Naringin Exerts Therapeutic Effects on Mice Colitis: A Study Based on Transcriptomics Combined With Functional Experiments

Abstract

Naringin has been shown to exert protective effects in an animal model of ulcerative colitis, but detailed mechanisms remain unclear. This study aimed to investigate function and signaling mechanisms underlying naringin-induced therapeutic effects on colitis. Two mouse models were established to mimic human Inflammatory bowel disease (IBD) by treating drinking water with dextran sodium sulphate or intra-colonic administration of 2, 4, 6-trinitrobenzene sulfonic acid. Transcriptomics combined with functional experiments were used to investigate underlying mechanisms. Colitis symptoms, including weight loss and high disease activity index were significantly reversed by naringin. The inflammatory response, oxidative reactions, and epithelial cell apoptosis that occur with colitis were also alleviated by naringin. After naringin treatment, transcriptomics results identified 753 differentially expressed mRNAs that were enriched in signaling pathways, including the neuroactive ligand-receptor interaction, calcium signaling, and peroxisome proliferator-activated receptor (PPAR) signaling. The naringin-induced alleviation of colitis was significantly inhibited by the PPAR-γ inhibitor BADGE. In IEC-6 and RAW264.7 cells incubated with lipopolysaccharide (LPS), NF-κB-p65, a downstream protein of PPAR-γ, was significantly increased. Naringin suppressed LPS-induced high expression of NF-κB-p65, which was inhibited by small interfering RNA targeting PPAR-γ. Our study clarifies detailed mechanisms underlying naringin-induced therapeutic effects on mice colitis, and PPAR-γ was found to be the main target of naringin by functional experiments both in vivo and in vitro. Our study supplies new scientific information for the use of naringin in colitis treatment.

Dehydrocostus Lactone Suppresses Dextran Sulfate Sodium-Induced Colitis by Targeting the IKKα/β-NF-κB and Keap1-Nrf2 Signalling Pathways

“…DSS and 2, 4, 6-Trinitrobenzene sulfonic acid (TNBS) are the two most commonly used colitis inducers. Among them, DSS-induced colitis is a classical acute inflammatory model characterized by the dysfunction of the mucosal barrier, while TNBS-induced colitis is a chronic inflammation mediated by T-cell immunity which can maintain a long time ( Dong J. et al, 2021 ; Dong J. Y. et al, 2021 ). In this study, using DSS-induced colitis model, we found that DCL treatment effectively attenuated DSS-induced colitis, which mainly manifested as weight loss, colon length shortening, inflammatory cell infiltration, and colonic barrier injury.…”

Novel flavin-containing monooxygenase protein FMO1 interacts with CAT2 to negatively regulate drought tolerance through ROS homeostasis and ABA signaling pathway in tomato

“…After sequencing, the filtered reads were aligned to the tomato genome (ITAG3.0). The mapped reads, differential expression, and gene enrichment were analysed as described previously [ 64 ].…”

Perindopril/Ambrosin Combination Mitigates Dextran Sulfate Sodium-Induced Colitis in Mice: Crosstalk between Toll-Like Receptor 4, the Pro-Inflammatory Pathways, and SIRT1/PPAR-γ Signaling

“…Forty-eight Balb/c male mice weighing about 16–26 g were obtained from a local source and kept in metabolic cages at 22–26 °C, 55–62% relative humidity, 12 h light, with free access to food and tap water ad libitum. Mice were randomized into six equal groups each of 8 mice by a laboratory technician who was unaware of the nature of the study as follows: control untreated group; DSS-induced colitis group drank distilled water containing 4% w/v DSS for 7 days [ 21 ]; DSS + CMC group received 0.5 mL CMC 1.5% solution by oral gavage; DSS + Perindopril group received perindopril by oral gavage in a dose of 1 mg/kg/day [ 22 ]; DSS + Ambrosin group received ambrosin by oral gavage in a dose of 10 mg/kg/day [ 18 ]; DSS + Perindopril + Ambrosin group was treated with perindopril concomitantly with ambrosin by oral gavage in the fore-mentioned doses. Treatment with CMC, perindopril, and ambrosin started one week before administration of DSS and continued during the administration of DSS.…”