Liquid Chromatography-High-Resolution Mass Spectroscopy-Based Metabolomics for Identification Cytotoxic Compounds...

Area of Science:

• Phytochemistry
• Pharmacology
• Metabolomics

Background:

• Acalypha indica is traditionally used for cancer treatment.
• Identifying specific bioactive compounds is crucial for understanding its therapeutic potential.
• A metabolomic approach offers a comprehensive strategy for drug discovery from natural sources.

Purpose of the Study:

• To employ a metabolomic strategy to identify cytotoxic compounds in Acalypha indica with potential anticancer properties.
• To correlate metabolite profiles with cytotoxic activity against MCF-7 cells.
• To investigate the binding affinity of identified compounds to the alpha-estrogen receptor.

Main Methods:

• Extraction of Acalypha indica leaves using various solvents (ethanol, ethyl acetate, chloroform, n-hexane).
• Cytotoxicity evaluation using MCF-7 cells to determine IC50 values.
• Metabolite profiling via liquid chromatography-high-resolution mass spectrometry (LC-HRMS).
• Statistical analysis including Principal Component Analysis (PCA) and Orthogonal Partial Least Squares-Discriminant Analysis (OPLS-DA).
• In silico analysis for receptor binding prediction.

Main Results:

• Cytotoxic activity (IC50 values) ranged from 51.88 ± 7.80 to 226.86 ± 13.27 µg/mL.
• LC-HRMS identified 27 metabolites, with PCA showing distinct profiles based on solvent extraction.
• OPLS-DA successfully correlated metabolite profiles with cytotoxic data, predicting six key compounds: hernanol, 13(S)-HpOTrE, (±)9-HpODE, (+)-catechin, traumatic acid, and theobromine.
• In silico analysis indicated that (+)-catechin and hernanol exhibit binding affinity to the alpha-estrogen receptor comparable to doxorubicin.

Conclusions:

• This study successfully identified six compounds from Acalypha indica contributing to its anticancer activity using a metabolomic approach.
• (+)-Catechin and hernanol show promise as potential anticancer agents due to their interaction with the alpha-estrogen receptor.
• The findings support the traditional use of Acalypha indica and provide a foundation for further investigation into its pharmaceutical applications.