The Compound Terminalia Chebula Extract Alleviates PEDV-Induced Colonic Injury in Suckling Piglets by Enhancing...

The protective effect of Compound terminalia chebula extract (HL) against colonic injury induced by Porcine epidemic diarrhea virus (PEDV) infection in neonatal piglets remains unclear. This study aimed to evaluate the mitigating effects of HL on PEDV-induced colonic injury and elucidate the underlying mechanisms. Eighteen 7-day-old Duroc × Landrace × Large White piglets (2.58 ± 0.05 kg) were randomly assigned to three groups (n = 6/group): CON (blank control), PEDV (infected), and HL + PEDV (HL-supplemented + infected). The 11-day trial included 3 days of acclimatization (days 0-3) and an 8-day experimental period (days 4-11). HL (10 mg/kg BW) was orally administered daily to the HL + PEDV group. On day 8, PEDV and HL + PEDV groups were challenged with 3 mL PEDV (3 × 10⁶ TCID₅₀/mL), while CON received Dulbecco's Modified Eagle Medium (DMEM). All piglets were euthanized on day 11 for colonic tissue collection. Results indicated that PEDV infection induced colonic injury, manifested by a significant increase in crypt depth and disruption of intestinal homeostasis. This was evidenced by impaired barrier integrity (upregulation of matrix metalloproteinase-7 gene [MMP7] and matrix metalloproteinase 13 gene [MMP13], mucus disorganization (elevation of mucin 5AC gene [MUC5AC]), oxidative stress (reduced catalase [CAT] activity and increased malondialdehyde [MDA] levels in serum and colon), and inflammation (upregulation of regenerative islet-derived protein 3γ gene [REG3G], S100 calcium-binding protein A8/A9 gene [S100A8/A9], and interleukin-1β gene [IL-1β]). Additionally, PEDV impaired colonic ion transport by downregulating calcium channel genes (Transient Receptor Potential Cation Channel Subfamily V Member 6 gene [TRPV6], Transient Receptor Potential Cation Channel Subfamily M Member 6 gene [TRPM6]). Notably, HL supplementation effectively reversed these adverse effects. HL restored colonic morphology, increased CAT activity, reduced MDA accumulation, and suppressed inflammatory gene expression. Furthermore, HL modulated the expression of genes involved in water and ion transport upregulating Aquaporin 7 gene (AQP7), Chloride Channel Accessory 4 gene (CLCA4), Sodium-Hydrogen Exchanger 3 gene (NHE3), Transient Receptor Potential Vanilloid 6 (TRPV6), and Transient Receptor Potential Melastatin 6 gene (TRPM6) and significantly inhibited PEDV replication, as indicated by the downregulation of the transcription levels of PEDV membranegene (M), nucleocapsid gene (N), and spike gene (S). Taken together, HL alleviates PEDV-triggered colonic tissue damage in suckling piglets via improving colonic antioxidant capacity, mitigating inflammatory response, partially regulating intestinal barrier and ion/water transport-related genes, and downregulating the transcription of PEDV structural genes at molecular and histological levels.