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Huangqin Decoction Delays Progress of Colitis-Associated Carcinogenesis by Regulating Nrf2/HO-1 Antioxidant Signal Pathway in Mice

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Chinese Journal of Integrative Medicine Aims and scope Submit manuscript

Abstract

Objective

To investigate the effect of Huangqin Decoction (HQD) on nuclear factor erythroid 2 related-factor 2 (Nrf2)/heme oxygenase (HO-1) signaling pathway by inducing the colitis-associated carcinogenesis (CAC) model mice with azoxymethane (AOM)/dextran sodium sulfate (DSS).

Methods

The chemical components of HQD were analyzed by liquid chromatography-quadrupole-time-of-flight mass spectrometry (LC-Q-TOF-MS/MS) to determine the molecular constituents of HQD. Totally 48 C57BL/6J mice were randomly divided into 6 groups by a random number table, including control, model (AOM/DSS), mesalazine (MS), low-, medium-, and high-dose HQD (HQD-L, HQD-M, and HQD-H) groups, 8 mice in each group. Except for the control group, the mice in the other groups were intraperitoneally injected with AOM (10 mg/kg) and administrated with 2.5% DSS orally for 1 week every two weeks (totally 3 rounds of DSS) to construct a colitis-associated carcinogenesis mouse model. The mice in the HQD-L, HQD-M and HQD-H groups were given HQD by gavage at doses of 2.925, 5.85, and 11.7 g/kg, respectively; the mice in the MS group was given a suspension of MS at a dose of 0.043 g/kg (totally 11 weeks). The serum levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were measured by enzyme-linked immunosorbent assay. The mRNA and protein expression levels of Nrf2, HO-1, and inhibitory KELCH like ECH-related protein 1 (Keap1) in colon tissue were detected by quantitative real-time PCR, immunohistochemistry, and Western blot, respectively.

Results

LC-Q-TOF-MS/MS analysis revealed that the chemical constituents of HQD include baicalin, paeoniflorin, and glycyrrhizic acid. Compared to the control group, significantly higher MDA levels and lower SOD levels were observed in the model group (P<0.05), whereas the expressions of Nrf2 and HO-1 were significantly decreased, and the expression of Keap1 increased (P<0.01). Compared with the model group, serum MDA level was decreased and SOD level was increased in the HQD-M, HQD-H and MS groups (P<0.05). Higher expressions of Nrf2 and HO-1 were observed in the HQD groups.

Conclusion

HQD may regulate the expression of Nrf2 and HO-1 in colon tissue, reduce the expression of MDA and increase the expression of SOD in serum, thus delaying the progress of CAC in AOM/DSS mice.

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Authors and Affiliations

  1. Department of Gastrointestinal Endoscopy, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, China

    Li-mei Gu

  2. Department of Gastroenterology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, China

    He-zhong Li, Hui Li, Lan-fu Wei, Cheng-yu Pan, Ke-xuan Wu & Yao-zhou Tian

  3. School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China

    Lei Gao

Authors
  1. Li-mei Gu
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  2. He-zhong Li
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  4. Hui Li
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  5. Lan-fu Wei
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  7. Ke-xuan Wu
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  8. Yao-zhou Tian
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Contributions

Conceptualization: Li HZ and Gu LM; investigation: Gu LM; methodology and analysis: Li HZ and Gao L; original draft preparation: Li HZ and Li H; review and editing: Wei LF; visualization: Wu KX and Pan CY; supervision: Tian YZ; project administration: Gu LM.

Corresponding author

Correspondence to Yao-zhou Tian.

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The authors declare no conflict of interest.

Additional information

Supported by the Natural Science Foundation Project of Nanjing University of Traditional Chinese Medicine (No. XZR2020030), Jiangsu Famous Traditional Chinese Medicine Inheritance Studio Project (Jiangsu Traditional Chinese Medicine Science and Education (No. 20SGzs003)

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Gu, Lm., Li, Hz., Gao, L. et al. Huangqin Decoction Delays Progress of Colitis-Associated Carcinogenesis by Regulating Nrf2/HO-1 Antioxidant Signal Pathway in Mice. Chin. J. Integr. Med. 30, 135–142 (2024). https://doi.org/10.1007/s11655-023-3554-y

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  • DOI: https://doi.org/10.1007/s11655-023-3554-y

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