Cytotoxic, apoptotic, anti-inflammatory and oxidative stress reduction potential of the defatted methanolic extract of the Areca catechu L. (Arecaceae) inflorescence in HepG2 cancer cell lines

The development of novel therapeutic agents with fewer adverse effects is crucial due to the persistent side effects of the current drugs, which are often required to treat both acute and chronic diseases characterised by inflammation and oxidative stress. This study investigated the anti-inflammatory and oxidative stress reduction potential of a defatted methanolic extract of Areca catechu L. inflorescence (ACME), rich in alkaloids and flavonoids, in lipopolysaccharide (LPS)-induced inflammatory and oxidative stress responses in HepG2 cancer cells. The MTT assay was used to evaluate the viability of HepG2 cells, which demonstrated a reduction in viability at various concentrations of ACME, with an IC50 value of 112.69 mu g/ml. Further investigation on the apoptotic potential of ACME demonstrated that it triggered both early and late apoptosis, as well as necrosis in HepG2 cancer cells. In vitro anti-inflammatory studies showed that ACME at concentrations of 28, 56, and 112 mu g/ml and equal concentrations of diclofenac significantly decreased the production of pro-inflammatory mediators (total COX, 5-LOX, MPO, iNOS, and NO) and cytokines (IL-1m, IL-6, and TNF-) in LPS-stimulated HepG2 cells. ACME at a concentration of 112 mu g/ml also improved cellular antioxidant status (SOD, CAT, GSH-Px, GSH, MDA, and total protein), reduced reactive oxygen species (ROS) levels, and maintained mitochondrial membrane potential (MMP). Moreover, ACME was found to significantly suppress LPS-induced activation of keap1, thereby preserving the expression of Nrf2, as confirmed by qRT-PCR. These findings suggest that ACME demonstrates significant anti-inflammatory and oxidative stress reduction potential, likely due to its effect on the Keap1-Nrf2 pathway.