Pancreatic Lipase Inhibition by Papaverine : Investigation by Simulated Molecular Docking and Subsequent in Vitro Evaluation

2013 ◽  
Vol 6 (3) ◽  
pp. 271-279 ◽  
Author(s):  
Ihab M. Al-Masri
Keyword(s):  
Molecular Docking ◽  
Pancreatic Lipase ◽  
In Vitro Evaluation ◽  
Pancreatic Lipase Inhibition ◽  
Lipase Inhibition

scholarly journals In Vitro Pancreatic Lipase Inhibition by Marine Fungi Purpureocillium lilacinum Associated with Stylissa sp. Sponge as Anti-obesity Agent

2021 ◽  
Vol 29 (1) ◽  
pp. 76-86
Author(s):  
Wendi Nurul Fadillah ◽  
Nampiah Sukarno ◽  
Dyah Iswantini ◽  
Min Rahminiwati ◽  
Novriyandi Hanif ◽  
...  
Keyword(s):  
Ethyl Acetate ◽  
Pancreatic Lipase ◽  
Metabolite Identification ◽  
Molecular Characteristics ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Purpureocillium Lilacinum ◽  
Pancreatic Lipase Inhibition ◽  
Lipase Inhibition

This study aimed to evaluate the potential of marine fungus Purpureocillium lilacinum isolated from an Indonesian marine sponge Stylissa sp. as an anti-obesity agent through pancreatic lipase inhibition assay. The fungus was identified as P. lilacinum through morphological and molecular characteristics. The fungal extract’s inhibition activity and kinetics were evaluated using spectrophotometry and Lineweaver-Burk plots. Ethyl acetate and butanol were used for extraction. Both extracts showed pancreatic lipase inhibition in a concentration-dependent manner. Both crude extracts were then fractionated once. All fractionated extracts showed inhibitory activity above 50%, with the highest activity found in fraction 5 of ethyl acetate at 93.41% inhibition. The best fractionated extract had an IC50value of 220.60 µg.mL-1. The most active fraction of P. lilacinum had a competitive-type inhibitor behavior as shown by the value of Vmax not significantly changing from 388.80 to 382.62 mM pNP.min-1, and the Michaelis-Menten constant (KM) increased from 2.02 to 5.47 mM in the presence of 500 µg.mL-1 fractionated extract. Metabolite identification with LC-MS/MS QTOF suggested that galangin, kaempferol, and quercetin were responsible for the observed lipase inhibition.

scholarly journals Synthesis, Drug Likeness and In-vitro Screening of Some Novel Quinazolinone Derivatives for Anti-Obesity Activity

2021 ◽  
pp. 81-92
Author(s):  
Pratik G. Modh ◽  
Laxman J. Patel
Keyword(s):  
Pancreatic Lipase ◽  
Synthesis Method ◽  
Proton Nmr ◽  
Lipolytic Enzyme ◽  
Coupling Reactions ◽  
Lipinski’S Rule ◽  
High Yields ◽  
Pancreatic Lipase Inhibition ◽  
Lipase Inhibition

Aim: A series of novel quinazolinone derivates was synthesized and assessed for their ability to inhibitory action on pancreatic lipase. The cyclization of quinazolinone-4(3H)-one derivatives was achieved, whereas carbon-carbon cross coupling reactions were carried out on cyclized quinazolinone-4(3H)-one. This synthesis method afforded corresponding 2, 3 and 6 substituted quinazolin-4(3H)-ones (3a to 3m) with moderate to high yields. Methods: Benzamide derivatives (1a-1b) were synthesized from anthranilic acid using acid-amine reaction, followed by cyclization using catalytic p-toluene sulfonic acid and oxidation using (diacetoxyiodo)benzene to give bromo substituted quinazolin-4(3H)-ones (2a-2b), which were cross coupled to suitable boronic acid using Suzuki-Miyaura condition to obtain desired compound (3a-3m). All synthesized compounds were characterized by FTIR, proton NMR, LC-MS analysis, checked for their drug likeness, absorption and evaluated for in vitro pancreatic lipase inhibition activity. Results: Analytical interpretation of all compounds with infrared, proton NMR and LC-MS spectroscopy confirmed their correct structure. All compounds (3a-3m) show good absorption and have reasonably good molecular properties except 3c and 3m which violate two criteria for Lipinski’s rule. Whereas, Compounds 3l and 3m showed IC50 value of 13.13±0.84 µg/mL and 13.80±1.27 µg/mL respectively comparable to the Orlistat (12.72±0.97µg/mL), a US FDA approved drug for the treatment of obesity. Conclusion: Pancreatic lipase is an important lipolytic enzyme, synthesized and secreted through pancreas, plays an important role in dietary trigycerol absorption and metabolism. Therefore, reducing fat absorption through pancreatic lipase inhibition is a promising strategy to treat obesity. Based upon our findings, compounds 3l and 3m can be further developed as potent anti-obesity agents.

scholarly journals Pancreatic Lipase Inhibitory Activity of Cassiamin A, a Bianthraquinone from Cassia siamea

2013 ◽  
Vol 8 (2) ◽  
pp. 1934578X1300800 ◽  
Author(s):  
Dilip Kumar ◽  
Aniket Karmase ◽  
Sneha Jagtap ◽  
Ruchi Shekhar ◽  
Kamlesh K Bhutani
Keyword(s):  
Pancreatic Lipase ◽  
Inhibitory Activity ◽  
Enzyme Inhibitors ◽  
Etoac Extract ◽  
Cassia Siamea ◽  
Bioassay Guided Fractionation ◽  
Pancreatic Lipase Inhibition ◽  
Lipase Inhibition ◽  
Indian Medicinal Plants

In continuation towards the discovery of potential antiobesity lead(s) from natural products, we have screened n-hexane, dichloromethane (DCM), ethyl acetate (EtOAc) and methanol (MeOH) extracts of 33 Indian medicinal plants (200 extracts) for in vitro pancreatic lipase inhibitory activity. Of the screened extracts, the EtOAc extract of Cassia siamea roots showed 74.3±1.4% enzyme inhibition at 250 μg/mL concentration. Bioassay guided fractionation of the active extract afforded 6 known compounds viz. chrysophanol (1), physcion (2), emodin (3), cassiamin A (4), friedelin (5) and cycloart-25-en-3β,24-diol (6). These compounds were further evaluated for pancreatic lipase inhibitory activity. Cassiamin A (4), a bianthraquinone, was found to be most active with an IC50 value of 41.8±1.2 μM and compounds 2 and 5 were found to be moderate enzyme inhibitors. Results indicate the antiobesity potential of C. siamea through pancreatic lipase inhibition.

scholarly journals Evaluation of Indonesian Anti-obesity Traditional Medicinal Plants: A Systematic Review and Meta-analysis on Pancreatic Lipase Inhibition Activity

2021 ◽  
Author(s):  
Hasim Hasim ◽  
Didah Nur Faridah ◽  
Frendy Ahmad Afandi ◽  
Eka Nurul Qomaliyah
Keyword(s):  
Systematic Review ◽  
Medicinal Plants ◽  
Pancreatic Lipase ◽  
Data Extraction ◽  
Meta Analysis ◽  
Analysis Data ◽  
Psidium Guajava ◽  
Pancreatic Lipase Inhibition ◽  
Lipase Inhibition

Abstract BackgroundResearches and publication discussing performance of medicinal plants as anti-obesity have proliferated in recent years. In the view of ethnopharmacology, empiric evidence of Indonesian medicinal plants in management of obesity is widely accepted. In attempt to find anti-obesity agent, it is evidenced that the disorder can be resolved through inhibition of pancreatic lipase since the mechanism allowed to retard absorption of fat into cells. This current work aimed to screen Indonesian medicinal plants by using ethnopharmacology and meta-analysis approaches, emphasizing their ability to deal with obesity via pancreatic lipase inhibition. MethodsThe study followed two stages, i.e. systematic review and meta-analysis. Data from 6 scientific (Scopus, Science Direct, Proquest, Ebsco, Cengage Library and Emerald) were collected, screened according to inclusion and exclusion criteria. The eligibility of the trials was determined according to criteria as follows: (1) design for lipase inhibition experiments; (2) population in all researches using in vitro protocols for antiobesity in last 10 years; (3) intervention for comparison between lipase inhibition IC50 properties of selected medicinal plants and orlistat; and (4) data adequacy enabling to estimate the standardized mean difference (SMD) and the corresponding 95% confidence interval (CI). Further, all published papers we reviewed were written in English. Furthermore, steps of meta-analysis were performed on the selected data. Extraction of data in these articles collected number of samples, average values and standard deviation of IC50. The values focused on IC50 of samples in inhibiting lipase activities performed by plant extracts and orlistat as control. ResultA total 10 selected data meet the inclusion criteria. Morever these plant can be found and common as traditional medicine plant in Indonesia ConclusionAs the results, there were top 10 anti-obesity medicinal plants as follows: i.e. kelor (Moringa oleifera) leaves, kemangi (Ocimum basilicum) leaves, asam jawa (Tamarindus indica) leaves, asam gelugur (Garcinia atroviridis) fruit, lengkuas (Alpinia galanga) rhizome, and kencur (Kaempferia galanga) rhizome, kumis kucing (Orthosipon aristatus) leaves, jambu biji leaves (Psidium guajava leavaes), serai wangi (Cymbopogon nardus) and kayu secang (Caesalpinia sappan).

scholarly journals Inhibitory Effects of Myricetrin and Dihydromyricetin toward α-Glucosidase and Pancreatic Lipase with Molecular Docking Analyses and Their Interaction

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Siyuan Mi ◽  
Jia Liu ◽  
Xiaojing Liu ◽  
Yishan Fu ◽  
Junjie Yi ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Phenolic Compounds ◽  
Hydrogen Bonds ◽  
Pancreatic Lipase ◽  
Hydrophobic Interactions ◽  
Synergistic Effects ◽  
Dependent Manner ◽  
Inhibitory Effects ◽  
Pancreatic Lipase Inhibition ◽  
Lipase Inhibition

The aim of the current study was to evaluate the interaction effects of myricetrin and dihydromyricetin in inhibiting α-glucosidase and pancreatic lipase at different combination ratios and concentrations and to illuminate the underlying mechanisms of their inhibitions by molecular docking analyses. Results showed that both phenolic compounds possessed good inhibitory effects toward two enzymes in a dose-dependent manner. Myricetrin demonstrated a stronger inhibition against α-glucosidase (IC50, 41.14 ± 2.52 and more than 200 μg/mL, respectively), while dihydromyricetin had a better pancreatic lipase inhibition (IC50, 244.96 ± 4.24 and 373.26 ± 21.36 μg/mL, respectively). Different interaction types were observed when myricetrin and dihydromyricetin inhibited α-glucosidase and pancreatic lipase in combination, which were closely related to the combination ratio and concentration. For α-glucosidase inhibition, synergistic effects were observed at relative low concentrations when the combination ratio of myricetrin to dihydromyricetin was set as 1 : 2, while strong synergistic effects existed at relative high concentrations for pancreatic lipase inhibition. In other combination ratios (1 : 1 or 2 : 1), additive and/or antagonistic effects occurred. Molecular docking analyses showed that myricetrin formed nine hydrogen bonds with α-glucosidase, while only three hydrogen bonds were formed between dihydromyricetin and α-glucosidase. However, these two phenolic compounds had similar hydrogen bonds and hydrophobic interactions with pancreatic lipase. The present study suggested that myricetrin and dihydromyricetin or food materials rich in these two phenolic compounds could be exploited as α-glucosidase and/or pancreatic lipase inhibitors to deal with health problems caused by excessive energy intake, and the combination ratio and concentration of these two phenolic compounds should be considered when producing new functional foods.

Sign in / Sign up

Export Citation Format

Share Document