Curcumin, a polyphenolic compound derived from dietary spice turmeric, possesses diverse pharmacologic effects including anti-inflammatory, antioxidant, antiproliferative and antiangiogenic activities. Phase I clinical trials have shown that curcumin is safe even at high doses (12 g/day) in humans but exhibit poor bioavailability. Major reasons contributing to the low plasma and tissue levels of curcumin appear to be due to poor absorption, rapid metabolism, and rapid systemic elimination. To improve the bioavailability of curcumin, numerous approaches have been undertaken. These approaches involve, first, the use of adjuvant like piperine that interferes with glucuronidation; second, the use of liposomal curcumin; third, curcumin nanoparticles; fourth, the use of curcumin phospholipid complex; and fifth, the use of structural analogues of curcumin (e.g., EF-24). The latter has been reported to have a rapid absorption with a peak plasma half-life. Despite the lower bioavailability, therapeutic efficacy of...

Bioavailability of curcumin: problems and promises.

Lipid peroxidation can be described generally as a process under which oxidants such as free radicals attack lipids containing carbon-carbon double bond(s), especially polyunsaturated fatty acids (PUFAs). Over the last four decades, an extensive body of literature regarding lipid peroxidation has shown its important role in cell biology and human health. Since the early 1970s, the total published research articles on the topic of lipid peroxidation was 98 (1970–1974) and has been increasing at almost 135-fold, by up to 13165 in last 4 years (2010–2013). New discoveries about the involvement in cellular physiology and pathology, as well as the control of lipid peroxidation, continue to emerge every day. Given the enormity of this field, this review focuses on biochemical concepts of lipid peroxidation, production, metabolism, and signaling mechanisms of two main omega-6 fatty acids lipid peroxidation products: malondialdehyde (MDA) and, in particular, 4-hydroxy-2-nonenal (4-HNE), summarizing not only its physiological and protective function as signaling molecule stimulating gene expression and cell survival, but also its cytotoxic role inhibiting gene expression and promoting cell death. Finally, overviews of in vivo mammalian model systems used to study the lipid peroxidation process, and common pathological processes linked to MDA and 4-HNE are shown.

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Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal.

Silver nanoparticles (Ag-np) are being used increasingly in wound dressings, catheters, and various household products due to their antimicrobial activity. The toxicity of starch-coated silver nanoparticles was studied using normal human lung fibroblast cells (IMR-90) and human glioblastoma cells (U251). The toxicity was evaluated using changes in cell morphology, cell viability, metabolic activity, and oxidative stress. Ag-np reduced ATP content of the cell caused damage to mitochondria and increased production of reactive oxygen species (ROS) in a dose-dependent manner. DNA damage, as measured by single cell gel electrophoresis (SCGE) and cytokinesis blocked micronucleus assay (CBMN), was also dose-dependent and more prominent in the cancer cells. The nanoparticle treatment caused cell cycle arrest in G2/M phase possibly due to repair of damaged DNA. Annexin-V propidium iodide (PI) staining showed no massive apoptosis or necrosis. The transmission electron microscopic (TEM) analysis indicated the presen...

Cytotoxicity and Genotoxicity of Silver Nanoparticles in Human Cells

I read this book the same weekend that the Packers took on the Rams, and the experience of the latter event, obviously, colored my judgment. Although I abhor anything that smacks of being a handbook (like, \"How to Earn a Merit Badge in Neurosurgery\") because too many volumes in biomedical science already evince a boyscout-like approach, I must confess that parts of this volume are fast, scholarly, and significant, with certain reservations. I like parts of this well-illustrated book because Dr. Sj6strand, without so stating, develops certain subjects on technique in relation to the acquisition of judgment and sophistication. And this is important! So, given that the author (like all of us) is somewhat deficient in some areas, and biased in others, the book is still valuable if the uninitiated reader swallows it in a general fashion, realizing full well that what will be required from the reader is a modulation to fit his vision, propreception, adaptation and response, and the kind of problem he is undertaking. A major deficiency of this book is revealed by comparison of its use of physics and of chemistry to provide understanding and background for the application of high resolution electron microscopy to problems in biology. Since the volume is keyed to high resolution electron microscopy, which is a sophisticated form of structural analysis, but really morphology in a modern guise, the physical and mechanical background of The instrument and its ancillary tools are simply and well presented. The potential use of chemical or cytochemical information as it relates to biological fine structure , however, is quite deficient. I wonder when even sophisticated morphol-ogists will consider fixation a reaction and not a technique; only then will the fundamentals become self-evident and predictable and this sine qua flon will become less mystical. Staining reactions (the most inadequate chapter) ought to be something more than a technique to selectively enhance contrast of morphological elements; it ought to give the structural addresses of some of the chemical residents of cell components. Is it pertinent that auto-radiography gets singled out for more complete coverage than other significant aspects of cytochemistry by a high resolution microscopist, when it has a built-in minimal error of 1,000 A in standard practice? I don't mean to blind-side (in strict football terminology) Dr. Sj6strand's efforts for what is \"routinely used in our laboratory\"; what is done is usually well done. It's just that …

Methods in Enzymology.

The Pharmacological Basis of Therapeutics A Textbook of Pharmacology, Toxicology and Therapeutics for Physicians and Medical Students. By Prof. Louis Goodman and Prof. Alfred Gilman. Pp. xiii + 1383. (New York: The Macmillan Company, 1941.) 50s. net.

The Pharmacological Basis of Therapeutics

Daucus carota commonly known as carrot, is widely used in European folk medicine for the treatment of jaundice and hepatic disorders. Oral administration of carrot extract (25 mL/kg/day) for 30 days produced significant hepatoprotection against lindane (20 mg/kg/day) induced hepatotoxicity in rats. The increased levels of serum enzymes namely aspartate transaminase, alanine transaminase, alkaline phosphatase and the levels of thiobarbituric acid reactive substances, cholesterol, triglycerides and LDL-cholesterol in lindane administered rats were observed to be decreased significantly in the lindane + carrot extract group. The carrot extract also restored the depressed antioxidants and HDL-cholesterol levels to near normal. The results of this study reveal that carrot could afford a significant protective effect against lindane-induced hepatotoxicity. © 1998 John Wiley & Sons, Ltd.

Protective effect of carrot (Daucus carota L.) against lindane ‐ induced hepatotoxicity in rats

Clinical research has confirmed the efficacy of several plants in the modulation of oxidative stress associated with diabetes mellitus. Scoparia dulcis plant extract is tried for prevention and treatment of diabetes mellitus induced experimentally by streptozotocin injection. A single dose of streptozotocin (45 mg/kg body weight) produced decrease in insulin, hyperglycemia, increased lipid peroxidation (Thiobarbituric reactive substances and lipid hydroperoxides) and decreased antioxidant levels (vitamin C, vitamin E, reduced glutathione, ceruloplasmin). Oral administration of an aqueous extract of Scoparia dulcis plant (200 mg/kg body weight) for 6 weeks to diabetic rats significantly increased the plasma insulin and plasma antioxidants and significantly decreased lipid peroxidation. The effect of Scoparia dulcis plant extract at 200 mg/kg body weight was better than that of glibenclamide, a reference drug.

Effect of scoparia dulcis (Sweet Broomweed) plant extract on plasma antioxidants in streptozotocin-induced experimental diabetes in male albino Wistar rats.

The present study was designed to investigate the effect of diosmin on the levels of glycoprotein components in plasma and tissues of streptozotocin (STZ)-nicotinamide (NA) induced diabetic rats. Diabetes was induced in male Wistar rats by a single intraperitoneal injection of STZ (45 mg/kg b. w). Diosmin (DS) (100 mg/kg b. w) was administered orally for 45days. The effects of diosmin on plasma glucose, plasma insulin, plasma and tissue glycoproteins were studied. The levels of plasma glucose and plasma glycoproteins were increased significantly whereas the level of plasma insulin was significantly decreased in diabetic rats. There was a significant decrease in the level of sialic acid and elevated levels of hexose, hexosamine and fucose in the liver and kidney of diabetic rats. Oral administration of diosmin to diabetic rats led to decreased levels of plasma glucose and plasma glycoproteins. The levels of plasma insulin and tissue sialic acid were increased, whereas the levels of tissue hexose, hexosamine and fucose were near normal. The present study indicates that diosmin possesses a significant beneficial effect on glycoproteins in addition to its antidiabetic effect.

Preventive effect of diosmin, a bioflavonoid, on glycoprotein changes in streptozotocin-nicotinamide-induced type 2 diabetic rats.

In the present study, the effect of succinic acid monoethyl ester (EMS) on the pattern of lipids and lipoproteins in streptozotocin-nicotinamide induced type 2 diabetes was investigated. Type 2 diabetes was induced in male Wistar rats by single intraperitoneal injection (i.p.) of 45 mg/kg streptozotocin, 15 min after the i.p administration of 110 mg/kg body weight of nicotinamide. The carboxylic nutrient EMS was administered intraperitonially at a dose of 8 Μmol/g body weight for 30 days. At the end of experimental period, the effect of EMS on plasma glucose, insulin, thiobarbituric acid reactive substances (TBARS) and hydroperoxide (HP) and serum triglycerides (TG), phospholipids (PL), free fatty acids (FFA), total cholesterol (TC), very low density lipoprotein-cholesterol (VLDL-C) and low density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C) and the percentage of antiatherogenic index (AAI) (ratio of HDL-C to total cholesterol) were studied. Administration of EMS to diabetic rats resulted in a signi. cant reduction in the elevated levels of plasma glucose, TBARS and hydroperoxides as well as TG, PL, FFA, TC, VLDL-C and LDC-C levels. The decreased plasma insulin and serum HDL-C and percentage of AAI in diabetic rats were also reversed towards near normal. The effect produced by EMS was compared with metformin, a reference drug. The results indicates that the administration of EMS and metformin to nicotinamide-streptozotocin diabetic rats normalized plasma glucose, insulin concentrations and caused marked improvement in altered lipids, lipoprotein and lipid peroxidation markers during diabetes. Our results show the antihyperlipidemic properties of EMS and metformin in addition to its antidiabetic action. Moreover, the antihyperlipidemic effect could represent a protective mechanism against the development of atherosclerosis.

Effect of a novel insulinotropic agent, succinic acid monoethyl ester, on lipids and lipoproteins levels in rats with streptozotocin-nicotinamide-induced type 2 diabetes.

Objective. Succnic acid mono ethyl ester (EMS) was recently proposed as an insulinotropic agent for the treatment of non-insulin dependent diabetes mellitus. In the present study the effect of EMS and Metformin on the activities of carbohydrate metabolic enzymes in streptozotocin–nicotinamide induced type 2 diabeteic model was investigated. Methods. EMS were injected intraperitonially at doses 2, 4, and 8 μ mol/g body weight (bw) respectively for 30 days, after which blood hemoglobin, glycosylated hemoglobin, plasma glucose and insulin, hexokinase, glucose-6-phosphatase, fructose-1, 6-bisphosphatase, glucose-6-phosphate dehydrogenase in liver and glycogen in liver and muscle were assayed. Results. Glucose, glycosylated hemoglobin, glucose-6-phosphatase and fructose-1,6-bis phosphatase were significantly increased and insulin, hemoglobin, hexokinase, glucose-6-phosphate dehydrogenase and glycogen were significantly decreased in diabetic rats. The enzyme activities were restored to the near normal levels in diabetic rats treated with EMS and Metformin. Conclusion. Our result suggest that non glucidic nutrientEMS may act as a potent antidiabetic and insulinotropic agent by restoring the above biochemical alterations in streptozotocin -nicotinamide induced type 2 diabetes.

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Succinic acid monoethyl ester and metformin regulates carbohydrate metabolic enzymes and improves glycemic control in streptozotocin-nicotinamide induced type 2 diabetic rats

Leelavinothan Pari

Papers

Protective effect of carrot (Daucus carota L.) against lindane ‐ induced hepatotoxicity in rats

Effect of scoparia dulcis (Sweet Broomweed) plant extract on plasma antioxidants in streptozotocin-induced experimental diabetes in male albino Wistar rats.

Preventive effect of diosmin, a bioflavonoid, on glycoprotein changes in streptozotocin-nicotinamide-induced type 2 diabetic rats.

Effect of a novel insulinotropic agent, succinic acid monoethyl ester, on lipids and lipoproteins levels in rats with streptozotocin-nicotinamide-induced type 2 diabetes.

Succinic acid monoethyl ester and metformin regulates carbohydrate metabolic enzymes and improves glycemic control in streptozotocin-nicotinamide induced type 2 diabetic rats