Chicoric acid enhances the antioxidative defense system and protects against inflammation and apoptosis associated with the colitis model induced by dextran sulfate sodium in rats

Abstract

Although several anticolitic drugs are available, their application is associated with numerous side effects. Here, the potential anticolitic e ciency of chicoric acid (CA; a hydroxycinnamic acid) against dextran sulfate sodium-induced colitis in rats was examined in rats. Animals were randomly assigned to the following ve groups: control, CA (100 mg/kg body weight), DSS [(DSS); 4% w/v], CA + DSS (100 mg/kg), and the 5-aminosalicylic acid (100 mg/kg) + DSS group. The obtained data revealed that CA signi cantly prevented the shortening of colon length in addition to alleviating colon histological changes in colitis rats. Meanwhile, the oxidative stress-related enzymes, in addition to malondialdehyde and nitric oxide, were markedly modulated by CA. The results also indicated that CA exerted an anti-apoptotic effect in the colitis rats by inhibiting pro-apoptogenic indices (Bax and caspase-3) and enhancing Bcl-2, the antiapoptogenic protein. Moreover, DSS caused an elevation of pro-in ammatory mediators, including interleukin-1β, tumor necrosis factor-α, myeloperoxidase, cyclooxygenase II, prostaglandin E2, and peroxisome proliferator-activated receptor gamma. Interestingly, these changes were signi cantly attenuated following the CA administration. At the molecular level, CA supplementation has increased the expression level of nuclear factor erythroid 2-related factor-2 (Nrf2) and decreased the expressions of nitric oxide synthase and mitogen-activated protein kinase 14. CA has been determined to lessen DSSinduced colitis by activating Nrf2 and its derived antioxidant molecules and suppressing in ammation and apoptosis cascades associated with the development of colitis; suggesting that CA could be used as an alternative naturally-derived anticolitic agent.

Chicoric Acid Alleviates Colitis via Targeting the Gut Microbiota Accompanied by Maintaining Intestinal Barrier Integrity and Inhibiting Inflammatory Responses

“…Upregulation of PPAR-γ can inhibit the transcription of inflammatory genes. Thus, the anti-inflammatory effect of CA may be partly attributed to its regulation of PPAR-γ expression level . Nrf2 is the core regulator of the oxidative stress response.…”

“…16 CA has been reported with the increasing of the level of oxidative stress-related factors, thereby inhibiting intestinal inflammation and apoptosis by activating nuclear factor erythroid 2-related factor-2 (Nrf2) and related antioxidant defense systems. 17 However, the intervention effect and specific mechanism of CA on colitis need to be investigated in depth, and the association between CA and gut microbiota also needs to be further confirmed.…”

“…CA can improve exercise capacity and diabetic myopathy by activating antioxidant responses, complementing regulation of mitochondrial biogenesis, improving glycogen synthesis, and inhibiting the development of inflammatory response . CA has been reported with the increasing of the level of oxidative stress-related factors, thereby inhibiting intestinal inflammation and apoptosis by activating nuclear factor erythroid 2-related factor-2 (Nrf2) and related antioxidant defense systems . However, the intervention effect and specific mechanism of CA on colitis need to be investigated in depth, and the association between CA and gut microbiota also needs to be further confirmed.…”