Protective effect of Shaoyao Decoction against colorectal cancer via the Keap1–Nrf2–ARE signaling pathway
Authors: Xiwen Zhang
Baojin Hua
Shakir M Saud
Xiaoyan Wang
Weidong Li
Journal: Journal of Ethnopharmacology (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Colitis; Colorectal cancer; Oxidative stress; Proinflammatory cytokines; Shaoyao decoction.
Affiliations: Department of Oncology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, No.5, Beixiange Road, Xicheng District, Beijing, 100053, China. Electronic address: ., Department of Family Medicine, Contra Costa Regional Medical Center, Martinez, CA, 94553, USA. Electronic address: ., Department of Scientific Research Management, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, No.5, Beixiange Road, Xicheng District, Beijing, 100053, China. Electronic address: .

Abstract:  Ethnopharmacological relevance: Ulcerative colitis is one of the three high risk factors for colorectal cancer. Studies have found that about 20% of cancers are caused by repeated chronic inflammatory stimuli over a long period of time. Ulcer-related colorectal cancer is one of the main causes of death in patients with ulcerative colitis. At present, surgery is the first choice for the treatment of colorectal cancer, combined with radiotherapy and chemotherapy, which have serious side effects. However, reportedly, a compound prescription of Chinese traditional medicine Shaoyao Decoction (SYD) commonly used to treat damp-heat dysentery has anti-colorectal cancer effect. Thus this study described the effect of SYD to AOM/DSS-induced colon cancer model. Aim of the study: In this study, modern biomedical approaches were employed for investigating the protective/preventive effects of SYD in mice with azoxymethane (AOM)/DSS-induced CRC. Materials and methods: The mice pretreated with AOM/DSS were randomly allocated to SYDL, SYDM, SYDH group and SASP (sulfasalazine) group. Mice without AOM/DSS treatment were randomly divided into PBS control group and SYD control group. Results: It was found that SYD inhibited the production of inflammatory cytokines, TNF-α, IL-1β, superoxide dismutase (SOD), and malonaldehyde (MDA), and increased the antioxidant indices, as measured by the mRNA expression of GR, TR, HO-1, γ-GCSc, γ-GCSm, NQO-1, UGT1A1, and UGT1A10 in AOM-treated mice. Particularly, the expressions rates of NF-κB and Ki-67 in the SYD-treated experimental groups were significantly lower than those in the model group, indicating that the proliferative ability of the CRC tissues was weaker in the SYD-treated experimental groups. Moreover, the positive levels of Nrf2 in the SYD-treated experimental groups were slightly higher than those in the model group, suggesting that SYD exhibited antioxidant activity. Conclusions: To sum up, our results suggest that SYD inhibits the development of acute/chronic colitis and prevents colitis-associated CRC by suppressing inflammation and preventing oxidative stress-induced cellular damage. 

Retracted: No

PubPeer comments:
 Figure 3 appears to include a repeated image, although of different horizontal dimensions. See red boxes. *** ![file] , 
 Results: It was found that SYD inhibited the production of inflammatory cytokines, TNF-u03b1, IL-1u03b2, superoxide dismutase (SOD), and malonaldehyde (MDA), and increased the antioxidant indices, as measured by the mRNA expression of GR, TR, HO-1, u03b3-GCSc, u03b3-GCSm, NQO-1, UGT1A1, and UGT1A10 in AOM-treated mice. Particularly, the expressions rates of NF-u03baB and Ki-67 in the SYD-treated experimental groups were significantly lower than those in the model group, indicating that the proliferative ability of the CRC tissues was weaker in the SYDtreated experimental groups. Moreover, the positive levels of Nrf2 in the SYD-treated experimental groups were slightly higher than those in the model group, suggesting that SYD exhibited antioxidant activity. This result is not correct. I agree that a high NrF2 expression and the corresponding enhancement of antioxidant activity were observed in the SYD-treated animals. Conversely, the proliferative ability of the CRC tissues would be high in SYD-treated animals than model control. However, author said that the proliferative ability of the CRC tissues is low. Please explain. , 
 ![file] , 
 February 2021 The authors regret that Fig. 3 (Top right: Microscopic view of colon on 28 day in mice) in our manuscript was incorrect. Due to a huge amount of photos we have taken for the experiment and a procedure error in the manuscript compilation, two of our photographs (PBS control and Model) in Fig. 3 were mistakenly placed in our accepted paper. We accidentally put the same photo for the PBS control and Model groups of colons on 28 day in mice. The Model group of colon should be replaced with the correct one as follow. This error does not change the scientific conclusions of the article in any way since results of the relative data were presented with originally obtained values. The figure legend and explanation remain the same. The authors would like to apologize for any inconvenience caused. ![file] ,