Berberis lyceum and Fumaria indica: in vitro cytotoxicity, antioxidant activity, and in silico screening of their selected phytochemicals as novel hepatitis C virus nonstructural protein 5A inhibitors

Abstract

Berberis lyceum and Fumaria indica are two Pakistani indigenous herbal medicines used to treat liver infections, including hepatitis C virus (HCV). This study aimed to evaluate the cytotoxicity, and antioxidant activity of these plant extracts and computationally screen their selected phytoconstituents as HCV NS5A inhibitors. The viability of HepG2 cells was assessed 24 h and 48 h post-treatment using colorimetric and dye exclusion methods. Antioxidant properties were examined by the 2,2-diphenyl-1-picrylhydrazyl (DPPH), reducing power, and total antioxidant capacity assays. Seventeen known phytochemicals identified from each plant were docked into the active binding site of HCV NS5A protein. The top hit ligands were analyzed for their druglikeness properties and the indices of absorption, distribution, metabolism, elimination, and toxicity (ADMET). The results showed that both plant extracts were non-toxic (CC₅₀ > 200 µg/ml). The IC₅₀ values of DPPH-radical scavenging activity were 51.02 ± 0.94 and 62.91 ± 1.85 µg/ml for B. lyceum and F. indica, respectively. They also exhibited reducing power and total antioxidant capacity.The phytochemicals were identified as potent HCV NS5A inhibitors with good druglikeness and ADMET properties. Six of the docked phytochemicals exhibited higher binding scores (-17.9 to −19.2 kcal/mol) with HCV NS5A protein than the standard drug, daclatasvir (-17.2 kcal/mol). Molecular dynamics (MD) simulation confirmed the stability of two compounds, berbamine and paprafumine at 100 ns with active site of HCV NS5A protein. The identified compounds through molecular docking and MD simulation could have potential as HCV NS5A inhibitor after further validation.

Communicated by Ramaswamy H. Sarma

Highlights

• The methanolic extracts of Berberis lyceum and Fumaria indica were found to be non-cytotoxic in human liver cells.

• The extracts exhibited antioxidant potential through their capacity of scavenging free radicals.

• The selected phytochemicals from those two plant species presented good drug-likeness and ADMET characteristics.

• Molecular docking and molecular dynamic simulation studies confirmed two compounds berbamine and paprafumine to be stable at 100 ns.

• Several of the natural compounds identified from Berberis lyceum and Fumaria indica were discovered to be potential candidates as HCV nonstructural protein 5A inhibitors.

Keywords:

• Berberis lyceum
• Fumaria indica
• cytotoxicity
• antioxidant activity
• HCV NS5A
• in silico molecular docking
• molecular dynamics simulation

Acknowledgements

We would like to thank the Centre of Excellence in Molecular Biology (CEMB) and the World Academy of Sciences (TWAS) for their support.

Disclosure statement

No conflict of interest related to this study.

Author contributions

KBL, ST, and AM prepared the plant material and performed the in vitro experiments. UAA and MS conducted docking analysis and molecular dynamics stimulation. KBL performed the statistical analysis and wrote the paper. BI conceived, designed and supervised the study. BI critically reviewed and edited the manuscript. BI and AAS proofread the final manuscript.