Application of fuscoporene in preparation of product for relieving intestinal injury of chicks induced by salmonella

Abstract

The application discloses application of fuscocerine in preparation of products for relieving intestinal injury of chicks induced by salmonella, and belongs to the technical field of veterinary drugs. In a model of intestinal inflammation salmonella infected chicks, the chicks are orally administered with 20 mg / kg BW fuscocerine. The experimental results show that the fuscocerine can significantly relieve the growth performance of the chicks, improve the diarrhea condition and fecal state of the chicks, and improve the intestinal structure and permeability of the chicks through ileal M cells, thereby relieving the intestinal injury of the chicks caused by intestinal inflammation salmonella. The method for resisting intestinal inflammation salmonella of the chicks is beneficial to replacing the traditional antibiotic treatment method, and helps the development of poultry breeding.

Description

Technical Field

[0001] This invention relates to the field of veterinary medicine technology, specifically to the application of linalool in the preparation of products that alleviate intestinal damage induced by Salmonella in chicks. Background Technology

[0002] The gut is not only the core site for nutrient absorption but also the first physiological barrier against external pathogens. Salmonella Enteritidis (SE) infection causes damage to the intestinal structure and function, directly disrupting intestinal homeostasis in livestock and poultry, reducing nutrient utilization, and significantly increasing the host's susceptibility to various infectious and inflammatory diseases. Salmonella Enteritidis is a Gram-negative, facultative anaerobic intracellular pathogen widely distributed globally and capable of infecting various animals. SE, in particular, induces intestinal inflammation, leading to reduced growth performance and even death in broilers, causing significant economic losses to the livestock and poultry industry. Morin (3,5,7,2',4'-pentahydroxyflavone) is a natural active substance isolated from plants, belonging to the flavonoid class of compounds. It is a secondary metabolite of phenols in plants and is widely distributed in nature. Morin has good antioxidant and anti-inflammatory effects. Currently, research on the pathogenic mechanism of Salmonella Enteritidis has made some progress, but many treatment options remain to be explored. Summary of the Invention

[0003] To address the aforementioned shortcomings of existing technologies, the purpose of this invention is to provide an application of linphelodes extract in the preparation of products that alleviate intestinal damage induced by Salmonella in chicks, thereby alleviating intestinal damage induced by enteritis-type Salmonella in chicks, improving diarrhea and fecal condition in chicks, and thus replacing traditional antibiotic treatment methods to support the development of poultry farming.

[0004] The technical solution of the present invention to solve the above-mentioned technical problems is as follows: providing the application of linalool in the preparation of products that alleviate intestinal damage induced by Salmonella in chicks.

[0005] Furthermore, intestinal damage can be ileal stem cell damage, intestinal oxidative damage, or intestinal organoid damage.

[0006] Furthermore, the product is either a pharmaceutical or a feed additive.

[0007] Furthermore, the concentration of linalool in the product is 10-40 mg / kg BW.

[0008] Furthermore, the product also includes pharmaceutically acceptable excipients or carriers.

[0009] Furthermore, the product is available in granules, tablets, or capsules.

[0010] This invention offers the following beneficial effects: In a chick model infected with Salmonella enteritidis, this invention uses 20 mg / kg BW linheziin administered orally to chicks. Experimental results show that linheziin can significantly alleviate growth performance in chicks, improve diarrhea and fecal condition, and improve intestinal structure and permeability through ileal M cells, thus alleviating intestinal damage caused by Salmonella enteritidis. The method for chicks to resist Salmonella enteritidis provided by this invention is beneficial for treating damage caused by bacterial infection, effectively replacing traditional antibiotic treatment methods, meeting green and environmentally friendly requirements, and has great application potential in actual production, contributing to the development of poultry farming. Attached Figure Description

[0011] Figure 1 Screening diagram for the optimal concentration of linheyne to alleviate enteritis-type Salmonella; Figure 2 A graph showing the changes in chick weight and feed intake; Figure 3 A diagram of the cloaca, cloaca, surrounding feathers, and feces of chicks after treatment with morin. Figure 4 H&E staining of the ileum of chicks after treatment with morin; Figure 5 A statistical chart showing the height of ileal villi and the depth of crypts in chicks; Figure 6 A statistical graph of fluorescence signal intensity for ileal biomarkers; Figure 7 Fluorescence images of ileal tight junction protein, ileal goblet cell marker MUC2, and ileal secretory cell progenitor marker SOX9; Figure 8 The graph shows the intestinal weight per unit of small intestine, transmembrane resistance values ​​of jejunum and ileum, and organ index of chicks after treatment with linalool. Detailed Implementation

[0012] The examples given below are for illustrative purposes only and are not intended to limit the scope of the invention. Unless otherwise specified, conditions in the examples are performed under standard conditions or as recommended by the manufacturer. Reagents or instruments whose manufacturers are not specified are all commercially available products.

[0013] Example 1: Determining the optimal dosage of morin. Thirty one-day-old Ma Huang chickens were randomly divided into six treatment groups, with five chickens in each group. There were no significant differences in the weight of the chicks among the treatment groups (see...). Figure 1The chicks were acclimatized for 3 days, with a trial period of 10 days. They had free access to water and feed throughout the trial period, and were fed at fixed times daily (3 times a day, 9:00, 13:00, and 19:00). Feed intake was recorded, and the chicks' growth was closely monitored. The control group (CON) chicks were administered PBS via gavage, while the SE group received 3×10⁻⁶ PBS via continuous gavage. 9 The treatment regimens were as follows: Group 1 received SE for 3 days via gavage, followed by 0 mg / kg BW Morin intervention for 7 days; Group 2 received SE for 3 days via gavage, followed by 10 mg / kg BW Morin intervention for 7 days; Group 3 received SE for 3 days via gavage, followed by 20 mg / kg BW Morin intervention for 7 days; and Group 4 received SE for 3 days via gavage, followed by 40 mg / kg BW Morin intervention for 7 days. Each chicken was administered 0.5 mL of Morin via gavage.

[0014] Depend on Figure 1 and 8 It was found that Salmonella challenge significantly reduced the body weight and average daily weight gain of chicks, while significantly increasing the relative weight of the liver, indicating that it induced growth inhibition and pathological liver damage in chicks. Adding 20 mg / kg Morin significantly alleviated SE-induced weight loss, decreased feed intake, and liver organ indices in chicks. Combined with measurements of small intestinal weight per unit area and TEER (transmembrane resistance) value, it was determined that adding 20 mg / kg Morin to the feed had the best effect in alleviating Salmonella-induced intestinal damage. Therefore, 20 mg / kg Morin was selected as the dosage for alleviating SE-induced intestinal damage in chicks in subsequent experiments.

[0015] Example 2: Phellinus linteus alleviates intestinal damage induced by Salmonella enteritidis. Three hundred and twenty one-day-old Ma Huang chickens were randomly divided into four treatment groups, with eight replicates per treatment group and ten chickens per replicate. There were no significant differences in chick weight among the treatment groups. Chicks were allowed free access to water and feed throughout the 10-day trial period. They were fed three times a day (9:00, 13:00, and 19:00), and feed intake was recorded. Chick growth was closely monitored. The control group (CON) received PBS via gavage, the Morin group received 20 mg / kg BW Morin via gavage for the last seven days, and the SE group received 3 × 10 mg / kg BW Morin via gavage for the first three days. 9 CFU / mL SE, Morin remission group (SE+Morin) was administered SE for 3 days followed by 20mg / kg BW Morin intervention for 7 days, with each chicken administered 0.5mL of Morin orally.

[0016] Depend on Figure 2 It can be seen that adding Morin to the feed can significantly alleviate the symptoms of weight loss, daily weight gain and reduced daily feed intake in chicks induced by Salmonella enteritidis.

[0017] Depend on Figure 3 It can be seen that Morin alleviates the decline in growth performance of chicks induced by Salmonella enteritidis. After 3 days of Morin treatment, the feces began to return to normal solid state, the cloaca and surrounding feathers were free of fecal contamination, the cloaca closed normally, and there was no residual secretion. By day 13, the morphology had improved to the level of the control group. According to the diarrhea rate statistics, Morin can significantly alleviate the diarrhea induced by Salmonella enteritidis in chicks.

[0018] Depend on Figure 4 It was found that, compared with the CON group, the SE group chicks had significantly shorter intestinal length and significantly lower weight per unit length; at the same time, the TEER value decreased significantly. After Morin treatment, all of the above indicators returned to the levels of the CON group, suggesting that Morin can alleviate the damage to intestinal morphology and barrier function of chicks caused by Salmonella enteritidis infection.

[0019] Depend on Figure 5 Compared to the CON group, the SE group showed a significant reduction in ileal villus length, indicating that Salmonella disrupted the ileal morphology and structure, drastically reducing the intestinal absorptive surface area and impairing nutrient absorption. Damaged and sloughed intestinal epithelium reflects intestinal mucosal damage. The significantly increased crypt depth indicates extensive proliferation of intestinal stem cells, representing compensatory repair of intestinal inflammation and mucosal damage. Salmonella-induced persistent intestinal inflammation, coupled with continuous damage and shedding of the intestinal epithelium, forced crypt proliferation and deepening as a compensatory mechanism. A significantly decreased villus-to-crypt ratio indicates intestinal barrier damage and increased permeability, allowing bacteria to easily translocate into the bloodstream, leading to systemic inflammation, hepatosplenomegaly, and organ damage; nutrient absorption is impaired, and growth is slow. After Morin treatment, villus length, crypt depth, and villus-to-crypt ratio essentially returned to the levels of the CON group, suggesting that Morin can alleviate the damage to the ileal morphology caused by Salmonella enteritidis infection in chicks.

[0020] Depend on Figure 6-7Compared with the CON group, SE treatment reduced the expression of ZO-1 (tight junction protein) in the ileum of chicks, SOX9 (a marker of ileal secretory cell progenitor cells), and MUC2 (a marker of ileal goblet cells). Notably, these indicators returned to the CON group levels after Morin supplementation, suggesting that Morin can effectively alleviate the stem cell differentiation function damage caused by Salmonella enteritidis, thereby maintaining normal intestinal cell differentiation. Furthermore, compared with the CON group, SE infection significantly upregulated the expression of key genes (ANXN5, Spi-B, and SOX8) throughout the entire M cell cycle—early initiation, mid-stage proliferation, and late-stage maturation—indicating that SE infection dramatically induces de novo differentiation, massive proliferation, and terminal maturation of intestinal M cells, significantly increasing the total number and degree of maturation and activation of intestinal M cells. After Morin intervention, the expression of markers throughout the early, mid, and late stages of the M cell cycle significantly decreased, demonstrating that Morin can inhibit Salmonella-induced abnormal differentiation and activation of intestinal M cells and block the infection-mediated M cell differentiation cascade. The presence of no difference in Morin expression between the treatment alone and the blank control group indicates that Morin, under physiological homeostasis, does not disrupt the basic differentiation program of intestinal M cells, but only specifically intervenes in the abnormal proliferation and differentiation of pathological M cells induced by pathogen infection.

[0021] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. Application of linalool in the preparation of products to alleviate intestinal damage induced by Salmonella in chicks.

2. The application according to claim 1, characterized in that, The intestinal damage refers to ileal stem cell damage, intestinal oxidative damage, or intestinal organoid damage.

3. The application according to claim 1, characterized in that, The product is a pharmaceutical or feed additive.

4. The application according to claim 3, characterized in that, The concentration of linalool in the product is 10-40 mg / kgBW.

5. The application according to claim 3 or 4, characterized in that, The product also includes pharmaceutically acceptable excipients or carriers.

6. The application according to claim 5, characterized in that, The product is available in granules, tablets, or capsules.

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