Page 39 - I. Chemical biology and drug discovery

Anti-inflammatory and anti-oxidative stress effects of puerarin

on dextran sulfate sodium-induced colitis mice model

Ji-Hyun Lee , Yong-Deok Jeon , Ji-Ye Lim , Dae-Ki Kim 1*
1
2
1

1 Department of Immunology and Institute of Medical Sciences, Medical School, Chonbuk National University, Jeonju, Jeonbuk 54907, Republic of Korea.

2 Department of Korean pharmacy, Woosuk University, 443 Samnye-ro, Samnye-eup, Wanju-Gun, Jeollabuk-do 55338, South Korea.

BACKGROUND & AIM

Ulcerative colitis (UC) is a chronic relapsing IBD, which is characterized by abdominal pain, diarrhea, and rectal bleeding. The aim of this study was to

investigate whether puerarin, one of the main components of the root of Pueraria lobata, exerts anti-inflammatory and anti-oxidative effects against UC. To

examine the anti-inflammatory and anti-oxidative effects of puerarin against colitis, we used a mouse model of dextran sulfate sodium (DSS)-induced

colitis. Administration of puerarin alleviated colon shortening, pathological damage to the colon, and myeloperoxidase (MPO) activity. Puerarin significantly

inhibited inflammation through the down-regulation of nuclear factor-κB (NF-κB) and the secretion of pro-inflammatory mediators. Moreover, puerarin

showed anti-oxidative effects through the regulation of the expression of the NF-E2 p45-related factor 2 (Nrf2) pathway and antioxidant enzymes. Puerarin

inhibited intestinal epithelial barrier dysfunction by increasing the expression of tight junction proteins. These results suggest that puerarin could be used

as a potential natural therapeutic for the prevention and treatment of inflammatory colitis diseases.

RESULTS

1
Ji-Hyun Lee , Yong-Deok Jeon , Ji-Ye Lim , Dae-Ki Kim 1*
1
2

Fig. 2. Effects of puerarin on the histological change, MPO

activity, and serum levels in DSS-induced colitis in mice. (A) The Fig.3. Effects of puerarin against the activation of the NF-κB

images of H&E staining (scale bar = 100 μm, 400× magnification) of signaling pathway and the expression of COX-2, iNOS, PGE , and
2
mice in each treatment group and (B) the histopathological score. (C) NO in DSS-induced colitis in mice. (A) Activation of NF-κB in colon
Fig. 1. Effects of puerarin in DSS-induced colitis in mice. (A) The

chemical structures of puerarin. (B) Experiment schedule for the model of MPO activity. (D–J) The serum levels of TNF-α, IL-1β, IL-6, AST, ALT, tissue (scale bar = 100 μm, 400× magnification). (B) Protein expression

DSS-induced colitis in mice. (C) Body weight change and (D) body weight creatinine, and BUN. All values are presented as the mean ± SD. The of COX-2 and iNOS in colon tissue. (C) The bar graph of the relative
###
gain. (E) DAI score. (F-G) Photographs of the colon and colon length. (H) data were analyzed by Bonferroni’s post-hoc test. p<0.001 versus intensities of western blotting bands. The mRNA expression of (D) COX-
*
***
**
The spleen index. All values are presented as the mean ± SD. The data Normal group; p<0.05, p<0.01, and p<0.001 versus DSS group. 2 and (E) iNOS in colon tissue. The expression of (F) PGE and (G) NO
2
were analyzed by Bonferroni’s post-hoc test. p<0.05, and ### p<0.001 in colon tissue. All values are presented as the mean ± SD. The data
#
versus Normal group; p<0.01, and p<0.001 versus DSS group. were analyzed by Bonferroni’s post-hoc test. ### p<0.001 versus Normal
***
**
group; p<0.05, p<0.01, and p<0.001 versus DSS group.
*
**
***

Fig.5. Effects of puerarin on oxidative stress in DSS-induced

colitis in mice. (A) Expression of Nrf2, HO-1, and NQO1 in colon

tissue (scale bar = 100 μm, 400× magnification). (B) Protein

expression of Nrf2, HO-1, and NQO1 in colon tissue. (C) The bar

Fi g . 4 . Effects of puerarin on the mRNA expression of pro- graph of the relative intensities of western blotting bands. The Fig.6. Effects of puerarin on intestinal barrier function in DSS-

inflammatory cytokines in DSS-induced colitis in mice. (A–D) The activities of (D) MDA, (E) CAT, (F) GSH, and (G) SOD were measured induced colitis in mice. (A) Expression of ZO-1, occludin, and claudin-

mRNA expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, and in colon tissue. All values are presented as the mean ± SD. The data 1 in colon tissue (scale bar = 100 μm, 400× magnification). (B) Protein

IFN-r). All values are presented as the mean ± SD. The data were were analyzed by Bonferroni’s post-hoc test. ## p<0.01 and ### p<0.001 expression of ZO-1, occludin, and claudin-1 in colon tissue. (C) The bar

*
**
analyzed by Bonferroni’s post-hoc test. ### p<0.001 versus Normal group; versus Normal group; p<0.05, p<0.01, and *** p<0.001 versus DSS graph of the relative intensities of western blotting bands. The mRNA
**
* p<0.05, p<0.01, and p<0.001 versus DSS group. group. expression of (D) ZO-1, (E) occludin, and (F) claudin-1 in colon tissue.
***

CONCLUSION ACKNOWLEDGEMENTS

In conclusion, puerarin showed clear protective effects, including anti-inflammatory and antioxidant

activity and the regulation of intestinal epithelial barrier in DSS-induced colitis mice. In particular, the This research was supported by “Research

anti-colitis effect of puerarin (50 mg/kg) was greatly improved in most factors compared with the anti- Base Construction Fund Support Program”

colitis effect of 5-ASA (50 mg/kg). Therefore, we suggest that puerarin could be used as a potential funded by Chonbuk National University in 2019.

natural therapeutic for the prevention and treatment of inflammatory colitis diseases.

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