时间标签：数据日期 2026-11-05 · 生成时间 2026-11-05 05:30（Asia/Shanghai）｜ 检索窗口 PubMed edat 2026/11/02 – 2026/11/06 ｜ 情报发生日期 2026-11-05
研究问题
Collectively, these findings demonstrate that NGR1 corrects ischemia-driven metabolic dysfunction by restoring bioenergetic equilibrium and reducing glycolytic flux, positioning it as a promising therapeutic agent for cerebral ischemia.To elucidate the mechanisms underlying neuronal metabolic reprogramming following ischemia, we investigated the CKLF1/CCR5 axis and associated signaling pathways in PC12 cells subjected to OGD.；NGR1 and Edaravone simultaneously suppressed pro-inflammatory mediators and upregulated anti-inflammatory cytokines, indicating robust anti-inflammatory capacity against post-ischemic neuroinflammation.3.4NGR1 represses CKLF1-mediated neuronal metabolic reprogramming post cerebral ischemiaIHC was performed to detect CKLF1 protein abundance in rat cortex and hippocampus to clarify whether NGR1 targets the CKLF1 cascade in vivo. pMCAO induced prominent CKLF1 overexpression, which was dose-dependently suppressed by 10–40 mg/kg NGR1 (Figures 4M–O).；This work identifies CKLF1 as the direct molecular target through which NGR1 confers anti-ischemic neuroprotection, and the absent therapeutic response in CKLF1−/− rats demonstrates the indispensable role of CKLF1, laying a mechanistic basis for developing NGR1-based therapies for ischemic stroke.To clarify whether CKLF1 mediates NGR1-regulated neuronal metabolic reprogramming, we detected the protein levels of CKLF1, CCR5, IL-1β, AMPK, mTOR, HIF-1α, PFKFB3 and GLUT3 in the cerebral cortex and hippocampus of wild-type (WT) and CKLF1−/− rats after pMCAO via WB.
方法
Patients commonly suffer persistent neurological deficits including hemiparesis, aphasia and cognitive dysfunction, with severe cases posing life-threatening risks (Kong et al., 2023).；Clinical data further validate its safety and therapeutic efficacy against acute ischemic stroke (Chen et al., 2008).Modern pharmacological research confirms that Panax notoginseng saponins (PNS) alleviate ischemic pathological progression via antiplatelet activity and improve neurological outcomes in stroke patients (Zhang et al., 2026).；Here, we verified CKLF1 as a direct binding partner of NGR1 via molecular docking and cellular/animal assays.
核心结论
Preclinical evidence demonstrates that inhibiting glycolysis or lactate dehydrogenase A (LDHA) curtails lactate overproduction, relieves cerebral acidosis and reduces infarct volume (Xiong et al., 2024).；Subsequent OGD challenges demonstrated maximal neuroprotection at 10 μM NGR1, with no significant enhancement at a higher dose (100 μM).；Based on these findings, further experiments employed NGR1 at 0.1, 1, and 10 μM to validate its dose-dependent efficacy.
局限
However, NGR1 exerted no corrective effects on these molecular dysregulations in CKLF1−/− rats, whose protein expression patterns were identical to vehicle-treated CKLF1−/− pMCAO rats.；Post-ischemic NGR1 improved short-term outcomes in pMCAO rats; however, this preclinical finding does not establish clinical benefit beyond the reperfusion window.；By contrast, NGR1 actively remodels intrinsic neuronal energy metabolism through CKLF1-mediated metabolic reprogramming, thereby enhancing neuronal resilience to the ischemic hypoperfusion microenvironment.While the present study provides robust multi-level evidence, several limitations should be acknowledged and may inform future investigations.
对本项目的价值
中高价值：属「干细胞 / 部分重编程与再生」方向；干细胞 / 再生 / 重编程栏目可用作本项目文献库与综述素材。 ｜ 价值分 3.0/5（★★★☆☆）
全文来源
PubMed PMC JATS（正文 57,960 字符，题名指纹 0.82，已过 PubMed PMCID 官方关联 + 题名指纹 + 正文长度归属校验）
原文题录
- 中文题名：三七皂苷 R1 经 CKLF1 依赖性抑制神经元代谢重编程减轻缺血性卒中
- 英文标题：Notoginsenoside R1 attenuates ischemic stroke via CKLF1-dependent suppression of neuronal metabolic reprogramming.
- 期刊与标识：Frontiers in pharmacology · PMID 42973581 · DOI 10.3389/fphar.2026.1964218 · PMC PMC13724343