Casticin prevents DSS induced ulcerative colitis in mice through inhibitions of NF‐κB pathway and ROS signaling

Abstract

Casticin, a compound purified from the Chinese herb Viticis Fructus, has been proven effective in preventing tumor progression in previous studies. Ulcerative colitis (UC) is a common inflammatory bowel disease that affects millions of people worldwide, but no effective and safe drugs are available. In this study, we aimed to study how did casticin affect UC by evaluating its effects on dextran sulfate sodium (DSS)-induced colitis in mice. Our data suggested that casticin attenuated body weight loss, colon length shortening, and pathological damage in the colon of DSS-treated mice. Casticin decreased reactive oxygen species level and chemocytokines (IL-1β, IL-6, TNF-α) productions in colon tissue. The decreased reactive oxygen species level and suppressed proinflammatory cytokines productions were also confirmed in casticin-treated LPS-stimulated RAW264.7 cells and hydrogen peroxide-treated CACO-2 cells in vitro. Mechanistically, casticin treatment prevented the profound activation of AKT signaling caused by DSS administration. And casticin inhibited the productions of proinflammatory chemocytokines through downregulating AKT/NF-κB pathway in macrophages. Meanwhile, data revealed that casticin increased expressions of endogenous antioxidants peroxiredoxin 3 and MnSOD were through activation in FOXO3α signaling by downregulating AKT signaling in colon epithelium cells. Our findings demonstrated that casticin alleviated DSS-induced UC by increasing the antioxidant enzyme peroxiredoxin 3 and MnSOD expressions, and decreasing the production of proinflammatory chemocytokines through inhibition of AKT signaling.

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

“…Casticin, a compound extracted from Vitex Fructus, showing anti-inflammatory and antitumor effects. Research suggests that casticin (10 mmol/L) treatment alleviates body weight loss, colon length shortening and pathological damage in the colon of dextran sulfate sodium (DSS)-treated mice, as well as inhibits the productions of pro-inflammatory chemocytokines through down-regulating AKT/NF-κB pathway in macrophages [44].…”

“…Heat-clearing and dampness-drying medicine Casticin RAW264.7 Repress the NF-κBp65 nucleus translocation [44] Baicalin DSS-induced colon tissue Reduce the protein levels of NF-κBp65 and p-NF-κBp65 [45] UC patients Decrease ratios of p-NF-κB/NF-κB [46] Wogonin Caco-2 cells Decrease NF-κB activity [47] Wogonoside DSS-induced colon tissues Inhibit nuclear translocation of NF-κBp65, phosphorylated p65 and NF-κB DNA binding activity [48] AOM/DSS-induced tumor tissues…”

Devil's claw (Harpagophytum procumbens) and chronic inflammatory diseases: A concise overview on preclinical and clinical data

“…Inflammatory bowel diseases (IBDs), particularly ulcerative colitis, have been long related to increased burden of oxidative stress (Achitei et al, 2013;Koutroubakis et al, 2004;Rezaie, Parker, & Abdollahi, 2007). To this regard, multiple studies revealed that antioxidant/antiinflammatory herbal extracts could be effective in the management of IBDs symptoms, particularly those related to increased oxidative stress (Chung et al, 2007;Lenoir et al, 2012;Ma et al, 2018;Zhang, Ma, Gao, Sun, & Zhang, 2017). In this context, a preliminary preclinical study was performed in order to evaluate protective effects of devil's claw in IBDs.…”

<p>Casticin Improves Respiratory Dysfunction and Attenuates Oxidative Stress and Inflammation via Inhibition of NF-ĸB in a Chronic Obstructive Pulmonary Disease Model of Chronic Cigarette Smoke-Exposed Rats</p>

“…(Family: Verbenaceae). 17 It displayed a wide range of pharmacological properties such as, anti-inflammatory, 18 anti-cancer, [19][20][21] ulcerative colitis, 22 antioxidant. 23 However, recently a study has been conducted to elucidate the effect of CST against COPD, but it does not provide any possible mechanism behind this pharmacological effect.…”