Abstract
Sini Decoction (SND), as a classic prescription of Traditional Chinese Medicine (TCM), has been proved to be clinically useful in cardiomyopathy and inflammatory bowel diseases. However, the role and mechanism of SND in colitis-associated cancer remains unclear. This study aims to evaluate the effect of SND on colorectal cancer(CRC) symptoms and further explore the changes of gut microbes mediated by SND extract in azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced CRC mice through 16 S rRNA sequencing. Our results indicated that treatment with SND extract could ameliorate the tumors' malignant degree by decreasing tumor number and size. Also, the expression levels of Cyclooxygenase 2 and Mucin-2, which are typical CRC biomarkers, were reduced compared to the CRC group. In the meantime, SND extract can upregulate CD8+ T lymphocytes' expression and Occludin in the colonic mucosal layer. Besides, SND inhibited the expression of CD4+ T cells and inflammatory cytokines in CRC tissue. According to bioinformatics analysis, SND extract was also suggested could modulate the gut microbial community. After the SND treatment, compared with the CRC mice model, the number of pathogenic bacteria showed a significant reduction, including Bacteroides fragilis and Sulphate-reducing bacteria; and SND increased the relative contents of the beneficial bacteria, including Lactobacillus, Bacillus coagulans, Akkermansia muciniphila, and Bifidobacterium. In summary, SND can effectively intervene in colorectal cancer development by regulating intestinal immunity, protecting the colonic mucosal barrier, and SND can change the intestinal microbiota composition in mice.
Highlights
Colorectal cancer(CRC) is one of the most common digestive tract cancers with a high fatality rate (Favoriti et al, 2016)
Composed of Fuzi(the root of Aconitum carmichaelii Debx), Zhigancao(the root of Glycyrrhiza uralensis Fisch), and Ganjiang(the root of Zingiber officinale Roscoe), Sini decoction(SND) is a classic Traditional Chinese Medicine (TCM) prescription in "Shang Han Lun." Current chemomics and pharmacology proved that the total alkaloids, total gingerols, total flavones, and total saponins are the primary active ingredients of Fuzi, Zhigancao, and Ganjiang in Sini Decoction (SND), respectively (Yue et al, 2009; Zhang and Ye, 2009; Chen et al, 2013)
Four typical peaks of Quercetin, Ammonium Glycyrrhizinate, 6-Gingerol, and Carbenoxolone were determined by comparing the reference substance(Figures 1B,C)
Summary
Colorectal cancer(CRC) is one of the most common digestive tract cancers with a high fatality rate (Favoriti et al, 2016). Patients with IBD are considered at high risk of CRC and receive anti-inflammatory treatment (Adami et al, 2016). Given the high rate of CRC recurrence accompanied by side effects in surgery and chemotherapy, there is an increasing interest in the use of complementary and alternative medicine (CAM) in which Traditional Chinese Medicine (TCM) has a vital place (Rahman et al, 2017). The increasing evidence that TCM could help relieve the CRC (Yu et al, 2015; Li, 2018) suggests that TCM has excellent colon cancer treatment potential
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