Modulation of PPAR-γ/Nrf2 and AGE/RAGE signaling contributes to the chrysin cardioprotection against myocardial damage following ischemia/reperfusion in diabetic rats.

IF 2.8 4区医学 Q2 PHARMACOLOGY & PHARMACY Journal of Pharmacy and Pharmacology Pub Date : 2024-11-29 DOI:10.1093/jpp/rgae140

Neha Rani, Dharamvir Singh Arya

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Abstract

Objective: Advanced glycation end products/receptor for AGEs (AGE/RAGE) signaling has a well-established role in the etiology of diabetic-related cardiovascular disorders. The purpose of the study was to elucidate the role of chrysin, a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist, against ischemia/reperfusion (IR) injury in diabetic rats and its functional interaction with the AGE/RAGE signaling pathway.

Methods: A single intraperitoneal injection of streptozotocin (STZ, 70 mg/kg) was administered to rats for induction of diabetes. Rats having blood glucose levels more than 300 mg/dl following a 72 hr STZ injection were classified as diabetic. PPAR-γ antagonist GW9662 (1 mg/kg, i.p.), chrysin (60 mg/kg, p.o.), or both were administered to diabetic rats for 4 weeks. On the 29th day, rats were given ischemia for 45 min and then reperfusion for 1 hr to induce myocardial infarction (MI).

Key findings: Pretreatment with chrysin significantly improved hemodynamic status, ventricular functions, and cardiac injury markers in diabetic myocardium. Increased PPAR-γ/Nrf2 and decreased RAGE protein expressions were linked to this improvement. Chrysin pretreatment resulted in the upregulation of endogenous antioxidants and reduced TBARS levels. Moreover, chrysin significantly decreased inflammation and apoptosis in diabetic myocardium.

Conclusion: PPAR-γ/Nrf2 co-activation by chrysin ameliorated IR-induced MI in diabetic rats, possibly via modulating AGE/RAGE signaling.

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PPAR-γ/Nrf2和AGE/RAGE信号转导的调节有助于蛹素对糖尿病大鼠心肌缺血/再灌注后心肌损伤的保护作用。

目的：AGEs晚期糖基化终产物/受体（AGE/RAGE）信号在糖尿病相关心血管疾病的病因学中具有明确的作用。本研究旨在阐明过氧化物酶体增殖物激活受体-γ (PPAR-γ)激动剂白杨素对糖尿病大鼠缺血/再灌注（IR）损伤的作用及其与AGE/RAGE信号通路的功能相互作用。方法：大鼠单次腹腔注射链脲佐菌素（STZ, 70 mg/kg）诱导糖尿病。注射STZ 72小时后血糖水平超过300 mg/dl的大鼠被归类为糖尿病。PPAR-γ拮抗剂GW9662 （1 mg/kg，口服）、白杨素（60 mg/kg，口服）或两者同时给予糖尿病大鼠4周。第29天，大鼠缺血45 min，再灌注1 hr诱导心肌梗死（MI）。主要发现：金菊素预处理可显著改善糖尿病心肌的血流动力学状态、心室功能和心脏损伤指标。PPAR-γ/Nrf2的增加和RAGE蛋白表达的减少与这种改善有关。菊花素预处理导致内源性抗氧化剂上调，TBARS水平降低。此外，黄菊花素还能显著降低糖尿病心肌的炎症和细胞凋亡。结论：大黄素共激活PPAR-γ/Nrf2可改善ir诱导的糖尿病大鼠心肌梗死，可能通过调节AGE/RAGE信号通路实现。

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来源期刊

Journal of Pharmacy and Pharmacology 医学-药学

CiteScore

6.60

自引率

0.00%

发文量

审稿时长

3 months

期刊介绍： JPP keeps pace with new research on how drug action may be optimized by new technologies, and attention is given to understanding and improving drug interactions in the body. At the same time, the journal maintains its established and well-respected core strengths in areas such as pharmaceutics and drug delivery, experimental and clinical pharmacology, biopharmaceutics and drug disposition, and drugs from natural sources. JPP publishes at least one special issue on a topical theme each year.