阅读说明：本技术 原儿茶酸在拮抗饲料伏马毒素中的应用 (Application of protocatechuic acid in antagonism of feed fumonisins ) 是由 何诚 何润春 张宇航 王艺晖 于 2020-07-31 设计创作，主要内容包括：本发明提供了原儿茶酸(3,4二羟基苯甲酸)在拮抗伏马毒素中的新用途,将原儿茶酸作为伏马毒素B1的拮抗剂,能抵抗饲料中主要霉菌毒素伏马毒素B1的活性,能有效抑制伏马毒素B1引起的畜禽疾病、从而大大降低畜禽的发病率和死淘率,有效提高畜禽的成活率和生产性能。(The invention provides a new application of protocatechuic acid (3, 4-dihydroxy benzoic acid) in antagonizing fumonisins, which takes protocatechuic acid as an antagonist of fumonisins B1, can resist the activity of main mycotoxin fumonisins B1 in feed, and can effectively inhibit livestock and poultry diseases caused by fumonisins B1, thereby greatly reducing the morbidity and death and elimination rate of livestock and poultry, and effectively improving the survival rate and production performance of livestock and poultry.)

1. Application of protocatechuic acid in preparation of fumonisin antagonist, antagonistic fumonisin feed additive, antagonistic fumonisin feed or mold remover.

2. The use according to claim 1, wherein the fumonisin is fumonisin B1.

3. A fumonisin antagonist comprising protocatechuic acid.

4. An antagonistic fumonisin feed additive comprising protocatechuic acid.

5. An antagonistic fumonisin feed comprising protocatechuic acid.

6. A mold remover of fumonisins comprises protocatechuic acid.

7. The feed according to claim 5, characterized in that it contains 1 to 1000g of protocatechuic acid per ton of feed.

8. The feed according to claim 5, wherein the feed comprises 10-100 g protocatechuic acid per ton of feed, preferably 50g protocatechuic acid per ton of feed.

9. A feed treatment method using protocatechuic acid as an antagonist to antagonize fumonisins in the feed.

10. The method according to claim 9, wherein the feed is supplemented with an effective amount of protocatechuic acid for a period of 1-3 hours at a temperature of 25-28 ℃.

Technical Field

The invention relates to a new application of protocatechuic acid, in particular to an application of protocatechuic acid in antagonizing fumonisin in feed.

Background

Protocatechuic acid (PCA) with chemical name of 3, 4-dihydroxybenzoic acid (CAS registry number of 99-50-3, molecular formula of (HO)2C6H3 COOH) and molecular weight of 154.12.

The compound is white to brown crystalline powder in nature and discolors in air. The density was 1.54g/cm 3. Melting point about 200 deg.C (decomposition). Dissolving in 50 parts of water; dissolving in ethanol and diethyl ether.

Protocatechuic acid is present in leaves of red plum, Stenoloma chusana, and Aquifoliaceae. Protocatechuic acid has various biological activities aiming at different molecular targets, and has the effects of resisting bacteria, oxidation, inflammation, hyperglycemia and neuroprotection. In addition, protocatechuic acid has a potential chemoprotective effect, which can be anti-tumor and neuroprotective. At present, protocatechuic acid is mainly applied to antiviral drugs. However, their use for combating pathogenic Bacillus cereus and for antagonizing mycotoxin has not been found to date.

With the rapid development of livestock and poultry breeding industry in recent years, the harm of feed-derived diseases is increasingly prominent, and the serious threat to human health is also caused. Fumonisin and the like generated by mildew of the feed are particularly serious in harm to livestock and poultry, and the healthy development of livestock and poultry breeding is severely restricted.

The hazards of fumonisins to the livestock and poultry industry: fumonisin (Fumonisin FB) is a mycotoxin, a water-soluble metabolite produced by Fusarium moniliforme (Fusarium moniliforme shell), and a structurally similar diester compound composed of different polyhydric alcohols and tricarballylic acid. Mainly pollutes grains and products thereof, and generates acute toxicity and potential carcinogenicity to certain livestock, and becomes another research hotspot after aflatoxin. On the 27 th 10 th 2017, the primary reference for the list of carcinogens published by international cancer research institute of world health organization, fumonisin B1, fusarium moniliforme and the toxins produced thereby (fumonisin B1, fumonisin B2 and fusaricidin C) are in the list of class 2B carcinogens. Fumonisins are mainly secondary metabolites produced by the propagation of fusarium moniliforme and f.proliferum under certain temperature and humidity conditions. Until 1988, Geideblomd et al first isolated fumonisin B1(FB1) from moldy corn. The grain is easily polluted by the two fungi in the processes of processing, storing and transporting, particularly when the temperature is proper, the growth and the propagation of the grain are facilitated, so that the toxin with similar structural properties is produced, wherein the toxin contains fumonisins B1, B2 and B3, more than 60 percent of fumonisins B1(FB1) has the highest toxicity. Therefore, fumonisins can cause serious harm to the animal husbandry and even human health through the processes of food processing, feed production and the like. Fumonisins B1 are inhibitors of sphinganine N-acyltransferase, a long carbon chain aminodiol, and have a pathogenesis in that when sphingolipid is metabolized, the fumonisins compete with Sphingosine for binding to sphinganine N-2 acyltransferase, which largely inhibits Sphingosine biosynthesis and severely hinders sphingolipid metabolism. Sphingolipids, which are an important component of eukaryotic cell membranes, play a crucial role in the growth and differentiation process of cells, and once the metabolic process is destroyed, the organism is induced to change a series of physiological indexes. Changes in sphinganine/sphingosine (Sa/So) ratios in blood, urine and tissues are important biological indicators for assessing fumonisin B1 exposure, and when the Sa/So ratio is increased, a series of acute and chronic diseases in humans and animals can be caused. Particularly, after the horses take fumonisins for a long time, the horses suffer from leukoencephalomalacia (ELEM), which is a typical neurotoxic disorder and is therefore named fumonisins. The toxicity of fumonisins includes immune system toxicity, neurotoxicity, hepatotoxicity, pulmonary toxicity, reproductive toxicity, carcinogenicity and the like, and animal species are influenced to cover horses, pigs, cows, rabbits, mice, poultry and the like. The effects of fumonisins on livestock are manifested by decreased feed intake, dysplasia, liver tissue damage and chronic liver dysfunction, acute pulmonary edema, impaired reproduction of lymphoblasts, and immunosuppression. The effects on poultry are manifested by decreased feed intake, acute pulmonary edema, liver dysfunction and immunosuppression.

Hazards to poultry farming: after 0.5mg/kg of FB1 is continuously injected into wings of the laying hens for a week, the laying rate is reduced from 98% to 79%, the feed intake and the egg weight of the laying hens are reduced to a certain degree, and the soft shell breaking egg rate is increased by 3%. Poor raw materials often contain high-concentration fumonisins, and laying hens suffer from diarrhea, black sticky excrement discharge, reduced feed intake and weight loss after eating poisoning. After absorption against macrophageThe cells and lymphocytes have toxic effect, reduce the activity of immune cells and cause great harm to the health of chicken flocks. The toxic effect of fumonisins B1 on chick embryos is mainly shown in aspects of lung toxicity, gastric ulcer, dysplasia and the like. The chicken embryo injected with certain dose of fumonisin B1 can obviously cause the chicken embryo to have poor development, form dead embryo and weak embryo, and cause the hatching rate to be reduced, even the hatched chicks have lighter weight than normal chicks. Javed et al inoculated 1, 10 and 100. mu. mol/mL fumonisin B1 to 10-day-old chick embryos, respectively, and found that the chick embryos had varying degrees of mortality. The autopsy finds that the liver, the kidney, the heart, the lung, the muscle, the bone, the intestine and the brain have lesions with different degrees, which indicates that the fumonisins have strong pathogenicity and certain lethality to the chick embryos. Henry et al determined the median lethal dose (ELD) of fumonisins B1 to chick embryos₅₀) 18.73 ug/piece, and severe bleeding was found in the head, neck and chest of the dead embryo.

2.2 hazards to livestock farming: fumonisin B1(FB1) caused porcine pulmonary edema. Research by scientists in the united states and south africa has shown that up to 0.4mg fumonisin/kg body weight per day can cause pulmonary edema in pigs and disorders of the porcine reproductive system. Gumprech et al fed pigs with FB 1-containing cultures at 20. mu.g/(kg. bw.d) found that FB1 first caused elevated Sphingosine (So) and sphinganine (Shpinganine, Sa) levels in all tissues and liver damage, followed by lung vesicle endothelial tissue damage, with total death within 5 days. Feeding pigs with a mouldy feed containing 10mg/kg body weight of FB1 for three months resulted in an increase in capillary permeability in the lungs, brain, cerebellum and kidneys. The fact that FB1 can inhibit the proliferation of porcine granulosa cells and promote the generation of progesterone is found by Cortinovis, and has potential toxicity to the production of sows. High concentrations of FB1 affected boar semen production and reproductive performance, thus FB1 was also seen to have some toxic effects on boars. When the feed containing 15.0mg/kg body weight FB1 is continuously fed to the pigs by Gcore for 6 months, the pigs finally have serious spleen atrophy and lymphocyte damage. Taranu et al found that FB1 reduced the vaccine-specific antibody response during vaccination, affecting the antibody titer of the vaccine. The fumonisins with different concentrations are continuously fed to 35-day-old rabbits for 196 days, the injuries of the kidney, the liver and the spleen are aggravated along with the increase of the concentration, and the acute poisoning of the rabbits can be caused by feeding the feed containing FB131.5 mg/kg. Fumonisins can also cause leukomalacia syndrome in horses, a neurological disorder in horses. According to the research result of south African scientists in 1988, the horse is injected with FB1 subcutaneously in an amount of 0.125mg/kg body weight every day, and the horse becomes crazy and crazy about 7 days or so and dies by colliding with the railing. The equine brain white matter was dissected for softening lesions. In 1991, a toxicological test is carried out on a mouse by south African researchers, and the test result shows that the prevalence rate of liver tumor of the mouse is found to be increased rapidly after the mouse is fed with fumonisin 50mg/kg of body weight for 18-26 months, which is evidence for finding that the fumonisin causes liver cancer for the first time.

Hazards to human food safety: mycotoxin and its metabolite affect the production performance of animal organism, and can remain in meat, egg, milk, etc., thereby entering human food chain, causing human mycotoxin poisoning, and endangering human health. After a certain amount of fumonisins are fed to the dairy cows, the normal physiological function of the livers of the dairy cows is destroyed, so that the toxin content in the milk is increased, the quality of the milk is reduced, the yield is reduced, and the milk fat in the milk is reduced. Muscle and egg samples of a plurality of provinces in China are collected and detected in the laboratory, the fumonisin content in the samples is detected, the highest residual quantity of eggs can reach 2879 mug/kg, the residual content in muscle tissues reaches 605 mug/kg, and the serious residual condition can greatly harm the body health after being taken for a long time. Peanuts are favorite food, and various mycotoxins including fumonisins are found in the peanuts and the products thereof through Zhuzhen Yi detection, which poses serious threats to the health of human food. Yanmeihua (Fumoni item 2009zx09502-025) detects that the positive rate of fumonisin in the obviously mildewed traditional Chinese medicinal materials reaches 60%, and the pollution level is 82.4-2349 mu g/kg.

The research progress of the fumonisins detoxification technology is that fumonisins mainly exist in food crops and food products thereof, and the corn pollution is the most common. The food crops are mildewed due to improper storage, and a large amount of fumonisins can be generated after the fusarium moniliforme is bred, which is a main source of the fumonisins. Its content is also affected by many environmental factors: temperature, humidity, drought conditions, storage conditions, etc., all contribute to the variation of fumonisins content. With the increasing emphasis on food safety of people in modern society, a large number of methods are adopted to try to reduce and eliminate the fumonisins content and toxicity and achieve certain effects. Mainly divided into physical, chemical and biological detoxification methods. The biological detoxification method comprises the following steps: microbial degradation method, enzyme degradation method. Bacterial degradation and enzymatic degradation have proven to be very effective in such methods. The detoxification method utilizes the biological characteristics that certain special microorganisms can absorb toxins, then metabolize the toxins into nontoxic substances, and finally absorb and utilize the nontoxic substances as nutrient sources, thereby achieving the purposes of degrading and converting fumonisins. Benedetti uses a soil enrichment culture method to obtain a comamonas strain in soil, and researches show that the comamonas strain degrades toxin after being ingested by FB1, and the toxin is absorbed and utilized to supplement the demand of the comamonas strain by using carbon and nitrogen elements contained in the comamonas strain. Duvick et al isolated and found that two black yeast fungi, Exophiala spinoera and Rhinocladiella atrovirens, could degrade FB1 as the sole carbon source to consume it. The enzyme degradation method is to find out a gene segment capable of degrading FB1 from the screened bacteria with high degradation efficiency, and to express the segment of gene in large quantity by means of genetic engineering to obtain a large quantity of effective detoxification substances. Ahrar Khan tries to antagonize the toxic effect of ochratoxin and aflatoxin on chickens by using beer yeast, and the result shows that the toxic effect of mycotoxin on chickens can be effectively reduced by feeding the chickens with the mildewed feed and the yeast simultaneously compared with the feeding of the mildewed feed group.

In conclusion, fumonisins are one of the important harm factors threatening the livestock and poultry breeding industry and the human food safety at present, so that how to solve the harm from the feed source and reduce the harm loss caused to the breeding industry and human is an urgent problem in the breeding market at present.

Disclosure of Invention

The invention aims to provide a new application of protocatechuic acid in antagonizing fumonisin FB1 in feed.

The research of the invention finds that protocatechuic acid has antagonistic action against fumonisin FB1, and in vitro experiments prove that the additive amount in the feed is 50 g/ton of feed, the action time is 2 hours, the temperature is 25-28 ℃, the pollution of fumonisin FB1 in the feed can be effectively antagonized, and the antagonistic rate reaches more than 92.4%. In vivo experiments also show that protocatechuic acid effectively inhibits livestock and poultry diseases caused by fumonisin FB1, thereby greatly reducing the morbidity and the death and culling rate of livestock and poultry.

Accordingly, the technical scheme of the invention is as follows:

application of protocatechuic acid in preparation of fumonisin antagonist, antagonistic fumonisin feed additive, antagonistic fumonisin feed or mold remover. Specifically, the fumonisin is fumonisin FB 1.

Further, the present invention provides a fumonisin antagonist comprising protocatechuic acid.

Further, the present invention provides an antagonistic fumonisin feed additive comprising protocatechuic acid.

Further, the present invention provides an antagonistic fumonisin feed, which contains protocatechuic acid.

Further, the present invention provides a mold remover comprising protocatechuic acid.

Adding protocatechuic acid into feed, wherein each ton of feed contains 1-1000 g protocatechuic acid, preferably 10-100 g protocatechuic acid, and more preferably 50g protocatechuic acid.

Further, the present invention provides a feed treatment method using protocatechuic acid as an antagonist to antagonize fumonisins in the feed.

Preferably, an effective amount of protocatechuic acid is added to the feed for 1-3 hours at a temperature of 25-28 ℃. 1-1000 g of protocatechuic acid can be added to each ton of feed, preferably 10-100 g of protocatechuic acid is added to each ton of feed, and more preferably 50g of protocatechuic acid is added to each ton of feed. The preferable amount of the fumonisins is determined by the amount of fumonisins which may be produced by the feed and mildew, and the amount of the protocatechuic acid is small when the feed is mildewed and large when the feed is mildewed. But usually 50g per ton is a suitable amount.

The invention has the following beneficial effects:

the invention takes protocatechuic acid as antagonist of fumonisins FB1, can resist the activity of main mycotoxins of fumonisins FB1 in feed, and can effectively inhibit livestock and poultry diseases caused by fumonisins FB1, thereby greatly reducing the morbidity and death and culling rate of livestock and poultry, and effectively improving the survival rate and the production performance of livestock and poultry.

Detailed Description

The following examples further illustrate the present invention but should not be construed as limiting the invention and as imposing limitations upon the scope thereof, as well as modifications or alterations to the methods, procedures or conditions of the present invention.