Mechanism of Action and Therapeutic Implications of Nrf2/HO-1 in Inflammatory Bowel Disease
Abstract
:1. Introduction
2. Antioxidant Nrf2/HO-1 Signaling Pathway
2.1. Structure and Function of Nrf2
2.2. Structure and Function of HO-1
2.3. Antioxidant Effect of the Nrf2/HO-1 Signal
3. Role of Nrf2/HO-1 in Normal Gut Development and Normal Gut Function
3.1. Role of Nrf2/HO-1 in Normal Intestinal Development
3.2. Role of Nrf2/HO-1 in Normal Intestinal Function
4. Role of Nrf2/HO-1 in IBD and IBD Complications
4.1. Role of Nrf2/HO-1 in IBD
4.1.1. Nrf2/HO-1 Attenuates Intestinal Inflammation and Injury by Controlling Oxidative Stress
4.1.2. Nrf2/HO-1 Promotes the Maintenance of the Intestinal Epithelial Barrier by Regulating Intestinal Microbiota
4.1.3. Nrf2/HO-1 Prevents Ferroptosis in Enterocytes
4.2. Role of Nrf2/HO-1 in the Complications of IBD (Intestinal Fibrosis and CRC)
4.2.1. Role of the Nrf2/HO-1 Pathway in Intestinal Fibrosis in IBD
4.2.2. Role of the Nrf2/HO-1 Pathway in IBD-Associated Colorectal Cancer
5. Phytochemicals Targeting the Nrf2/HO-1 Signaling Pathway in the Treatment of IBD
6. Conclusions and Opinions
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Categories | Natural Product | Experiment Models | Effective Dose | Associated Phenotypes | Potential Mechanism | PMID |
---|---|---|---|---|---|---|
Single drug | Licorice | DSS induced in mouse model | 160 mg/kg | IL-1β↓, IL-6↓, IL-17↓, TNF-α↓, SOD↑, GPX↑, MDA↓, Nrf2↑, PINK1↑, Parkin↑, HO-1↑, P62↑, LC3↑ | Nrf2/PINK1 pathway | 36705402 |
Licorice | DSS induced in mouse model | 160 mg/kg | MDA↓, IL-1β↓, IL-6↓, TNF-α↓, SOD↑, GSH-PX↑, IL-10↑, Nrf2↑, PINK1↑, Parkin↑, HO-1↑, ZO-1↑, Occludin↑, P62↑ | Nrf2/PINK1 signaling pathway | 38176667 | |
Crocus sativus | TNBS and DSS induced in mouse model | 20 mg/kg | Colon length↑, HO-1↑, GPX-2↑, TNF-α↓, IFN-γ↓ | Ahr/Nrf2 pathway | 34275090 | |
Tetrastigma hemsleyanum leaves | DSS induced in mouse model | - | Colon length↑, ZO-1↑, Occludin↑, Claudin-1↑, IL-1β↓, IL-6↓, TNF-α↓, SOD↑, CAT↑, HO-1↑, NQO1↑, GCLC↑, MPO↓, MDA↓, Nrf2↑ | Keap1/Nrf2 signaling pathway | 34747421 | |
Ficus pandurate Hance | DSS induced in mouse model | 480 mg/kg | MPO↓, ZO-1↑, Occludin↑, SOD↑, GSH-Px↑, NRF2↑, HO-1↑, NQO1↑, MDA↓, Keap1↓, NOX2↓ | Nrf2 pathway | 34966476 | |
Polyphenols | Paeoniflorin | LPS induced in Caco-2 cell | 100 μm | COX-2↓, INOS↓, TNF-α↓, IL-6↓, Occludin↑, ZO-1↑, Claudin-5↑ | Nrf2/HO-1 signaling pathway | 31473900 |
Puerarin | DSS induced in mouse model | 50 mg/kg | MPO↓, TNF-α↓, IL-1β↓, IL-6↓, IFN-r↓, Nrf2↑, HO-1↑, NQO1↑, MDA↓, CAT↑, GSH↑, SOD↑, ZO-1↑, Occludin↑, Claudin-1↑, COX-2↓, INOS↓ | Nrf2 pathway | 31981944 | |
Honokiol | DSS induced in mouse model | 40 mg/kg | IL-1β↓, IL-6↓, TNF-α↓, INOS↓, COX-2↓, ZO-1↑, Occludin↑, Claudin-1↑ | Nrf2/HO-1 signaling pathway | 36578522 | |
Myristicin | AA induced in rat model | 150 mg/kg | MPO↓, TNF-α↓, IL-1β↓, COX-2↓, IL-10↑, Nrf2↑, HO-1↑ | Nrf2/HO-1 signaling pathway | 36403646 | |
Dieckol | DSS induced in mouse model | 15 mg/kg | TNF-α↓, IL-1β↓, MDA↓, MPO↓, Nrf2↑, HO-1↑, Colon length↑ | Nrf2/HO-1 signaling pathway | 33331035 | |
Resveratrol | DSS induced in mouse model | 100 mg/kg | IL-6↓, IL-1β↓, TNF-α↓, IL-10↑, ZO-1↑, Occludin↑, Nrf2↑, HO-1↑ | Nrf2/HO-1 pathway | 38488031 | |
coumaric acid and syringic acid | AA induced in rat model | 150 mg/kg, 50 mg/kg | TNF-α↓, IL-1β↓, HO-1↑, Nrf2↑, NQO1↑ | Nrf2/HO-1 pathway | 37182450 | |
Luteolin | DSS induced in mouse model | 50 mg/kg | Colon length↑, INOS↓, TNF-α↓, IL-6↓, MDA↓, SOD↑, CAT↑, Nrf2↑, HO-1↑, NQO1↑ | Nrf2/HO-1 pathway | 27569028 | |
Rosmarinic Acid-Loaded Nanovesicles | DSS induced in mouse model | 20 mg/kg | MPO↓, TNF-α↓, IL-1β↓, NLRP3↓, ASC↓, caspase-1↓, Nrf2↑, HO-1↑ | NLRP3 pathway | 33530569 | |
Synthetic Imine Resveratrol Analog 2-Methoxyl-3,6-Dihydroxyl-IRA | DSS induced in mouse model | 200 mg/kg | Colon length↑, IL-6↓, TNF-α↓, HO-1↑, NLRP3↑ | Nrf2 pathway | 31885813 | |
Oligonol | DSS induced in mouse model | 100 mg/kg | Colon length↑, IL-1β↓, IL-6↓, TNF-α↓, HO-1↑, NQO-1↑ | Nrf2 pathway | 30149369 | |
Licochalcone A | DSS induced in mouse model | 80 mg/kg | Colon length↑, MPO↓, TNF-α↓, IL-1β↓, IL-6↓, COX-2↓, GSH↑, SOD↑, NO↓, Nrf2↑, HO-1↑, GCL↑, Keap-1↓ | Nrf2 pathway | 29710547 | |
Cyanidin-3-glucoside and resveratrol | Cytokine induced in HT-29 intestinal cells | 25 μM | Nrf2↑, HO-1↑, GSH/GSSG↑ | Nrf2 pathway | 27818126 | |
Carnosic acid | DSS induced in mouse model | 100 mg/kg | Colon length↑, TNF-α↓, IL-6↓, IFN-γ↓, IL-1β↓, IL-18↓, HO-1↑, GPX2↑, SOD↑, Nrf2↑, GSH↑, SOD↑, MDA↓, INOS↓ | Keap1/Nrf2 pathway | 28887507 | |
Sesamin | DSS induced in mouse model | 100 mg/kg | Colon length↑, IL-6↓, IL-1β↓, TNF-α↓, Nrf2↑, GSH↑, SOD↑, MDA↓, HO-1↑ | Nrf2 pathway | 31534619 | |
Polysaccharide | Astragalus polysaccharide | DSS induced in mouse model | 300 mg/kg | Histological damage↓, IFN-γ↓, IL-6↓, TNF-α↓, IL-1β↓, MDA↓, GSH↑ | Nrf2/HO-1 pathway | 34562468 |
Dandelion polysaccharide | DSS induced in mouse model | 300 mg/kg | Nrf2↑, HO-1↑, NQO-1↑, GSH↑, MDA↓, MPO↓, IL-1β↓, IL-6↓, TNF-α↓, INOS↓, Occludin↑, ZO-1↑ | Nrf2 pathway | 37893693 | |
Polysaccharides from garlic | DSS induced in mouse model | 300 mg/kg | Colon length↑, INOS↓, COX2↓, ZO-1↑, Occludin↑, MUC2↑, IL-1β↓, IL18↓, MDA↓, Keap-1↓, GPX4↑, SOD↑, HO-1↑, NQO1↑, Nrf2↑ | Nrf2 pathway | 36017235 | |
Aloe polysaccharides | DSS induced in mouse model | 100 mg/kg | Colon length↑, GSH↑, CAT↑,SOD↑, MPO↓, IFN-γ↓, MDA↓, TNF-α↓, IFN-γ↓, IL-1β↓, IL-6↓, IL-8↓, IL-17↓, ZO-1↑, Occludin↑, Nrf2↑, HO-I↑, NQO-1↑, IL-10↑, ZO-1↑, Claudin-1↑ | Nrf2/HO-1 signaling pathway | 34229016 | |
Dandelion polysaccharide | DSS induced in mouse model | 300 mg/kg | IL-1β↓, IL-6↓, TNF-α↓, INOS↓, ZO-1↑, Occludin↑, MDA↓, MPO↓ | Nrf2 pathway | 37893693 | |
Fucoidan | AA induced in rat model | 150 mg/kg | Colon length↑, IL-22↑, Nrf2↑, HO-1↑ | Nrf2 pathway | 35870906 | |
Terpenoids | Geniposide | DSS induced in mouse model | 60 mg/kg | Colon length↑, Histopathologic scores↓, ZO-1↑, Occludin↑, IL-1β↓, IL-6↓, TNF-α↓, MDA↓, NQO1↑, HO-1↑ | Nrf2/ARE signaling pathway | 37187359 |
Melianodiol | DSS induced in mouse model | 200 mg/kg | IL-10↑, IL-1β↓, TNF-α↓, MDA↓, NO↓, GSH↑, SOD↑, Nrf2↑, Keap-1↓, HO-1↑ | Nrf2 signaling pathway | 36312760 | |
Ruscogenin | TNBS induced in mouse model | 2 mg/mouse | TNF-α↓, IFN-γ↓, Nrf2↑, NQO1↑ | Nrf2/HO-1 signaling pathway | 35308175 | |
Crocin | AA induced in rat model | 20 mg/kg | Weight/length index↓, SOD↑, GSH↑, TAC↑, CAT↑, MDA↓, TNF-α↓, Nrf2↑, HO-1↑ | Nrf2/HO-1 signaling pathway | 30530041 | |
Ginsenoside Rg1 | DSS induced in mouse model | 200 mg/kg | Colon length↑, IL-1β↓, IL-6↓, TNF-α↓, SOD↑, MDA↓, MPO↓ | Nrf2/HO-1/NF-kB pathway | 38215064 | |
Triptolide | DSS induced in mouse model | 0.02 mg/kg | Colon length↑, Claudin-1↑, Occludin↑, IL-1β↓, IL-6↓, ROS↓ | NRF2/HO-1 signaling pathway | 33240279 | |
Masticadienonic acid | DSS induced in mouse model | 100 mg/kg | TNF-α↓, IL-1β↓, IL-6↓, MAPK↓, NF-κB↓, ZO-1↑, Occludin↑ | Nrf2/HO-1 and MAPK/NF-κB signaling pathway | 36403513 | |
Geniposide | DSS induced in mouse model | 40 mg/kg | IL-6↓, IL-1β↓, TNF-α↓, MDA↓, SOD↑, MPO↓, Nrf2↑, HO-1↑, p-NF-κBp65↓, p-IκBα↓ | Nrf2/HO-1/NF-κB pathway | 32787366 | |
Huzhangoside C | DSS induced in mouse model | - | Colon length↑, INOS↓, MDA↓, NO↓, Nrf2↑, SOD↑, GSH↑ | Nrf2 pathway | 38156815 | |
Nerolidol | DSS induced in mouse model | 150 mg/kg | MPO↓, IL-6↓, IL-1β↓, TNF-α↓, COX-2↓, INOS↓, Keap-1↓, Nrf2↑, SOD↑, HO-1↑ | Nrf2 pathway | 32650602 | |
Tussilagone | DSS induced in mouse model | 2.5 mg/kg | Colon length↑, MPO↓, INOS↓, COX-2↓, TNF-α↓, IL-6↓, Nrf2↑, HO-1↑ | Nrf2 pathway | 30142311 | |
Asperuloside | DSS induced in mouse model | 500 μg/kg | Colon length↑, Histopathological score↓, MPO↓, SOD↑, GSH-Px↑, MDA↓, Nrf2↑, HO-1↑, NQO1↑, TNF-α↓, IL-6↓, IL-10↑ | Nrf2/HO-1 pathway | 33974900 | |
D-Pinitol | DSS induced in mouse model | 40 mg/kg | Colon length↑, HO-1↑, NQO1↑, GSH↑, SOD↑, CAT↑, MPO↓, MDA↓, TNF-α↓, IFN-γ↓, IL-6↓, IL-1β↓, INOS↓, COX-2↓, IL-10↑ | Nrf2/ARE pathway | 33625409 | |
Sericic acid | DSS induced in mouse model | 50 mg/kg | Colon length↑, NO↓, TNF-α↓, IL-6↓, IL-1β↓, MDA↓, SOD↑, Nrf2↑, HO-1↑ | Nrf2 pathway | 36173058 | |
Loganic acid | DSS induced in mouse model | 30 mg/kg | Colon length↑, MDA↓, NO↓, MPO↓, GSH↑, IL-1β↓, IL-6↓, TNF-α↓, TLR4↓, NF-κB↓, MPO↓, IFN-γ↓, Nrf2↑, HO-1↑, SOD↑ | TLR4/NF-κB and SIRT1/Nrf2 pathway | 37421777 | |
Toosendanin | DSS induced in mouse model | 1 mg/kg | Colon length↑, MPO↓, TNF-α↓, IL-1β↓, IL-6↓, SOD↑, GSH↑, MDA↓, Nrf2↑, HO-1↑, ZO-1↑, Occludin↑ | Nrf2/HO-1 pathway | 31520988 | |
RH-F/C-NPs | DSS induced in mouse model | 25 mg/kg | Colon length↑, MPO↓, TNF-α↓, IL-1β↓, IL-6↓, TLR4↓, NF-κB↓, GSH-PX↑, SOD↑, MDA↓, Nrf2↑, HO-1↑, ZO-1↑, Claudin-1↑, Occludin↑ | TLR4/NF-κB and Nrf2/HO-1 signaling pathway | 36326017 | |
American ginseng, panaxynol, hexane fraction | DSS induced in mouse model | 75 mg/kg, 1 mg/kg, 75 mg/kg | COX2↓, HO-1↑ | Nrf2 pathway | 32575883 | |
Alkaloid | Oxyberberine | TNBS induced in rat model | 50 mg/kg | IL-4↑,TNF-α↓, IL-2↓, IL-8↓,IL-22↓, HO-1↑, GCLM↑, GCLC↑, NQO-1↑, SOD↑, GSH↑, MDA↓, ROS↓, CAT↑, Keap1↓, Nrf2↑ | Keap1/Nrf2/NF-κB pathway | 37247589 |
Oleracein E | TNBS induced in rat model | 20 mg/kg | IL-6↓, IL-1β↓, TNF-α↓, CAT↑, MPO↓, ROS↓, ZO-1↑, Occludin↑, Claudin-2↑, Nrf2↑, HO-1↑ | Nrf2/HO-1 pathway | 37395238 | |
Berberine | AA induced in rat model | 50 mg/kg | IL-1β↓, IL-6↓, TNF-α↓, MPO↓, GSH↑, SOD↑, CAT↑, GPx↑, MDA↓, NO↓, Nrf2↑, HO-1↑ | Nrf2/HO-1 pathway | 33061833 | |
Sinomenine | DSS induced in rat model | 40 mg/kg | Colon length↑, NO↓, MPO↓, SOD↑, CAT↑, GPx↑, MDA↓, TNF-α↓, IL-1β↓, IL-6↓, IL-10↑, HO-1↑, Nrf2↑, COX-2↓, INOS↓ | HO-1/Nrf2 pathway | 38573363 | |
Corynoline | DSS induced in mouse model | 30 mg/kg | Colon length↑, Histological scores↓, MPO↓, IL-1β↓, IL-6↓, TNF-α↓, SOD↑, CAT↑, ROS↓, Nrf2↑, HO-1↑, IκBα↓, NF-κB p65↓ | Nrf2/HO-1/NF-κB pathway | 35980837 | |
8-Oxypalmatine | DSS induced in mouse model | 50 mg/kg | Colon length↑, Histological scores↓, MPO↓, TNF-α↓, IL-1β↓, IFN-γ↓, IL-6↓, SOD↑, GSH↑, CAT↑, GSH-Px↑, MDA↓, NLRP3↓, Nrf2↑, HO-1↑ | Nrf2 signaling pathway | 35779424 | |
Leonurine | DSS induced in mouse model | 30 mg/kg | Colon length↑, TNF-α↓, IL-6↓, IL-1β↓, MDA↓, ROS↓, SOD↑, GSH↑, TLR4↓, p-NF-κB↓, Nrf2↑, HO-1↑ | Nrf2/HO-1 and TLR4/NF-κB pathway | 35253649 | |
Sanguinarine | NSAIDs-induced small intestinal inflammation in rat model | 3.3 mg/kg | TDI↓, CMDI↓, LDH↓, ZO-1↑, TNF-α↓, IL-6↓, IL-1β↓, SOD↑, MDA↓, Nrf2↑, HO-1↑, Keap-1↓, P-p65↓ | Nrf2/NF-κB pathways | 36304153 | |
Flavonoid | Galangin | DSS induced in mouse model | 40 mg/kg | TNF-α↓, IL-6↓, IL-10↑, MPO↓, SOD↑, COX-2↓, INOS↓, Nrf2↑, HO-1↑, GST↑, GSH↑, SOD↑ | Nrf2 pathway | 31147743 |
Cardamonin | TNBS and DSS induced in mouse model | 60 mg/kg | Colon length↑, Nrf2↑, NQO1↑, Trx1↑, SOD↑, HO-1↑, MPO↓, IL-1β↓, TNF-α↓, IL-6↓ | AhR/Nrf2/NQO1 pathway | 30071202 | |
Flavonoid isoliquiritigenin | TNF-α-induced HT-29 cells | 20 uM | Nrf2↑, HO-1↑, NQO1↑, IL-8↓, IL-1β↓, COX-2↓ | Nrf2 pathway | 28012970 | |
LL202 | TNBS induced in mouse model | 30 mg/kg | IL-1β↓, IL-6↓, TNF-α↓, SOD↑, GSH↑, TAC↑, MDA↓, Nrf2↑, HO-1↑ | Nrf2/HO-1 pathway | 30426485 | |
Alpinetin | DSS induced in mouse model | 100 mg/kg | Colon length↑, MPO↓, Occludin↑, ZO-1↑, Claudin-2↑, MDA↓, SOD↑, Nrf2↑, HO-1↑ | Nrf2/HO-1 signaling pathway | 29661352 | |
Diosmetin (3′,5,7-trihydroxy-4′-methoxy flavone) | DSS induced in mouse model | 50 mg/kg | Occludin↑, Claudin-1↑, ZO-1↑, IL-1β↓, IL-6↓, TNF-α↓, COX-2↓, GSH-Px↑, SOD↑, MDA↓, GSH↑, ROS↓, Nrf2↑, HO-1↑ | Nrf2 pathway | 34262136 | |
Diosmin | DSS induced in mouse model | 200 mg/kg | Colon length↑, GSH↑, CAT↑, Nrf2↑, HO-1↑, MDA↓, NO↓, Mucin-2↑, ZO-1↑, Histopathological score↓, NF-κB↓, TNF-α↓, IL-6↓, Claudin-1↑, Occludin↑ | NF-κB/Nrf2 pathway | 38500992 | |
Quercetin nanoparticles | DSS induced in mouse model | 20 mg/kg | GSH-Px↑, SOD↑, CAT↑, ROS↓, NO↓, MDA↓, IL-6↓, TNF-α↓, IFN-γ↓, IL-10↑, MUC-2↑, Occludin↑, Nrf2↑, HO-1↑, INOS↓, COX2↓ | Nrf2 pathway | 35884960 | |
Hyperoside | DSS induced in mouse model | 120 mg/kg | Colon length↑, MDA↓, TNF-α↓, IL-6↓, COX-2↓, IL-10↑, MDA↓, Nrf2↑, HO-1↑, SOD↑ | Nrf2 pathway | 29162986 | |
Sulforaphane | AA induced in rat model | 15 mg/kg | Colon length↑, Nrf2↑, HO-1↑, NO↓, MDA↓, GSH-Px↑, GSH↑ | Nrf2 pathway | 35754320 | |
Genistein | AA induced in rat model | 25 mg/kg | Nrf2↑, HO-1↑, Caspase-3↑ | Nrf2/HO-1 pathway | 37084167 | |
Diclofenac and eugenol hybrid | DSS induced in mouse model | 40 mg/kg | Colon length↑, p-NF-κB↓, NF-κB↓, HO-1↑, ROS↓, Nrf2↑, INOS↓ | Nrf2/HO-1 and INOS/NF-κB signaling pathway | 37517204 | |
Coumarins | Imperatorin | TNBS induced in rat model | 60 mg/kg | TNF-α↓, IL-6↓., Nrf2↑, ARE↑, HO-1↑ | Nrf2/ARE/HO-1 pathway | 33098052 |
Isofraxidin | DSS induced in mouse model | 80 mg/kg | Colon length↑, IL-8↓, TNF-α↓, MPO↓, ZO-1↑, IL-1β↓, IL18↓, ROS↓, Nrf2↑, HO-1↑, MDA↓, SOD↑ | Nrf2 pathway | 38280336 |
Natural Extract | Experiment Models | Effective Dose | Associated Phenotypes | Potential Mechanism | PMID | |
---|---|---|---|---|---|---|
Aucklandia lappa Decne extract | DSS induced in mouse model | 182 mg/kg | Colon length↑, TNF-α↓, IL-6↓, IL-1β↓ | Nrf2-HO-1 signaling pathway | 35623504 | |
Lotus Leaf Extract | LPS induced in mouse model | 200 mg/kg | ZO-1↑, Occludin↑, Claudin-1↑, IL-1β↓, IL-6↓, TNF-α↓, Nrf2↑, HO-1↑ | Nrf2/HO-1 signaling pathway | 38526570 | |
Grape seed proanthocyanidin extract | DSS induced in mouse model | - | IL-1β↓, IL-6↓, TNF-α↓, NO↓, MDA↓, SOD↑, NF-κB↓, Keap-1↓, Nrf2↑, HO-1↑ | NF-κB and Nrf2 pathway | 35692132 | |
Green pea hull | DSS induced in mouse model | 600 mg/kg | Colon length↑, MPO↓, Claudin-1↑, Occludin↑, ZO-1↑, MDA↓, SOD↑, CAT↑, TNF-α↓, IL-1β↓, IL-6↓, IL-10↑, Keap1↓, Nrf2↑, GCLC↑, HO-1↑, NQO1↑ | Keap1-Nrf2-ARE signaling pathway | 34829046 | |
Moringa seed extract | DSS induced in mouse model | 150 mg/kg | Colon length↑, TNF-α↓, NO↓, MPO↓, IL-1β↓, IL-6↓, TNF-α↓, INOS↓, Claudin-1↑, ZO-1↑, NQO1↑, HO-1↑ | Nrf2 Pathway | 28922365 | |
Extract of Rhus chinensis Mill. fruits | DSS induced in mouse model | 600 mg/kg | Colon length↑, MDA↓, MPO↓, TNF-α↓, IL-1β↓, IL-6↓, SOD↑, GSH↑, Occludin↑, ZO-1↑, Claudin-1↑, Nrf2↑, NQO1↑, HO-1↑, COX-2↓, INOS↓, | Nrf2 pathway | 34494061 | |
Bruguiera gymnorrhiza fruit | DSS induced in mouse model | 100 mg/kg | Colon length↑, MDA↓, TNF-α↓, IL-6↓, IL-1β↓, IFN-γ↓, IL-10↑, SOD↑, GSH↑, Nrf2↑, HO-1↑, NQO1↑, Keap1↓ | Keap1/Nrf2 pathway | 32116661 | |
ROS extract | DSS induced in mouse model | 500 mg/kg | Colon length↑, INOS↓, MPO↓, MDA↓, p-NF-κB↓, p-IKKα/β↓, Keap1↓, Nrf2↑, HO-1↑, SOD↑, TNF-α↓, IL-6↓, IL-1β↓ | Nrf2/NF-κB pathway | 35692958 | |
Perilla frutescens extract | DSS induced in mouse model | 100 mg/kg | COX-2↓, INOS↓, HO-1↑, Nrf2↑, TNF-α↓, IL-10↑ | Nrf2 pathway | 28848431 | |
Artemisia argyi extract | DSS induced in mouse model | 200 mg/kg | IL-6↓, IL-1β↓, TNF-α↓, p-IκBα↓, p-NF-κB↓, Cox2↓, Nrf2↑, HO-1↑, MPO↓, INOS↓ | NF-κB/Nrf2 pathway | 35277165 | |
Maggot extract | DSS induced in mouse model | 1000 mg/kg | Colon length↑, pIκB↓, IL-6↓, IL-1β↓, NFκB p65↓, TNF-α↓, Nrf2↑, HO-1↑, TGF-β1↓, SMADs↓ | TGF-β1/SMAD pathway | 34456904 | |
Iziphus spina-christi fruit extract | AA induced in rat model | 400 mg/kg | Colon length↑, NO↓, MPO↓, GSH↑, SOD↑, CAT↑, GPx↑, Nrf2↑, HO-1↑, IL-1β↓, INOS↓, TNF-α↓, COX-2↓ | Nrf2/HO-1 pathway | 29518435 | |
Extract of Mesua Assamica (King & prain) Kosterm. | DSS induced in mouse model | 200 mg/kg | Colon length↑, NO↓, MDA↓, MPO↓, GSH↑, IL-1β↓, IL-6↓, TNF-α↓, Nrf2↑, HO-1↑, SOD↑, | HO-1/Nrf2/SIRT1 signaling pathway | 36195303 | |
24Z-masticadienonic acid | DSS induced in mouse model | 100 mg/kg | Colon length↑, IL-1β↓, IL-6↓, TNF-α↓, Occludin↑, ZO-1↑, Nrf2↑, HO-1↑, NFκB p65↓, pIκB↓ | Nrf2/HO-1 and NF-κB pathway | 36403513 | |
Gingerenone A | DSS induced in mouse model | 20 mg/kg | IL-1β↓, IL-6↓, TNF-α↓, MDA↓, GSH↑, Nrf2↑, HO-1↑, NQO1↑, GPX4↑ | Nrf2–GPX4 signaling pathway | 36135333 |
Natural Extract | Experiment Models | Effective Dose | Associated Phenotypes | Potential Mechanism | PMID |
---|---|---|---|---|---|
Linagliptin | TNBS induced in rat model | 1.5 mg/kg | IL-6↓, TNF-α↓, MPO↓, IL-10↑, IL-6↓, TNF-α↓, IL-10↑, GSH↑, GPx↑, TAC↑, Nrf2↑, HO-1↑ | Nrf2/HO-1 pathway | 33667522 |
Carbocisteine | AA induced in rat model | 500 mg/kg | Histopathological score↓, TAC↑, HO-1↑, MPO↓, IL-6↓, TNF-α↓, IL-10↑, TLR4↓, Nrf2↑, NF-κB p-65↓ | Nrf2/HO-1 and NFκB pathway | 35754464 |
Olmesartan | AA induced in rat model | 10 mg/kg | Weight/length ratio↓, IL-6↓, TNF-α↓, IL-1β↓, TGF-β↓, IL-10↑, Nrf2↑, HO-1↑, NFĸB p65↓, MPO↓, TAC↑, SOD↑, GSH↑, CAT↑, MDA↓, IL-10↑ | NFκB and Nrf2/HO-1 pathway | 30594690 |
Nadroparin sodium | AA induced in rat model | 500 units/kg | NF-κB↓, AP-1↓, COX-2↓, IL-6↓, TNF-α↓, HO-1↑, Nrf2↑, MDA↓ | Nrf2/HO-1 and NF-κB pathway | 22350949 |
Levetiracetam | AA induced in mouse model | 100 mg/kg | Colon length↑, TNF-α↓, IL-6↓, IL-1β↓, IFN-γ↓, IL-10↑, TGF-β↑, INOS↓, NO↓, GSH↑, SOD↑, CAT↑, MDA↓, MPO↓, Nrf2↑, HO-1↑, p-NF-κB↓ | Nrf2/HO-1 and NF-κB pathway | 37068340 |
Ambroxol | AA induced in rat model | 200 mg/kg | Weight/length ratio↓, Nrf2↑, HO-1↑, IL-6↓, TNF-α↓, IL-10↑, CAT↑, TAC↑, MPO↓, IL-6↓, TNF-α↓, IL-10↑, IκBα↓, p65↓ | NF-κB/Nrf2 pathway | 35947115 |
Vildagliptin | AA induced in rat model | 10 mg/kg | Nrf2↑, HO-1↑, NQO1↑, TNF-α↓, NF-κB↓, IL-1β↓, PI3K↓, Akt↓ | PI3K/Akt/NFκB and Nrf2 signaling pathway | 33434756 |
Dapagliflozin | TNBS induced in rat model | 5 mg/kg | Weight/length ratio↓, TNF-α↓, MPO↓, IL-10↑, GSH↑, GPx↑, Nrf2↑, HO-1↑ | Nrf2/HO-1 pathway | 33412153 |
Sodium butyrate | DSS induced in mouse model | 10 mg/kg | Colon length↑, MPO↓, MDA↓, GSH↑, COX-2↓, Nrf2↑, HO-1↑, IL-6↓, TNF-α↓, NF-κB↓, IL-1β↓, IL-18↓, NF-κB p65↓, NLRP3↓ | NF-κB/NLRP3 and COX-2/Nrf2/HO-1 pathway | 36867295 |
N-benzyl-N-methyldecan-1-amine; decyl-(4-methoxy-benzyl)-methyl-amine | DNBS induced in rat model | 0.4 mg/kg | TNF-α↓, IL-1β↓, IL-6↓, HO1↑, Nrf2↑, MPO↓ | Nrf2 pathway | 37153778 |
NPs-PEG-FA/6-shogaol | DSS induced in mouse model | 15 mg/kg | MPO↓, TNF-α↓, IL-6↓, IL-1β↓, INOS↓, Nrf2↑, HO-1↑ | Nrf2 pathway | 28961808 |
PEA/Polydatin | DNBS induced in rat model | 10 mg/kg | MPO↓, MDA↓, IL-1β↓, TNF-α↓, NF-κB p65↓, IκB-α↑, INOS↓, SIRT-1↑, HO-1↑, Nrf2↑ | NF-κB/SIRT1/Nrf2 pathway | 33809584 |
Mo3Se4 nanoflakes | DSS induced in mouse model | 100 mg/kg | Histopathological scores↓, MPO↓, ROS↓, MDA↓, CAT↑, GPx↑, SOD↑, GSH↑, Keap1↓, Nrf2↑, NQO1↑, HO-1↑, IL-1β↓, IL-6↓, TNF-α↓, IFN-β↓, TLR4↓, p-NF-κB↓, IκBα↑, MUC-2↑, Claudin-1↑, Occludin↑, ZO-1↑ | Nrf2-Keap1 and TLR4/NF-кB pathway | 35985164 |
I.e. diselenide-bridged hyaluronic acid nanogel | DSS and TNBS induced in mouse model | 50 mg/kg | Colon length↑, MPO↓, MDA↓, SOD↑, HO-1↑, Nrf2↑, INOS↓, IL-6↓, TNF-a↓, IL-1β↓ | Nrf2/HO-1 pathway | 35861614 |
FA-97 | DSS induced in mouse model | 10 mg/kg | Colon length↑, MPO↓, INOS↓, IL-1β↓, IL-6↓, TNF-α↓, IL-12↓, IL-17↓, MDA↓, ROS↓, HO-1↑, NQO-1↑, Nrf2↑ | Nrf2/HO-1 pathway | 31969881 |
Mesalazine | TNBS induced in rat model | 30 mg/kg | Nrf2↑, HO-1↑, MPO↓, COX-2↓, INOS↓ | Nrf2-HO-1 pathway | 28473247 |
Telmisartan | DSS induced in rat model | 7 mg/kg | IL-1β↓, IL-6↓, TNF-α↓, Nrf2↑, HO-1↑, IL-10↑ | NF-κB pathway | 31326516 |
Coenzyme Q10 | AA induced in rat model | 100 mg/kg | Colon weight/colon length ratio↓, GSH↑, SOD↑, CAT↑, Nrf2↑, HO-1↑, MDA↓, TNF-α↓, Caspase-3↓ | Nrf2/HO-1 pathway | 28050757 |
Spermidine | DSS and TNBS induced in mouse model | 20 mM | TNF-α↓, IL-6↓, Occludin↑, Claudin-1↑, Claudin-3↑, Nrf2↑, HO1↑, NQO1↑, SOD↑ | AhR-Nrf2 pathway | 37104918 |
Miconazole | AA induced in rat model | 40 mg/kg | Histopathological score↓, MDA↓, SOD↑, GSH↑, IL-6↓, TNF-α↓, Nrf2↑, HO-1↑, IL-10↑, INOS↓, COX2↑, Caspase-3↓ | Nrf2/HO-1 signaling pathway | 35205169 |
Oat peptides | DSS induced in mouse model | 500 mg/kg | IL-6↓, IL-1β↓,TNF-α↓, MDA↓, SOD↑, ZO-1↑, Occludin↑, Claudin-1↑, Nrf2↑, Keap1↓, NQO1↑, HO-1↑ | Keap1-Nrf2 pathway | 38140314 |
Dimethyl fumarate | DSS induced in mouse model | 60 mg/kg | Colon length↑, MPO↓, INOS↓, IL-1β↓, IL-6↓, TNF-α↓, Nrf2↑, HO-1↑, NQO1↑ | Nrf2/ARE pathway | 27184504 |
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Yuan, L.; Wang, Y.; Li, N.; Yang, X.; Sun, X.; Tian, H.; Zhang, Y. Mechanism of Action and Therapeutic Implications of Nrf2/HO-1 in Inflammatory Bowel Disease. Antioxidants 2024, 13, 1012. https://doi.org/10.3390/antiox13081012
Yuan L, Wang Y, Li N, Yang X, Sun X, Tian H, Zhang Y. Mechanism of Action and Therapeutic Implications of Nrf2/HO-1 in Inflammatory Bowel Disease. Antioxidants. 2024; 13(8):1012. https://doi.org/10.3390/antiox13081012
Chicago/Turabian StyleYuan, Lingling, Yingyi Wang, Na Li, Xuli Yang, Xuhui Sun, Huai’e Tian, and Yi Zhang. 2024. "Mechanism of Action and Therapeutic Implications of Nrf2/HO-1 in Inflammatory Bowel Disease" Antioxidants 13, no. 8: 1012. https://doi.org/10.3390/antiox13081012
APA StyleYuan, L., Wang, Y., Li, N., Yang, X., Sun, X., Tian, H., & Zhang, Y. (2024). Mechanism of Action and Therapeutic Implications of Nrf2/HO-1 in Inflammatory Bowel Disease. Antioxidants, 13(8), 1012. https://doi.org/10.3390/antiox13081012