Ratnawati Ratnawati, Aswad Muhammad, Jumriani Jumriani, Nurhidayah Anggun, Azmin Muhammad Rayza, Filmaharani Filmaharani, Roosevelt Alfreds, Hardiyanti Widya, Latada Nadila Pratiwi, Mudjahid Mukarram, Nainu Firzan
Postgraduate Program in Pharmacy, Faculty of Pharmacy, Hasanuddin University, Tamalanrea, Makassar 90245, Indonesia.
Department of Pharmaceutical Science and Technology, Faculty of Pharmacy, Hasanuddin University, Tamalanrea, Makassar 90245, Indonesia.
ACS Omega. 2025 Apr 1;10(14):14052-14062. doi: 10.1021/acsomega.4c11062. eCollection 2025 Apr 15.
Hyperglycemia, characterized by elevated blood glucose levels, is a major risk factor for diabetes mellitus and its complications. While conventional therapies are effective, they are often associated with side effects and high costs, necessitating alternative strategies. This study evaluates the potential of caffeic acid (CA), a phenolic compound with reported antihyperglycemic properties, using both in silico and in vivo approaches. Molecular docking simulations revealed that CA demonstrates a strong binding affinity to protein tyrosine phosphatase 1B (PTP1B), a critical enzyme in glucose metabolism, with superior interaction profiles compared to the reference drug, ertiprotafib. In the in vivo studies, a model was used to investigate the effects of CA under hyperglycemic conditions induced by a high-sugar diet. Treatment with CA, particularly at a concentration of 500 μM, significantly reduced hemolymph glucose levels and improved several physiological and behavioral parameters, including survival rates, body size, body weight, and larval movement. Furthermore, gene expression analysis demonstrated that CA modulates key metabolic and stress-related pathways, enhancing glucose homeostasis and reducing metabolic stress. These findings highlight the dual utility of in silico and in vivo methodologies in elucidating the antihyperglycemic potential of CA. The results support the development of CA as a cost-effective and ethically viable therapeutic candidate with implications for diabetes management in resource-limited settings.
高血糖症以血糖水平升高为特征，是糖尿病及其并发症的主要危险因素。虽然传统疗法有效，但它们往往伴有副作用且成本高昂，因此需要替代策略。本研究使用计算机模拟和体内实验方法评估了咖啡酸（CA）的潜力，咖啡酸是一种具有抗高血糖特性报道的酚类化合物。分子对接模拟显示，CA对蛋白酪氨酸磷酸酶1B（PTP1B）具有很强的结合亲和力，PTP1B是葡萄糖代谢中的一种关键酶，与参考药物ertiprotafib相比，其相互作用特征更优。在体内研究中，使用一个模型来研究CA在高糖饮食诱导的高血糖条件下的作用。用CA处理，尤其是浓度为500μM时，显著降低了血淋巴葡萄糖水平，并改善了几个生理和行为参数，包括存活率、体型、体重和幼虫活动。此外，基因表达分析表明，CA调节关键的代谢和应激相关途径，增强葡萄糖稳态并减轻代谢应激。这些发现突出了计算机模拟和体内实验方法在阐明CA抗高血糖潜力方面的双重效用。结果支持将CA开发为一种具有成本效益且符合伦理的可行治疗候选物，对资源有限环境下的糖尿病管理具有重要意义。
