Qizhufang (ZSF) Ameliorates Hepatic Iron Overload via Signal Transducer and Activator of Transcription 3 (STAT3) Pathway.

Dongyu Xie, Haina Xie, Lin Liu, Guangwei Feng, Wenjing Jiang, Wei Huang, Donghao Xie
Author Information
  1. Dongyu Xie: Department of Spleen-Stomach, Zhenjiang Affiliated Hospital of Nanjing University of Chinese Medicine, Zhenjiang, Jiangsu, China (mainland).
  2. Haina Xie: School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, China (mainland).
  3. Lin Liu: Department of Pharmacy, Dahua Hospital, Shanghai, China (mainland).
  4. Guangwei Feng: Department of Pharmacy, Dahua Hospital, Shanghai, China (mainland).
  5. Wenjing Jiang: Department of Pharmacy, Dahua Hospital, Shanghai, China (mainland).
  6. Wei Huang: Department of Traditional Chinese Medicine, Dahua Hospital, Shanghai, China (mainland).
  7. Donghao Xie: Department of Pharmacy, Guanghua Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai, China (mainland).

Abstract

BACKGROUND Iron overload is a prominent characteristic of liver injury, but there is no effective treatment at present. Qizhufang (ZSF) is a Chinese herbal formula showed anti-HBV activities, improved liver function, and anti-fibrosis effect. ZSF showed a series of liver-protection functions, but whether ZSF can relieve hepatic iron overload is still unclear. MATERIAL AND METHODS Ferric ammonium citrate (FAC) was used to construct iron-overloaded LO2 cells. The cell apoptosis and proliferation were measured by flow cytometry and CCK-8 assay, respectively. ROS level was analyzed by fluorescence probe. RNA and protein expressions were assessed by real-time PCR and Western blot. RESULTS FAC upregulated apoptosis rate, ROS level, and expression of hepcidin and p-STAT3, but suppressed proliferation and expression of DMT1, FPN1, and CP in LO2 cells. However, Qizhufang (ZSF) reversed the effect of FAC. We also found that hepcidin overexpression suppressed the expressions of DMT1, FPN1, and CP, which were reversed by ZSF. Additionally, STAT3 inhibitor AG490 suppressed hepcidin expression. Moreover, exogenous IL-6 reversed the effect of ZSF on apoptosis rate, ROS level, and the expression of hepcidin, DMT1, FNP1, CP, and p-STAT3. CONCLUSIONS Qizhufang (ZSF) can ameliorate iron overload-induced injury by suppressing hepcidin via the STAT3 pathway in LO2 cells.

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MeSH Term

Apoptosis
Cell Line, Tumor
Cell Proliferation
China
Drugs, Chinese Herbal
Ferric Compounds
Hepcidins
Humans
Interleukin-6
Iron
Iron Overload
Liver
Medicine, Chinese Traditional
Quaternary Ammonium Compounds
Reactive Oxygen Species
STAT3 Transcription Factor
Signal Transduction

Chemicals

Drugs, Chinese Herbal
Ferric Compounds
Hepcidins
Interleukin-6
Quaternary Ammonium Compounds
Reactive Oxygen Species
STAT3 Transcription Factor
Iron
ferric ammonium citrate

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