The inflammatory response is the stress reactions to infection or injury so as to help the body return to normal as soon as possible. In central nervous system, the overactivated immune system causes irreversible damage to neurons and synapses, which results in cognitive impairment. Berberine, an isoquinoline alkaloid extracted from Coptidis Rhizoma, plays a powerful role in anti-inflammation. It has been reported that berberine significantly improved the decline of cognitive ability. Therefore, we carried out this work to find out the specific mechanism. We tested behaviorally that berberine administration did improve lipopolysaccharide (LPS)-induced cognitive impairment in C57BL/6J mice. We found that berberine reduced neuronal damage in the hippocampus by Nissl staining, and verified by western blot and immunofluorescence that berberine improved LPS-induced cognitive impairment through the SIRT1/nuclear factor E2-related factor 2 (NRF2)/nuclear factor-kappaB (NF-κB) signaling pathway. The results showed that berberine plays an anti-inflammatory and antioxidant role by targeting SIRT1/NRF2/NF-κB signaling pathway so as to reduce the cognitive impairment and neuronal damage caused by LPS in C57BL/6J mice. Berberine preprotection increased the expression of heme oxygenase-1 (HO-1) after activating NRF2 and inhibited the activation of NF-κB and the release of inducible NO synthase, which may be related to berberine activating SIRT1. However, the effect of reducing inflammatory response was inhibited after using SIRT1 inhibitor EX527 in vitro. This research explains the significance of anti-inflammatory in the treatment of cognitive impairment from different angles.
Keywords: SIRT1; berberine; cognitive impairment; lipopolysaccharide; neuroinflammation.