Extensive scientific research on curcumin, a natural compound present in the rhizomes of plant Curcuma longa Linn., demonstrated its antiinflammatory action. Curcumin was found to inhibit arachidonic acid metabolism, cyclooxygenase, lipoxygenase, cytokines (Interleukins and tumour necrosis factor) Nuclear factor-kB and release of steroidal hormones. Curcumin was reported to stabilize lysosomal membrane and cause uncoupling of oxidative phosphorylation besides having strong oxygen radical scavenging activity, which was responsible for its antiinflammatory property. In various animal studies, a dose range of 100-200 mg/kg body weight exhibited good antiinflammatory activity and seemed to have negligible adverse effect on human systems. Oral LD50 in mice was found to be more than 2.0 g/kg body weight.

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Diabetes mellitus is a group of syndromes characterized by hyperglycemia, altered metabolism of lipids, carbohydrates and protein and an increased risk of complication of vascular diseases. Type 2 diabetes mellitus is characterized by derangement of insulin secretion and an inability of the peripheral tissues to respond to insulin. In spite of the availability of many animal models for Type 2 diabetes mellitus including genetic and chemically induced, none of them simulate human Type 2 diabetes mellitus. An attempt has been made in the present review, to evaluate the neonatal streptozotocin-induced rat (n-STZ rats) model of Type 2 diabetes mellitus, for its potential advantages as a suitable model over the others. The n-STZ model (with alteration of dose and day of STZ injection) exhibits various stages of Type 2 diabetes mellitus such as impaired glucose tolerance, and mild, moderate and severe glycemia. The cells in n-STZ rats bear a resemblance to insulin secretory characteristics found in patients with Type 2 diabetes mellitus. Thus the n-STZ model can be considered as one of the suitable animal models of Type 2 diabetes mellitus.

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The blood brain barrier (BBB) represents one of the strictest barriers of in vivo therapeutic drug delivery. The barrier is defined by restricted exchange of hydrophilic compounds, small proteins and charged molecules between the plasma and central nervous system (CNS). For decades, the BBB has prevented the use of many therapeutic agents for treating Alzheimer's disease, stroke, brain tumor, head injury, spinal cord injury, depression, anxiety and other CNS disorders. Different attempts were made to deliver the drug across the BBB such as modification of therapeutic agents, altering the barrier integrity, carrier-mediated transport, invasive techniques, etc. However, opening the barrier by such means allows entry of toxins and undesirable molecules to the CNS, resulting in potentially significant damage. An attempt to overcome the barrier in vivo has focused on bypassing the BBB by using a novel, practical, simple and non-invasive approach i.e. intranasal delivery. This method works because of the unique connection which the olfactory and trigeminal nerves (involved in sensing odors and chemicals) provide between the brain and external environments. The olfactory epithelium acting as a gateway for substances entering the CNS and peripheral circulation is well known. Also, it is common knowledge that viral infections such as common cold, smallpox, measles, and chicken pox take place through the nasopharynx. The neural connections between the nasal mucosa and the brain provide a unique pathway for the non-invasive delivery of therapeutic agents to the CNS. This pathway also allows drugs which do not cross the BBB to enter the CNS and it eliminates the need for systemic delivery and thereby reducing unwanted systemic side effects. Intranasal delivery does not require any modification of therapeutic agents and does not require that drugs be coupled with any carrier. A wide variety of therapeutic agents, including both small molecules and macromolecules can be rapidly delivered to the CNS using this method. The present review discusses the various applications, advantages and limitations of this novel approach.

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Probiotics are nonpathogenic microbes used to confer health benefits to the recipient. The derangement of normal body flora has been held responsible for causation of various disorders. Probiotics have been tried in a number of infective and noninfective disorders and found useful, primarily because of their ability to supplement the normal body flora. Their use offers various advantages over-existing antimicrobial agents in being relatively cheap and safe. However, there are few reports of systemic fungemia associated with their use especially, in immunocompromised and severely debilitated patients. They also carry a risk of transferring resistance to other microbes including pathogens. In conclusion, more studies are required to establish their definite place in therapeutics.

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. The xanthones of Calophyllum inophyllum and Mesua Ferrea namely, dehydrocycloguanandin (DCG), calophyllin-B (CPB), jacareubin (JR), 6-desoxy jacareubin (DJR), mesuaxantbone-A (MXA), mesuaxanthone-B (MXB) and euxanthone (EX) were screened for various pharmacological effects in experimental animals. All the xanthones produced varying degrees of C.N.S. depression characterised by ptosis, sedation, decreased spontaneous motor activity, loss of muscle tone, potentiation of pentobarbitone sleeping time and ether anaerthesia in mice and rats.None of the xanthones had any analgesic, antipyretic and anticonvulsant activities. The xanthones did not produce any pharmacological effect in the cardiovascular system of frogs and dogs. All the xanthones exhibited anti inflammatory activity both by intraperitoneal and oral routes in rats as tested by carrageenin induced hind paw oedema, cotton pellet granuloma and granuloma pouch techniques, in normal and adrenalectomised rats. The xanthones did not have any mast cell membrane stabilising effect, and the degranulating effect of compound 48/80, diazoxide and Won-X-100 on rat peritoneal mast cells in vitro war not prevented. JR and DJR exhibited antiulcer activity in rats. The xanthones did not alter the prothrombin time in rats.

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The medicinal value of venoms has been known from ancient times. The active principles in venoms have been extensively investigated for their target specificity. Affinity for the primary sites responsible for lethality and efficacy at extremely low concentrations made these agents valuable tools or surrogates for basic biomedical research. The therapeutic effects of these agents are usually achieved by mechanisms that are different from that of conventional therapeutic agents. In the present paper, nonherbal natural therapeutic alternatives approved by the FDA, those that have undergone extensive clinical evaluation and shown promise in preclinical evaluation, or those that are isolated in pure form or subjected for the treatment to venoms are reviewed. These agents are suggested for the treatment of various diseases, including inflammatory, hematological, autoimmune, infectious, cardiovascular, malignant, neuromuscular, and psychotic diseases.

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Peptic ulcer disease (PUD) is a serious gastrointestinal disorder that requires a well targeted therapeutic strategy. A number of drugs including proton pump inhibitors and H2 receptor antagonists are available for the treatment of peptic ulcer, but clinical evaluation of these drugs has shown incidence of relapses, side effects, and drug interactions. This has been the rationale for the development of new antiulcer drugs and the search for novel molecules has been extended to herbal drugs that offer better protection and decreased relapse. Drugs of plant origin are gaining popularity and are being investigated for a number of disorders, including peptic ulcer. The present article reviews the antiulcerogenic and ulcer healing property of Ocimum sanctum , Allophylus serratus , Desmodium gagenticum, Azadirachta indica , Hemidesmus racemosus , Asparagus racemosus, and Musa sapientum. We have highlighted some of the important plants reported for their anti-ulcer and ulcer healing properties, in our laboratory and elsewhere during the last few years. Ayurvedic knowledge supported by modern science is necessary to isolate, characterise, and standardise the active constituents from herbal sources for antiulcer activity.

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Silymarin, a flavonolignan from the seeds of 'milk thistle' (Silybum marianum), has been widely used from ancient times because of its excellent hepatoprotective action. It is a mixture of mainly three flavonolignans, viz, silybin, silidianin, and silychristine, with silybin being the most active. Silymarin has been used medicinally to treat liver disorders, including acute and chronic viral hepatitis, toxin/drug-induced hepatitis, and cirrhosis and alcoholic liver diseases. It has also been reported to be effective in certain cancers. Its mechanism of action includes inhibition of hepatotoxin binding to receptor sites on the hepatocyte membrane; reduction of glutathione oxidation to enhance its level in the liver and intestine; antioxidant activity; and stimulation of ribosomal RNA polymerase and subsequent protein synthesis, leading to enhanced hepatocyte regeneration. It is orally absorbed but has very poor bioavailability due to its poor water solubility. This review focuses on the various pharmacological activities of silymarin including the clinical trials. For the first time, the review also looks at the formulation work that has been done to enhance its solubility, so as to increase its bioavailability and thus, its hepatoprotective action.

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International regulatory guidelines require that new chemical entities (NCEs) be tested first on animals (preclinical studies) for safety and efficacy before the start of clinical development. Long-term nonclinical studies such as carcinogenicity testing, the subject of the present review, is conducted in tandem with on-going clinical studies. Over the last few years, a number of regulatory changes have occurred in the regulatory requirements of carcinogenicity testing and the use of such data in human risk assessment process. The efforts are to provide a better mechanistic basis in interpretation of standard lifetime and short-term rodent bioassays. The major areas of focus of this review include the basic considerations for the lifetime rodent bioassay, the recommendations of the International Conference on Harmonization (ICH), and the development and validation of new short-term or alternative models for carcinogenicity testing. The objectives of these guidelines are to avoid the unnecessary use of animals in testing and to provide consistency in world wide regulatory assessments of applications. It will ultimately improve the precision in carcinogenicity testing, minimize the time requirement for such testing, and help to conserve the resources in the process of drug discovery and development.

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The use of cosmeceuticals has drastically risen in recent years. This significantly increases the armamentarium of the clinician in improving the treatment of skin, hair, and other conditions. They are at the juncture where wellness meets beauty and growing use by consumers is indicative of their popularity. This article focuses on skin, hair, and other cosmeceuticals and their regulatory aspects.

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Cardiac arrhythmias are of different types based on their mechanism and origin. The information gathered from animal studies has been instrumental in devising diagnostic and therapeutic strategies; so different animal models are needed for different types of arrhythmias. The origin and mechanism underlying clinical arrhythmias are of considerable significance, since knowledge of these processes may provide a basis for successful therapy. Various animal models that encompass different types of arrhythmias are reviewed. This review classifies various experimental models according to their origin, which are mainly supraventricular and ventricular. Also included are various transgenic animal models for arrhythmias.

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OBJECTIVE: To evaluate the antiinflammatory and analgesic activities of the aqueous extract of Spilanthes acmella (SPA) in experimental animal models. MATERIAL AND METHODS: SPA was evaluated for antiinflammatory action by carrageenan-induced rat paw edema. The analgesic activity was tested by acetic acid-induced writhing response in albino mice and tail flick method in albino rats. RESULTS: The aqueous extract of SPA in doses of 100, 200 and 400 mg/kg showed 52.6, 54.4 and 56.1% inhibition of paw edema respectively at the end of three hours and the percentage of protection from writhing was 46.9, 51.0 and 65.6 respectively. In the tail flick model, the aqueous extract of SPA in the above doses increased the pain threshold significantly after 30 min, 1, 2 and 4 h of administration. SPA showed dose-dependent action in all the experimental models. CONCLUSION: The present study indicates that SPA has significant antiinflammatory and analgesic properties.

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OBJECTIVE: To find out the hypoglycemic activity of Ficus hispida Linn. (bark) in normal and diabetic albino rats and to evaluate its probable mechanism of hypoglycemic activity if any. MATERIAL AND METHODS: Albino rats were divided into groups (n=6) receiving different treatments consisting of vehicle, water-soluble portion of the ethanol extract of Ficus hispida bark (FH) (1.25 g/kg) and standard antidiabetic drugs, glibenclamide (0.5 mg/kg) and 0.24 units of insulin (0.62 ml of 0.40 units/ml). Blood glucose was estimated by the glucose oxidase method in both normal and alloxan-induced diabetic rats before and 2 h after the administration of drugs. To find out the probable mechanism of action of FH as a hypoglycemic agent, i) the glycogen content of the liver, skeletal muscle and cardiac muscle, and ii) glucose uptake by isolated rat hemi-diaphragm were estimated. RESULTS: FH showed significant reduction of blood glucose level both in the normal (P<0.01) and diabetic (P<0.001) rats. However, the reduction in the blood glucose level was less than that of the standard drug, glibenclamide. FH also increased the uptake of glucose by rat hemi-diaphragm significantly (P<0.001). There was a significant increase in the glycogen content of the liver (P<0.05), skeletal muscle (P<0.01) and cardiac muscle (P<0.001). The amount of glycogen present in the cardiac muscle was more than the glycogen present in the skeletal muscle and liver. CONCLUSION: FH has significant hypoglycemic activity. Increased glycogenesis and enhanced peripheral uptake of glucose are the probable mechanisms involved in its hypoglycemic activity.

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OBJECTIVE: To evaluate the antibacterial potential of aqueous and acetone extracts of galls of Quercus infectoria by determination of Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) values. MATERIALS AND METHODS: The extracts from the galls of Q. infectoria at 10 mg/ml were screened against three Gram-positive bacteria (Staphylococcus aureus ATCC 25923, Staphylococcus epidermidis and Bacillus subtilis) and three Gram-negative bacteria (Escherichia coli NCTC 12079 serotype O157:H7, Salmonella typhimurium NCTC 74 and Pseudomonas aeruginosa ATCC 27853). The MIC of the extracts were then determined using the twofold serial microdilution technique at a concentration ranging from 5 mg/ml to 0.0024 mg/ml. The MBC values were finally obtained from the MIC microtiter wells which showed no turbidity after 24 hrs of incubation by subculturing method. RESULTS: Out of the six bacterial species tested, S. aureus was the most susceptible. On the other hand, the extracts showed weak inhibitory effect against S. epidermidis, B. subtilis, S. typhimurium and P. aeruginosa while there was no inhibition zone observed for E. coli O157. The MIC values of the extracts ranged from 0.0781 mg/ml to 1.25 mg/ml whereas the MBC values ranged from 0.3125 mg/ml to 2.50 mg/ml. The MBC values of aqueous extract against S. aureus and S. typhimurium were higher than their MIC values. The MBC value of acetone extract against S. aureus was also higher than its MIC value. Interestingly, however, the MIC and MBC values of acetone extract against S. typhimurium were the same (1.25 mg/ml). CONCLUSION: The aqueous and acetone extracts displayed similarities in their antimicrobial activity on the bacterial species and as such, the galls of Quercus infectoria are potentially good source of antimicrobial agents.

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Introducing a new drug to the market now costs an average of US$ 897 million and is a time consuming process. Discovering new uses for the old drugs offers the advantage of providing time tested drugs for the benefit of the patients. Serendipity plays an important role in this. This therapeutic option may provide cost effective treatment, especially for the developing countries with limited resources. This article focuses on the new potential uses of some common drugs. However, these options need to be pursued by more researches so that the potential benefits could be passed on to the patients.

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Calcitonin gene-related peptide (CGRP), a 37 amino acid neuropeptide, identified in multiple species, has widespread distribution and expression. CGRP acts through G protein-coupled receptors whose presence and changes in function modulate the peptide's effects in various tissues. Three receptor subtypes have been identified and CGRP's signal transduction through the receptors is dependent on two accessory proteins: Receptor activity modifying protein1 (RAMP1) and Receptor component protein (RCP). Several endogenous substances such as glucocorticoids, nitric oxide (NO), nerve growth factors (NGF), and steroid hormones modulate CGRP release and synthesis. Both peptide and non-peptide agonists and antagonists of CGRP receptors are being developed. Also the therapeutic benefits of some antagonists such as BIBN 4096 BS in migraine have been promising. This brief review provides a preliminary understanding of the diverse biological effects of the peptide in various systems. The current status of CGRP and its receptors in many pathophysiological states is not fully explored and future findings are greatly awaited.

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OBJECTIVE: To evaluate the effects of Centella asiatica (CA) upon pain (antinociception) and inflammation in rodent models. MATERIAL AND METHODS: The antinociceptive activity of the water extract of CA (10, 30, 100 and 300 mg/kg) was studied using acetic acid-induced writhing and hot-plate method in mice. The antiinflammatory activity of CA was studied in rats by prostaglandin E2-induced paw edema. RESULTS: Water extract of CA revealed significant antinociceptive activity with both the models. The activity was statistically similar to aspirin but less potent than morphine. The CA extract also revealed significant antiinflammatory activity. This effect was statistically similar to the non-steroidal antiinflammatory drug, mefenamic acid. CONCLUSION: These results suggest that the water extract of CA possesses antinociceptive and antiinflammatory activities.

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The lipid-lowering actions of statins are well known. However, recent studies provide compelling evidence that the clinical benefits of statin therapy may also be attributed to mechanisms independent of their cholesterol-lowering effects. These non-lipid-lowering (pleiotropic) effects of statin therapy are believed to include antiinflammatory actions, property to reverse endothelial dysfunction by decreasing LDL oxidation and increasing nitric oxide bioavailability. Their antioxidant actions, ability to provide plaque stability, favorable coagulation profile, ability to prevent platelet aggregation and normalize sympathetic outflow as well as their antiproliferative and immunosuppressive properties also contribute to the non-lipid-lowering effects. These pleiotropic effects shown by statin therapy offer many advantages over the currently available drugs for dyslipidemias. These additional benefits not only find therapeutic application in cardiovascular disorders but also in many other disease states.

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P-glycoprotein (P-gp) is a 170 kDa membrane-bound protein, an energy-dependent efflux transporter driven by ATP hydrolysis. It is responsible for multidrug resistance of many drugs. Physiologically, it is involved in limiting the harmful exposure of toxins, drugs, and xenobiotics to the body by extruding them out of cells. It is increasingly recognized to play an important modulating role in the pharmacokinetic properties of many clinically important therapeutic agents and because of its importance in pharmacokinetics, its screening has to be incorporated into the drug discovery process. The modulation of drug transporters through inhibition or induction by various drugs or herbs can lead to significant drug-drug or drug-herb interactions by affecting various pharmacokinetic parameters of the drug. In addition, genetic polymorphism of P-gp has also been reported, which may affect drug disposition, produce variable drug effects, and may change disease risk susceptibility. As drug interactions and genetic polymorphism are important factors to be considered during drug development, P-gp may have an impact on drug development in future.

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Aim: Hyperhomocysteinemia and vitamins B ₆ , B ₉ , and B ₁₂ deficiencies usually result in various neurological, vascular, ocular, renal, and pulmonary abnormalities. However, to date, there are no simultaneous detection methods available for determining homocysteine, vitamins B ₆ , B ₉ , and B ₁₂ levels in various biological fluids. In this study, we aim to develop a new validated simultaneous detection method for all four compounds to save both cost and time of analysis. Materials and Methods: The mobile phase consisted of a mixture of methanol and 1-heptanesulfonic acid sodium salt (33:67) with 0.05% triethylamine. The pH of the entire mixture was adjusted to 2.3 and the flow rate was 0.5 mL/min. Separation was achieved using a C-18 column (5 μm; 150 mm × 4.6 mm) maintained at 28°C in a column oven and the detection was conducted at 210 nm. Results: The method was linear between 50 and 1600 ng/mL for all of the drugs. The limits of detection for homocysteine, vitamins B ₆ , B ₉ , and B ₁₂ were 5, 5, 10, and 10 ng/mL, respectively, while the limits of quantification were 10, 10, 25, and 25 ng/L, respectively. The developed method achieved good precision and accuracy and complies with the Food and Drug Administration (FDA) requirements. Conclusion: The developed and validated method is suitable to be used for the routine analysis of homocysteine, vitamins B ₆ , B ₉ , and B ₁₂ simultaneously in human serum.

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