Efficacy of Astragali Radix extract in treatment of a mouse model of aristolochic acid Ⅰ-induced liver and renal injury by regulating the IL-6/STAT3 signaling pathway

Gerui ZHU; Yani PI; Jing WANG; Kai HUANG; Yuan PENG; Gaofeng CHEN; Chenghai LIU; Yanyan TAO

doi:10.3969/j.issn.1001-5256.2023.08.020

Volume 39 Issue 8

Aug. 2023

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Efficacy of Astragali Radix extract in treatment of a mouse model of aristolochic acid Ⅰ-induced liver and renal injury by regulating the IL-6/STAT3 signaling pathway

DOI: 10.3969/j.issn.1001-5256.2023.08.020

Gerui ZHU^{1, 2},
Yani PI¹,
Jing WANG¹,
Kai HUANG³,
Yuan PENG¹,
Gaofeng CHEN¹,
Chenghai LIU^{1, 3, 4},
Yanyan TAO^{1
,
,
,}

1.
Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
2.
Institute of TCM International Standardization, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
3.
Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai 201203, China
4.
Key Laboratory of Liver and Kidney Diseases, Ministry of Education, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China

Research funding:

Science and Technology Innovation Action Plan of the Shanghai Municipal Science and Technology Commission (19401901500);

Three-Year Action Plan of for the Development of TCM in Shanghai (ZY-〔2018-2020〕-CCCX- 5001)

More Information

Corresponding author: TAO Yanyan, taoyanyan1023@126.com (ORCID: 0000-0002-8962-3137)
Received Date: 2022-11-23
Accepted Date: 2023-01-18
Published Date: 2023-08-20

Abstract

Abstract

Objective To investigate the mechanism of action of Astragali Radix (AR) extract in improving aristolochic acid Ⅰ (AA Ⅰ)-induced acute liver and renal injury in mice by regulating the IL-6/STAT3 signaling pathway. Methods A total of 38 healthy male C57BL/6 mice were randomly divided into normal group with 8 mice, model group with 10 mice, AR group with 10 mice, and N-Acetyl-L-cysteine (NAC) group with 10 mice. The model group mice were intraperitoneally injected with 20 mg/kg AAⅠ once a day for 5 days. Normal mice were intraperitoneally injected with the same volume of Carboxymethyl cellulose sodium. AR group and NAC group received intraperitoneal injection of 20 mg/kg AAⅠ once a day for 3 days; On the 4th day, mice were gavaged with AR 75 mg/kg and NAC 150 mg/kg body mass doses, once a day, for 8 days. NAC was used as a positive control drug. After the end of administration and modeling, the mice were sacrificed to collect serum samples and liver and renal tissue samples. The kit was used to measure the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum creatinine (SCr), and blood urea nitrogen (BUN); HE staining was used to observe liver and renal histopathology; quantitative real-time PCR and immunohistochemistry were used to measure the expression level of p-STAT3 in the liver and renal tissue; ELISA was used to measure the expression levels of interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in the liver and renal tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the SNK-q test was used for further comparison between two groups. Results Compared with the normal group, the model group had a significant increase in kidney-to-body ratio (P < 0.05). Compared with the model group, the AR group had significant reductions in the levels of ALT, AST, SCr, and BUN (F=49.29, 31.31, 58.89, and 85.88, all P < 0.01). HE staining showed that AR could effectively alleviate AAⅠ -induced structural damage and inflammatory cell infiltration in the liver and renal tissue; quantitative real-time PCR and immunohistochemistry showed that AR could reduce the expression of p-STAT3 in the liver and renal tissues; ELISA showed that AR could downregulate the expression of IL-6, IL-1β, and TNF-α. NAC and AR had a similar effect with no significant differences. Conclusion AR exerts a protective effect against AAⅠ-induced acute liver and renal injury, possibly by inhibiting the activation of the IL-6/STAT3 signaling pathway and alleviating inflammatory response.
- Aristolochic Acid,
- Chemical and Drug Induced Liver Injury,
- Acute Kidney Injury,
- STAT3 Transcription Factor,
- Astmgali Radix

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References(26)

References

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Efficacy of Astragali Radix extract in treatment of a mouse model of aristolochic acid Ⅰ-induced liver and renal injury by regulating the IL-6/STAT3 signaling pathway

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Efficacy of Astragali Radix extract in treatment of a mouse model of aristolochic acid Ⅰ-induced liver and renal injury by regulating the IL-6/STAT3 signaling pathway

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