Baicalin-Geniposide glycosides inhibit PM2.5-induced brain damage in rats via the 5-LOX/LTB4 pathway

PM2.5-induced brain damage is related to systemic inflammation and oxidative stress, which can be caused by PM2.5 acting directly on the brain or indirectly by stimulating inflammation in the peripheral nervous system; however, the underlying pathological mechanisms are still unclear. Baicalin (BC) and geniposide glycosides (GD) are natural products that may exert neuroprotective effects by reducing inflammatory responses and oxidative damage. A mouse model of microglial polarization was established via in vitro exposure to PM2.5, and tracheal drip injection of PM2.5-suspended dust was used to simulate PM2.5-induced brain damage. The expression of polarization markers in mouse microglia, changes in the levels of inflammatory factors, and changes in memory, cerebral blood flow and 5-lipoxygenase/leukotriene B4 (5-LOX/LTB4) pathway proteins in a brain injury model rat were investigated via enzyme-linked immunosorbent assays, real-time fluorescence quantitative PCR and Western blotting techniques after baicalein-gardenia glycoside action. The most successful experimental animal model of PM2.5-induced brain damage in rats was achieved when the dye dose was 15 mg/kg and the dyeing time was 3 M. BC/GD is protective against PM2.5-induced brain damage in rats. Baicalin and gardenia ameliorate microglial activation and brain tissue inflammatory injury induced by PM2.5, and its protective effect is associated with the 5-LOX/LTB4 pathway. Baicalin-Geniposide glycoside prevents PM2.5-induced brain injury by activating the 5-LOX/LTB4 pathway and inhibiting inflammation and microglial polarization to the M2 type. ● In this study, a mouse microglia polarisation model and a rat brain injury animal model were established with PM2.5-contaminated poison, and the efficacy and mechanism of the combined action of baicalein-gardenia glycoside were explored. ● We carried out measurements to evaluate the activation state of mouse microglia following exposure to PM2.5 and the impacts on brain damage, inflammatory factors, and pathway proteins in the rat. ● The findings demonstrated that baicalein-gardenia glycoside alleviated the inflammatory injury of brain tissue caused by PM2.5-induced microglia activation and protected against brain damage in rats. ● We discovered that baicalein-gardenia glycoside could restrain excessive microglia activation, lower the levels of IL-6 and TNF-α, and mitigate PM2.5-induced brain injury by influencing the 5-LOX/LTB4 signalling pathway.