Unraveling the binding mechanism of asiatic acid with human serum albumin and its biological implications

Mahesh Gokara, Tirupathi Malavath, Suresh Kumar Kalangi, Pallu Reddana, Rajagopal Subramanyam

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Asiatic acid (AsA), a naturally occurring pentacyclictriterpenoid found in Centella asiatica, plays a major role in neuroprotection, anticancer, antioxidant, and hepatoprotective activities. Human serum albumin (HSA), a blood plasma protein, participates in the regulation of plasma osmotic pressure and transports endogenous and exogenous substances. The study undertaken to analyze the drug-binding mechanisms of HSA is crucial in understanding the bioavailability of drugs. In this study, we analyzed the cytotoxic activity of AsA on HepG2 (human hepatocellular carcinoma) cell lines and its binding, conformational, docking, molecular simulation studies with HSA under physiological pH 7.2. These studies revealed a clear decrease in the viability of HepG2 cells upon exposure to AsA in a dose-dependent manner with an IC50 of 45 M. Further studies showed the quenching of intrinsic fluorescence of HSA by AsA with a binding constant of KAsA = 3.86 ± 0.01 × 104 M-1, which corresponds to the free energy of (ΔG)-6.3 kcal M-1 at 25 °C. Circular dichroism (CD) studies revealed that there is a clear decrease in the -helical content from 57.50 ± 2.4 to 50% ± 2.3 and an increase in the β-turns from 25 ± 0.65 to 29% ± 0.91 and random coils from 17.5% ± 0.95 to 21% ± 1.2, suggesting partial unfolding of HSA. Autodock studies revealed that the AsA is bound to the subdomain IIA with hydrophobic and hydrophilic interactions. From molecular dynamics, simulation data (RMSD, Rg and RMSF) emphasized the local conformational changes and rigidity of the residues of both HSA and HSA-AsA complexes.

Original languageEnglish
Pages (from-to)1292-1302
Number of pages11
JournalJournal of Biomolecular Structure and Dynamics
Volume32
Issue number8
DOIs
Publication statusPublished - Aug 3 2014

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Serum Albumin
Blood Proteins
Molecular Docking Simulation
Centella
asiatic acid
Osmotic Pressure
Hep G2 Cells
Molecular Dynamics Simulation
Circular Dichroism
Hydrophobic and Hydrophilic Interactions
Pharmaceutical Preparations
Biological Availability
Inhibitory Concentration 50
Hepatocellular Carcinoma
Antioxidants
Fluorescence
Cell Line

Keywords

  • Asiatic acid
  • drug binding
  • fluorescence quenching
  • human serum albumin
  • molecular dynamics simulation

ASJC Scopus subject areas

  • Molecular Biology
  • Structural Biology
  • Medicine(all)

Cite this

Unraveling the binding mechanism of asiatic acid with human serum albumin and its biological implications. / Gokara, Mahesh; Malavath, Tirupathi; Kalangi, Suresh Kumar; Reddana, Pallu; Subramanyam, Rajagopal.

In: Journal of Biomolecular Structure and Dynamics, Vol. 32, No. 8, 03.08.2014, p. 1292-1302.

Research output: Contribution to journalArticle

Gokara, Mahesh ; Malavath, Tirupathi ; Kalangi, Suresh Kumar ; Reddana, Pallu ; Subramanyam, Rajagopal. / Unraveling the binding mechanism of asiatic acid with human serum albumin and its biological implications. In: Journal of Biomolecular Structure and Dynamics. 2014 ; Vol. 32, No. 8. pp. 1292-1302.
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