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

GU Li-mei; LI He-zhong; GAO Lei; LI Hui; WEI Lan-fu; PAN Cheng-yu; WU Ke-xuan; TIAN Yao-zhou

doi:10.1007/s11655-023-3554-y

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

Original Article | Updated：2024-02-22

- Huangqin Decoction Delays Progress of Colitis-Associated Carcinogenesis by Regulating Nrf2/HO-1 Antioxidant Signal Pathway in Mice
- Chinese Journal of Integrative Medicine Vol. 30, Issue 2, Pages: 135-142(2024)
- Affiliations：
  
  1.Department of Gastrointestinal Endoscopy, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing (210029), China
  2.Department of Gastroenterology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing (210028), China
  3.School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing (210023), China
- Author bio：
  
  Prof. TIAN Yao-zhou, E-mail: tianyaozhou1960@163.com
- Funds：
- DOI：10.1007/s11655-023-3554-y
  CLC：
- Published：2024-02，
  
  Published Online：12 July 2023，
  
  Accepted：08 May 2023
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GU Li-mei, LI He-zhong, GAO Lei, et al. Huangqin Decoction Delays Progress of Colitis-Associated Carcinogenesis by Regulating Nrf2/HO-1 Antioxidant Signal Pathway in Mice. [J]. Chinese Journal of Integrative Medicine 30(2):135-142(2024)
DOI：

GU Li-mei, LI He-zhong, GAO Lei, et al. Huangqin Decoction Delays Progress of Colitis-Associated Carcinogenesis by Regulating Nrf2/HO-1 Antioxidant Signal Pathway in Mice. [J]. Chinese Journal of Integrative Medicine 30(2):135-142(2024) DOI： 10.1007/s11655-023-3554-y.

摘要

目的:

探讨黄芩汤 (HQD) 对偶氮甲烷(AOM)/葡聚糖硫酸钠(DSS)诱导的结肠炎癌转化 (CAC) 模型小鼠Nrf2/HO-1信号通路的影响.

方法:

通过高效液相色谱法测定黄芩汤的化学成分. 将48只C57BL/6J 小鼠通过随机数字表法分为对照组、模型组、黄芩汤低 (HQD-L) 、中 (HQD-M) 、高 (HQD-H) 剂量组及Mesalazine组(MS)

每组8只. 除对照组外

其他组小鼠腹腔注射AOM后每隔两周给予2.5% DSS口服一周

共3次循环

建立CAC模型. HQD-L、HQD-M、HQD-H和MS组小鼠分别给予低 (2.925 g/kg) 、中 (5.85 g/kg) 、高 (11.7 g/kg) 剂量的黄芩汤和美沙拉嗪混悬液灌胃 (0.043 g/kg) . 对照组和模型组给予等体积的生理盐水灌胃

共11周. 采用ELISA法检测血清丙二醛 (MDA) 和超氧化物歧化酶 (SOD) 含量; 实时荧光定量 (RT-PCR) 法、Western blot法和免疫组化法检测结肠组织核因子红系2相关因子2 (Nrf2) 、血红素氧合酶 (HO-1) 、抑制性KELCH样ECH相关蛋白1 (Keap1) mRNA及蛋白表达水平.

结果:

高效液相色谱法分析表明黄芩汤中主要的化学成分为黄芩苷、芍药苷和甘草酸. 与对照组比较

模型组小鼠血清MDA明显升高

SOD明显降低 (

0.05) ; 结肠组织Nrf2及HO-1表达明显降低

Keap1表达水平明显升高 (

0.01) . 与模型组比较

HQD-M、HQD-H及MS组小鼠血清MDA含量明显降低

SOD水平升高 (

0.05) . HQD各剂量组结肠组织Nrf2和HO-1表达水平较高.

结论:

黄芩汤可能通过调控Nrf2/HO-1抗氧化通路

减少MDA水平

增加SOD表达

从而延缓AOM/DSS小鼠结肠炎癌转化过程.

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 (

0.05)

whereas the expressions of Nrf2 and HO-1 were significantly decreased

and the expression of Keap1 increased (

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 (

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.

关键词

Keywords

Huangqin Decoctioncolitis-associated carcinogenesisnuclear factor erythroid 2 related-factor 2/heme oxygenase signaling pathwayoxidative stressChinese medicine

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Gastroenterology Department, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine

Gastroenterology Department, Jiangsu Province Hospital on Integration of Chinese and Western Medicine

Jiangsu Province Academy of Traditional Chinese Medicine

Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology

Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology

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