Holarrhena pubescens Wall. ex G. Don Extracts Inhibit LPS-Irritated Oxidative Stress in Dendritic Cells

Abstract

Holarrhena pubescens Wall. ex G. Don (H. pubescens), belonging to the Apocynaceae family, is distributed in deciduous forests of the tropical Himalayas. H. pubescens is an important traditional medicinal plant, especially its seeds and barks. Therefore, we assessed the antioxidant capacity of H. pubescens extracts in Lipopolysaccharide (LPS)-induced dendritic cells (DCs) for sepsis treatment. Our results indicated that H. pubescens extracts with different doses (25 μg/mL, 50 μg/mL, 100 μg/mL) reduced the reactive oxygen species (ROS) level, and weakened the nitric oxide synthases (NOS) activity and nitric oxide (NO) level in LPS (100 ng/mL)-irritated DCs. In addition, H. pubescens extracts decreased the oxidized glutathione (GSSG) production but increased the reduced glutathione (GSH) production, thereby preserving the cellular reductive status owing to the raised GSH/GSSG ratio. Furthermore, H. pubescens extracts strengthened the antioxidant enzymes activity in LPS-induced DCs, such as glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD). Finally, we found that H. pubescens extracts significantly improved the expression of the nuclear factor erythroid 2-related factor 2 (Nrf2) and the heme oxygenase 1 (HO–1) in LPS-irritated DCs. These results indicated that H. pubescens extracts suppressed the LPS-irritated oxidative stress in DCs via Nrf2/HO–1 signaling pathway, providing a potential strategy for sepsis therapy.