Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, China.
Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou, China.
Rejuvenation Res. 2022 Oct;25(5):233-242. doi: 10.1089/rej.2022.0023. Epub 2022 Sep 26.
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 , 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 . This research explains the significance of anti-inflammatory in the treatment of cognitive impairment from different angles.
炎症反应是机体对感染或损伤的应激反应，以便尽快使机体恢复正常。在中枢神经系统中，过度激活的免疫系统会对神经元和突触造成不可逆转的损伤，从而导致认知障碍。小檗碱是从 中提取的一种异喹啉生物碱，具有强大的抗炎作用。有报道称，小檗碱显著改善了认知能力的下降。因此，我们开展了这项工作，以找出具体的机制。我们通过行为测试发现，小檗碱给药可改善 LPS 诱导的 C57BL/6J 小鼠认知障碍。我们发现，Nissl 染色显示小檗碱可减少海马神经元损伤，通过 Western blot 和免疫荧光验证，小檗碱通过 SIRT1/核因子 E2 相关因子 2 (NRF2)/核因子-κB (NF-κB) 信号通路改善 LPS 诱导的认知障碍。结果表明，小檗碱通过靶向 SIRT1/NRF2/NF-κB 信号通路发挥抗炎和抗氧化作用，从而减轻 LPS 诱导的 C57BL/6J 小鼠认知损伤和神经元损伤。小檗碱预处理通过激活 NRF2 增加血红素加氧酶-1 (HO-1) 的表达，抑制 NF-κB 的激活和诱导型一氧化氮合酶的释放，这可能与小檗碱激活 SIRT1 有关。然而，在用 SIRT1 抑制剂 EX527 抑制炎症反应后，降低炎症反应的效果被抑制。这项研究从不同角度解释了抗炎在认知障碍治疗中的意义。
