Effects of Medicinal Plants and Phytochemicals in Nrf2 Pathways during Inflammatory Bowel Diseases and Related Colorectal Cancer: A Comprehensive Review

Abstract

Inflammatory bowel diseases (IBDs) are related to nuclear factor erythroid 2-related factor 2 (Nrf2) dysregulation. In vitro and in vivo studies using phytocompounds as modulators of the Nrf2 signaling in IBD have already been published. However, no existing review emphasizes the whole scenario for the potential of plants and phytocompounds as regulators of Nrf2 in IBD models and colitis-associated colorectal carcinogenesis. For these reasons, this study aimed to build a review that could fill this void. The PubMed, EMBASE, COCHRANE, and Google Scholar databases were searched. The literature review showed that medicinal plants and phytochemicals regulated the Nrf2 on IBD and IBD-associated colorectal cancer by amplifying the expression of the Nrf2-mediated phase II detoxifying enzymes and diminishing NF-κB-related inflammation. These effects improve the bowel environment, mucosal barrier, colon, and crypt disruption, reduce ulceration and microbial translocation, and consequently, reduce the disease activity index (DAI). Moreover, the modulation of Nrf2 can regulate various genes involved in cellular redox, protein degradation, DNA repair, xenobiotic metabolism, and apoptosis, contributing to the prevention of colorectal cancer.

Immunological dimensions of neuroinflammation and microglial activation: exploring innovative immunomodulatory approaches to mitigate neuroinflammatory progression

“…Nrf2 is a member of the vertebrate Cap’n’Collar (CNC) transcription factor subfamily, a subset of the basic leucine zipper (bZip) transcription factors ( 139 , 140 ). This subfamily encompasses additional members such as nuclear factor E2-related factors 1 and 3 (Nrf1 and Nrf3) and p45 NF-E2 ( 141 ).…”

“…In theory, many cellular elements govern the stability of the Nrf2 protein, consequently influencing its movement into the nucleus. Among these factors, Keap1 emerges as the foremost player ( 140 , 143 ). Typically, Nrf2 is situated in the cytosol, forming a complex with Keap1 (Kelch-like ECH-associated protein 1), also recognized as an inhibitor of Nrf2 (INrf2), which is an actin-binding protein ( 144 ).…”

“…Several mechanisms have been proposed to clarify the separation of Nrf2 from Keap1 during periods of stress ( 150 ). Of particular note, two mechanisms have received substantial attention: the oxidation of cysteine residues in Keap1 and the binding of p62 to Keap1 ( 140 , 151 , 152 ). Keap1 is a protein-rich in cysteine, with specific cysteine residues as sensors responsive to electrophiles and ROS ( 153 ).…”

Impact of Heavy Metal Pollution in the Environment on the Metabolic Profile of Medicinal Plants and Their Therapeutic Potential

“…This activation initiates a cascade of events, leading to the transcription of genes responsible for antioxidant and detoxification processes. Nrf2, as a redox-sensitive transcription factor, becomes a central architect in the plants adaptive strategies, finely tuning gene expression to counteract the reactive species generated under heavy metal exposure [ 186 , 187 ].…”

Repurposing of RAS-Pathway Mediated Drugs for Intestinal Inflammation Related Diseases for Treating SARS-CoV-2 Infection

“…Ultimately, the disease activity index (DAI) was decreased. Additionally, NRF2 regulations can control a number of genes involved in cellular redox, protein deterioration, DNA repair, and apoptosis, assisting in the prevention of CRC [77].…”