PDF(Pubmed)
Abstract：
Diabetic neuropathy (DN) represents a common and debilitating complication of diabetes, affecting a significant proportion of patients. Despite available treatments focusing on symptom management, there remains an unmet need for therapies that address the underlying pathophysiology. In pursuit of novel interventions, this study evaluated the therapeutic effects of caffeic acid-a natural phenolic compound prevalent in various foods-on diabetic neuropathy using a mouse model, particularly examining its interaction with the Insulin-like Growth Factor 1 (IGF-1) signaling pathway. Caffeic acid was administered orally at two dosages (5 mg/kg and 10 mg/kg), and a comprehensive set of outcomes including fasting blood glucose levels, body weight, sensory behavior, spinal cord oxidative stress markers, inflammatory cytokines, and components of the IGF-1 signaling cascade were assessed. Additionally, to determine the specific contribution of IGF-1 signaling to the observed benefits, IGF1R inhibitor Picropodophyllin (PPP) was co-administered with caffeic acid. Our results demonstrated that caffeic acid, at both dosages, effectively reduced hyperglycemia and alleviated sensory behavioral deficits in diabetic mice. This was accompanied by a marked decrease in oxidative stress markers and an increase in antioxidant enzyme activities within the spinal cord. Significantly lowered microglial activation and inflammatory cytokine expression highlighted the potent antioxidative and anti-inflammatory effects of caffeic acid. Moreover, increases in both serum and spinal levels of IGF-1, along with elevated phosphorylated IGF1R, implicated the IGF-1 signaling pathway as a mediator of caffeic acid\'s neuroprotective actions. The partial reversal of caffeic acid\'s benefits by PPP substantiated the pivotal engagement of IGF-1 signaling in mediating its effects. Our findings delineate the capability of caffeic acid to mitigate DN symptoms, particularly through reducing spinal oxidative stress and inflammation, and pinpoint the integral role of IGF-1 signaling in these protective mechanisms. The insights gleaned from this study not only position caffeic acid as a promising dietary adjunct for managing diabetic neuropathy but also highlight the therapeutic potential of targeting spinal IGF-1 signaling as part of a strategic treatment approach.
摘要：
糖尿病神经病变（DN）是糖尿病的常见和衰弱的并发症，影响了相当大比例的患者。尽管现有的治疗方法侧重于症状管理，对于解决潜在病理生理学的疗法，仍然存在未满足的需求。为了追求新颖的干预措施，这项研究使用小鼠模型评估了咖啡酸-一种在各种食物中普遍存在的天然酚类化合物-对糖尿病神经病变的治疗作用，特别是检查其与胰岛素样生长因子1（IGF-1）信号通路的相互作用。咖啡酸以两种剂量（5mg/kg和10mg/kg）口服给药，和一组全面的结果，包括空腹血糖水平，体重,感官行为，脊髓氧化应激标志物，炎性细胞因子，和IGF-1信号级联的组分被评估。此外,为了确定IGF-1信号传导对观察到的益处的具体贡献，IGF1R抑制剂苦参白(PPP)与咖啡酸共同给药。我们的结果表明咖啡酸，在两种剂量下，可有效降低糖尿病小鼠的高血糖和减轻感觉行为缺陷。这伴随着氧化应激标志物的显着降低和脊髓内抗氧化酶活性的增加。显著降低的小胶质细胞活化和炎性细胞因子表达突出了咖啡酸的有效抗氧化和抗炎作用。此外，血清和脊髓IGF-1水平增加，伴随着磷酸化IGF1R升高，提示IGF-1信号通路是咖啡酸神经保护作用的介质。通过PPP部分逆转咖啡酸的益处证实了IGF-1信号在介导其作用中的关键参与。我们的发现描述了咖啡酸减轻DN症状的能力，特别是通过减少脊髓氧化应激和炎症，并指出IGF-1信号在这些保护机制中的整体作用。从这项研究中获得的见解不仅将咖啡酸定位为管理糖尿病神经病变的有前途的饮食辅助手段，而且还强调了靶向脊髓IGF-1信号作为战略治疗方法的一部分的治疗潜力。
