Aristolochic acids and phenolic compounds from Aristolochia balansae, their cancer cell inhibitory and radical scavenging activity

Abstract

Aristolochia balansae Franch. is an endemic plant species distributed in northern Vietnam. The bark of A. balansae is used to treat dysentery, urinary retention, and sometimes rheumatism. Our first examination of the presence of aristolochic acids in A. balansae led to the isolation and identification of four aristolochic acids together with β-sitosterol, narcissoside, and glucosyringic acid. Cytotoxic and antioxidative screening discovered the potent cytotoxicity against human cancer cell lines HepG-2 (IC₅₀ 19.21 μg/mL) and MCF-7 (IC₅₀ 19.52 μg/mL) as well as DPPH radical scavenging capacity (SC₅₀ 196.41 μg/mL) of aristolochic acid C (aristolochic acid IIIa). To gain a better knowledge of the mechanisms of action of aristolochic acid C against breast and liver cancer, the compound’s binding to HER2 and GSK-3 protein targets was further analyzed using a molecular docking approach. In the energy minimization models, aristolochic acid C showed a good position in the active site of the HER2 and GSK3β proteins with the lowest binding energy with a ∆G value of − 11.09 kcal/mol and − 8.129 kcal/mol, respectively. A theoretical thermodynamic study was also conducted to examine the radical scavenging mechanism of aristolochic acid C based on DFT calculation. DFT parameters, such as BDE (bond dissociation enthalpy), IP (ionization potential), ETE (electron transfer enthalpy), PDE (proton dissociation enthalpy), and PA (proton affinity), were used to characterize the antioxidative mechanisms of the compound in different environments: gas, water, and pentyl ethanoate. DFT calculation showed that the FHT mechanism was the main antiradical mechanism in the gaseous phase, but the SPLET mechanism may be more favored from a thermodynamic perspective in the water phase. The presence of the C-8 hydroxyl group is requisite for enhancing the antiradical activities of 6- and/or 8-hydroxyl-substituted derivatives of aristolochic acids.

Graphical abstract