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

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.

Untitled

“…1B). These changes are consistent with the study by Chen et al [16], which showed severe epithelial injury and in ammatory cell in ltration in the mucosa and sub mucosa in a DSS-treated group. By another study, a large number of histological lesions which included loss of crypts, edema, mucosal erosions, and in ltration of in ammatory cells in the mucosa were observed in mice treated with DSS [17].…”

“…Studies have demonstrated that barrier dysfunction alone is insuf cient to cause in ammatory bowel disease, it can lead to activation of immune responses that may affect disease development at later times. Pro-in ammatory cytokines such as TNF-and IL-1 have been shown to cause barrier dysfunction due to epithelial tight junction regulation [16,25].…”

Anti-Inflammatory Effects of Huangqin Decoction on Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice Through Regulation of the Gut Microbiota and Suppression of the Ras-PI3K-Akt-HIF-1α and NF-κB Pathways

“…The volumes of distilled water or DSS solution consumed by all of the animals were measured daily, and there were no significant differences in water consumption among the groups. HQD and ME were administered daily by oral gavage (Chen et al, 2016;Wang et al, 2018).…”

“…(jujube, 49 g). Recent studies showed that HQD alleviated inflammation through suppression of the nuclear factor-kappa B (NF-kB) pathway and regulation of the gut microbiota to improve the intestinal microenvironment in mouse models of dextran sulfate sodium (DSS)-induced UC (Chen et al, 2016;Zou et al, 2016;Yang et al, 2017). However, these studies did not clarify how the gut microbiota exerted effects on inflammatory pathways.…”

Targeting NF-κB pathway for treating ulcerative colitis: comprehensive regulatory characteristics of Chinese medicines

“…Clinically, Chinese medicines not only obviously improve symptoms and accelerate ulcer healing, but also alleviate adverse reactions of western medicine and enhance patients' quality of life. Therefore, Chinese medicines have become a hotspot in UC treatment in recent years [28][29][30][31][32].…”