# Piceatannol enhances antioxidant capacity and growth in weaned piglets by regulating of Nrf2-mediated redox homeostasis and modulating of the related gut microbiota

## TL;DR

Piceatannol, a natural compound, improves growth and antioxidant capacity in weaned piglets by regulating redox balance and gut microbiota.

## Contribution

This study demonstrates that piceatannol enhances piglet growth and antioxidant defenses through Nrf2 pathway activation and microbiota modulation.

## Key findings

- Piceatannol at 200 mg/kg improved growth performance and antioxidant capacity in piglets.
- Piceatannol modulated gut microbiota, increasing beneficial genera like Blautia and Faecalibacterium.
- Piceatannol protected intestinal cells from oxidative damage via Nrf2 pathway activation and inhibition of apoptosis.

## Abstract

Piglets are highly susceptible to oxidative stress, which can reduce growth performance and cause intestinal damage. Piceatannol (PIC), a natural bioactive substance enriched in Chinese rhubarb (Rheum officinale) and certain dark purple fruits, shows excellent antioxidant properties in our previous cell-based high-throughput screening. However, its effect on piglet growth performance and antioxidant capacity as well as underling mechanism has not been thoroughly investigated.

One hundred weaned pigs (28 days of age, 8.71 ± 0.20 kg) were randomly assigned to 4 treatments with 5 replicates of 5 pigs per replicate. The experimental diets consisted of: 1) basal diet, 2) basal diet + 100 mg/kg PIC, 3) basal diet + 200 mg/kg PIC, and 4) basal diet + 300 mg/kg PIC. On d 15 and 35, one pig from each replicate was selected for sampling. The growth performance was monitored during a 35-day trial. In addition, H2O2-challenged IPEC-J2 cells served as an in vitro model to investigate the antioxidant mechanisms of PIC. IPEC-J2 cells were treated with 1,000 μmol/L H2O2 in the presence or absence of 10 μmol/L PIC.

Dietary PIC at 200 mg/kg significantly enhanced growth performance, as evidenced by increased average daily gain and feed conversion rate (P < 0.05). PIC supplementation markedly improved systemic antioxidant capacity, with elevated serum total antioxidant capacity, catalase activity, and glutathione levels, along with reduced malondialdehyde content (P < 0.05). Notably, PIC modulated the gut microbiota composition, increasing the amounts of beneficial genera (e.g., Blautia and Faecalibacterium), and these microbial shifts significantly correlated with improved antioxidant indices. In vitro, PIC pretreatment effectively protected IPEC-J2 cells against H2O2-induced oxidative damage by reducing reactive oxygen species generation and lipid peroxidation (P < 0.01). Mechanistically, PIC exerts its antioxidant effects through Nrf2 pathway activation, upregulating endogenous antioxidant enzymes (P < 0.05) while simultaneously inhibiting apoptosis via the regulation of the Bcl-2/Bax ratio and caspase-3 cleavage (P < 0.01).

PIC improved the growth performance and health status of weaned piglets through the regulation of Nrf2-mediated redox homeostasis and modulation of the related gut microbiota, offering a potential new natural antioxidants for mitigating weaning stress in piglets.

The online version contains supplementary material available at 10.1186/s40104-025-01320-8.