Pathogenesis of Liver Fibrosis and Its TCM Therapeutic Perspectives.

Liver fibrosis is a pathological process of abnormal tissue proliferation in the liver caused by various pathogenic factors, which will further develop into cirrhosis or even hepatocellular carcinoma if liver injury is not intervened in time. As a diffuse progressive liver disease, its clinical manifestations are mostly excessive deposition of collagen-rich extracellular matrix resulting in scar formation due to liver injury. Hepatic fibrosis can be caused by hepatitis B and C, fatty liver, alcohol, and rare diseases such as hemochromatosis. As the metabolic center of the body, the liver regulates various vital activities. During the development of fibrosis, it is influenced by many other factors in addition to the central event of hepatic stellate cell activation. Currently, with the increasing understanding of TCM, the advantages of TCM with multiple components, pathways, and targets have been demonstrated. In this review, we will describe the factors influencing liver fibrosis, focusing on the effects of cells, intestinal flora, iron death, signaling pathways, autophagy and angiogenesis on liver fibrosis, and the therapeutic effects of herbal medicine on liver fibrosis.

Dietary Supplementation of Ferrous Glycine Chelate Improves Growth Performance of Piglets by Enhancing Serum Immune Antioxidant Properties, Modulating Microbial Structure and Its Metabolic Function in the Early Stage.

The present research aimed to explore the effect of dietary ferrous glycine chelate supplementation on performance, serum immune-antioxidant parameters, fecal volatile fatty acids, and microbiota in weaned piglets. A total of 80 healthy piglets (weaned at 28 day with an initial weight of 7.43 ± 1.51 kg) were separated into two treatments with five replicates of eight pigs each following a completely randomized block design. The diet was a corn-soybean basal diet with 2,000 mg/kg ferrous glycine chelates (FGC) or not (Ctrl). The serum and fecal samples were collected on days 14 and 28 of the experiment. The results indicated that dietary FGC supplementation improved (p < 0.05) the average daily gain and average daily feed intake overall, alleviated (p < 0.05) the diarrhea rate of piglets at the early stage, enhanced (p < 0.05) the levels of superoxide dismutase and catalase on day 14 and lowered (p < 0.05) the MDA level overall. Similarly, the levels of growth hormone and serum iron were increased (p < 0.05) in the FGC group. Moreover, dietary FGC supplementation was capable of modulating the microbial community structure of piglets in the early period, increasing (p < 0.05) the abundance of short-chain fatty acid-producing bacteria Tezzerella, decreasing (p < 0.05) the abundance of potentially pathogenic bacteria Slackia, Olsenella, and Prevotella as well as stimulating (p < 0.05) the propanoate and butanoate metabolisms. Briefly, dietary supplemented FGC ameliorates the performance and alleviated the diarrhea of piglets by enhancing antioxidant properties, improving iron transport, up-regulating the growth hormone, modulating the fecal microbiota, and increasing the metabolism function. Therefore, FGC is effective for early iron supplementation and growth of piglets and may be more effective in neonatal piglets.

Maternal supplementation with a combination of wheat bran and sugar beet pulp during late gestation and lactation improves growth and intestinal functions in piglets.

Maternal diet has a profound impact on growth and immune development of offspring. This study aimed to evaluate the effects of maternal supplementation with a combination of wheat bran (WB, a source of insoluble dietary fiber) and sugar beet pulp (SBP, a source of soluble dietary fiber) on growth and intestinal morphology, immunity, barrier function and microbiota in piglets. Thirty sows (Landrace × Yorkshire; 3-6 parity) were randomly allocated to 2 dietary treatments from d 85 of gestation to weaning (d 21 of lactation). The 2 dietary treatments were: a control diet (CON, a corn-soybean meal diet) and a dietary fiber diet (DF, 15% WB and 10% SBP during gestation and 7.5% WB and 5% SBP during lactation). Maternal DF supplementation improved growth, serum growth hormones and ileal morphology in piglets. Piglets fed DF showed enhanced intestinal barrier function as indicated by reduced serum concentrations of diamine oxidase and endotoxin, and increased ileal mRNA level of occludin. Maternal DF supplementation reduced pro-inflammatory cytokines in the colostrum, milk and serum of piglets. Furthermore, maternal DF supplementation decreased the colonic abundance of Subdoligranulum and Mogibacterium, and increased the colonic abundance of Lactobacillus and norank_f__Bacteroidales_S24-7_group and the colonic concentration of acetate and butyrate in piglets. In summary, maternal supplementation with a combination of SBP and WB during late gestation and lactation improved cytokines in colostrum and milk, growth, immune responses, intestinal morphology, barrier function and microbiota in piglets, which may be a potential strategy to improve offspring growth and intestinal functions.

Dietary 25-hydroxycholecalciferol supplementation improves performance, immunity, antioxidant status, intestinal morphology, and bone quality in weaned piglets.

BACKGROUND: 25-Hydroxycholecalciferol (25OHD3 ) is a new feed additive, which is a potential alternative to vitamin D3 in swine nutrition. The objective of this study was to determine the effects of different doses of 25OHD3 supplementation on performance, immunity, antioxidant capacity, intestinal morphology and bone quality in piglets. RESULTS: As dietary 25OHD3 supplementation increased, the average daily gain (ADG) improved (P < 0.05) quadratically during days 1-14, and tended to increase (P = 0.06) quadratically during the overall period of the experiment. Increasing 25OHD3 supplementation increased (linear effect, P < 0.05) the serum 25OHD3 level and serum glutathione peroxidase (GSH-Px) activity. On day 14, serum immunoglobulin A (IgA) was increased (linear and quadratic effects, P < 0.05) as dietary 25OHD3 supplementation increased. On day 28, serum IgA level was higher (P < 0.05) linearly and the complement 3 (C3) level was reduced (P < 0.05) linearly as dietary supplementation of 25OHD3 increased. The mucosal GSH-Px activity of the small intestine was higher (quadratic effect, P < 0.05) with increasing 25OHD3 supplementation. Jejunal villus height (P = 0.06) and villus height to crypt depth ratio (P = 0.07) tended to increase quadratically, and the villus height to crypt-depth ratio of the ileum increased (P < 0.05) linearly and quadratically with increasing 25OHD3 supplementation. Dietary supplementation with an increasing level of 25OHD3 increased breaking strength of tibias and femurs (quadratic effect, P < 0.05). CONCLUSION: Increasing dietary 25OHD3 supplementation partly improved performance, immunity, antioxidant status, intestinal morphology, and bone properties of weaned piglets. © 2020 Society of Chemical Industry.

Effects of maternal 25-hydroxycholecalciferol during the last week of gestation and lactation on serum parameters, intestinal morphology and microbiota in suckling piglets.

This study was conducted to test the effects of maternal 25-hydroxycholecalciferol (25OHD3) supplementation on serum parameters, intestinal morphology and microbiota in suckling piglets. The experiment started on day 107 of gestation and lasted until piglets were weaned on day 21 of lactation. Thirty-two sows were allocated randomly to two treatments (ND diet, basal diet with 2000 IU/kg of vitamin D3; 25-D diet, basal diet with 50 µg/kg 25OHD3). Results showed that maternal 25-D treatment increased (p < 0.05) serum 25OHD3 concentration in the umbilical cords, which led to higher (p < 0.05) serum 25OHD3 concentration of suckling piglets from 25-D sows. The GSH-Px activity in colostrum was higher (p < 0.05), as well as SOD and GSH-Px activities in milk, were higher (p < 0.05) in 25-D sows than ND sows. Compared with piglets suckling ND sows, piglets suckling 25-D sows had higher (p < 0.05) serum SOD activity on day 7, 14 and 21 of lactation. On day 21 of lactation, piglets form 25-D sows had greater (p < 0.05) serum levels of GH and IGF-I and lower (p < 0.05) serum DAO activity than those from ND sows. Piglets from 25-D sows had higher (p < 0.05) jejunal villus height than those from ND sows. Feeding 25OHD3 to sows tended to increase (p < 0.10) the species richness in the colonic digesta of suckling piglets, as reflected by the α-diversity index of Chao-1. In the caecal digesta, the α-diversity for bacterial community analysis of Simpson and Shannon was lower (p < 0.05) in 25-D piglets than ND piglets. The relative abundances of colonic Alloprevotella and caecal Lactobacillus were significantly higher, while the population of caecal [Eubacterium]_coprostanoligenes_group was lower (p < 0.05) in 25-D piglets than ND piglets. In conclusion, maternal 25OHD3 supplementation partly improved antioxidant status in sows and suckling piglets and altered gut microbiota in the hindgut of piglets.

Effects of Dietary Fatty Acids from Different Sources on Growth Performance, Meat Quality, Muscle Fatty Acid Deposition, and Antioxidant Capacity in Broilers.

This study aimed to investigate the efficiency of dietary fatty acids from various sources on growth performance, meat quality, muscle fatty acid deposition and antioxidant capacity in broilers. 126 Arbor Acres broilers (1 d-old, initial body weight of 45.5 ± 0.72 g) were randomly assigned to three treatments with seven cages per treatment and six broilers per cage. The dietary treatments included: (1) corn-soybean meal basal diet containing 3% soybean oil (control diet, CTL); (2) basal diet + 1% microalgae + 1% linseed oil + 1% soybean oil (ML); (3) basal diet + 2% fish oil + 1% soybean oil (FS). The trial consisted of phase 1 (day 1 to 21) and 2 (day 22 to 42). Compared with CTL, broilers fed ML or FS diet showed improved (p < 0.05) average daily gain in phase 1, 2, and overall (day 1 to 42), as well as a decreased (p < 0.05) feed conversion ratio in phase 1 and overall. On day 42, broilers supplemented with FS diet showed increased (p ≤ 0.05) the relative weights of pancreas and liver, as well as higher (p < 0.05) redness value in breast and thigh muscle compared with CTL. Broilers offered ML or FS diet had lower (p < 0.05) the relative weight of abdominal fat and total serum cholesterol content in phase 1, and increased (p < 0.05) contents of serum glucose, n-3 polyunsaturated fatty acids (PUFA), eicosacagetaenoic acid, docosahexaenoic acid, glutathione peroxidase, superoxide dismutase and total antioxidant capacity, as well as lower (p < 0.05) concentrations of malondialdehyde, n-6 PUFA, and n-6/n-3 PUFA ratio in breast and thigh muscle compared with CTL. This research indicates that diets supplemented with fish oil or a combination of microalgae and linseed oil experience improved performance, antioxidant capacities and n-3 PUFA profile in muscle of broilers compared with traditional soybean oil supplemented diets.

Effect of fibre sources on performance, serum parameters, intestinal morphology, digestive enzyme activities and microbiota in weaned pigs.

This study was conducted to evaluate the effects of wheat bran (WB) as insoluble fibre source, and sugar beet pulp (SBP) as soluble fibre source, on performance, serum parameters and intestinal health in weaned pigs. A total of 90 weaned pigs (BW: 7.33 ± 1.24 kg) were randomly assigned to three dietary treatments: (1) a control diet (CON) based on corn and soybean meal; (2) CON + 6% WB; (3) CON + 6% SBP. Each treatment had five replicate pens with six pigs per pen. The experimental period was divided into two phases (d 0 to 14 and d 14 to 28). Pigs in group WB tended to have greater avarage daily gain than those in group SBP. Compared with CON, SBP reduced (p < 0.05) the apparent total tract digestibility (ATTD) of dry matter, organic matter (OM), gross energy and neutral detergent fibre on d 14 and 28, while WB decreased (p < 0.05) the ATTD of OM on d 28. Pigs in group SBP had higher (p < 0.05) glucagon-like peptide 1 concentration than the other groups on d 14 and 28. The villus height to crypt depth (V:C) ratio of duodenum and jejunum in pigs fed diet WB were greater (p < 0.05) than in group SBP. The WB increased (p < 0.05) the V:C ratio of ileum compared with CON or SBP. Compared with SBP, WB increased (p < 0.05) the sucrase activity in the duodenum. Moreover, pigs in WB had higher (p < 0.05) activities of maltase and sucrase in the jejunum compared with CON or SBP. The abundances of Ruminococcaceae and Prevotellaceae were increased (p < 0.05) in WB, while the Lachnospiraceae abundance was increased (p < 0.05) in SBP. WB increased (p < 0.05) concentrations of acetate, butyrate and total short-chain fatty acids (SCFA), while SBP increased (p < 0.05) concentrations of acetate and total SCFA when compared with CON. In conclusion, WB was beneficial to performance in weaned pigs by improving morphology, enzyme activities and microbiota when compared with SBP, highlighting that effects of fibre depends on the fibre sources.

Effects of dietary fiber sources during late gestation and lactation on sow performance, milk quality, and intestinal health in piglets1.

This study was conducted to investigate the effects of dietary supplementation with 2 sources of fiber, sugar beet pulp (SBP), and wheat bran (WB), on sow performance, milk quality, and intestinal health in piglets. Forty-five multiparous sows at day 85 of gestation were allocated to the following 3 treatments: 1) a corn-soybean meal basal diet (CON); 2) the CON diet supplemented with 20% SBP in gestation and 10% SBP in lactation (SBP); and 3) the CON diet supplemented with 30% WB in gestation and 15% WB in lactation (WB). The SBP diets increased (P < 0.05) sow ADFI during lactation, litter and piglet weaning weight, piglet ADG, immunoglobulin A (IgA), and interleukin-10 (IL-10) levels in the colostrum and IgA levels in the milk, while the WB diets only increased (P < 0.05) IL-10 levels in the milk when compared with the CON diets. Piglets from SBP-fed sows had greater (P < 0.05) serum growth hormone and insulin-like growth factor-1 levels than those from WB-fed or CON-fed sows, whereas piglets from WB-fed sows had greater (P < 0.05) serum GH levels than those from CON-fed sows. Serum diamine oxidase activity, endotoxin, IL-6, and tumor necrosis factor-α (TNF-α) levels were reduced (P < 0.05) in piglets from SBP-fed or WB-fed sows. Piglets from SBP-fed sows also had greater (P < 0.05) serum IL-10 levels than those from CON-fed sows. The ileal mRNA expression of TNF-α was reduced (P < 0.05) in piglets from SBP-fed or WB-fed sows. Piglets from SBP-fed sows had lower (P < 0.05) IL-6 expression, and greater (P < 0.05) IL-10 expression and secretory immunoglobulin A (SIgA) levels in the ileum than those from WB- or CON-fed sows. Piglets from WB-fed sows had greater (P < 0.05) IL-10 expression and SIgA levels compared with those from CON-fed sows. The ileal mRNA expression of occludin in the ileum was greater (P < 0.05) in piglets from SBP-fed sows than those from CON-fed sows. The ileal mRNA expression of ZO-1 was greater (P < 0.05) in piglets from WB-fed sows than those from CON-fed sows, but lower (P < 0.05) than those from SBP-fed sows. Piglets from SBP-fed sows had greater (P < 0.05) abundance of Christensenellaceae and butyrate levels in the colon, while piglets from WB-fed sows had greater (P < 0.05) abundance of Lactobacillaceae. Collectively, maternal SBP supplementation was more effective than WB in improving milk quality, enhancing growth performance and intestinal barrier function, and ameliorating intestinal inflammation in piglets.

Maternal 25-hydroxycholecalciferol during lactation improves intestinal calcium absorption and bone properties in sow-suckling piglet pairs.

Lower maternal vitamin D status during lactation is a common health problem. The objectives of this study were to investigate the effects of maternal 25-hydroxycholecalciferol (25-OH-D3) supplementation during lactation on maternal and neonatal bone health in a sow model. 32 Large White × Landrace sows were assigned randomly to one of two diets supplemented with 2000 IU/kg vitamin D3 (ND) or 50 µg/kg 25-OH-D3 (25-D). The experiment began on day 107 of gestation and continued until weaning on day 21 of lactation. Maternal 25-OH-D3 supplementation significantly decreased milk n-6:n-3 PUFA ratio, which supported bone formation of piglets. Supplementation with 25-OH-D3 altered bone turnover rate of sows and piglets, as evidenced by higher bone-specific alkaline phosphatase (BALP) concentration in serum. 25-D sows had significantly higher bone density and mechanical properties of tibias and femurs than ND sows. Calcium (Ca) absorption rate was higher in 25-D sows than ND sows, which was caused partially by the increased mRNA expressions of renal 1α-hydroxylase (CYP27B1) and duodenal vitamin D receptor (VDR), transient receptor potential vanilloid 6 (TRPV6), and calcium-binding protein D9k (CaBP-D9k). Maternal 25-OH-D3 supplementation increased tibial and femoral Ca content by up-regulating Ca-related gene expression in kidney (CYP27B1), ileum (VDR and claudin-2), and colon (VDR and CaBP-D9k), thus, activating 1,25-dihydroxyvitamin D3 [1,25-(OH)2-D3]-dependent Ca transport in piglets. In conclusion, improved milk fatty acids and higher mRNA expressions of calcitropic genes triggered by maternal 25-OH-D3 supplementation would be the potential mechanism underlying the positive effects of 25-OH-D3 on maternal and neonatal bone health.