Human infants or piglets are vulnerable to intestinal microbe-caused disorders and inflammation due to their rapidly changing gut microbiota and immaturity of their immune systems at weaning. Resveratrol and curcumin have significant anti-inflammatory, bacteria-regulating and immune-promoting effects. The purpose of this study was to investigate whether dietary supplementation with resveratrol and curcumin can change the intestinal microbiota and alleviate intestinal inflammation induced by weaning in piglets. One hundred eighty piglets weaned at 21 ± 2 d were fed a control diet (CON group) or supplemented diet (300 mg/kg of antibiotics, ANT group; 300 mg/kg of resveratrol and curcumin, respectively, HRC group; 100 mg/kg of resveratrol and curcumin, respectively, LRC group; 300 mg/kg of resveratrol, RES group; 300 mg/kg of curcumin, CUR group) for 28 days. The results showed that compared with the CON group, curcumin alone and antibiotics decreased the copy numbers of Escherichia coli. Both curcumin and resveratrol down-regulated the level of Toll-like-receptor 4 mRNA and protein expression in the intestine to inhibit the release of critical inflammation molecules (interleukin-1β, tumor necrosis factor-α), and increase the secretion of immunoglobulin. Our results suggested that curcumin and resveratrol can regulate weaned piglet gut microbiota, down-regulate the TLR4 signaling pathway, alleviate intestinal inflammation, and ultimately increase intestinal immune function.

N⁶-Methyladenosine (m⁶A) is the most prevalent modification on eukaryotic messenger RNA (mRNA). Resveratrol and curcumin, which can exert many health-protective effects, may have a relationship with m⁶A RNA methylation. We hypothesized that the combination of resveratrol and curcumin could affect growth performance, intestinal mucosal integrity, m⁶A RNA methylation, and gene expression in weaning piglets. One hundred and eighty piglets weaned at 28 ± 2 days were fed a control diet or supplementary diets (300 mg/kg of antibiotics; 300 mg/kg of each resveratrol and curcumin; 100 mg/kg of each resveratrol and curcumin; 300 mg/kg of resveratrol; 300 mg/kg of curcumin) for 28 days. The results showed that the combination of resveratrol and curcumin improved growth performance and enhanced intestinal mucosal integrity and functions in weaning piglets. Resveratrol and curcumin also increased intestinal antioxidative capacity and mRNA expression of tight junction proteins. Furthermore, resveratrol and curcumin decreased the content of m⁶A and decreased the enrichment of m⁶A on the transcripts of tight junction proteins and on heme oxygenase-1 in the intestine. Our findings indicated that the combination of resveratrol and curcumin increased growth performance, enhanced intestine function, and protected piglet health, which may be associated with changes in m⁶A methylation and gene expression, suggesting that curcumin and resveratrol may be a potential natural alternative to antibiotics.

Aflatoxin B₁ (AFB₁) is one of the most dangerous mycotoxins in both humans and animals. Regulation of resveratrol is essential for the inhibition of AFB₁-induced oxidative stress and liver injury. Whether N⁶-methyladenosine (m⁶A) mRNA methylation participates in the crosstalk between resveratrol and AFB₁ is unclear. The objective of this study was to investigate the effects of AFB₁ and resveratrol in m⁶A RNA methylation and their crosstalk in the regulation of hepatic function in mice. Thirty-two C57BL/6J male mice were randomly assigned to a CON (basal diet), RES (basal diet + 500 mg/kg resveratrol), AFB₁ (basal diet + 600 μg/kg aflatoxin B₁), and ARE (basal diet + 500 mg/kg resveratrol and 600 μg/kg aflatoxin B₁) group for 4 weeks of feeding (n = 8/group). Briefly, redox status, apoptosis, and m⁶A modification in the liver were assessed. Compared to the CON group, the AFB₁ group showed increased activities of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT), prevalent vacuolization and cell edema, abnormal redox status, imbalance apoptosis, and especially, the higher expression of cleaved-caspase-3 protein. On the contrary, resveratrol ameliorated adverse hepatic function, via increasing hepatic antioxidative capacity and inhibiting the expression of cleaved-caspase-3 protein. Importantly, we noted that reactive oxygen species (ROS) content could be responsible for the alterations of m⁶A modification. Compared to the CON group, the AFB₁ group elevated the ROS accumulation, which led to the augment in m⁶A modification, whereas dietary resveratrol supplementation decreased ROS, followed by the reduction of m⁶A levels. In conclusion, our findings indicated that resveratrol decreased AFB₁-induced ROS accumulation, consequently contributing to the alterations of m⁶A modification, and eventually impacting on the hepatic function.

Curcumin has improved effects on antioxidant capacity via multiple mechanisms. Intrauterine growth retardation (IUGR) has had adverse influences on human health. IUGR is always associated with elevated oxidative stress and deficiencies in antioxidant defense. Therefore, we chose IUGR piglets as a model to investigate the effects of IUGR on antioxidant capacity of newborn and weaned piglets and determine how these alterations were regulated after supplementation with curcumin in weaned IUGR piglets. In experiment 1, eight normal-birth-weight (NBW) and eight IUGR newborn piglets were selected to determine the effect of IUGR on the antioxidant capacity of neonatal piglets. In experiment 2, thirty-two weaned piglets from four experimental groups: NBW, NC (curcumin supplementation), IUGR, IC (curcumin supplementation) were selected. The results showed that both IUGR newborn and weaned piglets exhibited oxidative damage and lower antioxidant enzymes activities in the liver compared with the NBW piglets. Dietary curcumin supplementation increased body-weight gain, feed intake, activities of antioxidant enzymes, and the expressions of nuclear factor, erythroid 2-like 2 (Nrf2) and heme oxygenase-1 (Hmox1) proteins in the liver of weaned piglets with IUGR. In conclusion, IUGR decreased the antioxidant capacity of newborn and weaned piglets. Curcumin could efficiently improve the growth, increase hepatic antioxidant capacity, and upregulate Nrf2 and Hmox1 levels in the liver of IUGR weaned piglets.

The purpose of this study was to explore the effects of curcumin on IUGR jejunum damage. A total of 24 IUGR and 12 normal-birth weight (NBW) female crossbred (Duroc × Landrace × Large White) piglets were randomly assigned into three groups at weaning (26 days): IUGR group, NBW group, and IUGR + CUR group, which were fed diets containing 0 mg/kg (NBW), 0 mg/kg (IUGR) and 200 mg/kg (IUGR + CUR) curcumin from 26 to 115 days of age. Results showed that dietary supplementation with 200 mg/kg curcumin significantly increased the total superoxide dismutase (T-SOD) activity and decreased the malondialdehyde (MDA) content in the jejunum of IUGR pigs (p < 0.05). Results of real-time PCR showed that the IUGR + CUR group significantly increased the gene expression of NF-E2-related factor 2 (Nrf2) (p < 0.05), and increased the glutamate-cysteine ligase catalytic subunit (GCLC), superoxide dismutase 1 (SOD1), glutamate-cysteine ligase modifier subunit (GCLM), and NAD(P)H quinone dehydrogenase 1 (NQO1) mRNA expression compared with the IUGR group (p < 0.05). Western blot results showed that dietary supplementation with 200 mg/kg curcumin significantly increased the protein levels of Nrf2 and NQO1. Compared with the IUGR group, pigs in IUGR + CUR group showed significantly decreased the levels of tumor necrosis factor-α (TNFα), interleukin-6 (IL-6), and interferon gamma (IFNγ) (p < 0.05), and increased the interleukin-2 (IL-2) level (p < 0.05). Dietary supplementation with 200 mg/kg curcumin significantly reduced cysteinyl aspartate specific proteinase 3 (caspase3), BCL2-associated X protein (bax), B-cellCLL/lymphoma 2 (bcl2), and heat-shock protein 70 (hsp70) mRNA expression, and increased occludin (ocln) mRNA expression (p < 0.05). In conclusion, dietary supplementation with 200 mg/kg curcumin can alleviate jejunum damage in IUGR growing pigs, through Nrf2/Keap1 pathway.