Inhibition of pancreatic lipase by berberine and dihydroberberine: an investigation by docking simulation and experiment
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Med Chem Res (2013) 22:2273–2278 DOI 10.1007/s00044-012-0221-9
ORIGINAL RESEARCH
Inhibition of pancreatic lipase by berberine and dihydroberberine: an investigation by docking simulation and experimental validation Mohammad Mohammad • Ihab M. Al-masri Ala Issa • Ayman Khdair • Yasser Bustanji
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Received: 7 June 2012 / Accepted: 24 August 2012 / Published online: 6 September 2012 Ó Springer Science+Business Media, LLC 2012
Abstract Berberine (BBR) and dihydroberberine (HBBR) were investigated as inhibitors of pancreatic lipase in an attempt to explore their potential hypolipidemic activities. The study included docking simulations and in vitro enzymatic inhibition assays. At the molecular level, docking simulations revealed several significant binding interactions between the docked natural compounds and the key amino acids in the binding pocket of the pancreatic lipase enzyme. BBR had similar pattern of binding interactions as HBBR; however, BBR has a permanent cationic center which is suggested to have an adverse influence on ligand–pancreatic lipase affinity. This trend is explainable by the proposition that ionized ligands favor hydration instead of docking into the binding site. This might explain the lower inhibitory activity of BBR comparing to HBBR, which appeared from their estimated IC50 values. The logarithmic regression of PL inhibition versus concentration revealed estimated IC50 values of 106 and 8.0 lg/mL for BBR and HBBR, respectively. Keywords Berberine Dihydroberberine Pancreatic lipase Obesity Docking simulations Enzyme inhibition
M. Mohammad (&) A. Issa Y. Bustanji Faculty of Pharmacy, University of Jordan, Amman 11942, Jordan e-mail: [email protected] I. M. Al-masri Faculty of Pharmacy, Al-Azhar University, Gaza, Gaza Strip, Palestine A. Khdair Faculty of Pharmacy, Applied Science University, Amman, Jordan
Introduction Obesity is one of the most common nutritional dilemmas in the modern countries and is considered a potential risk factor for the development of a plethora of devastating diseases, including insulin resistance and type 2 diabetes, lipid profile disorders, osteoarthritis, hyperuricemia, malignancies, and cardiovascular diseases which includes hypertension, coronary heart diseases, and stroke (Arbeeny, 2004; Cairns, 2005; Gurevich-Panigrahi et al., 2009). Many recent studies have placed obesity as one of the greatest threats to global health in this millennium. Recent reports showed that there are more than one billion overweight adults worldwide including at least 300 million classified as clinically obese with increased risk of morbidity and mortality (Arbeeny, 2004; Vega, 2001). Unfortunately, these numbers are growing in alarming rates. Obesity is considered as a metabolic disorder, which is mainly caused by an imbalance between the energy intake and expenditure. However, comprehensive understanding of the molecular mechanisms that tightly regulate body weight has afforded potential opportunities for therapeutic managements and offered renewed hope for int
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