St. John's Wort Attenuates Colorectal Carcinogenesis in Mice through Suppression of Inflammatory Signaling

Abstract

In spite of widespread use as well as epidemiological indications, there have been no investigations into the effect of St. John’s wort (SJW) extract on colorectal carcinogenesis in vivo. This study reports a systematic evaluation of the impact of dietary supplementation of SJW extract on azoxymethane (AOM)-induced colorectal carcinogenesis in mice. Mice were fed with either AIN-93G (control) diet or SJW extract-supplemented diet (SJW diet) prior to AOM treatment. SJW diet was found to significantly improve the overall survival of AOM-treated mice. Pre-treatment with the SJW diet significantly reduced body weight loss as well as decrease of serum albumin and cholesterol levels associated with AOM-induced colorectal tumorigenesis. SJW diet-fed mice showed a significant decrease in tumor multiplicity along with a decrease in incidence of large tumors and a trend towards decreased total tumor volume in a dose-dependent manner. A short-term study, which examined the effect of SJW prior to rectal bleeding, also showed decrease in colorectal polyps in SJW diet-fed mice. Nuclear factor kappa B (NF-κB) and extracellular signal-regulated kinase (ERK 1/2) pathways were attenuated by SJW administration. SJW extract resulted in early and continuous attenuation of these pathways in the colon epithelium of SJW diet-fed mice under both short term and long term treatment regimens. In conclusion, this study demonstrated the chemopreventive potential of SJW extract against colorectal cancer through attenuation of pro-inflammatory processes.

Anti-Tumor Activity of Hypericum perforatum L. and Hyperforin through Modulation of Inflammatory Signaling, ROS Generation and Proton Dynamics

“…A protective action against oncogenesis has also been shown by using SJW total extract. In a mouse experimental model of colorectal carcinogenesis induced by azoxymethane, Manna et al [ 150 ] reported the preventive potential of a dietary supplementation with SJW extract. Azoxymethane induces alkylation of DNA leading to mutations and tumorigenesis [ 150 ].…”

“…In a mouse experimental model of colorectal carcinogenesis induced by azoxymethane, Manna et al [ 150 ] reported the preventive potential of a dietary supplementation with SJW extract. Azoxymethane induces alkylation of DNA leading to mutations and tumorigenesis [ 150 ]. Diet enrichment with 5% SJW decreases the incidence of colorectal polyps and large tumors in azoxymethane-treated mice, finally improving overall animals’ survival.…”

“…Diet enrichment with 5% SJW decreases the incidence of colorectal polyps and large tumors in azoxymethane-treated mice, finally improving overall animals’ survival. In this model, at molecular level, it has been observed that NF-κB and ERK1/2 pathways are hampered by SJW, with a reduction in the mRNA expression level of NF-κB-elicited genes, such as TNF-α, IL-1β, MMP-7 and -9 and iNOS [ 150 ]. These results clearly indicate that preventive administration of SJW can decrease both the occurrence of colorectal tumors and the associated induction of inflammatory signaling [ 150 ].…”

“…In this model, at molecular level, it has been observed that NF-κB and ERK1/2 pathways are hampered by SJW, with a reduction in the mRNA expression level of NF-κB-elicited genes, such as TNF-α, IL-1β, MMP-7 and -9 and iNOS [ 150 ]. These results clearly indicate that preventive administration of SJW can decrease both the occurrence of colorectal tumors and the associated induction of inflammatory signaling [ 150 ]. Interestingly, the same mouse model of colorectal carcinogenesis has recently been showed to depend on NOX/ROS activity, since a low dose of diphenyleneiodonium (DPI), a NOX inhibitor, prevents the formation of azoxymethane-induced adenomatous polyps and inhibits the intestinal inflammatory response [ 151 ].…”

A New Polygenic Model for Nonfamilial Colorectal Cancer Inheritance Based on the Genetic Architecture of the Azoxymethane-Induced Mouse Model

“…approaches (Reddy 2004;Waly et al 2014;Manna et al 2015;Odun-Ayo et al 2015;Pedro et al 2016;Bi et al 2017;Md Nasir et al 2017;Wu et al 2017), and to identify genetic (Ruivenkamp et al 2003;Meunier et al 2010Meunier et al , 2011Meunier et al , 2013Eversley et al 2012;Liu et al 2012) and environmental (Bissahoyo et al 2005;Takahashi et al 2013;Piazzi et al 2019) factors that contribute to nonfamilial CRC susceptibility .…”