Rehmanniae Radix Praeparata aqueous extract improves hepatic ischemia/reperfusion injury by restoring intracellular iron homeostasis  

作　　者：ZHANG Yinhao JIA Kexin LI Yufei MA Zhi FAN Guifang LUO Ranyi LI Yajing YANG Yang LI Fanghong LIU Runping LIU Jia LI Xiaojiaoyang 

机构地区：[1]School of Life Sciences,Beijing University of Chinese Medicine,Beijing 100029,China [2]School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 100029,China Available online 20 Sep.,2024

出　　处：《Chinese Journal of Natural Medicines》2024年第9期769-784,共16页中国天然药物（英文版）

基　　金：supported by Beijing Nova Program(No.Z201100006820025);the National Natural Science Foundation of China(No.82274186);the Fundamental Research Funds for the Central Universities(No.2023-JYB-JBZD-046);the National High-Level Talents Special Support Program to LI Xiaojiaoyan;the National Key Research and Development Program on Modernization of Traditional Chinese Medicine(No.2022YFC3502100);Beijing Municipal Science&Technology Commission(No.7212174)。

摘　　要：Hepatic ischemia/reperfusion injury(HIRI)is a common pathophysiological condition occurring during or after liver resection and transplantation,leading to hepatic viability impairment and functional deterioration.Recently,ferroptosis,a newly recognized form of programmed cell death,has been implicated in IRI.Rehmanniae Radix Praeparata(RRP),extensively used in Chinese herbal medicine for its hepatoprotective,anti-inflammatory,and antioxidant properties,presents a potential therapeutic approach.However,the mechanisms by which RRP mitigates HIRI,particularly through the regulation of ferroptosis,remain unclear.In this study,we developed a HIRI mouse model and monocrotaline(MCT)-and erastin-induced in vitro hepatocyte injury models.We conducted whole-genome transcriptome analysis to elucidate the protective effects and mechanisms of RRP on HIRI.The RRP aqueous extract was characterized by the presence of acteoside,rehmannioside D,and 5-hydroxymethylfurfural.Our results demonstrate that the RRP aqueous extract ameliorated oxidative stress,reduced intracellular iron accumulation,and attenuated HIRI-induced liver damage.Additionally,RRP significantly inhibited hepatocyte death by restoring intracellular iron homeostasis both in vivo and in vitro.Mechanistically,the RRP aqueous extract reduced intrahepatocellular iron accumulation by inhibiting ZIP14-mediated iron uptake,promoting hepcidin-and ferroportin-mediated iron efflux,and ameliorating mitochondrial iron aggregation through upregulation of Cisd1 expression.Moreover,siRNA-mediated inhibition of hamp synergistically enhanced the RRP aqueous extract's inhibitory effect on ferroptosis.In conclusion,our study elucidates the mechanisms by which RRP aqueous extracts alleviate HIRI,highlighting the restoration of iron metabolic balance.These findings position RRP as a promising candidate for clinical intervention in HIRI treatment.

关 键 词：Hepatic ischemia/reperfusion injury Rehmanniae Radix Praeparata Ferroptosis Intracellular iron homeostasis 

分 类 号：R965[医药卫生—药理学]