Synergistic anti-inflammatory effects of Ganoderma lucidum polysaccharide and ganoderic acid A on LPS-induced RAW264.7 cells by inhibition of TLR4/NF-κB activation

Ganoderma lucidum, a food-grade medicinal mushroom, is rich in biologically active components that offer significant health benefits. This study investigated the synergistic anti-inflammatory effects of Ganoderma lucidum polysaccharide (GLP-1) and ganoderic acid A (GAA) in RAW264.7 cells. GLP-1 was a low molecular weight beta-D-glucan with an alternating backbone structure formed by -> 3)-beta-D-Glcp-(1 -> and -> 4)-beta-D-Glcp-(1 -> linkages. Notably, significant synergistic effects were observed at a mass concentration ratio of GAA: GLP-1 of 1:4. The combination of GLP-1 and GAA more effectively inhibited the production of NO, pro-inflammatory cytokines (IL-6, IL-1 beta and TNF-alpha) and reactive oxygen species (ROS) compared to each component alone. Additionally, the combination increased anti-inflammatory cytokine levels (IL-10) and restored mitochondrial membrane potential. RT-qPCR and Western blot results suggested that GLP-1 and GAA may co-target the TLR4/NF-kappa B signaling pathways to achieve their synergistic anti-inflammatory effects. These findings provide valuable insights for future synergistic application of active ingredients from natural products.