Dai Chongshan, Liu Mingchao, Zhang Qinzhi, Das Gupta Subhajit, Tang Shusheng, Shen Jianzhong
National Key Laboratory of Veterinary Public Health Security, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.
Beijing Key Laboratory of Detection Technology for Animal-Derived Food Safety, Beijing 100193, China.
Antioxidants (Basel). 2023 Feb 3;12(2):370. doi: 10.3390/antiox12020370.
Nootkatone (NKT), a major ingredient of Alpinia oxyphylla, exhibited potential nephroprotective effects; however, the precise molecular mechanisms remain poorly understood. This study aimed to study the nephroprotective effects of NKT and the underlying mechanisms in a mouse model. Our results showed that NKT pretreatment at the doses of 5, 10, and 20 mg/kg per day for 7 days significantly attenuates carbon tetrachloride (CCl)-induced increases of serum BUN and CRE and kidney pathology injury. NKT pretreatment also markedly inhibited oxidative stress, inflammatory response, and the activation of caspases-9 and -3 in kidneys of mice exposed to CCl. Meanwhile, NKT pretreatment downregulated the expression of NOX4, IL-1β, IL-6, and TNF-α proteins and NO levels in the kidney tissues. Moreover, NKT pretreatment upregulated the expression of Nrf2 and HO-1 mRNAs, and downregulated the expression of NF-κB, IL-1β, IL-6, TNF-α, and iNOS mRNAs in the kidneys of mice, compared to those in the CCl alone treatment group. In conclusion, our results reveal that NKT supplementation could protect against CCl exposure-induced oxidative stress and inflammatory response in the kidneys by inhibiting NOX4 and NF-κB pathways and activating the Nrf2/HO-1 pathway. Our current study highlights the therapeutic application of NKT for kidney diseases.
诺卡酮（NKT）是益智仁的主要成分，具有潜在的肾保护作用；然而，其确切的分子机制仍知之甚少。本研究旨在探讨NKT在小鼠模型中的肾保护作用及其潜在机制。我们的结果表明，每天以5、10和20mg/kg的剂量进行NKT预处理7天，可显著减轻四氯化碳（CCl）诱导的血清尿素氮（BUN）和肌酐（CRE）升高以及肾脏病理损伤。NKT预处理还显著抑制了暴露于CCl的小鼠肾脏中的氧化应激、炎症反应以及半胱天冬酶-9和-3的激活。同时，NKT预处理下调了肾脏组织中NOX4、IL-1β、IL-6和TNF-α蛋白的表达以及NO水平。此外，与单独CCl处理组相比，NKT预处理上调了小鼠肾脏中Nrf2和HO-1 mRNA的表达，并下调了NF-κB、IL-1β、IL-6、TNF-α和iNOS mRNA的表达。总之，我们的结果表明，补充NKT可通过抑制NOX4和NF-κB途径并激活Nrf2/HO-1途径，保护肾脏免受CCl暴露诱导的氧化应激和炎症反应。我们目前的研究突出了NKT在肾脏疾病治疗中的应用。
