Inflammatory bowel disease (IBD) is a special chronic intestinal inflammatory disease, which is mainly divided into Crohn's disease (CD) and ulcerative colitis (UC). Its occurrence is a complex process that regulated by multiple signaling pathways, including nuclear factor erythroid 2-related factor (Nrf2)/ antioxidant response element (ARE) signaling pathway. Nrf2/ARE pathway as the central defense mechanism against oxidative stress controls the expression of many antioxidant and anti-inflammatory genes in the nucleus, and plays a crucial role in the treatment of IBD. Various studies have proved that many natural compounds target Nrf2/ARE signaling pathway to treat IBD. Here, we introduced the regulatory mechanism of the Nrf2/ARE pathway, and its role in IBD and IBD complications (intestinal fibrosis and colorectal cancer (CRC)); summarized the research progress of Nrf2 targeted natural compounds and extracts in the treatment of IBD; and finally described the intestinal microbiota that alleviate or treat IBD via activating Nrf2/ARE signaling pathway. This review highlights the potential for targeting Nrf2/ARE pathway to treat IBD.

Inflammatory bowel disease (IBD) is characterized by chronic and relapsing intestinal inflammation, which currently lacks safe and effective medicines. Astragalus membranaceus (AM), also named Huangqi, is one of the most commonly used fundamental herbs in China. Here, we aimed to investigate mechanism and bioactive compounds of AM on treating sodium dodecyl sulfate (SDS)- induced colitis in Drosophila flies. Our data showed that AM extract (AME) supplementation had no toxic effect in flies, and protected flies against SDS-induced lifespan shortening, intestinal morphological damage, and colon length shortening. Moreover, AME supplementation remarkably rescued SDS-induced intestinal stem cell (ISC) overproliferation and increased reactive oxygen species (ROS) level in the intestine. Mechanistically, AME remarkably rescued the altered expression levels of genes and proteins in c-Jun N-terminal kinase (JNK) and JAK-STAT signaling pathways induced by SDS in gut. Additionally, formononetin, isoliquiritigenin, isorhamnetin, astragaloside I, astragaloside III, vanillic acid, and caffeic acid in AM had protection against SDS-induced inflammatory damage in flies. Taken together, AME could ameliorate the intestinal inflammation partially by suppressing oxidative stress-associated JNK signaling and JAK-STAT signaling pathways. AME may provide a theoretical basis for natural medicine toward treating intestinal inflammatory disease in human.

Nociception refers to the process of encoding and processing noxious stimuli, which allow animals to detect and avoid potentially harmful stimuli. Several types of stimuli can trigger nociceptive sensory transduction, including thermal, noxious chemicals, and harsh mechanical stimulation that depend on the corresponding nociceptors. In view of the high evolutionary conservation of the mechanisms that govern nociception from Drosophila melanogaster to mammals, investigation in the fruit fly Drosophila help us understand how the sensory nervous system works and what happen in nociception. Here, we present an overview of currently identified conserved genetics of nociception, the nociceptive sensory neurons responsible for detecting noxious stimuli, and various assays for evaluating different nociception. Finally, we cover development of anti-pain drug using fly model. These comparisons illustrate the value of using Drosophila as model for uncovering nociception mechanisms, which are essential for identifying new treatment goals and developing novel analgesics that are applicable to human health.

Chemotherapy leads to significant side effects in patients, especially in the gut, resulting in various clinical manifestations and enhanced economic pressure. Until now, many of the underlying mechanisms remain poorly understood. Here, we used Drosophila melanogaster (fruit fly) as in vivo model to delineate the side effects and underlying mechanisms of Irinotecan (CPT-11). The results showed that administration of CPT-11 delayed larval development, induced imbalance of male to female ratio in offspring, shortened lifespan, impaired locomotor ability, changed metabolic capacity, induced ovarian atrophy, and increased excretion. Further, CPT-11 supplementation dramatically caused intestinal damages, including decreased intestinal length, increased crop size, disrupted gastrointestinal acid-based homeostasis, induced epithelial cell death, and damaged the ultrastructure and mitochondria structure of epithelial cells. The cross-comparative analysis between transcriptome and bioinformation results showed that CPT-11 induced intestinal damage mainly via regulating the Toll-like receptor signaling, NF-kappa B signaling, MAPK signaling, FoxO signaling, and PI3K-AKT signaling pathways. In addition, CPT-11 led to the intestinal damage by increasing ROS accumulation. These observations raise the prospects of using Drosophila as a model for the rapid and systemic evaluation of chemotherapy-induced side effects and high-throughput screening of the protective drugs.