1-1-diphenyl-2-picrylhydrazyl and Obesity

Obesity is a global health problem characterized by excessive fat deposition in adipose tissues and can be managed by targeting pancreatic lipase (PL) activity. In the present study, we investigated the in vitro antioxidant and anti-obesity potentials of methanolic leaf extract of Justicia carnea(MEJC) using lipase inhibition kinetics model. In silico evaluations of MEJC bioactive compounds as potential drug-like agents and inhibitors of PL were also investigated using SwissADME prediction tool, semi-empirical quantum mechanics(SQM), molecular electrostatic potential(MEP) and molecular docking analysis. Gas chromatography-mass spectrometry(GC-MS) revealed presence of campesterol, stigmasterol, beta-amyrin etc. MEJC scavenged reactive species and inhibited PL activity via a mixed inhibition pattern (K

Topics: Anti-Obesity Agents; Antioxidants; Biphenyl Compounds; Enzyme Inhibitors; Humans; Justicia; Kinetics; Lipase; Molecular Docking Simulation; Obesity; Picrates; Plant Extracts; Plant Leaves; Quantum Theory

In this study, 15 commercial acidic drugs have been evaluated for pancreatic lipase (PL) inhibitory activity using an in vitro spectrophotometric method. The acidity was the basis of selection, since most PL inhibitors exhibit acidic groups and high lipophilicity. Orlistat was the robust reference agent for potency and efficacy determinations. In comparison to the cisplatin, the evaluation of the antineoplastic activities of selected drugs in a panel of colorectal cancer cell lines (HT-29, HCT-116, SW620, CACO-2, and SW480) and normal periodontal ligament fibroblasts for safety examination was performed by using a sulforhodamine procuring ascorbic acid as a reference in diphenyl-2-picryl-hydrazyl assay of radical scavenging properties was performed. This research revealed three highly acidic pharmacological classes with reasonable PL inhibitory activity in comparison to orlistat out of 15 selected drugs, namely sulfonylureas, fluoroquinolones, and proton pump inhibitors. Docking studies supported the hypothesis of a selection based on acidity, since it showed that the sulfonamide acid group (glyburide) is a remarkably potent interacting group with the enzyme. Failing to fulfill other structure-activity relationship requirements (lipophilicity) led to weak activity. Since the drugs are of different chemical classes with unknown mechanisms, they showed diverse antiproliferative activity. Some drugs such as atorvastatin and gemifloxacin showed higher antiproliferative activity than cisplatin with high-safety profiles against SW620 and SW480 cell lines, respectively, whereas lansoprazole and clopidogrel revealed comparable activity to cisplatin against HCT-116 and SW480, respectively. Unfortunately, selected tested drugs exhibited negligible radical scavenging activity versus ascorbic acid. Hit, Lead & Candidate Discovery.

Topics: Antineoplastic Agents; Biphenyl Compounds; Cell Line, Tumor; Cell Proliferation; Colorectal Neoplasms; Fibroblasts; Free Radical Scavengers; Humans; Lipase; Molecular Docking Simulation; Obesity; Picrates

Obesity is a one of the main global public health problems associated with chronic diseases such as coronary heart disease, diabetes and cancer. As a solution to obesity, we suggest Plantago albicans, which is a medicinal plant with several biological effects. This study assesses the possible anti-obesity protective properties of Plantago albicans in high fat diet-fed rats. 28 male Wistar rats were divided into 4 groups; a group which received normal diet (C), the second group was fed HDF diet (HDF), the third group was given normal diet supplemented with Plantago albicans (P.AL), and the fourth group received HDF supplemented with Plantago albicans (HDF+P.AL) (30mg/kg/day) for 7 weeks. Our results showed an increase in body weight of HDF rats by ∼16% as compared to the control group with an increase in the levels of total cholesterol (TC) as well as LDL-cholesterol, triglycerides (TG) in serum. Also, the concentration of TBARS increased in the liver and heart of HDF-fed rats as compared to the control group. The oral gavage of Plantago albicans extract to obese rats induced a reduction in their body weight, lipid accumulation in liver and heart tissue, compared to the high-fat diet control rats. The obtained results proved that the antioxidant potency of Plantago albicans extracts was correlated with their phenolic and flavonoid contents. The antioxidant capacity of the extract was evaluated by DPPH test (as EC50=250±2.12μg/mL) and FRAP tests (as EC50=27.77±0.14μg/mL). These results confirm the phytochemical and antioxidant impact of Plantago albicans extracts. Plantago albicans content was determined using validated HPLC methodology.

Topics: Animals; Anti-Obesity Agents; Antioxidants; Biomarkers; Biphenyl Compounds; Chromatography, High Pressure Liquid; Diet, High-Fat; Disease Models, Animal; Flavonoids; Fluorescence Recovery After Photobleaching; Lipids; Liver; Male; Myocardium; Obesity; Phenols; Phytotherapy; Picrates; Plant Extracts; Plant Leaves; Plantago; Plants, Medicinal; Rats, Wistar; Weight Gain

In order to better understand the antioxidant behavior of a series of polyphenolic 2'-hydroxychalcones, we describe the results of several chemical and biological studies, in vitro and in vivo. Single crystal X-ray methods elucidated their molecular structures and important intermolecular interactions such as H-bonding and molecular stacking in the crystal structures that contribute to our knowledge in explaining antioxidant activity. The results of experiments using the 1,1-diphenyl-2-dipicrylhydrazyl (DPPH) UV-vis spectroscopic method indicate that a hydroxyl group in position 5' induces the highest antioxidant activity. Consequently, 2,2',5'-trihydroxychalcone was selected for further study in vitro towards ROS scavenging in L-6 myoblasts and THP-1 human monocytes, where it shows an excellent antioxidant activity in a concentration range lower than that reported by most studies of related molecules. In addition, this chalcone shows a very selective activity: it inhibits the proliferation of leukemic cells, but it does not affect the normal L-6 myoblasts and human fibroblasts. In studying 2,2',5'-trihydroxychalcone's effect on weight gain and serum glucose and insulin levels in Zucker fatty (fa(-)/fa(-)) rats we found that supplementing the diet with a 10 mg/kg dose of this chalcone (3 times weekly) blunted the increase in glucose that co-occurs with weight gain over the 6-week treatment period. It is concluded that 2,2',5'-trihydroxychalcone has the potential to serve as a protective agent for some debilitating diseases.

Topics: Animals; Anti-Obesity Agents; Antioxidants; Biphenyl Compounds; Blood Glucose; Body Weight; Cell Line, Tumor; Cell Proliferation; Chalcones; Crystallography, X-Ray; Female; Fibroblasts; Humans; Hypoglycemic Agents; Insulin; Male; Monocytes; Myoblasts; Obesity; Picrates; Rats; Rats, Zucker