Cytotoxic Evaluation, Molecular Docking, Molecular Dynamics, and ADMET Prediction of Isolupalbigenin Isolated from Erythrina subumbrans (Hassk). Merr. (Fabaceae) Stem Bark: Unveiling Its Anticancer Efficacy

Tati Herlina, Abd Wahid Rizaldi Akili, Vicki Nishinarizki, Ari Hardianto, Allyn Pramudya Sulaeman, Shabarni Gaffar, Euis Julaeha, Tri Mayanti, Unang Supratman, Mohd Azlan Nafiah, Jalifah Binti Latip
https://doi.org/10.2147/OTT.S482469

Abstract

Introduction

Erythrina subumbrans, a medical plant found in sub-Saharan Africa and the Western Ghats of India, shows promise asa potential source of bioactive compounds to treat cancer. In our ongoing research on folk medical plants, we report the isolation offlavonoid compound from the stem bark of E. subumbrans along with its cytotoxic activity against breast cancer (MCF-7 and T47D),and cervical cancer (HeLa) cell lines.

Purpose

This study aimed to isolate secondary metabolite from the stem bark of E. subumbrans and evaluate its cytotoxic activity tosupport the use of folk medicinal plants as alternative therapy against cancer.

Methods

Isolupalbigenin was isolated from the stem bark of E. subumbrans by column chromatography. Cytotoxic activity againstbreast cancer (MCF-7 and T47D) and cervical cancer (HeLa) cell lines was evaluated using the MTT assay, whereas the in silico studywas evaluated using molecular docking and molecular dynamics against estrogen receptor alpha (ERα).

Result

The cytotoxic assay showed that isolupalbigenin inhibited the growth of MCF-7 cell with an IC50 of 31.62 µg∙mL −1, whileshowing no toxicity against normal human cells (Vero cell line). The molecular docking results suggested that isolupalbigenin can bindto ERα with a lower binding affinity than estradiol, whereas the stability of the isolupalbigenin-ERα complex was confirmed bymolecular dynamic simulation with a median Root Mean Square Deviation (RMSD) of 2.80 Å. Toxicity prediction suggested thatisolupalbigenin was less likely to cause hepatotoxicity or carcinogenicity, whereas pharmacokinetic prediction suggested thatisolupalbigenin has high intestinal absorption with medium Caco2 permeability. In addition, isolupalbigenin was predicted to havea medium volume of distribution (Vd).

Conclusions

Isolupalbigenin isolated from the stem bark of E. subumbrans with cytotoxic activity supports further development ofplants from the genus Erythrina as a medicinal plant for alternative therapy against cancer.

Keywords:

Erythrina subumbrans; Isolupalbigenin; Cytotoxic; In vitro; In silico