Eriocitrin prevents Sepsis-induced acute kidney injury through anti-inflammation and anti-oxidation via modulating Nrf2/DRP1/OPA1 signaling pathway.

Severe inflammation and oxidative stress are characteristics of sepsis-associated kidney injury with high morbidity and mortality. Eriocitrin (ERI) has shown promise in suppressing sepsis-associated kidney injury and LPS-induced periodontal disease, however, its efficacy in alleviating SAKI remains unexplored. This study aimed to investigate the therapeutic potential of ERI on SAKI through in vivo and in vitro experiments, elucidating its underlying mechanism. The therapeutic effects of ERI against SAKI were evaluated by survival rate, changes of serum creatinine (Scr) and blood urea nitrogen (BUN) and statistic of renal histological score in a Cecal ligation and puncture (CLP)-induced septic mice. Impactions about anti-coagulation, anti-inflammation, anti-oxidative stress and improvement of mitochondrial damage and mitochondrial morphology were further assayed. In vitro, HUVECs upon stimulation of LPS with or without different dosage of ERI, followed by evaluating changes in inflammation, mitochondrial dynamic equilibrium and signaling pathways. ERI demonstrated ameliorative effects on SAKI by attenuating inflammation, oxidative stress and coagulation evidenced by the improved survival rate, alleviated kidney histological injury, declined BUN and Scr in serum and diminished levels of inflammation cytokines, and coagulation factors. Mechanistically, ERI suppressed DRP1-regulated mitochondrial fission and promoted OPA1-modulated mitochondrial fusion by activating Nrf2 in septic mice and LPS-stimulated HUVECs, which maintained mitochondrial dynamic equilibrium, improved mitochondrial morphology, assured integrity of mitochondrial function, decreased oxidative stress, impeded overwhelming inflammation, and thus, played a pivotal role in ERI's protection against SAKI. Our data confirmed the therapeutic potential of ERI in mitigating SAKI，suggesting its viability as a pharmacological agent in clinic settings.

Wu M ，Huang Z ，Akuetteh PDP ，Huang Y ，Pan J ... -  《-》

Protection of procyanidin B2 on mitochondrial dynamics in sepsis associated acute kidney injury via promoting Nrf2 nuclear translocation.

Liu JX ，Yang C ，Liu ZJ ，Su HY ，Zhang WH ，Pan Q ，Liu HF ... -  《Aging-US》

Obeticholic acid ameliorates sepsis-induced renal mitochondrial damage by inhibiting the NF-κb signaling pathway.

Jing D ，Liu J ，Qin D ，Lin J ，Li T ，Li Y ，Duan M ... -  《-》

Tetrahydrocurcumin protects against sepsis-induced acute kidney injury via the SIRT1 pathway.

Li L ，Liu X ，Li S ，Wang Q ，Wang H ，Xu M ，An Y ... -  《-》

Curcumin attenuates inflammation and cell apoptosis through regulating NF-κB and JAK2/STAT3 signaling pathway against acute kidney injury.

Zhu H ，Wang X ，Wang X ，Liu B ，Yuan Y ，Zuo X ... -  《-》