Puerarin as a Phytochemical Modulator of Gastrointestinal Homeostasis in Livestock: Molecular Mechanisms and Translational Applications

Abstract

The gut serves as the main site for nutrient digestion and absorption. Simultaneously, it functions as the body's largest immune organ, playing a dual role in sustaining physiological equilibrium and offering immunological defense against intestinal ailments. Maintaining the structural and functional integrity of the intestine is paramount for ensuring animal health and productivity. Puerarin, a naturally derived isoflavonoid from the Pueraria species, exhibits multifaceted bioactivities, such as antioxidant, anti-inflammatory, antimicrobial, and immunomodulatory properties. Emerging evidence highlights puerarin's capacity to enhance gut health in farm animals through four pivotal mechanisms: (1) optimization of intestinal morphology via crypt-villus architecture remodeling, (2) augmentation of systemic and mucosal antioxidant defenses through Nrf2/ARE pathway activation, and (3) reinforcement of intestinal barrier function by regulating tight junction proteins (e.g., ZO-1, occludin), mucin secretion, intestinal mucosal immune barrier, the composition of microbiota, and the derived beneficial metabolites; (4) regulating the function of the intestinal nervous system via reshaping the distribution of intestinal neurons and neurotransmitter secretion function. This review synthesizes current knowledge on puerarin's protective effects on intestinal physiology in farm animals, systematically elucidates its underlying molecular targets (including TLR4/NF-κB, MAPK, and PI3K/Akt signaling pathways), and critically evaluates its translational potential in mitigating enteric disorders such as post-weaning diarrhea and inflammatory bowel disease in agricultural practices.

Keywords: intestinal barrier function; intestinal health; livestock and poultry production; puerarin.

Figure 1

Chemical structure of puerarin.

Figure 2

The absorption of puerarin and its metabolic pathways in the intestine and liver tissues. UGTs, UDP-glucuronosyltransferases; CYP450s, cytochrome P450s.

Figure 3

A working model of puerarin protecting against oxidative stress in the intestinal tissues. GSSG, oxidized glutathione; SOD, superoxide dismutase; SOD, superoxide dismutase; ROS, reactive oxygen species; H₂O₂, hydrogen peroxide; •OH, hydroxyl radical; O₂^•−, superoxide anion; O₂^•−, superoxide anion; Nrf2, nuclear factor erythroid 2-related factor 2; NQO1, NAD (P)H quinone oxidoreductase 1; NQO1, NAD (P)H quinone oxidoreductase 1; HO-1, heme oxygenase 1; GSH, glutathione; CAT, catalase; ETC, electron transport chain; ARE, antioxidant response element.

Figure 4

(A), intestinal barrier structure. (B), a working model of puerarin in maintaining the intestinal barrier function in the intestinal tissues. Puerarin supplementation can integrate and regulate the microbiological barrier (e.g., increase the levels of Akkermansia muciniphila and Lactobacillus, and decrease the levels of Bacteroidete), chemical barrier (e.g., increase the levels of short-chain fatty acids, indole-3-propionic acid, and secreted MUC2), physical barrier (improve the tight junctions in intestinal epithelial cells via upregulating the expression of zonula occluden-1, occludin, and claudin-1 proteins), and immunological barrier (e.g., increase the number of goblet cells and the levels of sIgA, and reduce the inflammatory response), and synergistically maintain the intestinal barrier function.