128 The Effect of natural product treatments on the hepatic metabolism of androstenone in boars.
Bibliographic record
Abstract
Abstract The pregnane X receptor (PXR), constitutive androstane receptor (CAR), and farnesoid X receptor (FXR) are ligand-activated nuclear receptors that modulate the hepatic metabolism of endogenous compounds, including androstenone, a testicular steroid produced by intact male pigs. Inefficient metabolism of androstenone contributes to its accumulation in adipose tissue, which promotes the development of boar taint, a meat quality issue characterized by off-odours and off-flavours in some heated pork products. Natural products (NPs) found in plants and herbal medicines act as ligands for PXR, CAR, and FXR in humans and may increase the hepatic metabolism of androstenone in boars. Therefore, this study examined the effects of several NPs, including hyperforin (HYP; PXR agonist), diallyl sulfide (DAS; CAR agonist), oleanolic acid (OA; FXR modulator), ginkgolide A (GINK; PXR and CAR agonist), and (Z)-guggulsterone (GUG; PXR agonist, CAR inverse agonist, FXR antagonist) on androstenone metabolism in porcine hepatocytes. Hepatocytes were isolated from the livers of 5-month-old crossbred [(Yorkshire x Landrace) x Duroc] boars (n=8) and incubated for 24 hours with NP treatments or dimethyl sulfoxide (DMSO) as a control. Cells were then treated with androstenone for 3 hours, after which culture media was collected for high-performance liquid chromatography analysis of androstenone metabolism and metabolite production. Hepatocytes were also harvested to assess gene expression via RT-qPCR. Statistical analysis was performed using a one-way ANOVA in SAS, with a significance threshold of p ≤ 0.05, and the Benjamini-Hochberg correction was applied to control for multiple comparisons. Relative to the DMSO control, NP treatments significantly altered the expression of key genes involved in hepatic androstenone metabolism. UGT1A6 was upregulated by GINK (p=0.05) and GUG (p=0.04) and downregulated by OA (p=0.004), while FXR expression increased with OA (p=0.02). NR2F1 was downregulated by DAS (p=0.03), GINK (p=0.03), and GUG (p=0.02), HNF4A by OA (p=0.008), and PGC1α by DAS (p=0.03) and GUG (p=0.05). NP treatments had minimal effects on overall androstenone metabolism relative to DMSO; however, treatment responses varied among individual boars. Relative to DMSO, DAS increased overall androstenone metabolism in 75% of boars, GINK, GUG, and HYP in 63%, and OA in 50%. Among positive responders, overall androstenone metabolism was significantly increased by DAS (p=0.04) and GUG (p=0.05). Additionally, DAS increased the production of Phase I androstenol metabolites (p=0.0008). These results suggest that DAS and GUG may be promising dietary treatments for boar taint but highlight the need to assess treatment responses on an individual basis. Future research should include in vivo feeding trials to evaluate the efficacy of these NPs and identify biomarkers associated with positive treatment outcomes to allow for their targeted and effective application to reduce boar taint.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".