Investigation on antineoplastic potential of Barleria lupulina Lindl: From phytochemical profiling to molecular dynamics simulation assessment

Abstract

Background

Barleria lupulina, a medicinal plant of India, South China and Southeast Asia, is known for its antioxidant and cytotoxic abilities. Although this plant has shown significant promise as an anticancer agent, the underlying mechanisms of action are yet to be explored. Objective: This study aimed to assess antiproliferative and proapoptotic potential of B. lupulina leaf extract with understanding of cellular and molecular mechanisms.

Materials and methods

The ethanolic extract was characterized using liquid chromatography-mass spectrometry and its anticancer activity was then assessed against Caco-2 colon cancer and A549 lung cancer cell lines.

Results

Phytochemical analysis of the extract revealed the presence of acetylbarlerin, decaffeoylacteoside, gallic acid, ipolamiide, leonuriside A, shanzhiside, and vanillic acid. The extract showed concentration-dependent cytotoxicity against both cancer cells. It induced early apoptosis at lower concentrations and late apoptosis at higher concentrations. Moreover, the extract noticeably reduced reactive oxygen species and mitochondrial membrane potential in a concentration-dependent way. The Western blot and quantitative reverse transcription polymerase chain reaction showed upregulation of Bax, caspase-8, caspase-9, and cluster of differentiation 95, and downregulation of Bcl-2. Molecular docking studies revealed that decaffeoylacteoside, gallic acid, and vanillic acid exhibited dual affinities for both caspase-8 and caspase-9, while acetylbarlerin, ipolamiide, leonuriside A, and shanzhiside showed selective affinities only for caspase-9.

Conclusion

The ethanolic leaf extract shows significant cytotoxic and proapoptotic activities, confirming its potential as a useful resource of bioactive compounds against cancer. Nevertheless, more in-depth investigations are necessary to realize the full potential of this medicinal plant for cancer therapy.