Nutraceutical based SIRT3 activators as therapeutic targets in Alzheimer's disease.

Alzheimer's disease (AD) is the most common neurodegenerative disease, and its incidence is increasing worldwide with increased lifespan. Currently, there is no effective treatment to cure or prevent the progression of AD, which indicates the need to develop novel therapeutic targets and agents. Sirtuins, especially SIRT3, a mitochondrial deacetylase, are NAD-dependent histone deacetylases involved in aging and longevity. Accumulating evidence indicates that SIRT3 dysfunction is strongly associated with pathologies of AD, hence, therapeutic modulation of SIRT3 activity may be a novel application to ameliorate the pathologies of AD. Natural products commonly used in traditional medicine have wide utility and appear to have therapeutic benefits for the treatment of neurodegenerative diseases such as AD. The present review summarizes the currently available natural SIRT3 activators and their potentially neuroprotective molecular mechanisms of action that make them a promising agent in the treatment and management of neurodegenerative diseases such as AD.

Elucidating the anti-melanoma effect and mechanisms of Hispolon.

There is a rapid increase in the incidence of melanoma which has led to a global crisis. Thus, there is a great need for developing novel, safe and effective drugs for the treatment of melanoma. Hispolon is a small molecular weight polyphenol derived from Phellinus linteus, which has antioxidant, anti-inflammatory and anti-proliferative activities. Hispolon has been reported to induce apoptosis in gastric cancer, hepatocellular carcinoma, and myeloid leukemia. However, the anticancer effect in melanoma is not well elucidated. Thus, our present study was to investigate the anti-cancer effect of hispolon on melanoma cancer cells. B16BL6 cells were treated with different concentrations of hispolon for 24 h and the effect on oxidative stress, mitochondrial functions, apoptosis and cell proliferation were studied. Hispolon is a potent generator of reactive oxygen species, nitrite and lipid peroxide levels. Furthermore, it significantly inhibits the expression of Bcl-2 and promotes the expression of Bax, increases the activity of caspase 1 and 3, inhibits mitochondrial Complex I and IV activities. By the above mechanisms, hispolon dose-dependently exhibited the antimelanoma effect similar to the well established pharmacological agent, curcumin. Thus, hispolon can be a potent anti-melanoma drug in the future if the pharmacodynamic effects and the toxicological studies are appropriately carried out.

Concurrent nicotine exposure to prenatal alcohol consumption alters the hippocampal and cortical neurotoxicity.

AIMS: This study investigated the neurotoxic effects of prenatal alcohol and nicotine exposure in the cortex and hippocampus of rodents. MAIN METHODS: Behavioral alterations, electrophysiological changes, and biochemical markers associated with cholinergic neurotransmission, neural oxidative stress, mitochondrial function, and apoptosis were evaluated. KEY FINDINGS: Prenatal alcohol exposure induced the generation of ROS, nitrite and lipid peroxide, decreased mitochondrial Complex-I and IV activities, increased Caspase-1 and 3 activities, had no effect on cholinergic neurotransmission, increased expression of PSD-95, decreased LTP and decreased performance on spatial memory tasks. However, nicotine exposure, in addition to alcohol exposure, was found to mitigate the negative effects of alcohol alone on ROS generation and spatial memory task performances. Furthermore, we also studied the role of ILK in prenatal alcohol and nicotine exposure. SIGNIFICANCE: Prenatal Smoking and/or drinking is a major health concern around the world. Thus, our current study may lead to better insights into the molecular mechanisms of fetal alcohol and nicotine exposure on the developing offspring.

Assessment of the cerebellar neurotoxic effects of nicotine in prenatal alcohol exposure in rats.

The adverse effects of prenatal nicotine and alcohol exposure on human reproductive outcomes are a major scientific and public health concern. In the United States, substantial percentage of women (20-25%) of childbearing age currently smoke cigarettes and consume alcohol, and only a small percentage of these individuals quit after learning of their pregnancy. However, there are very few scientific reports on the effect of nicotine in prenatal alcohol exposure on the cerebellum of the offspring. Therefore, this study was conducted to investigate the cerebellar neurotoxic effects of nicotine in a rodent model of Fetal Alcohol Spectrum Disorder (FASD). In this study, we evaluated the behavioral changes, biochemical markers of oxidative stress and apoptosis, mitochondrial functions and the molecular mechanisms associated with nicotine in prenatal alcohol exposure on the cerebellum. Prenatal nicotine and alcohol exposure induced oxidative stress, did not affect the mitochondrial functions, increased the monoamine oxidase activity, increased caspase expression and decreased ILK, PSD-95 and GLUR1 expression without affecting the GSK-3ß. Thus, our current study of prenatal alcohol and nicotine exposure on cerebellar neurotoxicity may lead to new scientific perceptions and novel and suitable therapeutic actions in the future.