School of Clinical Medicine, Ningxia Medical University, Yinchuan, 750004, Ningxia Hui Autonomous Region, People's Republic of China.
Ningxia Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Medical Sciences, General Hospital of Ningxia Medical University, Yinchuan, 750004, Ningxia Hui Autonomous Region, China.
J Transl Med. 2023 Oct 31;21(1):770. doi: 10.1186/s12967-023-04648-9.
Lycium barbarum polysaccharide (LBP) is an active ingredient extracted from Lycium barbarum that inhibits neuroinflammation, and Lycium barbarum glycopeptide (LbGp) is a glycoprotein with immunological activity that was purified and isolated from LBP. Previous studies have shown that LbGp can regulate the immune microenvironment, but its specific mechanism of action remains unclear.
In this study, we aimed to explore the mechanism of action of LbGp in the treatment of spinal cord injury through metabolomics and molecular experiments.
SD male rats were randomly assigned to three experimental groups, and after establishing the spinal cord hemisection model, LbGp was administered orally. Spinal cord tissue was sampled on the seventh day after surgery for molecular and metabolomic experiments. In vitro, LbGp was administered to mimic the inflammatory microenvironment by activating microglia, and its mechanism of action in suppressing neuroinflammation was further elaborated using metabolomics and molecular biology techniques such as western blotting and q-PCR.
In vivo and in vitro experiments found that LbGp can improve the inflammatory microenvironment by inhibiting the NF-kB and pyroptosis pathways. Furthermore, LbGp induced the secretion of docosahexaenoic acid (DHA) by microglia, and DHA inhibited neuroinflammation through the MAPK/NF-κB and pyroptosis pathways.
In summary, we hypothesize that LbGp improves the inflammatory microenvironment by regulating the secretion of DHA by microglia and thereby inhibiting the MAPK/NF-κB and pyroptosis pathways and promoting nerve repair and motor function recovery. This study provides a new direction for the treatment of spinal cord injury and elucidates the potential mechanism of action of LbGp.
枸杞多糖(LBP)是从枸杞中提取的一种活性成分,具有抑制神经炎症的作用,枸杞糖肽(LbGp)是从 LBP 中分离纯化得到的具有免疫活性的糖蛋白。先前的研究表明,LbGp 可以调节免疫微环境,但具体作用机制尚不清楚。
本研究旨在通过代谢组学和分子实验探讨 LbGp 治疗脊髓损伤的作用机制。
SD 雄性大鼠随机分为 3 组,建立脊髓半横切模型后给予 LbGp 灌胃。术后第 7 天取脊髓组织进行分子和代谢组学实验。体外通过激活小胶质细胞模拟炎症微环境,给予 LbGp,进一步采用 Western blot、q-PCR 等分子生物学技术探讨其抑制神经炎症的作用机制。
体内和体外实验均发现 LbGp 可通过抑制 NF-κB 和细胞焦亡通路改善炎症微环境。此外,LbGp 诱导小胶质细胞分泌二十二碳六烯酸(DHA),DHA 通过 MAPK/NF-κB 和细胞焦亡通路抑制神经炎症。
综上所述,我们假设 LbGp 通过调节小胶质细胞 DHA 的分泌来改善炎症微环境,从而抑制 MAPK/NF-κB 和细胞焦亡通路,促进神经修复和运动功能恢复。本研究为脊髓损伤的治疗提供了新的方向,并阐明了 LbGp 的潜在作用机制。