Bioactive polyphenols from Isodon serra with antioxidant and hepatoprotective activities in vitro and in vivo

Abstract

Isodon serra is a medicinal plant with notable antioxidant potential underlying its hepatoprotective properties, suggesting the presence of highly active antioxidant constituents. To identify these bioactive components, the target compounds were isolated and structurally elucidated using chromatographic and spectroscopic techniques. Antioxidant activities were evaluated using DPPH radical scavenging and ferric reducing antioxidant power (FRAP) assays, together with tert-butyl hydroperoxide (t-BHP)-induced oxidative stress models in vitro and in vivo. As a result, ten monomeric compounds were isolated from I. serra, including two new compounds, labiserins A (1) and B (2), which were identified as a carboxylated α-pyrone derivative and a dihydrobenzofuran neolignan, respectively. Compound 7 showed the highest potency (EC₅₀ = 10.9 ± 0.4 µM), which was nearly tenfold lower than that of vitamin C (EC₅₀ = 101.1 ± 3.1 µM). In HepG2 cells, 7 dose-dependently attenuated t-BHP-induced cell death, while significantly reducing intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) levels and enhancing superoxide dismutase (SOD) activity. qRT-PCR analysis indicated that its hepatoprotective effect is associated with transcriptional modulation of Keap1 and suppression of NF-κB-mediated inflammatory responses. In mice, 7 significantly reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, diminished hepatic MDA accumulation, and ameliorated t-BHP-induced histopathological liver damage. Collectively, these findings reveal new antioxidant polyphenols from I. serra and identify 7 as a potent hepatoprotective constituent in vitro and in vivo.