Wang Andong, Yang Yuru, He Yaonan, Chen Guangtong, Ling Bai, Cheng Xiaotian
School of Pharmacy, Nantong University, Nantong, Jiangsu, China.
Department of Pharmacy, The Yancheng Clinical College of Xuzhou Medical University & The First People's Hospital of Yancheng, Yancheng, Jiangsu, China.
Front Endocrinol (Lausanne). 2025 Jul 30;16:1594782. doi: 10.3389/fendo.2025.1594782. eCollection 2025.
L. is one of the most significant genes in the Gramineae family, and the peel of L. (YMP), an unproven folk remedy for diabetes, has not been well studied. Diabetic nephropathy (DN) is one of the most well-known and dangerous microvascular effects of diabetes mellitus. The effects and mechanisms of YMP on metabolic reprogramming are largely unknown.
The components of YMP were systematically identified using UPLC-Q-TOF-MS/MS. A network pharmacology study between DN and significant components was then carried out. The pharmacological trials of YMP were evaluated in mice with diabetes. measurements were made of the biochemical activity, anti-inflammatory, and antioxidant properties. Moreover, UHPLC-LTQ-Orbitrap MS was used to do investigations on the metabolomics of serum and urine. Ultimately, transcriptomics analysis was utilized to clarify the complex processes by which the transcription factor influences DN.
43 components were systematically identified from YMP. It was found by network pharmacology analysis that signal transduction, namely metabolic disruption, involved pathways with a high degree of engagement. Experimental verification showed that YMP administration increased glomerular hypertrophy, collagenous tissue proliferation, urine microalbumin/creatinine ratio, inflammatory response remission, and oxidative stress promotion . Treatment with YMP may affect the pathways that are involved in the metabolism of amino acids and energy, as well as reverse metabolite abnormalities. YMP has the ability to restore the levels of metabolites like Gluconolactone, -Ribulose 5-phosphate, Xylulose 5-phosphate, -Alanine, -Aspartic acid, Glutamic acid, Citrulline, -Arginine, -Leucine, -Valine, -Isoleucine, and so on. Metabolic reprogramming of energy metabolism was demonstrated. By transcriptomics, when STZ is administered, the GPI, GAPDH, G6PC, HK2, HK1, and HK3 genes associated with glycolysis/gluconeogenesis were significantly elevated from the model groups. However, the pentose phosphate pathway-related genes G6PD, PGLS, RPE, TALDO1, and HXLB significantly elevated when YMP was administered.
This study was the first to show that YMP corrected disruptions in the pentose phosphate pathway and amino acid metabolism, alleviated diabetes-induced pathological changes in the kidneys of diabetic mice, and had a regulating effect on the liver glycolipid metabolism. By investigating the novel pharmacological effect of traditional Chinese medicine and encouraging in-depth study and development, this work may offer a new experimental foundation and theoretical direction for the sensible application of YMP on DN.
L. 是禾本科中最重要的基因之一，L. 的果皮（YMP）是一种未经证实的糖尿病民间疗法，尚未得到充分研究。糖尿病肾病（DN）是糖尿病最著名且危险的微血管并发症之一。YMP 对代谢重编程的影响及其机制在很大程度上尚不清楚。
采用超高效液相色谱 - 四极杆飞行时间串联质谱（UPLC - Q - TOF - MS/MS）系统鉴定 YMP 的成分。随后进行了 DN 与重要成分之间的网络药理学研究。在糖尿病小鼠中评估 YMP 的药理试验。检测其生化活性、抗炎和抗氧化特性。此外，使用超高效液相色谱 - 线性离子阱轨道阱质谱（UHPLC - LTQ - Orbitrap MS）对血清和尿液进行代谢组学研究。最终，利用转录组学分析来阐明转录因子影响 DN 的复杂过程。
从 YMP 中系统鉴定出 43 种成分。通过网络药理学分析发现，信号转导，即代谢紊乱，涉及高度参与的通路。实验验证表明，给予 YMP 可增加肾小球肥大、胶原组织增殖、尿微量白蛋白/肌酐比值，缓解炎症反应并促进氧化应激。YMP 治疗可能影响氨基酸和能量代谢相关通路，并逆转代谢异常。YMP 能够恢复葡萄糖酸内酯、5 - 磷酸核糖、5 - 磷酸木酮糖、丙氨酸、天冬氨酸、谷氨酸、瓜氨酸、精氨酸、亮氨酸、缬氨酸、异亮氨酸等代谢物的水平。证实了能量代谢的代谢重编程。通过转录组学分析，当给予链脲佐菌素（STZ）时，与糖酵解/糖异生相关的葡萄糖磷酸异构酶（GPI）、甘油醛 - 3 - 磷酸脱氢酶（GAPDH）、葡萄糖 - 6 - 磷酸酶（G6PC）、己糖激酶 2（HK2）、己糖激酶 1（HK1）和己糖激酶 3（HK3）基因在模型组中显著升高。然而，当给予 YMP 时，与磷酸戊糖途径相关的葡萄糖 - 6 - 磷酸脱氢酶（G6PD）、6 - 磷酸葡萄糖酸内酯酶（PGLS）、核糖 - 5 - 磷酸异构酶（RPE）、转醛醇酶 1（TALDO1）和 6 - 磷酸己糖酸内酯酶（HXLB）基因显著升高。
本研究首次表明，YMP 纠正了磷酸戊糖途径和氨基酸代谢的紊乱，减轻了糖尿病小鼠肾脏中糖尿病诱导的病理变化，并对肝脏糖脂代谢具有调节作用。通过研究中药的新药理作用并鼓励深入研究和开发，这项工作可能为 YMP 在 DN 上的合理应用提供新的实验基础和理论方向。
