Effects of Telmisartan, an AT1 receptor antagonist, on mitochondria-specific genes expression in a mouse MPTP model of Parkinsonism.

Background: Mitochondrial dysfunction plays a crucial role in Parkinson's disease (PD) pathogenesis. The present study was undertaken to investigate the effects of Telmisartan (TEL), an angiotensin II type 1 receptor (AT1R) blocker, on the mitochondria-specific genes expression in a mouse model of Parkinsonism. Materials and methods: Mice were divided into 5 groups with 6 in each; Group I received 0.5% CMC (control) + saline, Group II received 0.5% CMC + 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (positive control), Group III & IV received MPTP + TEL 3 and 10 mg/kg, p.o. respectively, Group V received TEL 10 mg/kg, p.o. (drug control). MPTP was given 80 mg/kg intraperitoneal in two divided doses (40 mg/kg × 2 at 16 h time interval). Vehicle or TEL was administered 1 h before the MPTP injection. Motor function was assessed 48 h after the first dose of MPTP and animals were euthanized to collect brain. Results: Mice intoxicated with MPTP showed locomotor deficits and significant upregulation of α-synuclein (α-syn), downregulation of metastasis-associated protein 1 (MTA1), and Ubiquitin C-terminal hydrolase L1 (UCHL1) in the substantia nigra pars compacta (SNpc) and Striatum (STr) regions of brains. In addition, MPTP intoxication down-regulated mitochondria-specific genes such as DJ-1, PTEN-induced putative kinase 1 (PINK1), Parkin, enriched with leucine repeats kinase 2 (LRRK2) gene expfression. Pre-treatment with TEL restored locomotor functions and upregulated PINK1, Parkin, LRRK2, DJ-1, MTA1 and UCHL1. Conclusion: The present study evidences that TEL has the ability to improve mitochondrial functions in PD.

An overview on medicinal perspective of thiazolidine-2,4-dione: A remarkable scaffold in the treatment of type 2 diabetes.

Diabetes or diabetes mellitus is a complex or polygenic disorder, which is characterized by increased levels of glucose (hyperglycemia) and deficiency in insulin secretion or resistance to insulin over an elongated period in the liver and peripheral tissues. Thiazolidine-2,4-dione (TZD) is a privileged scaffold and an outstanding heterocyclic moiety in the field of drug discovery, which provides various opportunities in exploring this moiety as an antidiabetic agent. In the past few years, various novel synthetic approaches had been undertaken to synthesize different derivatives to explore them as more potent antidiabetic agents with devoid of side effects (i.e., edema, weight gain, and bladder cancer) of clinically used TZD (pioglitazone and rosiglitazone). In this review, an effort has been made to summarize the up to date research work of various synthetic strategies for TZD derivatives as well as their biological significance and clinical studies of TZDs in combination with other category as antidiabetic agents. This review also highlights the structure-activity relationships and the molecular docking studies to convey the interaction of various synthesized novel derivatives with its receptor site.

Molecular understanding of Epigallocatechin gallate (EGCG) in cardiovascular and metabolic diseases.

ETHNOPHARMACOLOGICAL RELEVANCE: The compound epigallocatechin-3-gallate (EGCG), the major polyphenolic compound present in green tea [Camellia sinensis (Theaceae], has shown numerous cardiovascular health promoting activity through modulating various pathways. However, molecular understanding of the cardiovascular protective role of EGCG has not been reported. AIM OF THE REVIEW: This review aims to compile the preclinical and clinical studies that had been done on EGCG to investigate its protective effect on cardiovascular and metabolic diseases in order to provide a systematic guidance for future research. MATERIALS AND METHODS: Research papers related to EGCG were obtained from the major scientific databases, for example, Science direct, PubMed, NCBI, Springer and Google scholar, from 1995 to 2017. RESULTS: EGCG was found to exhibit a wide range of therapeutic properties including anti-atherosclerosis, anti-cardiac hypertrophy, anti-myocardial infarction, anti-diabetes, anti-inflammatory and antioxidant. These therapeutic effects are mainly associated with the inhibition of LDL cholesterol (anti-atherosclerosis), inhibition of NF-κB (anti-cardiac hypertrophy), inhibition of MPO activity (anti-myocardial infarction), reduction in plasma glucose and glycated haemoglobin level (anti-diabetes), reduction of inflammatory markers (anti-inflammatory) and the inhibition of ROS generation (antioxidant). CONCLUSION: EGCG shows different biological activities and in this review, a compilation of how this bioactive molecule plays its role in treating cardiovascular and metabolic diseases was discussed.

Effects of nanosuspension and inclusion complex techniques on the in vitro protease inhibitory activity of naproxen

This study investigated the effects of nanosuspension and inclusion complex techniques on in vitro trypsin inhibitory activity of naproxen—a member of the propionic acid derivatives, which are a group of antipyretic, analgesic, and non-steroidal anti-inflammatory drugs. Nanosuspension and inclusion complex techniques were used to increase the solubility and anti-inflammatory efficacy of naproxen. The evaporative precipitation into aqueous solution (EPAS) technique and the kneading methods were used to prepare the nanosuspension and inclusion complex of naproxen, respectively. We also used an in vitro protease inhibitory assay to investigate the anti-inflammatory effect of modified naproxen formulations. Physiochemical properties of modified naproxen formulations were analyzed using UV, IR spectra, and solubility studies. Beta-cyclodextrin inclusion complex of naproxen was found to have a lower percentage of antitryptic activity than a pure nanosuspension of naproxen did. In conclusion, nanosuspension of naproxen has a greater anti-inflammatory effect than the other two tested formulations. This is because the nanosuspension formulation reduces the particle size of naproxen. Based on these results, the antitryptic activity of naproxen nanosuspension was noteworthy; therefore, this formulation can be used for the management of inflammatory disorders.

O objetivo do presente estudo foi investigar a atividade anti-inflamatória in vitro de nanossuspensões e do complexo de inclusão contendo naproxeno. Esse fármaco é derivado de ácido propiônico, com ação analgésica, antipirética e antiinflamatória. A obtenção dessas formulações teve por finalidade o aumento da solubilidade e da atividade anti-inflamatória do fármaco. Os métodos por precipitação em solução aquosa por evaporação e por empastagem foram modificados para a obtenção da nanossuspensão e do complexo de inclusão, respectivamente. Para a avaliação da atividade anti-inflamatória das formulações utilizou-se ensaio in vitro modificado de inibição de tripsina. As propriedades físico-químicas das formulações propostas foram determinadas utilizando espectroscopia UV e de infravermelho, além de estudos de solubilidade. O complexo de inclusão de naproxeno apresentou menor atividade antitripsina, quando comparado ao composto livre e à nanossuspensão. Em conclusão, entre as formulações avaliadas, a nanossuspensão de naproxeno apresentou maior efeito anti-inflamatório. Esse efeito foi devido à redução da dimensão das partículas de naproxeno para a escala nanométrica. Com base nos resultados obtidos, a atividade da nanossuspensão de naproxeno foi notável. Dessa forma, essa formulação apresenta potencial para o tratamento de distúrbios inflamatórios.