Pharmacognosy Magazine

ORIGINAL ARTICLE
Year
: 2016  |  Volume : 12  |  Issue : 48  |  Page : 319--325

Ursolic acid, a natural pentacylcic triterpene from Ochrosia elliptica and its role in the management of certain neglected tropical diseases


Rola M Labib1, Sherif S Ebada3, Fadia S Youssef3, Mohamed L Ashour3, Samir A Ross2 
1 Department of Pharmacognosy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt; National Center for Natural Products Research, MS, USA
2 National Center for Natural Products Research; Department of BioMolecular Sciences, School of Pharmacy, University of Mississippi, University, MS, USA

Correspondence Address:
Dr. Rola M Labib
Faculty of Pharmacy, Ain Shams University, Abassia, Cairo, Egypt

Background: Leishmaniasis and African trypanosomiasis are recognized as the leading causes of mortality and morbidity with the greatest prevalence in the developing countries. They affect more than one billion of the poorest people on the globe. Objective: To find a cheap, affordable, safe, and efficacious antileshmanial and antitrypanosomal natural drug and to elucidate its probable mode of action. Materials and Methods: Phytochemical investigation of the non-polar fraction of the methanol extract of leaves of Ochrosia elliptica Labill. (Apocyanaceae) resulted in the isolation of ursolic acid, which was unambiguously determined based on HR-ESI-FTMS, extensive 1D and 2D NMR spectroscopy. It was further tested for its cytotoxicity, antimicrobial, antimalarial, antileishmanial, and trypanocidal potency. in-silico molecular modeling studies were conducted on six vital parasitic enzymes including farnesyl diphosphate synthase, N -myristoyl transferase, pteridine reductase 1, trypanothione reductase, methionyl-tRNA synthetase, and inosine–adenosine–guanosine nucleoside hydrolase to discover its potential mode of action as antitrypanosomal and antileishmanial agent. Results: Ursolic acid displayed considerable antitrypanosomal and antileishmanial activities with IC50 values ranging between 1.53 and 8.79 μg/mL. It showed superior antitrypanosomal activity as compared to the standard drug difluoromethylornithine (DFMO), with higher binding affinities towards trypanothione reductase and pteridine reductase 1. It displayed free binding energy of -30.73 and -50.08 kcal/mole towards the previously mentioned enzymes, respectively. In addition, ursolic acid exhibited considerable affinities to farnesyl diphosphate synthase, N -myristoyl transferase and methionyl-tRNA synthetase with free binding energies ranging from -42.54 to -63.93 kcal/mole. Conclusion: Ursolic acid offers a safe, effective and cheap antitrypanosomal and antileishmanial candidate acting on several key parasitic enzymes. Abbreviations used: AHT: African Human Trypanosomiasis, ATCC: American type cell culture, BuOH: n -butanol, DCM: dichloromethane, DFMO: difluoromethylornithine, EtOAc: ethyl acetate, FCS: fetal calf serum, HMBC: Heteronuclear Multiple Bond Correlation, HMQC: Heteronuclear Multiple-Quantum Correlation, HR-ESI-FTMS: High Resolution Electrospray ionozation Mass Spectrometry, MENA: Middle East and North Africa, MeOH: Methanol, MRSA: Methicillin-resistant Staphylococcus aureus , NTDs: Neglected tropical diseases, TLC: Thin layer chromatography, UA: Ursolic acid, UV: Ultra violet, WHO: World Health Organization.


How to cite this article:
Labib RM, Ebada SS, Youssef FS, Ashour ML, Ross SA. Ursolic acid, a natural pentacylcic triterpene from Ochrosia elliptica and its role in the management of certain neglected tropical diseases.Phcog Mag 2016;12:319-325


How to cite this URL:
Labib RM, Ebada SS, Youssef FS, Ashour ML, Ross SA. Ursolic acid, a natural pentacylcic triterpene from Ochrosia elliptica and its role in the management of certain neglected tropical diseases. Phcog Mag [serial online] 2016 [cited 2020 Apr 4 ];12:319-325
Available from: http://www.phcog.com/article.asp?issn=0973-1296;year=2016;volume=12;issue=48;spage=319;epage=325;aulast=Labib;type=0