EXPLORING THE THERAPEUTIC POTENTIAL OF AM114: A BORONIC CHALCONE DERIVATIVE INDUCE APOPTOSIS AND SUPPRESS PROINFLAMMATORY CYTOKINES AND CHEMOKINES IN INTERLEUKIN-1β STIMULATED HUMAN THP-1 DERIVED MACROPHAGES

CHITRA SELVARAJAN; NALINI GANESAN

doi:10.22159/ijpps.2024v16i3.50391

Authors

CHITRA SELVARAJAN Department of Biochemistry, New Prince Shri Bhavani Arts and Science College, Medavakkam, Chennai-100, India https://orcid.org/0000-0002-8920-6341
NALINI GANESAN Department of Biochemistry, Sri Ramachandra Institute of Higher Education and Research, Sri, Ramachandra University, Porur, Chennai-116, India https://orcid.org/0000-0001-8663-0625

DOI:

https://doi.org/10.22159/ijpps.2024v16i3.50391

Keywords:

Inflammation, THP-1 derived macrophages, Apoptosis, Caspase-3, Pro-inflammatory cytokines

Abstract

Objective: Chalcones and their derivatives display a wide range of pharmacological activities. This study examined the effects of AM114, a boronic-chalcone derivative, on human THP-1-derived macrophages with and without interleukin-1β (IL-1β) stimulation.

Methods: AM114 and Aspirin-treated THP-1-derived macrophages underwent activation with or without interleukin-1β. The IC₅₀ concentrations of AM114 and Aspirin were determined through an MTT test. Apoptosis was measured using various techniques, including staining with acridine orange/Ethidium bromide, Hoechst 33342, and rhodamine 123 assays. Caspase-3 activity was measured using the spectrofluorimetric technique, while DNA fragmentation was assessed via agarose gel electrophoresis. Pro-inflammatory cytokines such as interleukin-6 (IL-6) and chemokines like interleukin-8 (IL-8) were measured using enzyme-linked immunosorbent assays.

Results: AM114 and Aspirin showed dose-dependent cytotoxic effects on THP-1 macrophages. Induction of apoptosis was detected in AM114-treated THP-1 macrophages activated with IL-1β compared to macrophages without IL-1β. The gradation of dye uptake, membrane blebbing, increased caspase-3 activity, and DNA fragmentation ensures the induction of apoptosis, which indicates the cell's morphological changes, biochemical processes, and mitochondrial activity. Treating AM114 in IL-1β-activated THP-1 macrophages significantly reduced pro-inflammatory cytokines (IL-6) and chemokines (IL-8), suggesting its anti-cytokine potential in inflammatory diseases.

Conclusion: The study results emphasize that AM114 could act as an anti-inflammatory agent by triggering apoptosis and reducing the release of cytokines and chemokines in inflammatory conditions. As a result, it may be used as a therapeutic option for inflammatory diseases.

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