Naoxueshu oral liquid promotes hematoma absorption by targeting CD36 in M2 microglia via TLR4/MyD88/NF-κB signaling pathway in rats with intracerebral hemorrhage

Intracerebral hemorrhage (ICH) is a major public health issue that leads to elevated rates of death and disability and has few proven treatments. Naoxueshu oral liquid (NXS), a TCM patent drug, is widely used in patients with ICH. Although a series of clinical studies have confirmed the efficacy and safety of NXS, the underlying mechanism of hematoma absorption is unclear.Our work aimed to elucidate the effect and mechanism of NXS on hematoma absorption in rats with ICH.Induction of ICH model in the rats with intracerebral injection of collagenase VII, followed by treatment with NXS and Edaravone as a control neuroprotection medication. Neural functional recovery was assessed using mNSS, foot fault test, corner test, forelimb grip-traction test, and adhesive removal test. Hematoma absorption was assessed by the spectrophotometric hemoglobin assay with Drabkin's reagent. The protein expression of CD36, M2 microglia marker (CD206 and YM-1) and TLR4/MyD88/NF-κB pathway related proteins were determined by Western blot and immunofluorescence.NXS could significantly ameliorate the ICH recovery of neural and locomotor function as well as reduce hemorrhage volume. NXS could increase the expression of CD36 expressed in M2 microglia and promote M2 microglia polarization. Simultaneously, NXS significantly suppressed protein expressions of TLR4, MyD88, and NF-κB following ICH in rats. The results indicated that lipopolysaccharide (LPS), TLR4 specific agonist, could partially reverse the change in ICH rats administrated with NXS.NXS promotes hematoma absorption by targeting CD36 expression in M2 microglia via TLR4/MyD88/NF-κB signaling pathway in rats with ICH. Collectively, current research provides a novel theoretical basis for the clinical application of NXS.