Protective effects of Huangqin Decoction against ulcerative colitis and associated cancer in mice

// Gang Chen 1, 2, 3, * , Yang Yang 1, 2, * , Chunping Hu 1, 2 , Xiaolan Cheng 1, 2 , Yuehua Xu 1, 2 , Xueting Cai 1, 2 , Min Wang 3 , Chung S. Yang 4 , Peng Cao 1, 2 1 Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, Jiangsu, China 2 Laboratory of Cellular and Molecular Biology, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, Jiangsu, China 3 School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, Jiangsu, China 4 Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA * These authors contributed equally to this work Correspondence to: Peng Cao, email: pcao79@yahoo.com Chung S. Yang, email: csyang@pharmacy.rutgers.edu Keywords: Huangqin Decoction, ulcerative colitis, colitis-associated cancer, anti-inflammation and antioxidant Received: March 29, 2016 Accepted: August 12, 2016 Published: August 19, 2016 ABSTRACT Individuals with ulcerative colitis (UC) are at a high risk for developing colorectal cancer (CRC). Huangqin Decoction (HQD), a traditional Chinese medicinal formula chronicled in the Shang Han Lun , is commonly used to treat gastrointestinal symptoms. However, experimental evidence for supporting the clinical practice is lacking. This study used modern biomedical approaches to investigate the protective/preventive effects of HQD in dextran sulfate sodium (DSS)-induced acute/chronic UC and azoxymethane (AOM)/DSS-induced CRC in mice. HQDs were prepared in 4 different ways: HQD-1 and HQD-2 were prepared in boiling water, whereas HQD-3 and HQD-4 were prepared in heated ethanol (70%). For HQD-1 and HQD-3, the 4 constituent herbs were processed together, whereas for HQD-2 and HQD4, these herbs were processed individually and then combined. The mice were administered 9.1 g/kg HQD via oral gavage daily. HQD-1 significantly inhibited DSS-induced acute UC, whereas HQD-3 and HQD-4 exhibited mild ameliorative effects; but HQD-2 had no protective effect and resulted in a higher mortality rate. This higher mortality rate may be due to the greater abundance of baicalein and wogonin in HQD-2 than HQD-1. Furthermore, HQD-1 protected against DSS-induced chronic UC and significantly inhibited AOM/DSS-induced CRC in mice. HQD-1 also inhibited the production of inflammatory cytokines and increased antioxidant capacity both in chronic DSS and AOM/DSS treated mice. Overall, HQD-1 inhibits the development of acute/chronic colitis and prevents colitis-associated CRC, possibly by inhibiting inflammation and preventing oxidative stress induced cellular damage.