# Natural Product-Induced Modulation of Androstenone Metabolism in Porcine Hepatocytes

## TL;DR

This study explores how natural compounds from garlic and guggul plant can help reduce boar taint in pigs by affecting liver metabolism.

## Contribution

The study identifies diallyl sulfide and (Z)-guggulsterone as potential natural treatments for boar taint based on their effect on androstenone metabolism in boar liver cells.

## Key findings

- Diallyl sulfide and (Z)-guggulsterone increased androstenone breakdown in some boar liver cells.
- UGT1A6 was upregulated by PXR and CAR agonists and downregulated by FXR agonists.
- Positive responders had lower basal expression of UGT2B31 and higher expression of FXR and PXR compared to non-responders.

## Abstract

Natural product-derived compounds have been increasingly studied for their potential to treat metabolic diseases. They may also be effective treatments for boar taint, a metabolic issue in intact male pigs (boars), which negatively impacts pork quality. Using cells isolated from boar livers, we found that diallyl sulfide (from garlic) and (Z)-guggulsterone (from the guggul plant) increased the breakdown of androstenone, the primary compound responsible for boar taint. However, these treatments were only effective in a subset of animals. Future feeding trials are warranted to evaluate the efficacy of these natural products as dietary interventions for boar taint and to identify markers that can distinguish animals likely to respond to treatment from those that will not.

The nuclear receptors pregnane X receptor (PXR), constitutive androstane receptor (CAR), and farnesoid X receptor (FXR) regulate the hepatic metabolism of androstenone, a testicular steroid that accumulates in the fat of intact male pigs and causes boar taint. This study evaluated natural product-derived compounds and conventional agonists targeting these nuclear receptors for their effects on androstenone metabolism in primary hepatocytes from slaughter-weight boars, to assess their potential as treatments for boar taint. Cells were incubated with natural products, conventional agonists, or dimethyl sulfoxide (DMSO; control), then being treated with androstenone. Culture media and cells were analyzed to assess changes in androstenone metabolism and gene expression. UGT1A6 was upregulated by treatments targeting both PXR and CAR and downregulated by FXR agonists. Additionally, PGC1α and NR2F1 were downregulated by compounds targeting PXR/CAR, while FXR and NR0B2 were upregulated and HNF4α downregulated by treatments acting on FXR. The natural products diallyl sulfide (DAS) and (Z)-guggulsterone (GUG) increased overall androstenone metabolism (DAS, GUG) and the production of Phase I androstenol metabolites (DAS), but only in hepatocyte culture replicates that responded positively to these treatments. Although gene expression was similar between positive-response and negative/non-responsive replicates following treatments, negative/non-responsive replicates for several treatments had higher basal expression of UGT2B31, UGT2A1, and SIRT1 and lower basal expression of FXR, PXR, and NR0B1 compared to positive-response replicates. These findings suggest that DAS and GUG may be promising treatments for boar taint, specifically in animals with lower basal rates of androstenone metabolism and higher expression of key nuclear receptors.