Platycodin D attenuates diabetic renal ischemia/reperfusion injury by enhancing mitophagy and suppressing MAPK/NF-κB signaling activation

IF 4.2 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2025-08-21 DOI:10.1016/j.bbadis.2025.168026

Xuke Qin , Jin Liu , Xiaojie Zhao , Lei Wang , Xiuheng Liu , Zhiyuan Chen

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引用次数: 0

Abstract

The global incidence of diabetes mellitus (DM) is rapidly rising, and DM worsens renal ischemia/reperfusion (I/R) injury, a major cause of high-mortality acute kidney injury (AKI). Therefore, preventing renal I/R injury in DM is crucial. Platycodin D (PD), a compound from Platycodon grandiflorum roots, is known to activate AMP-activated protein kinase (AMPK).

Numerous studies have demonstrated that AMPK activation has protective effects in diabetes mellitus (DM) and ischemia/reperfusion (I/R) injury. However, the impact of PD on renal I/R injury in DM and its underlying mechanisms remain unclear. Our experiments revealed that PD treatment via gavage significantly alleviated kidney tissue damage and cell apoptosis in diabetic renal I/R injury. Additionally, PD reduced reactive oxygen species (ROS) levels, and transmission electron microscopy (TEM) indicated a notable discovery in mitophagosome formation. The expression levels of P-AMPK, light chain 3B (LC3B)-II, PTEN-induced putative protein kinase 1 (PINK1) and Parkin all increased under PD treatment, while sequestosome 1 (P62) level decreased. Importantly, AMPK antagonist Compound C (CC) abolished these effects. Additionally, our transcriptomic profiling revealed that PD treatment significantly suppressed MAPK/NF-κB signaling activation. Through functional rescue experiments, we mechanistically demonstrated that PD-mediated AMPK phosphorylation governs this regulatory axis. AMPK inhibition abolished PD's effects on both MAPK/NF-κB suppression, establishing AMPK activation as the upstream modulator. Overall, PD may reduce renal I/R injury in DM through AMPK/PINK1/Parkin-mediated mitophagy and inhibiting MAPK/NF-κB pathway.

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桔梗素D通过增强线粒体自噬和抑制MAPK/NF-κB信号激活来减轻糖尿病肾缺血再灌注损伤

糖尿病（DM）的全球发病率正在迅速上升，并且糖尿病加重了肾缺血/再灌注（I/R）损伤，是导致高死亡率急性肾损伤（AKI）的主要原因。因此，预防糖尿病患者肾I/R损伤至关重要。桔梗苷D （Platycodin D， PD）是桔梗根中的一种化合物，可以激活amp活化蛋白激酶（AMPK）。大量研究表明AMPK激活对糖尿病（DM）和缺血/再灌注（I/R）损伤具有保护作用。然而，PD对DM患者肾I/R损伤的影响及其潜在机制尚不清楚。我们的实验发现，PD灌胃治疗可显著减轻糖尿病肾I/R损伤的肾组织损伤和细胞凋亡。此外，PD降低了活性氧（ROS）水平，透射电子显微镜（TEM）显示在丝裂体形成中有显著的发现。PD治疗后，P-AMPK、轻链3B (LC3B)-II、pten诱导的推定蛋白激酶1 （PINK1）和Parkin的表达水平均升高，而sequestosome 1 （P62）的表达水平下降。重要的是，AMPK拮抗剂化合物C （CC）消除了这些作用。此外，我们的转录组学分析显示，PD治疗显著抑制MAPK/NF-κB信号的激活。通过功能修复实验，我们从机制上证明了pd介导的AMPK磷酸化控制着这一调节轴。AMPK抑制消除了PD对MAPK/NF-κB抑制的影响，确立了AMPK激活作为上游调节剂的地位。总的来说，PD可能通过AMPK/PINK1/ parkinson介导的有丝分裂和抑制MAPK/NF-κB通路来减轻DM的肾I/R损伤。

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来源期刊

Biochimica et biophysica acta. Molecular basis of disease 生物-生化与分子生物学

CiteScore

12.30

自引率

0.00%

发文量

218

审稿时长

32 days

期刊介绍： BBA Molecular Basis of Disease addresses the biochemistry and molecular genetics of disease processes and models of human disease. This journal covers aspects of aging, cancer, metabolic-, neurological-, and immunological-based disease. Manuscripts focused on using animal models to elucidate biochemical and mechanistic insight in each of these conditions, are particularly encouraged. Manuscripts should emphasize the underlying mechanisms of disease pathways and provide novel contributions to the understanding and/or treatment of these disorders. Highly descriptive and method development submissions may be declined without full review. The submission of uninvited reviews to BBA - Molecular Basis of Disease is strongly discouraged, and any such uninvited review should be accompanied by a coverletter outlining the compelling reasons why the review should be considered.