MitoNEET (CISD1) Knockout Mice Show Signs of Striatal Mitochondrial Dysfunction and a Parkinson's Disease Phenotype.

Mitochondrial dysfunction is thought to play a significant role in neurodegeneration observed in Parkinson's disease (PD), yet the mechanisms underlying this pathology remain unclear. Here, we demonstrate that loss of mitoNEET (CISD1), an iron-sulfur containing protein that regulates mitochondrial bioenergetics, results in mitochondrial dysfunction and loss of striatal dopamine and tyrosine hydroxylase. Mitochondria isolated from mice lacking mitoNEET were dysfunctional as revealed by elevated reactive oxygen species (ROS) and reduced capacity to produce ATP.

Structure-activity and in vivo evaluation of a novel lipoprotein lipase (LPL) activator.

Elevated triglycerides (TG) contribute towards increased risk for cardiovascular disease. Lipoprotein lipase (LPL) is an enzyme that is responsible for the metabolism of core triglycerides of very-low density lipoproteins (VLDL) and chylomicrons in the vasculature. In this study, we explored the structure-activity relationships of our lead compound (C10d) that we have previously identified as an LPL agonist.

Emerging strategies of targeting lipoprotein lipase for metabolic and cardiovascular diseases.

Although statins and other pharmacological approaches have improved the management of lipid abnormalities, there exists a need for newer treatment modalities especially for the management of hypertriglyceridemia. Lipoprotein lipase (LPL), by promoting hydrolytic cleavage of the triglyceride core of lipoproteins, is a crucial node in the management of plasma lipid levels. Although LPL expression and activity modulation is observed as a pleiotropic action of some the commonly used lipid lowering drugs, the deliberate development of drugs targeting LPL has not occurred yet.

Identification of small molecules that bind to the mitochondrial protein mitoNEET.

MitoNEET (CISD1) is a 2Fe-2S iron-sulfur cluster protein belonging to the zinc-finger protein family. Recently mitoNEET has been shown to be a major role player in the mitochondrial function associated with metabolic type diseases such as obesity and cancers. The anti-diabetic drug pioglitazone and rosiglitazone were the first identified ligands to mitoNEET.

Inducible Nitric Oxide Inhibitors Block NMDA Antagonist-Stimulated Motoric Behaviors and Medial Prefrontal Cortical Glutamate Efflux.

Nitric oxide (NO) plays a critical role in the motoric and glutamate releasing action of N-methyl-D-aspartate (NMDA)-antagonist stimulants. Earlier studies utilized neuronal nitric oxide synthase inhibitors (nNOS) for studying the neurobehavioral effects of non-competitive NMDA-antagonist stimulants such as dizocilpine (MK-801) and phencyclidine (PCP). This study explores the role of the inducible nitric oxide synthase inhibitors (iNOS) aminoguanidine (AG) and (-)-epigallocatechin-3-gallate (EGCG) in NMDA-antagonist induced motoric behavior and prefrontal cortical glutamate efflux.

Evolution of a Natural Products and Nutraceuticals Course in the Pharmacy Curriculum.

Objective. To develop, implement, and modify a required, second-year pharmacy course that provides an understanding of the scientific, therapeutic, and clinical principles, as well as the evidence-based medicine underlying the use of natural products. Design.

Pharmacotherapy of Alzheimer's disease: current and future trends.

Alzheimer's disease (AD) and its related dementia has shown an alarming rise in the global population. Although considerable efforts have been made to develop effective therapeutic agents for AD therapy, drug development has not met significant clinical success. Current pharmacotherapy of AD is limited to cholinesterase inhibitors and the N-methyl-D-aspartate antagonist memantine.

Pomegranate Bioactive Constituents Suppress Cell Proliferation and Induce Apoptosis in an Experimental Model of Hepatocellular Carcinoma: Role of Wnt/ β -Catenin Signaling Pathway.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide, and chemoprevention represents a viable approach in lowering the mortality of this disease. Pomegranate fruit, an abundant source of anti-inflammatory phytochemicals, is gaining tremendous attention for its wide-spectrum health benefits. We previously reported that a characterized pomegranate emulsion (PE) prevents diethylnitrosamine (DENA)-induced rat hepatocarcinogenesis though inhibition of nuclear factor-kappaB (NF- κ B).

Chemopreventive and therapeutic potential of tea polyphenols in hepatocellular cancer.

The prophylactic and therapeutic properties of tea have been attributed to green tea catechins and black tea theaflavins besides several other polyphenolic compounds. Tea polyphenols possess potent antioxidant and antiinflammatory properties and modulate several signaling pathways. These biochemical facets of tea polyphenols are responsible for its anticancer properties.

Chemopreventive effect of a novel oleanane triterpenoid in a chemically induced rodent model of breast cancer.

Breast cancer represents one of the most frequently diagnosed cancers and predominant causes of death in women worldwide. The value of preventive therapy to limit the devastating impact of breast cancer is well established. Various plant triterpenoids and their synthetic analogs have shown significant promise as potent chemopreventive agents in breast cancer.

Dietary phytochemicals in the chemoprevention and treatment of hepatocellular carcinoma: in vivo evidence, molecular targets, and clinical relevance.

Hepatocellular carcinoma (HCC), one of the most common and lethal cancers, is a growing menace in modern society. Until recently, the majority of detected cases of liver cancer have been found in the developing nations of Asia and Africa; however, its occurrence has significantly increased in the United States. HCC occurs due to several etiologies, such as alcoholism, dietary carcinogens, iron overload, viral hepatitis, as well as several hepatic chronic diseases.

Angiogenesis in hepatocellular carcinoma: a potential target for chemoprevention and therapy.

Hepatocellular carcinoma (HCC) remains one of the most lethal cancers in the world. Since current treatment options including surgical resection and liver transplantation offer limited therapeutic benefits, there exists a need to evaluate novel therapeutic strategies for the amelioration of HCC. Hepatic tumors are highly vascularized, possessing a rich network of blood vessels and capillaries and there exist an angiogenic component to the tumor growth observed in HCC.

Black currant anthocyanins abrogate oxidative stress through Nrf2- mediated antioxidant mechanisms in a rat model of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC), considered to be one of the most lethal cancers with almost > 1 million deaths reported annually worldwide, remains a devastating disease with no known effective cure. Hence, chemopreventive strategies come into play, offering an effective and safe mode of treatment, ideal to ward off potential cancer risks and mortality. A major predisposing condition, pertinent to the development and progression of HCC is oxidative stress.

Pomegranate phytoconstituents blunt the inflammatory cascade in a chemically induced rodent model of hepatocellular carcinogenesis.

Liver cancer, predominantly hepatocellular carcinoma (HCC), represents a complex and fatal malignancy driven primarily by oxidative stress and inflammation. Due to dismal prognosis and limited therapeutic intervention, chemoprevention has emerged as a viable approach to reduce the morbidity and mortality of HCC. Pomegranate fruit is a rich source of phytochemicals endowed with potent antioxidant and anti-inflammatory properties.

Dimebon attenuates methamphetamine, but not MPTP, striatal dopamine depletion.

Dimebon is an anti-histamine with central nervous system activity. In this report the effects of dimebon as a neuroprotectant in animal models of Parkinson's disease were tested as assessed in methamphetamine- and MPTP-induced striatal dopaminergic toxicity. Dimebon (1mg/kg) administered at 30 min prior to methamphetamine (40mg/kg) significantly reduced the amount of striatal dopamine depletion in mice, without altering the initial methamphetamine-induced increase in body temperature.

The health benefits of blackcurrants.

The blackcurrant (Ribes nigrum L., Grossulariceae), a small, perennial shrub native to central Europe and northern Asia, is cultivated throughout the world, including the United States. In addition to its anecdotal use in traditional herbal medicine, modern laboratories have demonstrated the potent anti-inflammatory, antioxidant and antimicrobial effects of blackcurrant constituents on a myriad of disease states.

Curcumin and neurodegenerative diseases: a perspective.

Introduction: Curcumin, a dietary polyphenol found in the curry spice turmeric, possesses potent antioxidant and anti-inflammatory properties and an ability to modulate multiple targets implicated in the pathogenesis of chronic illness. Curcumin has shown therapeutic potential for neurodegenerative diseases including Alzheimer's disease (AD) and Parkinson's disease (PD).

Areas Covered: This article highlights the background and epidemiological evidence of curcumin's health benefits and its pharmacodynamic and pharmacokinetic profile.

Markers associated with testosterone enhancement of methamphetamine-induced striatal dopaminergic neurotoxicity.

Intact male CD-1 mice received an injection of testosterone propionate (TP--5 ug), progesterone (P--5 mg), the oil vehicle or remained untreated (control). At 24 hours after hormonal treatments the mice received an injection of methamphetamine (MA--40 mg/kg) and rectal temperatures were measured. At 5 days post-MA, assays were performed to assess effects of these treatments.

Black currant phytoconstituents exert chemoprevention of diethylnitrosamine-initiated hepatocarcinogenesis by suppression of the inflammatory response.

Black currant fruits containing high amounts of anthocyanins are known to possess potent antioxidant and anti-inflammatory properties. We have previously reported that anthocyanin-rich black currant skin extract (BCSE) inhibits diethylnitrosamine (DENA)-initiated hepatocarcinogenesis in rats although the underlying mechanisms are not fully understood. Our present study investigates the anti-inflammatory mechanisms of BCSE during DENA rat liver carcinogenesis.

In vivo brain microdialysis: advances in neuropsychopharmacology and drug discovery.

INTRODUCTION: Microdialysis is an important in vivo sampling technique, useful in the assay of extracellular tissue fluid. The technique has both pre-clinical and clinical applications but is most widely used in neuroscience. The in vivo microdialysis technique allows measurement of neurotransmitters such as acetycholine (ACh), the biogenic amines including dopamine (DA), norepinephrine (NE) and serotonin (5-HT), amino acids such as glutamate (Glu) and gamma aminobutyric acid (GABA), as well as the metabolites of the aforementioned neurotransmitters, and neuropeptides in neuronal extracellular fluid in discrete brain regions of laboratory animals such as rodents and non-human primates.

Alteration of hepatic proinflammatory cytokines is involved in the resveratrol-mediated chemoprevention of chemically-induced hepatocarcinogenesis.

Hepatocellular carcinoma (HCC), one of the most common cancers in the world, is a leading cause of cancerrelated mortality. HCC develops most frequently in the background of oxidative stress and chronic hepatic inflammation due to viral infections, alcohol abuse as well as exposure to environmental and dietary carcinogens. As the prognosis of HCC is extremely poor and mostly unresponsive to current chemotherapeutic treatment regimens, novel preventive approaches like chemoprevention are urgently needed.

Natural products of dietary origin as lead compounds in virtual screening and drug design.

Natural products have been found to be useful in the treatment of several diseases across the ages. In this article, we review the use of natural products, obtained from dietary sources, as lead compounds in developing novel therapeutic agents. These compounds have shown tremendous promise in the prevention and as well as treatment of a variety of chronic ailments.

Curcumin and liver cancer: a review.

Primary liver cancer, also known as hepatocellular carcinoma (HCC), is one of the most lethal cancers having worldwide prevalence. Although most HCC cases are reported in the developing countries of Asia and Africa, there has been an alarming increase in HCC cases in Western Europe as well as United States. Chronic liver diseases, viral hepatitis, alcoholism as well as dietary carcinogens, such as aflatoxins and nitrosoamines, contribute to HCC.

Pomegranate-mediated chemoprevention of experimental hepatocarcinogenesis involves Nrf2-regulated antioxidant mechanisms.

Hepatocellular carcinoma (HCC), one of the most prevalent and lethal cancers, has shown an alarming rise in the USA. Without effective therapy for HCC, novel chemopreventive strategies may effectively circumvent the current morbidity and mortality. Oxidative stress predisposes to hepatocarcinogenesis and is the major driving force of HCC.

Anthocyanin-rich black currant (Ribes nigrum L.) extract affords chemoprevention against diethylnitrosamine-induced hepatocellular carcinogenesis in rats.

Anthocyanins are known to possess potent anticarcinogenic properties against several cancers thus demonstrating potential for cancer prevention. Black currant (Ribes nigrum L., Grossulariaceae) fruits have a high anthocyanin content.