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JournalISSN: 1043-6618

Pharmacological Research

About: Pharmacological Research is an academic journal. The journal publishes majorly in the area(s): Receptor & Oxidative stress. It has an ISSN identifier of 1043-6618. Over the lifetime, 7218 publication(s) have been published receiving 193241 citation(s). The journal is also known as: Pharmacol. Res. & Pharmacological Research Communications. more

Topics: Receptor, Oxidative stress, Population more

Journal ArticleDOI: 10.1016/J.PHRS.2007.01.012
A V Rao1, L G Rao1Institutions (1)
Abstract: Oxidative stress is an important contributor to the risk of chronic diseases. Dietary guidelines recommend increased consumption of fruits and vegetables to combat the incidence of human diseases such as cancer, cardiovascular disease, osteoporosis and diabetes. Fruits and vegetables are good sources of antioxidant phytochemicals that mitigate the damaging effect of oxidative stress. Carotenoids are a group of phytochemicals that are responsible for different colors of the foods. They are recognized as playing an important role in the prevention of human diseases and maintaining good health. In addition to being potent antioxidants some carotenoids also contribute to dietary vitamin A. There is scientific evidence in support of the beneficial role of phytochemicals in the prevention of several chronic diseases. Although the chemistry of carotenoids has been studied extensively, their bioavailability, metabolism and biological functions are only now beginning to be investigated. Recent interest in carotenoids has focused on the role of lycopene in human health. Unlike some other carotenoids, lycopene does not have pro-vitamin A properties. Because of the unsaturated nature of lycopene it is considered to be a potent antioxidant and a singlet oxygen quencher. This article will review carotenoids in general and lycopene in particular for their role in human health. more

Topics: Phytochemical (60%), Carotenoid (53%)

1,586 Citations

Journal ArticleDOI: 10.1016/J.PHRS.2005.05.004
Abstract: The objective of the present study was to develop a rat model that replicates the natural history and metabolic characteristics of human type 2 diabetes and is also suitable for pharmacological screening. Male Sprague-Dawley rats (160-180 g) were divided into two groups and fed with commercially available normal pellet diet (NPD) (12% calories as fat) or in-house prepared high-fat diet (HFD) (58% calories as fat), respectively, for a period of 2 weeks. The HFD-fed rats exhibited significant increase in body weight, basal plasma glucose (PGL), insulin (PI), triglycerides (PTG) and total cholesterol (PTC) levels as compared to NPD-fed control rats. Besides, the HFD rats showed significant reduction in glucose disappearance rate (K-value) on intravenous insulin glucose tolerance test (IVIGTT). Hyperinsulinemia together with reduced glucose disappearance rate (K-value) suggested that the feeding of HFD-induced insulin resistance in rats. After 2 weeks of dietary manipulation, a subset of the rats from both groups was injected intraperitoneally with low dose of streptozotocin (STZ) (35 mg kg(-1)). Insulin-resistant HFD-fed rats developed frank hyperglycemia upon STZ injection that, however, caused only mild elevation in PGL in NPD-fed rats. Though there was significant reduction in PI level after STZ injection in HFD rats, the reduction observed was only to a level that was comparable with NPD-fed control rats. In addition, the levels of PTG and PTC were further accentuated after STZ treatment in HFD-fed rats. In contrast, STZ (35 mg kg(-1), i.p.) failed to significantly alter PI, PTG and PTC levels in NPD-fed rats. Thus, these fat-fed/STZ-treated rats simulate natural disease progression and metabolic characteristics typical of individuals at increased risk of developing type 2 diabetes because of insulin resistance and obesity. Further, the fat-fed/STZ-treated rats were found to be sensitive for glucose lowering effects of insulin sensitizing (pioglitazone) as well as insulinotropic (glipizide) agents. Besides, the effect of pioglitazone and glipizide on the plasma lipid parameters (PTG and PTC) was shown in these diabetic rats. The present study represents that the combination of HFD-fed and low-dose STZ-treated rat serves as an alternative animal model for type 2 diabetes simulating the human syndrome that is also suitable for testing anti-diabetic agents for the treatment of type 2 diabetes. more

Topics: Insulin resistance (60%), Glucose tolerance test (57%), Insulin (56%) more

1,385 Citations

Journal ArticleDOI: 10.1016/J.PHRS.2012.04.005
Abstract: ERK1 and ERK2 are related protein-serine/threonine kinases that participate in the Ras-Raf-MEK-ERK signal transduction cascade. This cascade participates in the regulation of a large variety of processes including cell adhesion, cell cycle progression, cell migration, cell survival, differentiation, metabolism, proliferation, and transcription. MEK1/2 catalyze the phosphorylation of human ERK1/2 at Tyr204/187 and then Thr202/185. The phosphorylation of both tyrosine and threonine is required for enzyme activation. Whereas the Raf kinase and MEK families have narrow substrate specificity, ERK1/2 catalyze the phosphorylation of hundreds of cytoplasmic and nuclear substrates including regulatory molecules and transcription factors. ERK1/2 are proline-directed kinases that preferentially catalyze the phosphorylation of substrates containing a Pro-Xxx-Ser/Thr-Pro sequence. Besides this primary structure requirement, many ERK1/2 substrates possess a D-docking site, an F-docking site, or both. A variety of scaffold proteins including KSR1/2, IQGAP1, MP1, β-Arrestin1/2 participate in the regulation of the ERK1/2 MAP kinase cascade. The regulatory dephosphorylation of ERK1/2 is mediated by protein-tyrosine specific phosphatases, protein-serine/threonine phosphatases, and dual specificity phosphatases. The combination of kinases and phosphatases make the overall process reversible. The ERK1/2 catalyzed phosphorylation of nuclear transcription factors including those of Ets, Elk, and c-Fos represents an important function and requires the translocation of ERK1/2 into the nucleus by active and passive processes involving the nuclear pore. These transcription factors participate in the immediate early gene response. The activity of the Ras-Raf-MEK-ERK cascade is increased in about one-third of all human cancers, and inhibition of components of this cascade by targeted inhibitors represents an important anti-tumor strategy. Thus far, however, only inhibition of mutant B-Raf (Val600Glu) has been found to be therapeutically efficacious. more

1,087 Citations

Open accessJournal ArticleDOI: 10.1006/PHRS.1999.0495
Lloyd A. Horrocks, Young K. Yeo1Institutions (1)
Abstract: Docosahexaenoic acid DHA is essential for the growth and functional development of the brain in infants. DHA is also required for maintenance of normal brain function in adults. The inclusion of plentiful DHA in the diet improves learning ability, whereas deficiencies of DHA are associated with deficits in learning. DHA is taken up by the brain in preference to other fatty acids. The turnover of DHA in the brain is very fast, more so than is generally realized. The visual acuity of healthy, full-term, formula-fed infants is increased when their formula includes DHA. During the last 50 years, many infants have been fed formula diets lacking DHA and other omega-3 fatty acids. DHA deficiencies are associated with foetal alcohol syndrome, attention deficit hyperactivity disorder, cystic fibrosis, phenylketonuria, unipolar depression, aggressive hostility, and adrenoleukodystrophy. De- creases in DHA in the brain are associated with cognitive decline during aging and with onset of sporadic Alzheimer disease. The leading cause of death in western nations is cardiovascular disease. Epidemiological studies have shown a strong correlation between fish consumption and reduction in sudden death from myocardial infarction. The reduction is approximately 50% with 200 mg day y1 of DHA from fish. DHA is the active component in fish. Not only does fish oil reduce triglycerides in the blood and decrease thrombosis, but it also prevents cardiac arrhythmias. The association of DHA deficiency with depression is the reason for the robust positive correlation between depression and myocardial infarc- tion. Patients with cardiovascular disease or Type II diabetes are often advised to adopt a low-fat diet with a high proportion of carbohydrate. A study with women shows that this type of diet increases plasma triglycerides and the severity of Type II diabetes and coronary . heart disease. DHA is present in fatty fish salmon, tuna, mackerel and mother's milk. DHA is present at low levels in meat and eggs, but is not usually present in infant formulas. EPA, another long-chain n-3 fatty acid, is also present in fatty fish. The shorter chain n-3 fatty acid, a-linolenic acid, is not converted very well to DHA in man. These longchain n-3 . fatty acids also known as omega-3 fatty acids are now becoming available in some foods, especially infant formula and eggs in Europe and Japan. Fish oil decreases the proliferation of tumour cells, whereas arachidonic acid, a longchain n-6 fatty acid, increases their proliferation. These opposite effects are also seen with inflammation, particularly with rheumatoid arthritis, and with asthma. DHA has a positive effect on diseases such as hypertension, arthritis, atherosclerosis, depression, adult-onset diabetes mellitus, myocar- dial infarction, thrombosis, and some cancers. Q 1999 Academic Press more

Topics: Docosahexaenoic acid (61%), Fish oil (58%), Fatty acid (54%) more

928 Citations

Open accessJournal Article
Abstract: Proteinase-activated receptors are a recently described, novel family of seven-transmembrane G-protein-coupled receptors. Rather then being stimulated through ligand receptor occupancy, activation is initiated by cleavage of the N terminus of the receptor by a serine protease resulting in the generation of a new tethered ligand that interacts with the receptor within extracellular loop-2. To date, four proteinase-activated receptors (PARs) have been identified, with distinct N-terminal cleavage sites and tethered ligand pharmacology. In addition to the progress in the generation of PAR-1 antagonists, we describe the role of thrombin in such processes as wound healing and the evidence implicating PAR-1 in vascular disorders and cancer. We also identify advances in the understanding of PAR-1-mediated intracellular signaling and receptor desensitization. The cellular functions, signaling events, and desensitization processes involved in PAR-2 activation are also assessed. However, other major aspects of PAR-2 are highlighted, in particular the ability of several serine protease enzymes, in addition to trypsin, to function as activators of PAR-2. The likely physiological and pathophysiological roles for PAR-2 in skin, intestine, blood vessels, and the peripheral nervous system are considered in the context of PAR-2 activation by multiple serine proteases. The recent discovery of PAR-3 and PAR-4 as additional thrombin-sensitive PARs further highlights the complexity in assessing the effects of thrombin in several different systems, an issue that remains to be fully addressed. These discoveries have also highlighted possible PAR-PAR interactions at both functional and molecular levels. The future identification of other PARs and their modes of activation are an important future direction for this expanding field of study. more

901 Citations

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Journal's top 5 most impactful authors

Amirhossein Sahebkar

49 papers, 1.9K citations

Maciej Banach

19 papers, 489 citations

Liang Liu

15 papers, 237 citations

Gian Vincenzo Zuccotti

14 papers, 438 citations

Achille P. Caputi

13 papers, 483 citations

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