Therapeutics aimed at blocking the cannabinoid 1 (CB1) receptor for treatment of obesity resulted in significant improvements in liver function, glucose uptake and pancreatic β-cell function independent of weight loss or CB1 receptor blockade in the brain, suggesting that peripherally-acting only CB1 receptor blockers may be useful therapeutic agents. Neuropsychiatric side effects and lack of tissue specificity precluded clinical use of first-generation, centrally acting CB1 receptor blockers. In this study we specifically analyzed the potential relevance to diabetes of human CB1 receptor isoforms in extraneural tissues involved in glucose metabolism. We identified an isoform of the human CB1 receptor (CB1b) that is highly expressed in β-cells and hepatocytes but not in the brain. Importantly, CB1b shows stronger affinity for the inverse agonist JD-5037 than for rimonabant compared to CB1 full length. Most relevant to the field, CB1b is a potent regulator of adenylyl cyclase activity in peripheral metabolic tissues. CB1b blockade by JD-5037 results in stronger adenylyl cyclase activation compared to rimonabant and it is a better enhancer of insulin secretion in β-cells. We propose this isoform as a principal pharmacological target for the treatment of metabolic disorders involving glucose metabolism.

The research aims to indicate which of the structural elements of monoterpenes are responsible for their antioxidant activity. The activity was determined spectrophotometrically with the use of the DPPH(•) assay. It has been shown that π bonds are responsible for the chain-breaking antioxidant activity of monoterpenes. It has been proved, for the first time, that blocking of conjugated double bonds leads to a decrease of the antioxidant activity of monoterpenes. A probable reaction mechanism between monoterpenes and DPPH(•) has been proposed. It has been indicated that the antioxidant activity of monoterpenes strongly depends on the polarity of solvent used in the experiments. The presented results may stimulate additional research in the field of terpenoid antioxidants.

Natural product extracts are a rich source of bioactive compounds. As a result, the screening of natural products for the identification of novel biologically active metabolites has been an essential part of several drug discovery programs. It is estimated that more than 70% of all drugs approved from 1981 and 2006, were either derived from or structurally similar to nature based compounds indicating the necessity for the development of a rapid method for the identification of novel compounds from plant extracts. The screening of biological matrices for the identification of novel modulators is nevertheless still challenging. In this review we discuss current techniques in phytochemical analysis and the identification of biologically active components.

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Parkinson’s disease is an age-associated neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons from the midbrain. Epidemiological studies have implicated exposures to environmental toxins like the herbicide paraquat as major contributors to Parkinson’s disease etiology in both mammalian and invertebrate models. We have employed a paraquat-induced Parkinson’s disease model in Drosophila as an inexpensive in vivo platform to screen therapeutics from natural products. We have identified the polymethoxyflavonoid, GardeninA, with neuroprotective potential against paraquat-induced parkinsonian symptoms involving reduced survival, mobility defects, and loss of dopaminergic neurons. GardeninA-mediated neuroprotection is not solely dependent on its antioxidant activities but also involves modulation of the neuroinflammatory and cellular death responses. Furthermore, we have successfully shown GardeninA bioavailability in the fly heads after oral administration using ultra-performance liquid chromatography and mass spectrometry. Our findings reveal a molecular mechanistic insight into GardeninA-mediated neuroprotection against environmental toxin-induced Parkinson’s disease pathogenesis for novel therapeutic intervention.