionality. Results showed increased apoptosis in SKBR3 cells co-cultured with CAR-T cells compared to the control (non–transduced T-cells). This study demonstrates that CAR introduction helps overcome the innate limitations of native T-cells leading to cancer cell apoptosis. We recommend future studies should focus on in vivo cytotoxicity of CAR-T cells against ERBB2 expressing tumours.

219 Galangin, a dietary flavonoid reduces mitochondrial damage in streptozotocin-induced diabetic rats

Introduction Hyperglycemia-induced ROS generation within mitochondria plays a major role in the development of diabetic complications. Mitochondria are one of the most important cell organelles in diabetes research because of its crucial role as a regulator of energy balance. The present study was aimed to evaluate the effect galangin, a flavonoid, on oxidative mitochondrial damage in in streptozotocin (STZ)-induced diabetic rats. Materials and methods Diabetes was induced by intraperitoneal administration of low dose of STZ (40 mg/kg body weight (BW)) into male albino Wistar rats. Galangin (8 mg/kg BW) or glibenclamide (600 µg/kg BW) was given orally daily once for 45 days to normal and STZ-induced diabetic rats. Results Diabetic rats showed a significant (p<0.05) increase in kidney and heart mitochondrial oxidant (Thiobarbituric acid reactive substance) levels and a significant decrease in enzymatic (superoxide dismutase, glutathione peroxidase) and non-enzymatic (reduced glutathione) antioxidants levels as compared to control rats. The activities of mitochondrial enzymes such as isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, and malate dehydrogenase and mitochondrial respiratory chain enzymes such as NADH dehydrogenase and Cytochrome c-oxidase were decreased significantly (p<0.05) in diabetic rats as compared to control rats. Administration of galangin to diabetic rats resulted in the following findings as compared to diabetic control rats: the oxidant levels decreased significantly (p<0.05); the enzymatic and non-enzymatic antioxidants levels increased significantly (p<0.05); and the function of mitochondrial enzymes and the mitochondrial respiratory chain enzymes increased significantly (p<0.05). Conclusion From the results, we conclude that galangin could maintain kidney and heart mitochondrial function in diabetic rats.