Protective effect of hydroxysafflor yellow A on renal ischemia‑­reperfusion injury by targeting the Akt‑Nrf2 axis in mice

Abstract

Ischemic/reperfusion (I/R) injury is the primary cause of acute kidney injury (AKI). Hydroxysafflor yellow A (HSYA), a natural compound isolated from Carthamus tinctorius L., has been found to possess anti-inflammatory and antioxidant properties. However, the protective effects and potential mechanism of HSYA on I/R-induced AKI remains unclear. In the present study, the in vitro hypoxia/reoxygenation (H/R) and in vivo renal I/R models were employed to investigate the renal protective effects and molecular mechanisms of HSYA on I/R-induced AKI. The present results indicated that HSYA pretreatment significantly ameliorated renal damage and dysfunction in the I/R injury mice via enhancing the antioxidant capacity and suppressing the oxidative stress injury, inflammatory response, and apoptosis. Mechanistic studies showed that HSYA could upregulate Akt/GSK-3β/Fyn-Nrf2 axis-mediated antioxidant gene expression both in vitro and in vivo. Moreover, HSYA-mediated improvement in antioxidant, anti-inflammatory, and anti-apoptotic effects in H/R-treated HK-2 cells was abrogated by Akt inhibitor LY294002 supplementation. In summary, the present results demonstrated that HSYA attenuated kidney oxidative stress, inflammation response, and apoptosis induced by I/R, at least in part, via activating the Akt/GSK-3β/Fyn-Nrf2 axis pathway. These findings provided evidence that HSYA may be applied as a potential therapeutic agent in the treatment of I/R induced AKI.

A biophoton method for identifying the quality states of fresh Chinese herbs

“…Currently, HSYA and kaempferol are commonly used as quality control indicators of safflower. HSYA is the most effective water-soluble component of safflower with pharmacological effects, including anticoagulant, antioxidant, anti-inflammatory, anti-myocardial ischemia, and neuroprotective activities ( Kong et al, 2022 ; Wang et al, 2022 ). It is widely used in the clinical treatment of cardiovascular and cerebrovascular diseases ( Shi et al, 2022 ).…”

Sulforaphane alleviates lung ischemia‑reperfusion injury through activating Nrf‑2/HO‑1 signaling

“…HO-1 catalyzes the breakdown of heme to produce biliverdin, ferrous ions, and carbon monoxide, all of which are essential components of the inflammatory process ( 39 ). The homodimeric luteinase NQO1 promotes the elimination of hydrazine, which can produce harmful semihydroquinone radicals through the redox cycle, by catalyzing the reduction of hydrazine to hydroquinone ( 26 , 39 ). CAT promotes the synthesis of intracellular catalase, which catalyzes the decomposition of H 2 O 2 into H 2 O and O 2 ( 40 ).…”

“…P0006; Beyotime Institute of Biotechnology). Western blot analyses were performed as described previously ( 26 ). Briefly, SDS-PAGE was performed by heating the samples for 8 min at 100˚C and loading 10 µg/lane of the proteins onto a 5-15% linear acrylamide gradient gel.…”

Cordyceps cicadae ameliorates inflammatory responses, oxidative stress, and fibrosis by targeting the PI3K/mTOR‐mediated autophagy pathway in the renal of MRL/lpr mice

“…Hematoxylin and eosin (H&E) and Masson's trichrome staining were performed as described previously 21,22 . Kidney tissues were fixed using 10% formaldehyde for 24 h at 4°C, embedded in paraffin, cut into 4 µm sections and mounted on slides.…”

“…Hematoxylin and eosin (H&E) and Masson's trichrome staining were performed as described previously. 21 , 22 Kidney tissues were fixed using 10% formaldehyde for 24 h at 4°C, embedded in paraffin, cut into 4 µm sections and mounted on slides. The prepared slides were deparaffinized twice in xylene at room temperature and rehydrated using an ethanol gradient before being stained independently with Masson's trichrome (5 min, room temperature) and H&E (5 min, room temperature).…”