Objective:

2

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:

2

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:

2

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:

2

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.