Assembling the evidence…
The Nrf2/Keap1 axis plays a crucial role in the development of gastrointestinal (GI) tract and the maintenance of its proper functionality.
mechanistic and knockout evidence supports the direction, though the evidence base is primarily preclinical
This axis also seems to be a promising candidate for prevention of inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), as well as their severe complications such as intestinal fibrosis and colorectal cancer.
therapeutic promise rests mainly on favorable animal studies with limited and contradictory human evidence
Some currently used drugs such as ASA, telmisartan or non-conventional treatments including plant extracts or nanoparticles may be effective in IBD treatment in animals.
animal studies report benefit, but source selection and study quality are not critically assessed
Nrf2 may play a dual role in CRC progression and may thus act as a pharmacological target in CRC.
preclinical and observational evidence supports opposing stage-dependent roles without clinical validation
Derived from the full evaluation — not a separate score.
Strengths
The review connects Nrf2/Keap1 biology to intestinal development, barrier integrity, IBD, fibrosis, colorectal cancer, and microbiota rather than treating these topics separately.
↳ Abstract; sections on GI development, GI functionality, IBD, fibrosis, CRC, and gut microbiota
The IBD section contrasts decreased and increased Nrf2 levels in patients and reports that constitutive activation aggravated acute inflammation. The CRC section likewise distinguishes protective from tumor-promoting effects.
↳ The role of Nrf2/Keap1 in IBD, pp. 8–9; The role of Nrf2/Keap1 axis in colorectal cancer, pp. 12–13
Table 2 records compounds, doses, administration schedules, animal models, disease types, pathway effects, and references, creating a practical starting point for preclinical research.
↳ Table 2, pp. 14–18
Limitations
Table 2 presents an extended sequence of beneficial preclinical interventions without discussing failed compounds, publication bias, replication, or core study-quality features. This limits how confidently the apparent consistency can be interpreted.
↳ Therapeutic potential of Nrf2/Keap1 axis modulation in IBD; Table 2, pp. 14–18
The article provides no search strategy, databases, inclusion criteria, or explanation of how studies and compounds were selected. Readers therefore cannot assess the completeness or selection balance of the synthesis.
↳ Paper-wide; no methods or literature-selection section
Most therapeutic evidence comes from DSS, TNBS, or acetic-acid rodent models, but the review does not trace their translational limitations into its conclusions about IBD prevention or treatment.
↳ Therapeutic potential section; Table 2; Conclusion
The article's strongest feature is its organized integration of pathway biology with intestinal barrier function, IBD, fibrosis, colorectal cancer, and microbiota. Its treatment of discordant patient findings and the dual role of Nrf2 provides needed mechanistic balance. That balance is not sustained in the therapeutic section, where Table 2 largely presents favorable animal studies without a selection method or critical appraisal. Consequently, the review functions better as a hypothesis-generating reference than as a dependable assessment of therapeutic readiness.
Nabu’s assessment, alongside the field’s view.
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Limited2.8
The review consolidates Nrf2/Keap1 evidence across intestinal development, IBD, fibrosis, colorectal cancer, therapeutics, and microbiota, with Table 2 serving as a useful compound catalogue. Its advance is incremental because it does not resolve the conflicting human findings or the pathway's context-dependent effects.
“the effect of Nrf2 and Keap1 on development of UC still remains elusive”
The progression from molecular biology to disease mechanisms and therapeutic implications is traceable, and most claims are tied to cited studies. Table 2 predominantly compiles beneficial preclinical outcomes without a source-selection method, study-quality appraisal, failed interventions, or publication-bias discussion.
“The Nrf2/Keap1 axis offers new perspectives for IBD drugs”
Section headings, two figures, and two tables make the broad mechanistic argument readily followable, while the abstract and conclusion generally preserve animal-model qualifiers. Dense terminology and isolated wording problems, including the Puerarin summary and the directive CRC recommendation, modestly reduce precision.
“may be effective in IBD treatment in animals”
The review engages directly with discordant human Nrf2 levels, acute-versus-chronic effects, and Nrf2's dual role in colorectal cancer. It does not explain how the limitations of DSS, TNBS, and acetic-acid models constrain the therapeutic interpretation of Table 2.
“both an excessive production of ROS and an over-induction of antioxidant enzymes can be detrimental”
Caveats4 of 4 checks
The review is internally coherent and explicitly reports conflicting findings about Nrf2 in IBD and colorectal cancer rather than concealing them. No original statistical analyses or results-method mismatches require reliability escalation.
The article reports no original human or animal experimentation, making ethics approval and primary-data availability requirements inapplicable. Missing declarations in the supplied text were treated as unknown rather than demonstrated misconduct.
Flags: 0 declared / 5 total
150 of 157 checkable references verified
158 references in manuscript 1 are books, websites or datasets — counted, but not index-checkable citation details diverge from the cited records for 41 references
No retraction notice found in Retraction Watch.
Sources: Retraction Watch ✓
Low2.5
Specific drugs, natural products, nanoparticles, and the Keap1–Nrf2 interaction give researchers concrete candidates to investigate. The review does not identify a particular clinical program, organization, or decision process positioned to use the synthesis.
“some currently used drugs such as ASA, telmisartan”
Therapeutic support consists primarily of cell experiments and chemically induced mouse or rat colitis models, while human evidence is observational. No Nrf2-directed human IBD therapeutic proof of concept or deployment pathway is described.
“may be effective in IBD treatment in animals”
Convergence across DSS, TNBS, and acetic-acid models and across mice and rats supports some preclinical generality. Transfer to human IBD remains uncertain because patient findings are limited and discordant and model boundary conditions are not examined.
“The discrepancy within the level of Nrf2 in IBD patients may be associated with a disease duration”
The review connects recent mechanistic studies to an organized catalogue of candidate interventions that can guide hypothesis generation and later systematic synthesis. Its trajectory contribution remains incremental because it does not identify or resolve a specific gap left by prior reviews.
“future studies are needed to clarify the complex role of Nrf2/Keap1 axis”
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