Oil-in-water nanoemulsions comprising Berberine in olive oil: biological activities, binding mechanisms to human serum albumin or holo-transferrin and QMMD simulations
Atena Sharifi-Rad, Jamshid Mehrzad, Majid Darroudi, Mohammad Reza Saberi, Jamshidkhan Chamani
Abstract
Berberine is widely used in traditional Iranian medicine to treat diabetes and inflammatory conditions. This study was aimed at developing a method for the preparation of Berberine nanoparticles (Nano-Ber) in order to improve its aqueous-phase solubility and its complex formation with human serum albumin (HSA) and holo-transferrin (HTF) from the viewpoint of interaction behavior. Nano-Ber was prepared with olive oil as the oil phase, Tween 80 as the surfactant and Span 60 as the co-surfactant. Nano-Ber was obtained with a spherical shape and a mean particle size of 43.7 ± 3.6 nm, with an optimal oil:surfactant:co-surfactant ratio of 1:2:2, w/w/w. The antioxidant activity of Nano-Ber in comparison with Berberine was tested using DPPH and it was found that Nano-Ber had a large antioxidant activity. The cytotoxicity effects of Nano-Ber and Berberine on HepG2 were compared by MTT assay and detected in the treated HepG2 cells at concentrations up to 0.1 mM. The binding constants of HSA-Nano-Ber and HTF-Nano-Ber complexes formation were (2.93 ± 0.02) × 104 and (9.62 ± 0.03) × 103 M−1, respectively. Hydrogen bonds and van der Waals interactions were the predominant forces in the HSA-Nano-Ber and HTF-Nano-Ber complexes, and the process of Nano-Ber binding HSA and HTF was driven by ΔH0 = –122.76 kJ mol−1, ΔS0 = –325.49 J mol−1K−1 for HSA and ΔH0 = –125.09 kJ mol−1, ΔS0 = –43.37 J mol−1K−1 for HTF. The results of the simulation demonstrated that the Nano-Ber molecules were stabilized on the surface of final aggregates through both hydrophilic and hydrophobic interactions.Communicated by Ramaswamy Sarma