Renoprotective effect of esculetin against ischemic acute kidney injury-diabetic comorbidity

Dagar, Neha; Habshi, Tahib; Shelke, Vishwadeep; Jadhav, Hemant R.; Gaikwad, Anil Bhanudas

doi:10.1080/10715762.2024.2313738

Cited by 5 publications

(1 citation statement)

References 61 publications

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“…Besides, esculetin reduced mitochondrial oxidative stress by increasing the expression of Nrf2 and Keap1. Esculetin may alleviate mitochondrial dysfunction by inducing PINK1/Parkin mediated mitophagy, suggesting that esculetin is expected to become an effective therapy to prevent AKI-diabetes comorbidity ( Dagar N,et al, 2024 ).…”

Section: Chinese Botanical Drugs For Treating Dkd By Regulating Mitop...mentioning

confidence: 99%

Chinese botanical drugs targeting mitophagy to alleviate diabetic kidney disease, a comprehensive review

Ma,

Li,

Zhang

et al. 2024

Front. Pharmacol.

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Diabetic kidney disease (DKD) is one of the chronic microvascular complications caused by diabetes, which is characterized by persistent albuminuria and/or progressive decline of estimated glomerular filtration rate (eGFR), and has been the major cause of dialysis around the world. At present, although the treatments for DKD including lifestyle modification, glycemic control and even using of Sodium-glucose cotransporter 2 (SGLT2) inhibitors can relieve kidney damage caused to a certain extent, there is still a lack of effective treatment schemes that can prevent DKD progressing to ESRD. It is urgent to find new complementary and effective therapeutic agents. Growing animal researches have shown that mitophagy makes a great difference to the pathogenesis of DKD, therefore, exploration of new drugs that target the restoration of mitophagy maybe a potential perspective treatment for DKD. The use of Chinese botanical drugs (CBD) has been identified to be an effective treatment option for DKD. There is growing concern on the molecular mechanism of CBD for treatment of DKD by regulating mitophagy. In this review, we highlight the current findings regarding the function of mitophagy in the pathological damages and progression of DKD and summarize the contributions of CBD that ameliorate renal injuries in DKD by interfering with mitophagy, which will help us further explain the mechanism of CBD in treatment for DKD and explore potential therapeutic strategies for DKD.

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Section: Chinese Botanical Drugs For Treating Dkd By Regulating Mitop...mentioning

confidence: 99%

Chinese botanical drugs targeting mitophagy to alleviate diabetic kidney disease, a comprehensive review

Ma,

Li,

Zhang

et al. 2024

Front. Pharmacol.

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The protective effects of esculetin against Doxorubicin‐Induced hepatotoxicity in rats: Insights into the modulation of Caspase, FOXOs, and heat shock protein pathways

Kizir,

Yeşilkent,

Öztürk

et al. 2024

J Biochem & Molecular Tox

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Doxorubicin (DOX) is an anthracycline antibiotic widely employed to treat carcinoma. Nevertheless, severe cardiotoxic side effects restrict its clinical use. Esculetin, a natural flavonoid, is found abundantly in plants. This study evaluated the protective effects of esculetin against DOX‐induced hepatotoxicity in rat livers. Forty‐eight rats were randomly divided into six groups with eight rats in each group: control (I), DOX (II), esculetin (III, 50 mg/kg), esculetin (IV, 100 mg/kg), DOX+esculetin 50 (V, DOX+esculetin 50 mg/kg), and DOX+esculetin 100 (VI, DOX+esculetin 100 mg/kg). The administration of esculetin effectively mitigated alterations in the measured biochemical parameters induced by DOX. Gene expression analyses demonstrated that esculetin treatment significantly reduced the DOX‐induced expression of Foxo1, Hspa1a, Hsp4a, Hsp5a, Casp3, and Casp9 while increasing the DOX‐induced expression of Foxo3. These findings suggest that esculetin, with its antioxidant and anti‐inflammatory effects, might be a therapeutic option for protecting against DOX‐induced hepatotoxicity.

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Novel dysregulated long non‐coding RNAs in the acute kidney injury‐to‐chronic kidney diseases transition unraveled by transcriptomic analysis

Puri,

Majumder,

Gaikwad

2024

Pharmacology Res & Perspec

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Acute kidney injury (AKI)‐to‐chronic kidney disease (CKD) transition involves a complex pathomechanism, including inflammation, apoptosis, and fibrosis where long non‐coding RNAs (lncRNAs) play a crucial role in their regulation. However, to date, only a few lncRNAs have been discovered to be involved in the AKI‐to‐CKD transition. Therefore, this study aims to investigate the dysregulated lncRNAs in the AKI‐to‐CKD transition in vitro and in vivo. To mimic AKI‐to‐CKD transition both in vivo and in vitro, bilateral ischemia‐reperfusion (IR) kidney injury was performed in Wistar rats (male), and normal rat kidney epithelial cell (NRK52E) cells were treated with exogenous transforming growth factor‐β1 (TGF‐β1). Further processing and analysis of samples collected from these studies (e.g., biochemical, histopathology, immunofluorescence, and RNA isolation) were also performed, and transcriptomic analysis was performed to identify the dysregulated lncRNAs. Rats subjected to IR showed a significant increase in kidney injury markers (creatinine, blood urea nitrogen (BUN), kidney injury molecule‐1(KIM‐1), and neutrophil gelatinase‐associated lipocalin (NGAL) along with altered cell morphology). Apoptosis, inflammation, and fibrosis markers were markedly increased during the AKI‐to‐CKD transition. Furthermore, transcriptomic analysis revealed 62 and 84 unregulated and 95 and 92 downregulated lncRNAs in vivo and in vitro, respectively. Additionally, functional enrichment analysis revealed their involvement in various pathways, including the tumor necrosis factor (TNF), wingless‐related integration site (Wnt), and hypoxia‐inducible factor‐1 (HIF‐1) signaling pathways. These identified dysregulated lncRNAs significantly contribute to AKI‐to‐CKD transition, and their knockin/out can aid in developing targeted therapeutic interventions against AKI‐to‐CKD transition.

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Renoprotective effect of esculetin against ischemic acute kidney injury-diabetic comorbidity

Cited by 5 publications

References 61 publications

Chinese botanical drugs targeting mitophagy to alleviate diabetic kidney disease, a comprehensive review

Chinese botanical drugs targeting mitophagy to alleviate diabetic kidney disease, a comprehensive review

The protective effects of esculetin against Doxorubicin‐Induced hepatotoxicity in rats: Insights into the modulation of Caspase, FOXOs, and heat shock protein pathways

Novel dysregulated long non‐coding RNAs in the acute kidney injury‐to‐chronic kidney diseases transition unraveled by transcriptomic analysis

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