Guangdong Provincial Key Laboratory of Advanced Drug Delivery, Guangdong Pharmaceutical University, Guangzhou, 510006, PR China; Guangdong Provincial Engineering Center of Topical Precise Drug Delivery System, Guangdong Pharmaceutical University, Guangzhou, 510006, PR China; School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou, 510006, PR China.
New Drug Research and Development Center, Guangdong Pharmaceutical University, Guangzhou, 510006, PR China.
J Ethnopharmacol. 2024 Jan 30;319(Pt 3):117250. doi: 10.1016/j.jep.2023.117250. Epub 2023 Oct 11.
ETHNOPHARMACOLOGICAL RELEVANCE: Based on the theory of traditional Chinese medicine (TCM), diabetic cardiomyopathy (DCM) belongs to the category of "Xiaoke disease" according to the symptoms, and "stasis-heat" is the main pathogenesis of DCM. The Chinese medicine Anemarrhena asphodeloides Bunge (AAB), as a representative of heat-clearing and engendering fluid, is often used clinically in the treatment of DCM. Anemarrhena asphodeloides Bunge total saponins (RATS) are the main bioactive components of AAB, the modern pharmacologic effects of RATS are anti-inflammatory, hypoglycemic, and cardioprotective. However, the potential protective mechanisms of RATS against DCM remain largely undiscovered. AIM OF THE STUDY: The primary goal of this study was to explore the effect of RATS on DCM and its mechanism of action. MATERIALS AND METHODS: Streptozotocin and a high-fat diet were used to induce DCM in rats. UHPLC/Q-TOF-MS was used to determine the chemical components of RATS. The degenerative alterations and apoptotic cells in the heart were assessed by HE staining and TUNEL. Network pharmacology was used to anticipate the probable targets and important pathways of RATS. The alterations in metabolites and main metabolic pathways in heart tissue were discovered using H-NMR metabolomics. Ultimately, immunohistochemistry was used to find critical pathway protein expression. RESULTS: First of all, UHPLC/Q-TOF-MS analysis showed that RATS contained 11 active ingredients. In animal experiments, we found that RATS lowered blood glucose and lipid levels in DCM rats, and alleviated cardiac pathological damage, and decreased cardiomyocyte apoptosis. Furthermore, the study found that RATS effectively reduced inflammatory factor release and the level of oxidative stress. Mechanistically, RATS downregulated the expression levels of PI3K, AKT, HIF-1α, LDHA, and GLUT4 proteins. Additionally, glycolysis was discovered to be a crucial pathway for RATS in the therapy of DCM. CONCLUSIONS: Our findings suggest that the protective effect of RATS on DCM may be attributed to the inhibition of the PI3K/AKT/HIF-1α pathway and the correction of glycolytic metabolism.
基于传统中医（TCM）理论，糖尿病性心肌病（DCM）根据症状属于“消渴病”范畴，“瘀热”是 DCM 的主要发病机制。中药知母（AAB）作为清热生津的代表药物，常用于临床治疗 DCM。知母总皂苷（RATS）是 AAB 的主要生物活性成分，RATS 的现代药理作用具有抗炎、降血糖和心脏保护作用。然而，RATS 对 DCM 的潜在保护机制在很大程度上仍未被发现。
本研究的主要目的是探讨 RATS 对 DCM 的作用及其作用机制。
采用链脲佐菌素和高脂饮食诱导大鼠 DCM。采用 UHPLC/Q-TOF-MS 测定 RATS 的化学成分。HE 染色和 TUNEL 评估心脏的退行性改变和凋亡细胞。网络药理学用于预测 RATS 的可能靶点和重要途径。采用 1 H-NMR 代谢组学发现心脏组织中代谢物和主要代谢途径的变化。最后，免疫组化用于发现关键途径蛋白表达。
首先，UHPLC/Q-TOF-MS 分析表明 RATS 含有 11 种活性成分。在动物实验中，我们发现 RATS 降低了 DCM 大鼠的血糖和血脂水平，缓解了心脏病理损伤，减少了心肌细胞凋亡。此外，研究发现 RATS 有效降低了炎症因子释放和氧化应激水平。在机制上，RATS 下调了 PI3K、AKT、HIF-1α、LDHA 和 GLUT4 蛋白的表达水平。此外，还发现糖酵解是 RATS 治疗 DCM 的关键途径。
综上所述，我们的研究结果表明，RATS 对 DCM 的保护作用可能归因于抑制 PI3K/AKT/HIF-1α 途径和纠正糖酵解代谢。
J Multidiscip Healthc. 2025-2-13
Zotero 插件