Senkyunolide I alleviates renal Ischemia-Reperfusion injury by inhibiting oxidative stress, endoplasmic reticulum stress and apoptosis

Ya-Lin Zhu; Jie Huang; Xue-Ying Chen; Jian Xie; Qing Yang; Jia-Feng Wang; Xiao-Ming Deng

doi:10.1016/j.intimp.2021.108393

Senkyunolide I alleviates renal Ischemia-Reperfusion injury by inhibiting oxidative stress, endoplasmic reticulum stress and apoptosis

Int Immunopharmacol. 2022 Jan:102:108393. doi: 10.1016/j.intimp.2021.108393. Epub 2021 Nov 30.

Authors

Ya-Lin Zhu¹, Jie Huang¹, Xue-Ying Chen¹, Jian Xie¹, Qing Yang¹, Jia-Feng Wang², Xiao-Ming Deng³

Affiliations

¹ Faculty of Anesthesiology, Changhai Hospital, Naval Medical University, Shanghai, China.
² Faculty of Anesthesiology, Changhai Hospital, Naval Medical University, Shanghai, China. Electronic address: jfwang@smmu.edu.cn.
³ Faculty of Anesthesiology, Changhai Hospital, Naval Medical University, Shanghai, China. Electronic address: deng_x@yahoo.com.

PMID: 34857480
DOI: 10.1016/j.intimp.2021.108393

Abstract

Background: Ligusticum striatum DC. is traditionally used to treat ischemic diseases because of its potent effect against blood stasis and thrombosis, including various cardiovascular, cerebral and renal diseases. Senkyunolide I (SEI), which is the major active phthalide ingredient of Ligusticum striatum DC., is mainly distributed in kidney and has been shown to attenuate ischemia reperfusion injury in liver. However, the underlying effect of SEI against renal ischemia-reperfusion injury (IRI) remain unclear.

Methods: Renal ischemia reperfusion mice model was established by clamping bilateral renal pedicles. In vitro oxidative stress model was induced by H₂O₂. Level of blood urea nitrogen (BUN) and serum creatinine (SCr) was tested for in vivo model evaluation, while cell viability was tested using CCK8 to evaluate in vitro model. SEI solution containing 1% DMSO was injected intraperitoneally in the I/R group, while normal saline containing 1% DMSO injected in the Sham group. Reduced glutathione (GSH) solution containing 1% DMSO was used as a positive control.

Results: SEI protected renal function and structural integrity. It reversed the I/R-induced elevation of BUN, SCr levels and renal pathological injury. The secretion of proinflammatory cytokines including TNF-α and IL-6 was inhibited, and the renal apoptosis was attenuated by SEI. In addition, SEI played a protective role by reducing the production of reactive oxidative species (ROS), as shown by the elevated expression of antioxidant proteins including Nrf2, HO-1, NQO1, and reduced expression of endoplasmic reticulum stress (ERS) related proteins including GRP78 and CHOP. It also attenuated HK2 cell injury in an in vitro model induced by H₂O₂.

Conclusions: SEI alleviates renal injury induced by ischemia reperfusion with anti-inflammatory, anti-endoplasmic reticulum stress, anti-oxidative and anti-apoptotic effect.

Keywords: Apoptosis; Endoplasmic reticulum stress; Oxidative stress; Renal ischemia-reperfusion; Senkyunolide I.

MeSH terms

Animals
Anti-Inflammatory Agents / therapeutic use*
Apoptosis / drug effects*
Benzofurans / therapeutic use*
Blood Urea Nitrogen
Creatinine / blood
Endoplasmic Reticulum Stress / drug effects*
Kidney / blood supply
Kidney / drug effects
Kidney / metabolism
Kidney Diseases / drug therapy*
Male
Mice
Mice, Inbred C57BL
Oxidative Stress / drug effects*
Reperfusion Injury / drug therapy*

Substances

Anti-Inflammatory Agents
Benzofurans
senkyunolide I
Creatinine