Hepatoprotective Potential of Green Synthesized Nanoparticles from <i>Citrus reticulata</i> Peel Extract against HFS Diet-Induced NASH in Mice, Integrated with Chemical Profiling and Molecular Modeling
Bibliographic record
Abstract
High Resolution Image Download MS PowerPoint Slide Citrus reticulata is known for its wide variety of secondary metabolites, including essential oil, alkaloids, flavonoids, and phenolic acids, which are considered the reason for its diverse potential medical uses. Herein, Citrus reticulata extract was prepared using different formulas of metal oxide nanoparticles as ZnO NPs and MgO NPs with 22.5 ± 1.3 and 18.3 ± 1.5 nm average particle sizes, respectively. The protective effects of Citrus reticulata extract and its two nano formulas against NASH induced by a high-fat, high-sucrose (HFS) diet in mice were evaluated. The NASH mice showed hepatic steatosis, inflammation, reduced liver function, increased body, liver, and fat weights, elevated hepatic index, and disrupted serum lipid profiles. Additionally, the mice displayed heightened hepatic oxidative stress and increased expression of inflammatory and profibrotic markers, along with altered lipid metabolism, indicated by elevated levels of SIRT-1, FGF-21, and SREBP-1c. Notably, treatment with Citrus reticulata extract and its metallic nanoparticle formulations alleviated these abnormalities, with the most significant improvement observed in the MgO NP formulation. Finally, Citrus reticulata extract was subjected to a deep phytochemical screening through Liquid chromatography combined with mass spectrometry (LC–MS/MS) analysis, revealing the presence of a high diversity of polyphenolics that may contribute to the suggested therapeutic effects of the Citrus reticulata crude extract. A molecular docking study highlighted the binding affinities of all identified flavonoid compounds, especially Quercetin, toward IL-1β, TNF-α, and TGF-β target proteins. This shows good translation for the cumulative anti-inflammatory effect depicted by the Citrus reticulata crude extract. Thermodynamic stability of Quercetin toward each bound proinflammatory protein was confirmed through 150 ns all-atom molecular dynamics simulations. Overall, current findings suggest that Citrus reticulata exerts a protective effect against NASH, which could be enhanced by nano formulas.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".