<p>Effects of Huaier Extract on Ameliorating Colitis-Associated Colorectal Tumorigenesis in Mice</p>

Abstract

Background: Huaier extract has been a part of traditional Chinese medicine (TCM) for roughly 1600 years and may serve as a potential anti-cancer drug as it is associated with good efficacy and low toxicity. Individuals with inflammatory bowel disease (IBD) are at a higher chance of being diagnosed with colorectal cancer (CRC) and as Huaier extract may potentially influence tumorigenesis, we set out to determine the effect of Huaier extract on colitis-associated CRC. Methods: The CRC mouse model, established through azoxymethane (AOM) and dextran sulfate sodium (DSS), was administered Huaier extract. Weight loss, colon length, tumor number and tumor size were evaluated macroscopically. Pro-inflammatory cytokine expression and STAT3 phosphorylation were assessed in the colon using ELISA, Western blot and/ or immunohistochemistry. Results: Huaier extract improved the severity of colitis-associated tumorigenesis compared with control group, with attenuated weight loss and longer colons. Tumor number, size and load were drastically decreased in mice treated with Huaier. Histological assessment suggested that Huaier could decrease histological injury of the colon tissue. Additionally, Huaier extract treatment led to reduced pro-inflammatory cytokine levels (TNF-α, IL-6, IFN-γ and IL-1β) and a decrease of STAT3 phosphorylation in colon tissue. Additionally, present findings demonstrated that Huaier extract inhibited cell proliferation and induced apoptosis in CRC cells HCT116 and HCT8. The migration and invasion of CRC cells were markedly inhibited upon exposure to Huaier treatment. The apoptosis-associated protein levels (P53, Bax, Bcl-2, pro-caspase-3 and cleavage caspase-3) showed significant differences after the administration of Huaier extract in HCT116 and HCT8 cells. In vivo, the administration of Huaier extract to mice inhibited tumor growth and yielded a similar profile of apoptotic proteins expression p53, Bcl-2, pro-caspase-3 and cleaved caspase-3 while no significant differences in Bax were observed. Moreover, the ratio of TUNEL-positive/apoptotic cells was markedly increased in the Huaier-treated mice. Conclusion: Huaier extract may reduce the IBD-associated tumor development by suppressing pro-inflammatory cytokine levels and STAT3 stimulation.

Ficus pandurata Hance Inhibits Ulcerative Colitis and Colitis-Associated Secondary Liver Damage of Mice by Enhancing Antioxidation Activity

“…Therefore, herbal medicines or prescriptions with the functions of heat-clearing, detoxication, activating blood, and eliminating dampness would have good therapeutic efficacy against IBD, such as Trametes robiniophila Murr., Curcuma longa L., and Plantago depressa Willd. [ 17 , 34 , 35 ]. Ficus pandurata Hance, mainly containing the chemical constituents of triterpenes, flavonoids, coumarins, sterols, and so on [ 36 , 37 ], had been recorded to possess the functions of clearing heat, detoxification, and anti-inflammation in the traditional Chinese medicine documentation [ 22 ].…”

Chang qing formula ameliorates colitis-associated colorectal cancer via suppressing IL-17/NF-κB/STAT3 pathway in mice as revealed by network pharmacology study

“…The incidence of CRC has been reported to be 60% higher in patients with IBD, particularly those with ulcerative colitis (UC), than in the general population ( Friis et al, 2015 ). Inflammatory cytokines play important roles in tumor development ( Zou et al, 2020 ), the persistent inflammation can activate the proliferation of premalignant cells and inhibit their apoptosis ( Wang and Karin, 2015 ). Noteworthy, CAC can be delayed or even prevented by treatment with anti-inflammatory drugs, suggesting that inflammatory processes are involved in tumor onset ( Lasry et al, 2016 ).…”

Network Pharmacology and Molecular Docking Analysis to Explore the Mechanism of Huaiqihuang-Mediated Alleviation of Henoch–Schönlein Purpura Nephritis

“…STAT3 activation can produce various immunosuppressive factors such as IL-6, IL-10, TGF β , and CCL2 [ 26 ]. Previous studies have shown that Huaier can interact with STAT3 [ 27 ]. Unexpectedly, we observed a poor binding between HJ (MOL003889 and MOL009760) and STAT3.…”