Search

Acetyl-11-keto-beta-boswellic acid (AKBA), a potent anti-inflammatory compound purified from Boswellia species, was investigated in a preclinical study for its potential in preventing and treating non-alcoholic fatty liver disease (NAFLD), the most common chronic inflammatory liver disorder. The study involved thirty-six male Wistar rats, equally divided into prevention and treatment groups. In the prevention group, rats were given a high fructose diet (HFrD) and treated with AKBA for 6 weeks, while in the treatment group, rats were fed HFrD for 6 weeks and then given a normal diet with AKBA for 2 weeks. At the end of the study, various parameters were analyzed including liver tissues and serum levels of insulin, leptin, adiponectin, monocyte chemoattractant protein-1 (MCP-1), transforming growth factor beta (TGF-β), interferon gamma (INF-ϒ), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α). Additionally, the expression levels of genes related to the inflammasome complex and peroxisome proliferator-activated receptor gamma (PPAR-ϒ), as well as the levels of phosphorylated and non-phosphorylated AMP-activated protein kinase alpha-1 (AMPK-α1) protein, were measured. The results showed that AKBA improved NAFLD-related serum parameters and inflammatory markers and suppressed PPAR-ϒ and inflammasome complex-related genes involved in hepatic steatosis in both groups. Additionally, AKBA prevented the reduction of the active and inactive forms of AMPK-α1 in the prevention group, which is a cellular energy regulator that helps suppress NAFLD progression. In conclusion, AKBA has a beneficial effect on preventing and avoiding the progression of NAFLD by preserving lipid metabolism, improving hepatic steatosis, and suppressing liver inflammation. [ABSTRACT FROM AUTHOR]

In this work, a novel series of pyridazine-triazole hybrid molecules were prepared and evaluated as inhibitors of rat intestinal α-glucosidase enzyme. Amongst all newly synthesized compounds, 10k showed good inhibition in the series with IC50 value of 1.7 µM which is 100 folds stronger than positive control, acarbose. The cytotoxicity revealed that this compound is not toxic against normal cell line, HDF. The docking studies showed that triazole ring plays an important role in the binding interactions with the active site. The insertion of compound 10k into the active pocket of α-glucosidase and formation of hydrogen bonds with Leu677 was observed from docking studies. The kinetic studies revealed that this compound has uncompetitive mode of inhibition against α-glucosidase enzyme. [ABSTRACT FROM AUTHOR]

In this paper, pyridazin derivatives containing different thiobenzyl moieties were synthesized and screened for their inhibitory activities against rat intestinal α-glucosidase enzyme. The final products were easily obtained without the need to harsh purification steps. The in vitro results revealed that all the synthesized compounds were more potent (IC50s = 26.3–148.9 μM) than the clinically used drug, acarbose. The kinetic study revealed the competitive inhibition behavior of compound 5m (Ki = −56 μM). Docking studies showed imperative interactions such as hydrogen bonding, Pi-Pi T-shaped, and Pi-anion interactions confirming the observed activity. The RMSD value was determined less than 3 Å and validated the study. [ABSTRACT FROM AUTHOR]