Hepatotoxicity prevention in Acetaminophen-induced HepG2 cells by red betel (Piper crocatum Ruiz and Pav) extract from Indonesia via antioxidant, anti-inflammatory, and anti-necrotic

Acetaminophen (APAP) is a widely used analgesic, but it may cause liver injury (hepatotoxicity) via oxidative stress that induced by N-acetyl-p-benzoquinone imine (NAPQI) in long term usage or overdose. Multiple inflammatory mediators were also found to contribute for this effect. Many medicinal plants was known for its antioxidant and anti-inflammatory activities and one of them is Red betel (Piper crocatum Ruiz and Pav) from Indonesia. In this study, the red betel leaves extract (RBLE) protective effect against APAP-induced HepG2 cells was determined. APAP-induced HepG2 as hepatotoxicity cell model was treated with RBLE at 25 and 100 μg/mL. Protective effects of RBLE toward hepatotoxicity were evaluated by several parameters: tumor necrosis factor-α (TNF-α) concentration, reactive oxygen species (ROS) level, live cells percentage, apoptotic cells percentage, necrotic cells percentage, death cells percentage, CYP2E1 and GPX gene expression. The RBLE treatments (both 25 and 100 μg/mL) increased CYP2E1 and GPX gene expression also live cells percentage, while decreased ROS level, TNF-α concentration, also the percentage of death and necrotic cells. Red Betel leaves ethanol extract has hepatoprotective effect via anti-inflammatory, anti-necrotic, and antioxidant potency in liver injury model.