A Comprehensive Review of Phytonutrients as a Dietary Therapy for Obesity.

Obesity is a complex medical condition mainly caused by eating habits, genetics, lifestyle, and medicine. The present study deals with traditional diets like the Mediterranean diet, Nordic diet, African Heritage diet, Asian diet, and DASH, as these are considered to be sustainable diets for curing obesity. However, the bioavailability of phytonutrients consumed in the diet may vary, depending on several factors such as digestion and absorption of phytonutrients, interaction with other substances, cooking processes, and individual differences. Hence, several phytochemicals, like polyphenols, alkaloids, saponins, terpenoids, etc., have been investigated to assess their efficiencies and safety in the prevention and treatment of obesity. These phytochemicals have anti-obesity effects, mediated via modulation of many pathways, such as decreased lipogenesis, lipid absorption, accelerated lipolysis, energy intake, expenditure, and preadipocyte differentiation and proliferation. Owing to these anti-obesity effects, new food formulations incorporating these phytonutrients were introduced that can be beneficial in reducing the prevalence of obesity and promoting public health.

Cyclic di-peptide in situ inhibited protein-aggregation.

An increasing number of neurodegenerative diseases seem to be associated with protein misfolding that often leads to misfolded protein aggregates with a ß-sheet conformation and accumulation in the brain which directly contributes to or modulates the associated pathology. Protein aggregation diseases like Huntington's disease results from the deposition of aggregated huntingtin proteins within the nucleus, transmissible prion encephalopathies occur due to extracellular deposition of pathogenic prion proteins whereas Alzheimer's disease from the accumulation of both extracellular ß-amyloid and intracellular hyperphosphorylated tau protein aggregates. In the generalized purpose, we have taken the core sequence of amyloid-ß (responsible for its aggregation) as the aggregating peptide (AP). Among the various emerging therapeutic approaches against aggregation-related degenerative diseases such as diminishing the monomeric precursor protein, inhibiting aggregation, or blocking aggregation-induced cellular toxicity pathways, we focussed on the strategy based on the inhibition of protein aggregation using rationally designed peptide inhibitors comprising both the recognition and ß-breaking component in the sequence. The "O â†’ N acyl migration" concept was used to form cyclic peptide in situ for the generation of a bent unit which may act as disruption moiety for the inhibition process. The kinetics of aggregation was characterized by various biophysical tools (ThT-assay, TEM, CD, and FTIR). Results implied that the designed inhibitor peptides (IP) might be valuable to inhibit all the related aggregated peptides.

Breaker peptides against amyloid-ß aggregation: a potential therapeutic strategy for Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder, for which blocking the early steps of extracellular misfolded amyloid-ß (Aß) aggregation is a promising therapeutic approach. However, the pathological features of AD progression include the accumulation of intracellular tau protein, membrane-catalyzed cell death and the abnormal deposition of Aß. Here, we focus on anti-amyloid breaker peptides derived from the Aß sequence and non-Aß-based peptides containing both natural and modified amino acids. Critical aspects of the breaker peptides include N-methylation, conformational restriction through cyclization, incorporation of unnatural amino acid, fluorinated molecules, polymeric nanoparticles and PEGylation. This review confers a general idea of such breaker peptides with in vitro and in vivo studies, which may advance our understanding of AD pathology and develop an effective treatment strategy against AD.

In-situ side-chain peptide cyclization as a breaker strategy against the amyloid aggregating peptide.

Accumulation and deposition of misfolded amyloid ß (Aß) peptide outside the nerve cells are one of the major causes of Alzheimer's disease (AD). To date, one of the promising therapeutic strategies for AD is to block the early steps associated with the aggregation of Aß peptide. We have developed synthetic breaker peptides derived from the original Aß sequences that undergo self-cyclization in situ. We have focussed and replaced Val-18 (of Aß) by side-chain modified glutamic acid (Glu-OBn) to generate adequate turn through in-situ peptide cyclization to disrupt the ß-sheet structure of Aß. The disruption of amyloid fibril formation and the mechanism of the 'inhibition of aggregation' were studied by various biophysical methods, such as ThT-assay, TEM, Congo-red birefringence study. CD and FTIR spectroscopy were used to characterize the conformational change during the aggregation process. Results suggest that designed breaker peptides may be useful to inhibit and disrupt not only Aß peptide but related peptides that undergo aggregation.