Protective effects of Salvianolic acid B on rat ferroptosis in myocardial infarction through upregulating the Nrf2 signaling pathway.

Accumulating evidence has highlighted the role of ferroptosis, a novel type of programmed cell death involved in the pathological process of myocardial infarction (MI). However, the underlying mechanism of ferroptosis in mediating MI is complicated that needs to be further investigated. Salvianolic acid B (Sal B) extracted from the traditional Chinese medicine (TCM) herb Salvia miltiorrhiza possesses pharmacological function against MI, which provides us with a new direction to explore the effect of Sal B on ferroptosis after myocardial ischemic injury. In the present study, iron accumulation and expression levels of ferroptosis-related proteins in MI rats altered in a time-dependent manner. Importantly, treatment of ferroptosis inhibitors ferrostatin-1 (Fer-1) or deferoxamine (DFO) reversed typical changes of ferroptosis, including iron overload, lipid peroxide accumulation, mitochondrial damage, and specific expression levels of ferroptosis-related proteins, thereby alleviating myocardial injury in rats. Similar results were observed in Sal B-treated MI rats in a dose-dependent manner. In addition, NFE2-related factor 2 (Nrf2) was strongly activated by the treatment of Sal B. In vivo knockdown of Nrf2 in MI rats enhanced ferroptosis and damaged the protective effect of Sal B on MI. Furthermore, Sal B administration was unable to significantly reverse expression levels of target genes of Nrf2 that were associated with iron homeostasis and oxidative stress (e.g., HO-1, xCT, Gpx4, Fth1, and Fpn1) in MI rats after knockdown of Nrf2. Taken together, Sal B contributed to protecting MI by inhibiting ferroptosis via activating the Nrf2 signaling pathway.

Naringenin Ameliorates Renovascular Hypertensive Renal Damage by Normalizing the Balance of Renin-Angiotensin System Components in Rats.

Background: Naringenin, a member of the dihydroflavone family, has been shown to have a protective function in multiple diseases. We previously demonstrated that naringenin played a protective role in hypertensive myocardial hypertrophy by decreasing angiotensin-converting enzyme (ACE) expression. The kidney is a primary target organ of hypertension. The present study tested the effect of naringenin on renovascular hypertensive kidney damage and explored the underlying mechanism. Methods and Results: An animal model of renovascular hypertension was established by performing 2-kidney, 1-clip (2K1C) surgery in Sprague Dawley rats. Naringenin (200 mg/kg/day) or vehicle was administered for 10 weeks. Blood pressure and urinary protein were continuously monitored. Plasma parameters, renal pathology and gene expression of nonclipped kidneys were evaluated by enzyme-linked immunosorbent assay, histology, immunohistochemistry, real-time polymerase chain reaction, and Western blot at the end of the study. Rats that underwent 2K1C surgery exhibited marked elevations of blood pressure and plasma Ang II levels and renal damage, including mesangial expansion, interstitial fibrosis, and arteriolar thickening in the nonclipped kidneys. Naringenin significantly ameliorated hypertensive nephropathy and retarded the rise of Ang II levels in peripheral blood but had no effect on blood pressure. 2K1C rats exhibited increases in the ACE/ACE2 protein ratio and AT1R/AT2R protein ratio in the nonclipped kidney compared with sham rats, and these increases were significantly suppressed by naringenin treatment. Conclusions: Naringenin attenuated renal damage in a rat model of renovascular hypertension by normalizing the imbalance of renin-angiotensin system activation. Our results suggest a potential treatment strategy for hypertensive nephropathy.