Structural Characterization of a Novel Galactoarabinan from Baphicacanthus cusia and Its Protective Effects Against Oxidative Stress and Inflammation via the PI3K/Akt and Nrf2/HO-1 Signaling Axes

The roots of Baphicacanthus cusia (Nees) Bremek, commonly known as Nan-Ban-Lan-Gen, have been used for a long time in traditional Chinese medicine to manage inflammatory and infectious diseases. However, the structural features and bioactive potential of its polysaccharides have not been extensively studied. In the present study, a novel homogeneous polysaccharide (BcP-b2) was isolated from the roots of B. cusia, and its bioactivity was evaluated using an activity-guided purification strategy. Multi-dimensional structural analysis identified BcP-b2 as a highly branched galactoarabinan with a molecular weight of ~38.1 kDa, featuring a well-defined backbone and a variety of side chains. In vitro and in vivo assays demonstrated that BcP-b2 attenuated the accumulation of reactive oxygen species (ROS) and enhanced the activities of endogenous antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px). Additionally, BcP-b2 activated macrophages under basal conditions and alleviated lipopolysaccharide (LPS)-induced cytotoxicity and inflammatory mediator release. Transcriptomic and Western blot analyses revealed that these dual effects were achieved through the simultaneous suppression of the PI3K/Akt inflammatory axis and activation of the Nrf2/HO-1 antioxidant pathway, concomitant with enhanced nuclear translocation of Nrf2. These findings provide a molecular basis for the ethno-pharmacological use of Nan-Ban-Lan-Gen and identify BcP-b2 as a promising candidate for further investigation as a potential therapeutic agent.