Effects of ellagic acid supplementation to peripartum diets on physiological metabolism and kidding performance of female goats

【Objective】 This study aimed to investigate the effects of ellagic acid （EA） supplementation to peripartum diets on physiological metabolism and kidding performance of female goats， and to clarify the regulatory role of EA in negative energy balance （NEB） of peripartum female goats， providing theoretical basis for applying EA as a novel feed additive in precise nutritional regulation and management of peripartum female goats. 【Method】 A total of 36 healthy pregnant female Guizhou black goats at 122 d of gestation were randomly divided into different groups：control group （CON， fed basal diet）， low-dose EA group （LEA， basal diet + 70 mg/kg EA）， medium-dose EA group （MEA， basal diet + 140 mg/kg EA）， and high-dose EA group （HEA， basal diet + 210 mg/kg EA）. After parturition， the litter size， live kid number， weak kid number， and aborted kid number of female goats in each group were recorded， as well as birth weight， height at withers， body length， chest circumference， and cannon bone circumference of kids. Blood samples were collected at the 21^st d prepartum （d_-21）， day of parturition （d₀）， and the 21^st d postpartum （d₂₁） for the determination of blood physiological biochemical parameters， serum antioxidant indicators， and immune indicators； meanwhile， network pharmacology was used to analyze the action targets of urolithin A （UA）， a metabolite of ellagic acid. 【Result】 There were no significant differences in abortion rate， kidding rate， and kid survival rate between treatment groups （P>0.05， the same below）， however， the weak kid rate of the three EA supplementation groups was significantly lower than that of the CON group （P<0.05， the same below）. EA supplementation to peripartum diets effectively increased kid birth weight， weaning weight， and average daily gain （ADG）， with the HEA group showing the highest ADG， which was significantly higher than the CON and LEA groups. EA supplementation significantly affected serum glucose （GLU）， non-esterified fatty acid （NEFA）， and total protein （TP） contents of female goats， but had no significant effect on albumin （ALB）， triglyceride （TG）， and total cholesterol （TC） contents. Meanwhile， EA supplementation effectively enhanced total antioxidant capacity （T-AOC） level and superoxide dismutase （SOD） activity， but the contents of malondialdehyde （MDA） and reactive oxygen species （ROS） decreased significantly with the increase of EA dosage. The levels of interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， and interleukin-1β （IL-1β） in serum of female goats gradually declined with increasing EA dosage， while the levels of immunoglobulin M （IgM）， immunoglobulin G （IgG）， and immunoglobulin A （IgA） gradually increased with increasing EA dosage. Based on network pharmacology， the potential mechanism of UA in alleviating NEB was investigated， with 184 potential targets for UA alleviating NEB； according to comprehensive core target network analysis and KEGG signaling pathway enrichment analysis， 5 core targets （EGFR， HRAS， AKT1， IGF1R， RAF1） for UA alleviating NEB were screened out， among which the core target AKT1 had the lowest binding energy with UA （-6.67 kcal/mol）. 【Conclusion】 After being converted into UA by intestinal microorganisms in goats， EA can regulate energy metabolism and antioxidant stress via the AKT1 target， thereby effectively alleviating NEB in peripartum female goats and indirectly promoting the growth and development of kids. In practical production， the optimal EA dosage in the diet of peripartum does is 210 mg/kg.