J Cancer Prev.  2019 Jun;24(2):129-138. 10.15430/JCP.2019.24.2.129.

Baicalein Inhibits Dextran Sulfate Sodium-induced Mouse Colitis

Affiliations
  • 1Tumor Microenvironment Global Core Research Center and Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Korea. surh@snu.ac.kr
  • 2Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea.
  • 3Univera Co., Ltd., Seoul, Korea.
  • 4College of Pharmacy, Chungbuk National University, Cheongju, Korea.
  • 5Department of Food Science and Biotechnology, College of Knowledge-Based Services Engineering, Sungshin Women’s University, Seoul, Korea. nhkdec28@gmail.com

Abstract

BACKGROUND
Baicalein is a bioactive flavone that is originally extracted from the root of Scutellaria baicalensis Georgi. This plant has long served as Chinese herbal medicine in the management of multiple diseases including inflammatory bowel diseases. Although it has been revealed that baicalein inhibits experimental colitis in mice, the molecular mechanisms still remain largely unrecognized.
METHODS
The experimental colitis was induced in mice by 3% dextran sulfate sodium (DSS) in drinking water. The mice were given baicalein (10 or 25 mg/kg) by gavage for 7 days before and after DSS administration. Expression of COX-2 and inducible nitric oxide synthase (iNOS) and molecules involved in NF-κB signaling, such as inhibitor of κBα (IκBα), pIκBα, p65, and phospho-p65 was examined by Western blot analysis in the tissue of the mouse colon. Activity of IκB kinase β (IKKβ) was assessed by measuring the relative amount of radioactive γ-phosphate of ATP transferred to the IκBα substrate protein. The expression and phosphorylation of STAT3 and its target gene cyclin D1 were also measured.
RESULTS
Baicalein prominently mitigated the severity of DSS-induced colitis in mice. It inhibited the expression of COX-2 and iNOS. Moreover, baicalein attenuated activity and phosphorylation of IKKβ and subsequent degradation of IκBα. Baicalein suppressed the phosphorylation and nuclear translocation of p65, resulting in a reduced DNA binding activity of NF-κB. Baicalein also suppressed the phosphorylation of STAT3 and expression of cyclin D1. Baicalein exhibited the synergistic effect on inhibition of COX-2 induced by DSS with curcumin, an ingredient of turmeric.
CONCLUSIONS
Protective effects of baicalein on DSS-induced colitis are associated with suppression of NF-κB and STAT3 signaling pathways, which may contribute to its cancer preventive effects on colon carcinogenesis.

Keyword

Baicalein; Colitis; NF-κB; Cyclooxygenase-2; Anti-inflammation

MeSH Terms

Adenosine Triphosphate
Animals
Asian Continental Ancestry Group
Blotting, Western
Carcinogenesis
Colitis*
Colon
Curcuma
Curcumin
Cyclin D1
Cyclooxygenase 2
Dextran Sulfate*
Dextrans*
DNA
Drinking Water
Herbal Medicine
Humans
Inflammatory Bowel Diseases
Mice*
Nitric Oxide Synthase Type II
Phosphorylation
Phosphotransferases
Plants
Scutellaria baicalensis
Adenosine Triphosphate
Curcumin
Cyclin D1
Cyclooxygenase 2
DNA
Dextran Sulfate
Dextrans
Drinking Water
Nitric Oxide Synthase Type II
Phosphotransferases
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