Geniposide attenuates dextran sulfate sodium-induced colitis in mice via Nrf-2/HO-1/NF-κB pathway. 2020

Huiju Yang, and Yinzi Yue, and Yan Li, and Lianlin Su, and Shuai Yan
Department of Anorectal Surgery, The Third Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, China.

BACKGROUND Geniposide (GE) is the main component in gardenia fruit. This study aimed to investigate the protective effects and potential mechanisms of GE on dextran sulfate sodium (DSS)-induced colitis in mice and lipopolysaccharide (LPS)-induced RAW 264.7 cells. METHODS The in vivo acute colitis experimental model was established by administering drinking water containing 3% DSS to the mice for 7 days. GE was administered to the mice via oral gavage at 20 and 40 mg/kg for 7 days. Colon length, colon myeloperoxidase (MPO) level, serum and colon malondialdehyde (MDA) levels, and superoxide dismutase (SOD) activity were determined, and histological evaluation was performed. The levels of interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-α (TNF-α) in the serum and colon were detected. The expression of proteins of the nuclear factor E2 related factor 2 (Nrf-2)/HO-1/ NF-κB pathway in the colon was detected. The in vitro model of LPS-induced RAW 264.7 cells to simulate enteritis model. Cell viability, IL-6, IL-1β, and TNF-α levels in the cell supernatant were measured. The MPO levels in RAW 264.7 cells and DSS-induced mice and MDA and SOD levels in the cell supernatant were measured. The expression of proteins of the Nrf-2/HO-1/NF-κB pathway in RAW 264.7 cells was determined. RESULTS GE treatment resulted in significant histological changes and reduced the expression of inflammatory mediators IL-6, IL-1β, and TNF-α the in serum, colon, and cell supernatant effectively. Parenteral nutrition reduced MPO content in the colon and RAW 264.7 cells. GE treatment increased SOD levels in the serum, colon, and cell supernatant. GE restored the protein expression of the Nrf-2/HO-1/ NF-κB pathway in RAW 264.7 cells and nude mice, and these changes were blocked significantly by Nrf-2 siRNA. CONCLUSIONS These findings demonstrated that GE ameliorated inflammation and oxidative stress in experimental colitis via modulation of the Nrf-2/HO-1/NF-κB pathway. Thus, GE could serve as a potential therapeutic agent for the treatment of ulcerative colitis (UC).

UI MeSH Term Description Entries
D008819 Mice, Nude Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses. Athymic Mice,Mice, Athymic,Nude Mice,Mouse, Athymic,Mouse, Nude,Athymic Mouse,Nude Mouse
D003092 Colitis Inflammation of the COLON section of the large intestine (INTESTINE, LARGE), usually with symptoms such as DIARRHEA (often with blood and mucus), ABDOMINAL PAIN, and FEVER. Colitides
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D016264 Dextran Sulfate Long-chain polymer of glucose containing 17-20% sulfur. It has been used as an anticoagulant and also has been shown to inhibit the binding of HIV-1 to CD4-POSITIVE T-LYMPHOCYTES. It is commonly used as both an experimental and clinical laboratory reagent and has been investigated for use as an antiviral agent, in the treatment of hypolipidemia, and for the prevention of free radical damage, among other applications. Sodium Dextran Sulfate,Dextran Sulfate Sodium,Dextran Sulfate, Sodium,Sulfate Sodium, Dextran,Sulfate, Dextran,Sulfate, Sodium Dextran
D016328 NF-kappa B Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA. Immunoglobulin Enhancer-Binding Protein,NF-kappa B Complex,Nuclear Factor kappa B,Transcription Factor NF-kB,kappa B Enhancer Binding Protein,Ig-EBP-1,NF-kB,NF-kappaB,Nuclear Factor-Kappab,Complex, NF-kappa B,Enhancer-Binding Protein, Immunoglobulin,Factor NF-kB, Transcription,Factor-Kappab, Nuclear,Ig EBP 1,Immunoglobulin Enhancer Binding Protein,NF kB,NF kappa B Complex,NF kappaB,NF-kB, Transcription Factor,Nuclear Factor Kappab,Transcription Factor NF kB
D051267 NF-E2-Related Factor 2 A basic-leucine zipper transcription factor that was originally described as a transcriptional regulator controlling expression of the BETA-GLOBIN gene. It may regulate the expression of a wide variety of genes that play a role in protecting cells from oxidative damage. Nfe2l2 Protein,Nuclear Factor (Erythroid-Derived 2)-Like 2 Protein,Nuclear Factor E2-Related Factor 2,NF E2 Related Factor 2,Nuclear Factor E2 Related Factor 2
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D039823 Iridoids A type of MONOTERPENES, derived from geraniol. They have the general form of cyclopentanopyran, but in some cases, one of the rings is broken as in the case of secoiridoid. They are different from the similarly named iridals (TRITERPENES). Iridoid,Iridoid Derivatives,Secoiridoids,Iridoid Aglycones,Aglycones, Iridoid,Derivatives, Iridoid

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