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Journal of Animal Science logoLink to Journal of Animal Science
. 2021 Nov 26;99(12):skab354. doi: 10.1093/jas/skab354

Micelle silymarin supplementation to sows’ diet from day 109 of gestation to entire lactation period enhances reproductive performance and affects serum hormones and metabolites

Qianqian Zhang 1, Je Min Ahn 1, In Ho Kim 1,
PMCID: PMC8682956  PMID: 34850001

Abstract

The aim of the present study was to explore the influences of varying doses of micelle silymarin (0%, 0.05%, 0.1%, and 0.2%) supplementation on sows’ feed intake, milk yields, serum hormones, and litter growth using 40 multiparous sows (Landrace × Yorkshire, parity from 3 to 5) from the 109th prenatal day to the 21st postnatal day. Each treatment included 10 sows and each sow was used as an experimental unit. On weaning day, litter weight and litter weight gain were linearly improved (P < 0.01, both), corresponding to the increasing dose of silymarin micelle in the diet. Also, litter weight, litter weight gain, and average daily gain (ADG) of piglets born to treated sows exceeded (P < 0.05) those of offspring from the control sows (0% micelle silymarin). Feed intake in week 1, week 2, and the entire lactation period was increased (linear, P < 0.01) as micelle silymarin dose increased. Body weight (BW) loss of sows during lactation was linearly reduced (P = 0.003) with the increasing amounts of micelle silymarin. Average daily milk yields during lactation were also linearly increased (P = 0.002) in treated sows, exceeding (P = 0.046) that of control sows. Also, uniform increases were observed (P = 0.037) in fat content in milk produced by treated sows on day 14 of lactation. Epinephrine concentrations and aspartate aminotransferase (AST) activity in sow serum on day 21 postpartum were linearly declined (P = 0.010) as micelle silymarin dose increased, and were both declined (P < 0.05) in treated sows compared with the control. In addition, treated sows’ serum had higher activity of superoxide dismutase (SOD) at parturition and glutathione peroxidase (GSH-Px), lower oxidized glutathione (GSSG) concentrations, and GSSG/GSH (glutathione) ratio (all, P < 0.01) on day 21 of lactation. Moreover, offspring from micelle silymarin-treated sows tended to (0.05 < P <0.1) have higher serum catalase (CAT) activity and total antioxidant capacity (T-AOC) concentrations. Taken together, the results showed that sows fed increasing levels of micelle silymarin from the 109th prenatal day to the 21st postnatal day had an incremental dose-dependent effect on higher feed intake, diminished BW loss, greater milk yields, and greater litter weight at weaning, and 0.2% of micelle silymarin could be optimal to achieve the better effect.

Keywords: feed intake, litter weight, micelle silymarin, milk yields, serum metabolite, sow

Introduction

Along with the escalation of litter sizes pushed by artificial breeding technology, the greater demand for milk yields contradicts sows’ low appetite during the early postpartum period (Wheeler and Walters, 2001). Inadequate milk generation directly constrains the optimal growth of neonatal piglets and impacts mortality rates of underweight piglets (Quesnel et al., 2007). More body weight (BW) loss in nursing sows converting maternal fat to produce milk (Lundgren et al., 2014), prolongs the estrus-wean interval and decreases the rates of both pregnancy and embryo survival (Koketsu 1996a; Koketsu 1996b). Consequently, lactating nutrient intake becomes a critical factor concerning neonatal piglet growth and individual BW loss (Eissen et al., 2003). However, the lactation yield is influenced, in part, by prolactin (Capasso et al., 2009; Farmer et al., 2016). Moreover, the greater oxidant stress during farrowing produces an excess of free radicals and cortisol, which exacerbates inflammation (Kaiser et al., 2018). Therefore, to improve the production efficiency of sows, it is necessary to reduce stress at farrowing and improve feeding behavior during lactation.

Silymarin extracted from milk thistle fruit is mainly comprised of silybin (the most active ingredient), silydianin, and silychristin, which are all-natural flavonoid lignan compounds (Kaur et al., 2011). However, normal silymarin has poor water-solubility property resulting in low biological activity in bodies. Historically, silymarin has, for more than 2000 years, been known for protecting the liver and curing cap mushroom poisoning (Wellington & Jarvis, 2001; Gazak et al., 2007). Compelling evidence corroborates the functions of silymarin, which involves not only anti-oxidation (Surai, 2015; Wang et al., 2019b) and anti-inflammation (Nazemian et al., 2010) but also the promotion of liver tissue regeneration and the easing of liver toxicity in animals and humans (Radko and Cybulski, 2007; Gillessen and Schmidt, 2020). In mammalian experiments, it had been provided that breastfeeding women who took oral silymarin increased the quantities of milk (Pierro et al., 2008; Zecca et al., 2016). Furthermore, the secretagogue effect of silymarin for prolactin concentrations in rats and sows during late gestation was reported (Loisel et al., 2013; Mohammed et al., 2014; Farmer et al., 2014). However, when 12 g per day of silymarin was provided to sows from the 107th prenatal day until the farrowing day, neither prolactin concentrations, hepatic status, nor piglet growth was affected (Loisel et al., 2013). Meanwhile, sows whose diet was supplemented with 40 g/d of silymarin supplemented from the 108th prenatal day to the 20th postnatal day displayed augmented feed intake, milk yields, and weaning litter weight (Jiang et al., 2020). However, the dietary supplementation of 1 g/d and 8 g/d of silymarin to suckling sows, neither impacted feed intake, backfat (BF) thickness, nor piglet growth (Farmer et al., 2017). Importantly, when coated in a hydrophobic substance by a polymer prevents, micelle silymarin is prevented from being decomposed in the oral cavity, therefore its solubilization capacity has been improved a lot (Javed et al., 2011). Until now, the effects of absorbable micelle silymarin have not been verified in sow nutrition even though the coated silymarin has been proven to be better absorbed into cells in vitro and mice intestines in vivo (Sui et al., 2010; Shangguan et al., 2015; Kesharwani et al., 2020). Taking the better absorption mechanics of micelle silymarin into account, this study purposed to identify the appropriate dosage of micelle silymarin on perinatal and lactating sows. Accordingly, this experiment was designed with varying doses of coated micelle silymarin (0%, 0.05%, 0.1%, and 0.2%) from day 109 of gestation until the entire lactation period to explore their effects on sow feed intake, serum hormone levels, milk index, and litter performance.

Materials and Methods

The experiment was conducted at the swine experimental unit of Dankook University (Cheonan, Republic of South Korea). Procedures implemented on animals and sampling collection complied with the regulations set by the Animal Care and Use Committee of Dankook University. The micelle silymarin purchased from Synergen Company (Gyeonggi-do, South Korea) is composed of 10.8% silybin, 16.3% silydianin, and 7.0% silychristin, and coated by chitosan, with an effective content of 250 g/kg.

Experimental design, diets, and management

Forty multiparous sows (Landrace × Yorkshire, parity 3–5, with estrus synchronization) and body condition scores (BCS, 2~3) were chosen as test subjects. They were artificially inseminated twice (after 12 and 24 h) with semen from Landrace boars to achieve estrus synchronization. During pregnancy, feeding rations (16.73% CP, 14.18 MJ/kg digestible energy, and 0.79% lysine) were given and met the nutritional recommendation value of NRC (2012). All sows were housed in a limit bar (2.0 m × 0.8 m) with the half-slatted floor in the gestation room and supplemented with 2.6 kg of feed (at 0900 and 1400 h) daily. On day 108 of gestation, all sows were transferred to the farrowing room (2.0 × 0.8 m) with a fully slatted floor, and the measurements of BF thickness and BW were performed. Subsequently, under average BF thickness of 18.80 mm (SD 1.21), parity of 3.95(SD 0.77), and BW of 219.20 kg (SD17.95), 40 sows were randomly allotted to four treatments. Each treatment included 10 sows, and the individual sow was regarded as an experimental unit. Table 1 shows the specific parity information for each treatment. From the 109th day of gestation, sows were provided with lactating diet that met the NRC (2012) requirements (Table 2) until day 21 of lactation. The four treatments included a control group (basal diet without micelle silymarin) and three treatment groups which included the addition of varying doses (0.05%, 0.1%, and 0.2%) of micelle silymarin to the basal diet.

Table 1.

The number of sows’ parity in each treatment

Items Micelle silymarin (% of diet)
0 0.05 0.1 0.2
3rd parity 3 3 4 3
4th parity 5 4 4 3
5th parity 2 3 2 4
Total number 10 10 10 10

Table 2.

Ingredients and chemical composition of basal diet during lactation (as-fed basis)

Ingredients, % DM basis Lactation
Corn 56.53
Wheat 10.00
Soybean meal, 43% 20.00
Wheat bran 6.00
Fish meal, 67% CP 2.00
Soybean oil 1.00
CaHPO4 1.30
Limestone 1.20
Salt 0.40
Choline chloride, 50% 0.15
l-Lysine HCl, 78.5% 0.28
l-Threonine, 98.5% 0.12
dl-Methionine, 99.8% 0.02
Vitamin–mineral premix1 1.00
Total 100.00
Chemical composition2 (%)
 Digestible energy (Mcal/kg) 3284
 Crude protein 17.37
 Crude fat 9.99
 Crude ash 4.28
 Crude fiber 3.14
 Total lysine 1.09
 Calcium 0.98
Total phosphorus 0.68
Available phosphorus 0.37

1Vitamin–mineral premix provided the following per kilogram of basal diet: vitamin A, 12,000 IU; vitamin D3, 2,800 IU; vitamin E, 100 mg; vitamin K 3.5 mg; vitamin B1 3.5mg, vitamin B2 8.5 mg, d-biotin, 420 μg; folacin, 2.5 mg; niacin, 35 mg; d-pantothenic acid, 21 mg; vitamin B6, 3.5 mg; vitamin B12, 35 μg; copper, 10 mg; iodine, 0.21 mg; iron, 120 mg; manganese, 30 mg; selenium, 0.23 mg; zinc, 80 mg. The sources of the trace elements were CuSO4 ·5H2O, KI, FeSO4, MnSO4 ·H2O, Na2 SeO3, and ZnSO4, separately.

2 Calculated values.

At farrowing (the farrowing day was taken as the day 0 of lactation), the number of live piglets, stillborn piglets (deformed piglets were considered stillborn), and mummified fetuses were recorded, and the birth weights of the live piglets were measured individually. Considering the same number of total live piglets which occurred per treatment, no cross-fostering was involved. Piglets were scheduled to receive plastic ear tags and supplementary iron, as well as routine procedures for tail docking, tooth clipping, and castration on the third day of age. Piglets were kept in incubators set at 22–32 °C, with the temperature controlled by supplementary heating lamps. The feed (provided at 0830,1400, and 2000 h) was given from 1 kg at day 1 of lactation and gradually increased by 1.0 kg per day until day 6. After that sow could access freely to feed until day 21 of lactation. During lactation, feed consumption of individual sow was recorded daily. All animals could drink water ad libitum. Since suckling piglets were not offered creep feed, piglet weight gain was considered to be associated with dam’s milk yields. After weaning, the 40 sows were transferred to the gestation pen, and then the estrus interval was recorded. When the sow stood and respond to the backpressure test with the attendance of a boar, she was deemed to be in estrus. Estrus identification was done at 1000 and 1500 h daily, and the period from weaning to estrus was labeled as the wean-to-estrus interval.

Measurement

The measurement of BF thickness and BW of unfed sows was carried out on the 108th prenatal day, and the 1st and 21st postnatal days. The BF thickness was measured at the left side dorsal midline (distance 65 mm) of the 10th rib with ultrasound (Renco Lean-Meater, USA). On day 21 of lactation, the BW of individual piglets was weighed. During the postnatal period, the mortality of piglets was recorded daily. The fecal score referenced the 5-point system of Hu et al. (2021) was performed for individual sows across the last two weeks of gestation and the first three weeks of lactation.

The BCS evaluation was executed on day 108 of gestation, postnatal after 24 h, and again on day 21, using the 5-point principle of Knauer and Baitinger (2015) focusing on the hip and backbone of sow. The details of each score were as follows: 1= appears very thin; 2 = the palm feels firmness (of bone) without pressure; 3 = the palm can be depressed when touching; 4 = the hand cannot discern bone forms; and 5= obesity.

Sample collection

To assess the digestion and absorption of nutrients, a supplement of 2.5 g/kg chromic oxide (Duksan Techopia Co., Ltd. Cheonan, South Korea) was added to the sows’ diets during days 15 to 21of the lactation period. Fecal samples were gathered on days 19, 20, and 21 of this period (from eight sows per treatment) by stimulating the sow’s anal sphincter to induce defecation, and 10% dilute sulfuric acid and toluene (Duksan Techopia Co., Ltd. Cheonan, South Korea) were used to fix the manure. These three days’ feces were mixed in equal proportions and then refrigerated at −20 °C prior to analysis.

Blood samples (10 mL) were collected using K3EDTA evacuated tubes (3.0 ml; Greiner Bio-One, Kramsmenster, Austria) from the ear vein of 8 fasted sows per treatment on day 109 of gestation, farrowing day, and day 21 of lactation, and offspring blood (8 piglets randomly selected from per treatment) before suckling colostrum at farrowing and on postnatal 14th day. Serum from blood was obtained by centrifuging at 4 °C, 4,000 × g for 10 min and then kept at −20 °C.

Colostrum and milk samples were collected as detailed by Zhang et al. (2020). Collection of 20 mL colostrum from the front, middle, and back nipples (8 sows per treatment) was conducted from the birth of the first piglet at farrowing. Milk collection (20 mL) was induced by injecting 1 mL of oxytocin into the ear vein on day 14 of lactation. Cleaning nipples was carried out in advance using 0.1% potassium permanganate (Duksan Techopia Co., Ltd. Cheonan, South Korea). All samples were kept at the −20 °C freezer.

Assay of sow serum metabolites

The prevalence of marker enzymes, including aspartate aminotransferase (AST) and alanine aminotransferase (ALT) associated with liver health, was determined using commercial kits (Product NO: C0010-2-1and C009-2) and a microplate reader (SpectraMax190, MD) at wavelengths of 510 and 505 nm. The coefficient of variation (CV) ranged from 10% (intra-assay) to 15% (inter-assay). Concentrations of epinephrine and norepinephrine were measured using Porcine Epinephrine and Porcine Noradrenaline ELISA Kits with the assistance of a microplate reader. In these instances, the intra- and inter-assay CVs were under 10%, and under 12%, respectively. All kits were purchased from Nanjing Jiancheng Institute of Bioengineering (Nanjing, China), and duplicate measurements were obtained for all samples. Lastly, levels of glucose, urea nitrogen, and triglycerides were measured in parallel using automatic biochemical analysis instrumentation (Hitachi 7600, Japan).

Analysis of oxidant and antioxidant concentrations

The oxidant index of oxidized glutathione (GSSG), and antioxidant indices relating to glutathione (GSH), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) in sow serum were determined with reagent test kits in duplicate, and strictly in accordance with the product manual. Total antioxidant capacity (T-AOC) and malondialdehyde (MDA) reagent kits were used to assay the colostrum and milk. The antioxidant capacity of suckling piglets was evaluated by T-AOC, SOD, GSH-Px, MDA, and catalase (CAT) assay kits. All kits were purchased from Cell Biolabs, Inc. (San Diego, CA), and the CVs in intra-and inter-assay were under 10% and 12%, respectively, for all indices.

Cortisol, oxytocin, and prolactin assays in sow serum

Cortisol and prolactin concentrations in sow serum were monitored using the corresponding ELISA kit (Product NO. abx150311 and abx360863; Abbexa, Cambridge, UK). The CVs were consistently under 10% (for intra-) and 12% (inter-assay) for all indices. The sensitivity for evaluating cortisol, oxytocin, and prolactin was 5.15 ng/mL, 0.1 g/mL, and 0.07 ng/mL, respectively.

Assay for colostrum and milk composition

Thawed samples of colostrum and milk were analyzed using LactoScope FTIR automatic milk analyzer (Delta, Netherlands), with the intent of assessing the fat, protein, and lactose contents. The results were calculated as percentages of colostrum and milk. Evaluation of milk yields during lactation depended on the average daily gain (ADG) of individual piglets and the number of litters as per the following equation (Wang et al., 2011): milk yields = individual piglet ADG × number of litters × days of lactation × 4. From this, it concluded the average daily milk production of sows.

Determination of apparent total tract digestibility

Frozen of feedstuff and feces were thawed and weighted before being put into an electric oven (Daihan Scientific Co., Ltd, Seoul, South Korea) and heated to 72 °C for up to 60 h until a constant weight of product was obtained, and it was then ground through a 40-mesh screen. Parallel content determination was carried out for individual samples. Dry matter in feed and feces samples was assayed with method 930.15 (AOAC, 2000). Nitrogen levels were determined by using the principle of Method 920.40 (AOAC, 2000), with Kjeltec8400 instrumentation (FOSS, Denmark). For gross energy measurement, caloric content generated from the burning of feed and fecal was measured via a Parr 6400 calorimeter (Parr Instrument Co., Moline, IL). The concentrations of Cr2O3 were recorded according to the method reported by Lei and Kim (2014). The calculation of apparent total tract digestibility (ATTD) was carried out as follows: digestibility, (%) = [1−{(Nf×Cr2O3d) ∕ (Nd×Cr2O3f)}] ×100, where Nf and Nd represented nutrient concentration, and Cr2O3f and Cr2O3d represented chromium concentration, each in feces and diet, respectively. These values were all presented as percentages of the total dry matter.

Data analysis

In this study, none of the results taken from any of the sows were discarded because all litters contained more than seven piglets and there was no major medical issue, whereas the data collection abided by the fundamental of fixed variables whose results were completely random. The sow indices, litter weight, and diarrhea were treated in individual sows as discrete experimental units. Similarly, nursing piglet indices regarded an individual piglet as a unit.

All data were checked for homogeneity of its variances and with the Shapiro–Wilk test to inspect its normality. Analysis was performed using the statistical model of the mixed procedure (SAS 9.4 Institute Inc., Cary, NC): Yij = μ + Ti + eij, where Y is the analyzed variable, μ is the overall mean, Ti is the fixed effect of the ith treatment, and eij is the error term specific to the sow identified assigned to the ith treatment. The linear and quadratic trends in the effects caused by micelle silymarin, and the comparison between the control group and micelle silymarin groups were analyzed using an orthogonal polynomial comparison. A probability of P < 0.05 was viewed as significant while instances of 0.05 < P < 0.1 were not.

Results

Reproduction performance of sows

The sow reproduction indices are shown in Table 3, which shows the stillborn rate was linearly declined, while the incidence of live births was linearly increased (P = 0.021, 0.029, respectively), each with the increasing micelle silymarin levels in the diet.

Table 3.

Reproduction of sows1

Items Micelle silymarin (% of diet) CON vs. Micelle Silymarin P-value
0 0.05 0.1 0.2 Linear Quadratic
Total number born 12.33 ± 0.67 12.22 ± 0.67 12.77 ± 0.64 12.22 ± 0.40 0.916 0.975 0.627
No. of alive piglet 11.67 ± 0.65 11.11 ± 0.35 11.78 ± 0.62 11.78 ± 0.47 0.858 0.663 0.777
No. of stillbirths 1.11 ± 0.26 1.00 ± 0.24 0.67 ± 0.17 0.44 ± 0.18 0.108 0.021 0.803
Born alive rate, % 91.44 ± 0.02 91.78 ± 0.02 92.22 ± 0.01 96.22 ± 0.01 0.289 0.029 0.410
Litter weight alive at parturition, kg 16.44 ± 0.89 17.04 ± 1.01 16.91 ± 0.74 17.96 ± 0.55 0.366 0.209 0.887
Average weight of piglets born alive, kg 1.51 ± 0.03 1.52 ± 0.03 1.59 ± 0.05 1.54 ± 0.03 0.315 0.362 0.265

1Values are presented as means ± SE, n = 10.

The growth indices of the offspring are provided in Table 4, which shows the mortality rate of suckling piglets during lactation was diminished (P = 0.063) as micelle silymarin addition increased. Litter weight, litter weight gain, individual piglet weight, and piglet ADG at weaning were each linearly improved with the increment in dietary micelle silymarin (P < 0.01). Notably, these piglets were both heavier (P < 0.05) (by weight) and faster growing (by ADG) than the offspring of control sows.

Table 4.

Effect of sows’ intake of micelle silymarin from the 109th prenatal day to the 21st postnatal day on growth performance of suckling piglets1

Items Micelle silymarin (% of diet) CON vs. Micelle Silymarin P-value
0 0.05 0.1 0.2 Linear Quadratic
Litter size at weaning, n 11.11 ± 0.70 10.67 ± 0.33 11.22 ± 0.60 11.67 ± 0.41 0.904 0.311 0.580
Mortality rate during lactation, % 4.97 ± 1.61 3.87 ± 1.53 4.52 ± 1.93 0.79 ± 0.70 0.286 0.063 0.501
Litter weight at weaning, kg 65.27 ± 3.05 68.19 ± 2.77 71.22 ± 3.14 77.38 ± 2.28 0.040 0.003 0.970
Litter weight gain, kg 48.83 ± 2.21 51.15 ± 2.31 54.31 ± 2.70 59.42 ± 1.92 0.028 0.002 0.996
Individual piglet weight, kg 6.02 ± 0.10 6.32 ± 0.07 6.37 ± 0.10 6.66 ± 0.15 0.002 <0.001 0.538
ADG of piglet, g 214.56 ± 4.59 225.22 ± 4.38 231.33 ± 5.40 243.44 ± 6.44 0.004 <0.001 0.623

1Values are presented as means ± SE, n = 10.

Table 5 shows the basic conditions of prenatal and postnatal sows. There was a linear improvement in feed intake (P < 0.05) during week 1, week 2, and the overall lactation period. The BW loss was markedly declined (P= 0.003) in response to the increasing micelle silymarin, but was universally lower (P = 0.082) among treated sows than in control sows. However, the wean-to-estrus interval, BF thickness, diarrhea, and BCS were similar (P > 0.05) among all groups.

Table 5.

Effect of sows’ intake of micelle silymarin from the 109th prenatal day to the 21st postnatal day on feed intake, BF thickness, BW, wean-to-estrus interval, BCS, and diarrhea1

Items Micelle silymarin (% of diet) CON vs. Micelle Silymarin P-value
0 0.05 0.1 0.2 Linear Quadratic
Parity 3.9 ± 0.4 4.0 ± 0.3 3.8 ± 0.3 4.1 ± 0.2 0.830 0.661 0.675
Feed intake during week 1of lactation, kg 3.85 ± 0.03 3.82 ± 0.03 3.89 ± 0.03 3.93 ± 0.02 0.365 0.014 0.584
Feed intake during week 2 of lactation, kg 8.11 ± 0.03 8.07 ± 0.03 8.20 ± 0.04 8.28 ± 0.05 0.079 < 0.001 0.660
Feed intake during week 3 of lactation, kg 9.78 ± 0.12 9.76 ± 0.12 9.90 ± 0.13 9.80 ± 0.11 0.806 0.823 0.063
Feed intake during overall lactation, kg 7.24 ± 0.02 7.21 ± 0.01 7.32 ± 0.03 7.34 ± 0.03 0.092 0.001 0.919
BW on day 108 of gestation, kg 213.51 ± 8.54 223.96 ± 3.81 215.46 ± 7.18 223.84 ± 3.27 0.292 0.386 0.941
BW on day 1 of lactation, kg 194.37 ± 8.74 204.29 ± 3.38 196.36 ± 7.33 203.99 ± 3.45 0.324 0.429 0.924
BW on day 21 of lactation, kg 177.26 ± 8.36 186.84 ± 3.17 180.61 ± 7.33 188.22 ± 3.57 0.262 0.314 0.891
BW loss during lactation, kg 17.12 ± 0.44 17.44 ± 0.43 15.74 ± 0.30 15.77 ± 0.37 0.082 0.003 0.543
BF thickness on day 108 of gestation, mm 18.78 ± 0.49 19.01 ± 0.46 18.72 ± 0.32 18.68 ± 0.41 0.958 0.745 0.853
BF thickness on day 1 of lactation, mm 17.89 ± 0.52 18.26 ± 0.44 18.19 ± 0.28 18.37 ± 0.44 0.443 0.484 0.791
BF thickness on day 21 of lactation, mm 15.92 ± 0.56 16.11 ± 0.72 16.50 ± 0.58 16.50 ± 0.44 0.509 0.454 0.732
BF thickness loss during lactation, mm 5.00 ± 0.91 5.00 ± 0.91 4.90 ± 0.91 4.80 ± 0.91 0.925 0.862 0.986
Wean-to-estrus interval, d 4.6 ± 0.4 4.3 ± 0.3 4.9 ± 0.4 4.6 ± 0.4 0.935 0.829 0.714
BCS
 On day 108 of gestation 3.39 ± 0.07 3.17 ± 0.08 3.39 ± 0.07 3.39 ± 0.07 0.405 0.465 0.354
 24 h after parturition 3.17 ± 0.12 3.11 ± 0.11 3.22 ± 0.09 3.23 ± 0.09 0.755 0.319 0.794
 On day 21 of lactation 2.78 ± 0.09 2.67 ± 0.08 2.72 ± 0.08 2.66 ± 0.08 0.356 0.481 0.756
 Diarrhea 2 wk before farrowing 2.96 ± 0.06 2.97 ± 0.07 2.95 ± 0.06 3.11 ± 0.11 0.752 0.146 0.425
 Diarrhea during lactation 3.09 ± 0.03 3.07 ± 0.02 3.08 ± 0.02 3.07 ± 0.03 0.742 0.521 0.975

1Values are presented as means ± SE, n = 10.

Apparent total tract digestibility

Notably, no significant effects of the treatment were observed on ATTD of dry matter, nitrogen, and gross energy (Table 6).

Table 6.

Effect of sows’ intake of micelle silymarin from the 109th prenatal day to the 21st postnatal day on sow nutrient digestibility1(%)

Items Micelle silymarin (% of diet) CON vs. Micelle Silymarin P-value
0 0.05 0.1 0.2 Linear Quadratic
Dry matter 73.04 ± 1.84 74.05 ± 0.80 72.93 ± 0.63 71.29 ± 0.32 0.821 0.144 0.373
Nitrogen 70.39 ± 1.49 71.43 ± 1.09 70.69 ± 0.22 70.00 ± 0.38 0.807 0.641 0.549
Gross energy 71.08 ± 2.09 71.86 ± 0.82 71.66 ± 0.73 70.11 ± 0.47 0.926 0.467 0.406

1Values are presented as means ± SE, n = 8.

Milk yields and composition

Milk production and composition analysis are shown in Table 7. A dose-dependent increment (P = 0.002) in milk yields was shown as a response to incremental addition of micelle silymarin, and higher upper limit of milk yields (P = 0.046) was found in treated sows compared to the control. The fat content in milk was linearly increased as dietary micelle silymarin increased (P = 0.037) and tended to be higher (P = 0.087) in treated sows compared with the control sows on day 14 of lactation.

Table 7.

Effect of sows’ intake of micelle silymarin from the 109th prenatal day to the 21st postnatal day on the nutrient content of colostrum and milk1

Items Micelle silymarin (% of diet) CON vs. Micelle Silymarin P-value
0 0.05 0.1 0.2 Linear Quadratic
Average daily milk yields, kg/d 9.40 ± 0.48 9.64± 0.44 10.32± 0.43 11.32 ± 0.37 0.046 0.002 0.820
Colostrum at farrowing
 Fat, % 4.24 ± 0.10 4.32 ± 0.10 4.33 ± 0.05 4.34 ± 0.04 0.932 0.613 0.833
 Protein, % 6.54 ± 0.15 6.28 ± 0.14 6.51 ± 0.12 6.47 ± 0.12 0.448 0.953 0.600
 Lactose, % 9.28 ± 0.10 9.12 ± 0.12 9.30 ± 0.14 9.16 ± 0.08 0.485 0.642 0.959
Milk on day 14 of lactation
 Fat, % 6.36 ± 0.11 6.59 ± 0.11 6.41 ± 0.03 6.73 ± 0.15 0.087 0.037 0.652
 Protein, % 5.92 ± 0.10 5.83 ± 0.09 5.87 ± 0.13 6.03 ± 0.15 0.971 0.360 0.370
 Lactose, % 5.11 ± 0.09 5.00 ± 0.17 4.90 ± 0.03 5.13 ± 0.03 0.368 0.791 0.070

1Values are presented as means ± SE, n = 8.

Sow serum cortisol, prolactin, and oxytocin concentrations

Table 8 provides the variations in serum hormones levels during lactation. The concentrations of cortisol, prolactin, and oxytocin were similar among four groups on day 109 of lactation. At farrowing, cortisol concentrations were reduced (linear, P = 0.004) as micelle silymarin dose increased, with treated sows having lower (P = 0.051 at farrowing and P = 0.083 on day 21 of lactation) cortisol concentrations than their counterparts. In addition, serum prolactin concentrations in treated sows were augmented (P = 0.094) compared to those in control sows and tended to linearly rise (P = 0.085) with an increasing dose of micelle silymarin.

Table 8.

Effect of sows’ intake of micelle silymarin from the 109th prenatal day to the 21st postnatal day on the concentrations of cortisol, prolactin, and oxytocin in sow serum1

Items Micelle silymarin (% of diet) CON vs. Micelle Silymarin P-value
0 0.05 0.1 0.2 Linear Quadratic
On day 109 of gestation
 Cortisol, ng/mL 33.26 ± 0.78 29.56 ± 1.13 35.19 ± 1.39 34.70 ± 1.81 0.942 0.110 0.690
 Prolactin, ng/mL 199.88 ± 3.95 205.75 ± 8.27 193.65 ± 7.17 212.06 ± 6.65 0.614 0.288 0.303
 Oxytocin, pg/mL 5.11 ± 0.15 5.02 ± 0.13 5.32 ± 0.2 5.36 ± 0.22 0.492 0.146 0.977
At farrowing
 Cortisol, ng/mL 47.37 ± 2.00 46.26 ± 0.96 44.52 ± 1.00 41.63 ± 1.28 0.051 0.004 0.931
 Prolactin, ng/mL 229.66 ± 6.60 237.75 ± 6.11 230.33 ± 3.55 220.55 ± 4.44 0.984 0.105 0.218
 Oxytocin, pg/ml 3.95 ± 0.05 4.21 ± 0.12 3.84 ± 0.14 4.08 ± 0.09 0.468 0.816 0.689
On day 21 of lactation
 Cortisol, ng/mL 22.33 ± 0.70 21.35 ± 0.24 21.08 ± 0.66 21.21 ± 0.43 0.080 0.201 0.213
 Prolactin, ng/mL 209.13 ± 3.38 216.75 ± 4.73 214.38 ± 2.80 220.63 ± 4.94 0.094 0.085 0.768
 Oxytocin, pg/mL 3.21 ± 0.08 3.08 ± 0.06 3.23 ± 0.11 3.04 ± 0.07 0.347 0.258 0.578

1Values are presented as means ± SE, n = 8.

Sow serum metabolites

As shown in Table 9, serum metabolites were similar among groups at the beginning. At farrowing, epinephrine and norepinephrine concentrations in sow serum both displayed a downtrend with dietary content of micelle silymarin increased (P = 0.071 quadratic; P = 0.058, linear, respectively). On day 21 of lactation, the epinephrine concentrations and AST activity were linearly declined (both P < 0.05) with the increasing micelle silymarin amounts, and were significantly lowered in treated sows (P < 0.05) compared to the control sows.

Table 9.

Effect of sows’ intake of micelle silymarin from the 109th prenatal day to the 21st postnatal day on sow serum metabolites1

Items Micelle silymarin (% of diet) CON vs. Micelle Silymarin P-value
0 0.05 0.1 0.2 Linear Quadratic
On day 109 of gestation
 Epinephrine, pg/mL 22.28 ± 2.31 19.85 ± 0.87 21.56 ± 1.08 23.80 ± 1.57 0.631 0.301 0.118
 Norepinephrine, pg/mL 378.25 ±7.82 380.10 ± 4.37 356.42 ± 10.55 364.74 ± 6.47 0.216 0.111 0.302
 AST, U/L 69.88 ± 6.68 72.38 ± 2.65 73.63 ±1.95 68.75 ± 3.05 0.576 0.657 0.563
 ALT, U/L 46.38 ± 1.58 44.49 ± 2.89 47.40 ± 2.24 43.53 ± 1.62 0.622 0.462 0.581
 Glucose, mmol/L 4.82 ± 0.12 4.87 ± 0.12 4.80 ± 0.14 4.85 ± 0.12 0.923 0.972 0.924
 Triglycerides, mmol/L 1.67 ± 0.07 1.65 ± 0.07 1.64 ± 0.07 1.67 ± 0.06 0.845 0.945 0.730
 Urea nitrogen, mmol/L 4.98 ± 0.12 4.93 ± 0.14 4.97 ± 0.14 4.98 ± 0.16 0.803 0.938 0.907
At farrowing
 Epinephrine, pg/mL 77.18 ± 0.95 73.16 ± 2.18 73.11 ± 2.56 77.73 ± 2.69 0.333 0.623 0.071
 Norepinephrine, pg/mL 273.08 ± 3.64 269.75 ± 4.19 269.52 ± 5.61 258.47 ± 7.21 0.256 0.058 0.641
 AST, U/L 69.63 ± 1.34 71.50 ± 1.33 68.12 ± 1.09 67.75 ± 1.36 0.729 0.112 0.753
 ALT, U/L 35.88 ± 1.11 38.75 ± 1.62 31.50 ± 1.44 36.75 ± 2.07 0.911 0.788 0.171
 Glucose, mmol/L 4.54 ± 0.16 4.68 ± 0.09 4.61 ± 0.07 4.62 ± 0.07 0.420 0.751 0.554
 Triglycerides, mmol/L 1.53 ± 0.04 1.51 ± 0.04 1.52 ± 0.03 1.61 ± 0.03 0.731 0.109 0.251
 Urea Nitrogen, mmol/L 4.47 ± 0.10 4.52 ± 0.06 4.48 ± 0.06 4.52 ± 0.07 0.690 0.741 0.972
On day 21 of lactation
 Epinephrine, pg/mL 72.86 ± 1.68 65.20 ± 3.35 68.80 ± 1.19 60.91 ± 1.39 0.003 0.001 0.896
 Norepinephrine, pg/mL 386.86 ± 3.25 385.21 ± 3.33 389.28 ± 4.72 379.13 ± 5.03 0.632 0.217 0.328
 AST, U/L 64.25 ± 1.60 60.75 ± 1.99 63.25 ± 0.53 57.63 ± 1.34 0.037 0.007 0.545
 ALT, U/L 43.13 ± 1.42 44.75 ± 1.60 40.63 ± 2.01 45.38 ± 1.70 0.817 0.526 0.249
 Glucose, mmol/L 3.74 ± 0.07 3.75 ± 0.05 3.80 ± 0.04 3.76 ± 0.07 0.709 0.847 0.573
 Triglycerides, mmol/L 2.15 ± 0.08 2.15 ± 0.08 2.17 ± 0.08 2.18 ± 0.09 0.838 0.780 0.967
 Urea nitrogen, mmol/L 4.79 ± 0.08 4.71 ± 0.09 4.78 ± 0.18 4.75 ± 0.12 0.741 0.936 0.902

1Values are presented as means ± SE, n = 8.

Oxidant and antioxidant indices in sow serum and milk

From Table 10, it can be seen that serum SOD activity for sows fed micelle silymarin was enhanced (at farrowing: quadratic, P < 0.001; at day 21of lactation: linear and quadratic, both P < 0.001), and superior (P < 0.01) at farrowing compared to the control. At farrowing, GSSG concentrations (P = 0.002, linear) were increased as dietary micelle silymarin dose increased. In addition, GSSG/GSH ratio was increased (P < 0.05) in treated sows than in control sows. However, on day 21 of lactation, the GSSG concentrations and GSSG/GSH ratio were both decreased with rising levels of dietary micelle silymarin (P < 0.01, both linear and quadratic), and they were all lower (P < 0.01) in treated sows than in control sows. When compared with the control, the GSH-Px activity was increased (P = 0.002) in treated sows on day 21 of lactation.

Table 10.

Effect of sows’ intake of micelle silymarin from the 109th prenatal day to the 21st postnatal day on oxidant and antioxidant indices1 of sow serum

Items Micelle silymarin (% of diet) CON vs. Micelle Silymarin P-value
0 0.05 0.1 0.2 Linear Quadratic
On day 109 of gestation
 SOD, U/mL 76.63 ± 7.28 79.38 ± 5.48 71.50 ± 5.12 87.00 ± 5.87 0.703 0.269 0.280
 GSH-Px, U/mL 918.63 ± 36.97 914.00 ± 22.64 943.75 ± 24.25 918.50 ± 25.88 0.835 0.910 0.602
 GSH, μg/ml 9.63 ± 0.13 9.81 ± 0.31 9.62 ± 0.17 9.51 ± 0.16 0.948 0.480 0.615
 GSSG, μg/ml 1.08 ± 0.04 1.21 ± 0.05 0.99 ± 0.04 1.56 ± 0.06 0.477 0.708 0.371
 GSSG/GSH 0.112 ± 0.004 0.123 ± 0.004 0.103 ± 0.005 0.121± 0.006 0.447 0.439 0.231
At farrowing
 SOD, U/mL 95.96 ± 2.06 60.01 ± 2.54 91.86 ± 2.45 82.18 ± 2.22 < 0.001 0.467 < 0.001
 GSH-Px, U/mL 998.49 ± 32.66 988.00 ± 18.92 995.41 ± 13.37 999.41 ± 13.37 0.877 0.892 0.805
 GSH, ug/ml 10.3 8± 0.16 9.50 ± 0.30 10.42 ± 0.14 10.49 ± 0.12 0.286 0.129 0.134
 GSSG, μg/ml 0.99 ± 0.03 1.32 ± 0.06 0.93 ± 0.04 1.32 ± 0.06 0.001 0.002 0.194
 GSSG/GSH 0.093 ± 0.003 0.151 ± 0.005 0.085 ± 0.005 0.120 ± 0.007 < 0.001 0.328 0.658
On day 21 of lactation
 SOD, U/mL 95.38 ± 2.37 72.63 ± 3.04 97.13± 2.01 112.88 ± 4.00 0.735 < 0.001 < 0.001
 GSH-Px, U/mL 991.75 ± 1.40 1006.13 ± 4.33 994.38 ± 1.89 1002.13 ± 3.45 0.002 0.148 0.481
 GSH, μg/ml 10.39 ± 0.15 11.10 ± 0.19 10.00 ± 0.26 10.65 ± 0.22 0.430 0.940 0.551
 GSSG, μg/ml 1.59 ± 0.03 1.47 ± 0.03 1.50 ± 0.01 1.06 ± 0.04 < 0.001 < 0.001 0.005
 GSSG/GSH 0.154 ± 0.003 0.132 ± 0.003 0.155 ± 0.004 0.100 ± 0.004 < 0.001 < 0.001 < 0.001

1Values are presented as means ± SE, n = 8.

In Table 11, no treatment effect (P > 0.05) on T-AOC and MDA concentrations in colostrum and milk was discerned.

Table 11.

Effect of sows’ intake of micelle silymarin from the 109th prenatal day to the 21st postnatal day on oxidation and antioxidation indices of colostrum and milk

Items Micelle silymarin (% of diet) CON vs. Micelle Silymarin P-value
0 0.05 0.1 0.2 Linear Quadratic
Colostrum at farrowing
 T-AOC, U/mL 4.11 ± 0.05 3.96 ± 0.04 4.09 ± 0.07 4.00 ± 0.05 0.121 0.375 0.695
 MDA, nmol/mL 4.64 ± 0.05 4.71 ± 0.06 4.66 ± 0.08 4.62 ± 0.11 0.792 0.719 0.604
Milk on day 14 of lactation
 T-AOC, U/mL 4.11 ± 0.05 3.98 ± 0.03 4.06 ± 0.05 4.00 ± 0.05 0.056 0.234 0.448
 MDA, nmol/mL 5.32 ± 0.02 5.26 ± 0.03 5.38 ± 0.05 5.24 ± 0.04 0.656 0.345 0.162

Values are presented as means ± SE, n = 8.

Oxidant and antioxidant indices in offspring serum

As per Table 12, the activity of GSH-Px, SOD, and CAT, and the concentrations of T-AOC and MDA in nursing piglet serum were all relatively consistent (P > 0.05) in all groups at farrowing, while the CAT activity and T-AOC concentrations tended to be higher (0.05 < P < 0.1), and MDA concentrations was lower (P = 0.05) in offspring serum from micelle silymarin-fed sows when compared to those from control sows at day 14 of age.

Table 12.

Effect of sows’ intake of micelle silymarin from the 109th prenatal day to the 21st postnatal day on serum oxidation and anti-oxidation indices of suckling piglets

Items Micelle silymarin (% of diet) CON vs. Micelle Silymarin P-value
0 0.05 0.1 0.2 Linear Quadratic
On day 0 of age
 GSH-Px, U/mL 645.9 ± 3.3 642.1 ± 2.5 646.3 ± 3.2 648.3 ± 2.3 0.920 0.335 0.504
 SOD, U/mL 73.30 ± 0.85 72.30 ± 0.92 74.11 ± 0.88 74.36 ± 1.04 0.905 0.274 0.736
 CAT, U/mL 30.79 ± 0.42 31.63 ± 0.14 31.08 ± 0.31 31.40 ± 0.33 0.122 0.390 0.509
 T-AOC, U/mL 1.53 ± 0.03 1.55 ± 0.02 1.52 ± 0.02 1.54 ± 0.02 0.676 0.707 0.853
 MDA, nmol/mL 4.35 ± 0.02 4.32 ± 0.02 4.37 ± 0.04 4.40 ± 0.03 0.749 0.109 0.464
On day 14 of age
 GSH-Px, U/mL 1234.3 ± 8.8 1232.5 ± 5.4 1233.3 ± 5.9 1252.0 ± 5.9 0.918 0.923 0.839
 SOD, U/mL 80.87 ± 0.66 80.19 ± 0.46 82.37 ± 0.86 81.27 ± 0.67 0.612 0.383 0.396
 CAT, U/mL 29.35 ± 0.31 30.70 ± 0.34 29.69 ± 0.42 30.03 ± 0.42 0.079 0.582 0.337
 T-AOC, U/mL 1.80 ± 0.02 1.84 ± 0.07 1.85 ± 0.02 1.85 ± 0.07 0.077 0.163 0.314
 MDA, nmol/mL 4.84 ± 0.03 4.80 ± 0.03 4.84 ± 0.02 4.76 ± 0.03 0.050 0.460 0.250

Values are presented as means ± SE, n = 8.

Discussion

The physical condition of the lactating sows is a decisive factor in the performance of the subsequent reproductive cycle, i.e., weaning piglet weight and the growth rate after weaning. Since scarce milk production would hinder the optimum growth of offspring in the absence of creep feed, this study explored the supplemental effect of micelle silymarin in different doses to sows from the perinatal period to lactation.

Stillbirths and live birth rates

It was clear that a supplement of micelle silymarin after day 108 of gestation could not affect the number of newborn piglets regardless of live births or stillbirths. However, the increasing level of dietary micelle silymarin linearly declined the number of stillbirths. Indeed, the reasons for stillbirths birth vary greatly. The entangled umbilical cord, dystocia (Lozier et al., 2021), litter size that is too large (Wolf et al., 2008), duration of farrowing (Christianson,1992), the weight of the surviving piglets, and insufficient power of sows in the later farrowing are all causes of the stillbirth (Langendijk and Plush, 2019). More importantly, the absence of supervision is another major element that may have contributed to the stillbirth rates observed (Wang et al., 2019a). In this case, it was difficult to determine the cause for stillbirths because of too late addition of micelle silymarin. Since there was no difference in the total number born among groups, it may be that incidental variations in the number of stillbirths naturally resulted in increased live-born rates.

Growth performance of suckling piglets

Beyond original expectations, supplementing sows’ diets with rising doses of micelle silymarin increased the litter weight, litter weight gain, individual piglet weight, and ADG of suckling piglets at weaning. This agreed with the application of 40 g/d silymarin to lactating sows leading to prompted growth of suckling piglets as reported by Jiang et al. (2020). In the absence of creep feed during lactation, the only nutritious source for the greater weight of suckling piglets was the milk from sows with the supplemented diet (Burris and Baugus, 1955). Definitively, milk yields were significantly improved from silymarin-fed sows, which corresponded to previous work that showed similar effects in perinatal dairy cows, nursing sows, and breastfeeding women (Pierro et al., 2008; Onmaz et al., 2017; Ovsiienko, 2020). The probability was that piglets sucked more milk and grew faster (Miao et al. 2019). Research showed that maternal nutrition during lactation was influential in promoting the ADG of offspring although the influence of genetic selection, litter size, and firstborn piglet birth weight on milk production was not observed in this study (King, 2000; Miao et al., 2019). The incremental feed intake of treated sows may have equipped the sows with adequate nutrients to be utilized for enhanced milk synthesis (Lundgren et al., 2014). Khamisabadi (2020) explained that silymarin may promote the early arrival of peak milk yields of post parturient ewes, thus more milk was produced. Moreover, clinical research found higher milk yields were closely related to the function of prolactin, a hormone used for stimulating breast cell growth and boosting milk secretion (Loisel et al., 2013). This study showed that sows fed micelle silymarin tended to secrete more prolactin on weaning days, and analogous results had been obtained from female rats (Capasso et al., 2009; Capasso et al., 2014).

Possibly the excellent growth of suckling pigs implicated the high-quality milk.

Because Alexopoulos et al. (2004) showed neonatal piglets who consumed milk with higher fat and protein content from sows treated with probiotics, gained weight more quickly. As our results showed, sows supplemented with silymarin tended to improve fat content in their milk on day 14 of lactation. The improved fat content was also found when cows provided 7.7 g/d silymarin during the perinatal period (Garavaglia et al., 2015). Upper limits of fat content in milk may be connected with higher prolactin concentrations in micelle silymarin-treated sows due to its enhancement of amino acids, glucose, and fat absorption (Kucker et al.,1994). Although the concentrations of glucose and triglycerides, and the gross energy digestibility for fat synthesis were not affected by micelle silymarin addition.

Feed intake and BW loss of sows during lactation

The analysis demonstrated on sow nutrition level, feed intake, and piglet birth weight all had an impact upon BW loss of lactating sows (Kruse et al., 2011). In the current study, with the provision of the diet having the same nutrition level and the piglet birth weights at farrowing were similar, so it indicated that the vital factor influencing the lessened BW loss was the increment in feed intake. The result tied directly into and corroborated the research of Jiang et al. (2020) on nursing sows. Nevertheless, sows were observed to have low feed appetite within 7 d of parturition because of strong insulin resistance owing to metabolic syndrome (Père and Etienne, 2007). Excessive free radicals during late pregnancy and parturition also attenuated digestion and absorption due to metabolic syndrome (Cao et al., 2019), whereas Sayin et al. (2016) confirmed that silymarin alleviated insulin resistance and inflammation, benefiting from promoted metabolism of silybin. The absorbable micelle silymarin perhaps eased insulin resistance and improved antioxidant capacity to improve feed intake. It is well-known that improved feed intake plays an influential role in preventing fat mobilization during lactation, thereby reducing BW loss (Koketsu et al., 1996b). The declined BW loss in sows treated with micelle silymarin mirrored the influence of silymarin on lactating dairy cows as reported by Onmaz et al. (2017). More importantly, this trend in reduced BW loss contributed to fast body condition recovery and reduced sow culling rate (Koketsu et al., 1996a). Despite BF thickness loss, body condition scores, and analytical results of diarrhea did not differ among groups.

Oxidative and antioxidative indicators in sow serum, milk, and piglet serum

Sows suffer oxidative stress during late gestation and lactation, especially at farrowing (Tan et al., 2015), caused by the overproduction of free radicals, eroding the dynamic balance of oxidation and reduction. Sometimes, this stress is even transferred to newborns from the maternal (Inanc et al., 2005). As reported earlier, the antioxidant effect of silymarin on lessening MDA concentrations and augmenting CAT and SOD activity had been verified in lactating sows and post-parturient ewes (Farmer et al., 2014; Jiang et al., 2020; Khamisabadi, 2020). Present findings showed that micelle silymarin-fed sows exhibited superior SOD and GSH-Px activity in serum. As a vital part of the antioxidant enzyme system, SOD converts superoxide radicals to H2O2 and O2 (Su et al., 2017). Silymarin could accelerate the synthesis of glutathione to enhance the antioxidant property (Gillessen and Schmidt, 2020). Simultaneously, GSH-Px could decompose hydroperoxide and hydrogen peroxide in animals based on GSH as hydrogen, and produce GSSG (Métayer et al., 2008). The lower GSSG concentrations and decreased GSSG/GSH ratio on postnatal day 21were found in this study. The reduced GSSG/GSH ratio reflected the minor oxidative stress in sows (Zitka et al., 2012; Sentellas et al., 2014). The antioxidant properties of micelle silymarin were in given the structure of silybin, silydianin, and silychristin formed by hydroxyl groups on phenol and benzene that could combine with oxygen free radicals (Gillessen and Schmidt, 2020). However, the GSSG concentrations and GSSG/ GSH ratio increased in treated sows, which may indicate the oxidative stress was greater at farrowing.

To verify whether this antioxidant property could be transmitted to the suckling piglets through breast milk, the T-AOC and MDA of colostrum and milk were measured, along with the oxidation and antioxidant indices of the firstborn piglet serum. Unfortunately, no augmented antioxidant characteristics were observed in colostrum and milk from sows dosed with micelle silymarin. Even so, the CAT activity and T-AOC concentrations of offspring serum from treated sows on day 14 postpartum both tended to increase. It was estimated that the enhanced antioxidant capacity in the offspring may be relevant in reinforcing immunity through suckling more milk in such cases where this property may not be directly transmitted via milk.

Serum cortisol and prolactin concentrations

Based on existing studies, sows that undergo abrupt stress during late gestation and at farrowing, promote elevated cortisol concentrations in their blood (Willcox et al.,1983; Tsuma et al.,1998). In this study, cortisol concentrations were lower in micelle silymarin-treated sows, corresponding to the effect of silymarin on reduced cortisol concentrations in rats and horses (Thakare et al., 2016; Dockalova et al., 2021). Notably, there was a positive correlation between lipid antioxidants and cortisol concentrations (Khamisabadi, 2020). The improved serum SOD and GSH-Px activity, and T-AOC concentrations may relieve the production of cortisol. The beneficial influence of depressing cortisol concentrations, in part, reduced endotoxin-induced mastitis, neonatal diarrhea, and stress (Zhang et al., 2020).

Prolactin was produced mainly during pregnancy and lactation to promote the development of mammary glands, and the subsequent synthesis and secretion of milk (Freeman et al., 2000). However, 4 g/d silymarin provided to sow during the wean-to-estrus interval period did not affect prolactin concentrations as reported by Loisel et al. (2013). Contrary to this finding, treated sows presented here tended to have increased prolactin concentrations on 21 d of lactation concurring with results of investigations into gestating gilts (Farmer et al., 2014) and the normal state of female rats (Capasso et al., 2009; Capasso, 2014). Other research suggests that prolactin secretion was regulated by multi-factor including dopamine and estrogen (Freeman et al., 2000). Jiang et al. (2020) found that silymarin stimulated the secretion of estrogen and prolactin at farrowing. The estrogen could urge the pituitary gland to release prolactin and increase the expression of prolactin receptor genes (Foisnet et al., 2010). Perhaps the influence of supplemented micelle silymarin on prolactin was affected by estrogen.

Serum metabolites

The concentrations of AST and ALT in serum could reflect the health of the liver as damaged hepatic tissue has greater cell membrane permeability resulting in releasing more AST and ALT in serum (Onmaz et al., 2017). The decreased AST activity on 21 d of lactation was found when dietary micelles silymarin increased, which was consistent with the results obtained from silymarin-fed horses (Dockalova et al., 2021). Eminzade et al. (2008) confirmed that drug-induced liver poisoning in rats was accompanied by a multiplied increase in AST and ALT, while the supplement of silymarin could ease the drug-induced hepatotoxicity and reduce AST and ALT concentrations. Perhaps, the reduced AST was the manifestation of silymarin to protect the liver. Like cortisol, epinephrine was raised when the body was under emergency stress (Tilton et al.,1996), while the diminished epinephrine concentrations with dietary micelle silymarin was probably related to the enhancive antioxidant capacity. Similar to numerous reports concerning liver protection (Abenavoli et al., 2010), this study also indirectly indicated the protective effects of micelle silymarin on the liver of lactating sows.

Conclusions

Taken together, feeding sows with incremental levels of micelle silymarin showed a dose-dependent increasing effect on feed intake, BW loss reduction, milk yields, and litter weight at weaning. Treated sows had lower BW loss and higher feed intake which may reduce fat mobilization and prompted milk synthesis. Litter weaning weight and litter weight gain could be affected by boosted milk yields as well as superior fat content induced by enhanced prolactin concentrations in treated sows. A decline in cortisol concentrations, GSSG, GSSG/GSH, and enhanced SOD activity showed an overall effect of easing the stress in sows fed micelle silymarin during lactation. However, antioxidant properties may not be transferred to piglets through sow milk as reflected by the similar MDA and T-AOC concentrations in colostrum and milk. Findings indicated that sows fed micellar silymarin suffered no adverse effects, while the dose of 0.2% achieved the best benefits.

Acknowledgments

We sincerely appreciate Santi Upadhaya for revising the paper and the laboratory staff for their help in animal experiments and sample collection.

Glossary

Abbreviations

ADG

average daily gain

ALT

alanine aminotransferase

AST

aspartate aminotransferase

ATTD

apparent total tract digestibility;

BCS

body condition scores

BF

backfat

BW

body weight

CAT

catalase

GSH

glutathione

GSSG

oxidized glutathione

GSH-Px

glutathione peroxidase

MDA

malondialdehyde

SOD

superoxide dismutase

T-AOC

total antioxidant capacity

Funding

We promise that no funding was provided for this work. This study has not been influenced by any organization or person.

Authors’ Contributions

Q.Z.: formal analysis and writing—original draft. J.M.A.: conceptualization and methodology. I.H.K.: resources, supervision, funding acquisition, project administration, and Writing—review and editing.

Conflict of interest statement

The authors declare no real or perceived conflicts of interest.

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