Synergistic Effect of Huangqin Decoction Combined Treatment With Radix Actinidiae chinensis on DSS and AOM-Induced Colorectal Cancer

Abstract

Objective: To demonstrate the effectiveness of Huangqin decoction (Huangqin Tang in Chinese, HQT) combined with Radix Actinidiae chinensis (Tengligen in Chinese, TLG) under the guidance of “dampness–heat theory” in preventing and treating colorectal cancer (CRC) with dampness–heat accumulation and to preliminarily reveal its mechanism.Methods: The mice model of CRC was established by intraperitoneal injection of AOM combined with consumption of 2.5% DSS solution, and celecoxib, HQT, TLG, and their combination (HQT + TLG) were administered at the same time. The physical signs and death of the mice were observed daily. At the end of the experiment, the colorectal tissue was dissected, and the tumor was observed and counted. HE staining and Masson’s staining were used to observe the histopathological changes of colon. Expression levels of TNF-α, IL-6, and IL-10 in colorectal tissue were detected by ELISA, and the expression of TNF-α was observed by immunofluorescence. TUNEL assay was used to observe the apoptosis of tumor tissues, and immunohistochemistry was used to observe the expression of Ki-67 and occludin. The mRNA expression levels of claudin-1, occludin, ZO-1, and IL-6 and IL-17 were detected by RT-PCR, and occludin, ZO-1, NF-κB, and STAT3 protein levels were detected by Western blot. The composition of intestinal flora was analyzed by 16S rRNA.Results: HQT + TLG could significantly reduce the mortality of model mice and improve the intestinal mucosal inflammatory cell infiltration and high-grade intraepithelial neoplasia in model mice. All administration groups show a great reduction in the levels of IL-6 and TNF-α in the colorectal tissues of model mice, and increase in the level of IL-10, the total number of CD3+ T cells, the proportion of CD3+CD4+ T cells, and the ratio of CD4/CD8. HQT and HQT + TLG could significantly change the composition of intestinal flora and increase the abundance of Firmicutes and Patescibacteria.Conclusion: HQT and TLG combination has a good effect on inhibiting AOM-DSS-induced CRC. This function may be related to improving the composition of the intestinal flora, regulating the proportion of T-cell subsets in colorectal lymphoid tissue to improve inflammatory response, and downregulating the expression of claudin-1, inhibiting the activation of IL-6/STAT3 signaling pathway to improving abnormal hyperplasia.

Novel MAGL Inhibitors Alleviate LPS-Induced Acute Kidney Injury by Inhibiting NLRP3 Inflammatory Vesicles, Modulating Intestinal Flora, Repairing the Intestinal Barrier, and Interfering with Serum Metabolism

“…Desulfobacterota and Proteobacteria have been reported to be able to accelerate the progression of inflammatory diseases by activating inflammatory vesicle signaling pathways [24], and M-18C was able to reduce the abundance of Desulfobacterota and Proteobacteria in the intestinal tract of AKI mice. There is evidence that Deferribacterota and Mucispirillum are strongly associated with intestinal inflammation and the risk of kidney disease [25][26][27][28], whereas in our experiments, we found that Deferribacterota abundance was elevated in the intestinal tracts of AKI mice, and M-18C intervention significantly reduced Deferribacterota abundance. Wei et al demonstrated that the abundance of Tuzzerella was positively correlated with urea nitrogen, reactive oxygen species, and IL-1β in the serum of hyperuricemic mice [29,30], and M-18C was able to reduce the abundance of Tuzzerella in the intestines of AKI mice.…”

Huang Qin decoction increases SLC6A4 expression and blocks the NFκB-mediated NLRP3/Caspase1/GSDMD pathway to disrupt colitis-associated carcinogenesis

“…Here, we further observed that similar to mesalazine, HQD exhibited an antitumor effect on mice induced with CAC. Although HQD has been shown to effectively inhibit DSS-induced colitis alone or by synergizing with Radix Actinidiae chinensis , this main function was associated with altering the composition of the intestinal flora and modifying the proportion of T-cell subsets in colorectal lymphoid tissues (Huang et al 2022a , b ). Therefore, the immunoregulatory function of HQD needs to be further explored and verified.…”