What Is the Use of Echinacea Extract in Animal Feeding?

Echinacea is a perennial herb in the Asteraceae family that is native to North America. There are eight species and several varieties in the genus, of which only three are used as herbal supplements: purple coneflower, narrow-leaved echinacea and white echinacea. Echinacea was used as a medicine by the North American Indians in the 18th century and quickly spread throughout the United States. Throughout the 19th century, it was the most widely used plant in the United States. In recent years, due to the widespread use of antibiotics and their additives in livestock and poultry production, many bacteria have become increasingly resistant, leading to increasingly complex livestock and poultry diseases, higher mortality and infectivity, and a serious threat to the health of livestock, poultry and humans. Echinacea extract is not prone to drug resistance, has no residual toxicity, has few side effects, and provides stable and long-lasting prevention. In foreign countries, Echinacea is used as a livestock and poultry health product and dietary supplement. In China, Echinacea extract is mainly used as a feed additive and immune enhancer in livestock and poultry production to enhance immune function and production performance and improve economic efficiency.

1 Biological characteristics

The main components of Echinacea extract include caffeic acid derivatives, alkylamide compounds and polysaccharides.

1.1 Caffeic acid derivatives

Echinacea purpurea ethanol extracts from the aboveground and root parts contain caffeic acid derivatives. Sun Liping et al. used HPLC combined with hierarchical cluster analysis to obtain seven caffeic acid derivatives, including 3,4-dihydroxybenzoic acid, chlorogenic acid, caffeic acid, eugenic acid, p-coumaric acid, Ferulic acid and cichoric acid, of which cichoric acid is the highest, chlorogenic acid and caffeic acid are the second highest [1]. The content of cichoric acid is highest at the ripe stage, and decreases after the ripe stage. It is usually found in high amounts in the roots and flowers of Echinacea purpurea, and is often extracted after fresh Echinacea purpurea flowers are treated with steam to inactivate the enzymes [2-3].

1.2 Alkylamides

Methanol extracts from the roots of Echinacea purpurea contain alkylamide compounds. Lu Ying et al. used HSCCC combined with HPLC to isolate eight high-purity alkylamide compounds from the roots of Echinacea purpurea. After concentration, the remaining six compounds were crystallized, namely ①Undeca- 2Z, 4E-diene-8, 10-diynoic acid isobutylamide; ②Dodeca-2E, 4Z-diene-8, 10-diynoic acid iso ‐ butylamide; ③ Dodeca-2Z, 4Ediene-8, 10-diynoic acid isobutylamid; ④Dodeca-2E, 4Z-diene- 8, 10- diynoic acid 2-methylbutylamid; ⑤ Dodeca-2E, 4E , 8Z , 10E-tetraenoic acid isobutylamide; ⑥ Dodeca-2E, 4E, 8Z, 10Z-tetraenoic acid iso ‐ butylamide, of which the highest content is Dodeca-2E, 4E, 8Z, 10Z-tetraenoic acid isobutylamide [4]. Alkyl amides are present in low concentrations during the vegetative stage, gradually increasing with growth. They are usually highest at the top of the plant, and are best extracted with petroleum ether [3, 4]. 

1.3 Polysaccharides

The aerial parts of Echinacea purpurea extract contain polysaccharides (4-methoxyl glucose, arabinose, xylan, fructan, rhamnose and galactose), the leaves and stems contain xyloglucan, and the fresh plant press juice contains pectin-like polysaccharides. Zhang Meiling used pre-column derivatization with PMP to obtain the six main monosaccharide components of the polysaccharide, namely, mannose, glucuronic acid, rhamnose, glucose, xylose and arabinose, of which xylose is the most abundant [7]. Polysaccharides are found in both echinacea purpurea and echinacea angustifolia, and ultrasonic extraction is recommended [3, 5].

In addition, echinacea purpurea extract also contains flavonoids, steroids and many inorganic elements.

2 Pharmacological effects

2.1 Immunomodulatory effects

Echinacea extract has a regulatory effect on both nonspecific and specific immunity in immunosuppressed mice. Song Hongwei et al. found through mouse control experiments that the carbon clearance ability of the low, medium and high dose groups was significantly higher than that of the immunosuppressed group, and the immune organ index was significantly higher. At the same time, it also significantly reduced the weight of the spleen induced by cyclophosphamide, and reduced the total number of white blood cells and the number of neutrophils in the peripheral blood. Therefore, it can be used as an effective immunomodulator [6]. In addition, Echinacea polysaccharide can improve the humoral and cellular immune levels of immunosuppressed mice. Studies have found that Echinacea polysaccharides can increase the index of immune organs in mice, raise the level of immunoglobulins in the blood serum, and promote the proliferation of T lymphocytes and the secretion of cytokines IL-2, IFN-γ, and IFN-α in mice with immune suppression caused by cyclophosphamide. The arabinogalactan in the polysaccharides can dose-dependently stimulate the phagocytic function of macrophages. Currently, research on the immunomodulatory effects of Echinacea focuses on humoral and cellular immunity. Numerous basic studies have shown that Echinacea has a good immunostimulatory effect on the animal body. With the deepening of research on mucosal immunity, the effect of Echinacea on respiratory mucosal immunity and intestinal mucosal immunity can be explored in the future.

2.2 Anti-inflammatory effect

Studies have shown that the extracts of Echinacea flowers and adventitious roots can inhibit the release of pro-inflammatory mediators and have good anti-inflammatory activity. As one of the important active ingredients in Echinacea extracts, echinacoside can regulate the release and expression of inflammatory factors, and has an immune anti-inflammatory effect. Its mechanism of action involves the inhibition of mRNA and protein level regulation. Xu Tianli et al. used Echinacea as the research object and administered the obtained Echinacea purified polysaccharide to mice by gavage. The results showed that Echinacea purified polysaccharide can reduce xylene-induced ear swelling in mice and significantly inhibit the inflammatory response in mice. Compared with dexamethasone, Echinacea purified polysaccharide was not found to significantly damage the immune system of mice, indicating that Echinacea purified polysaccharide can effectively inhibit inflammation [7]. Inflammatory responses in the body have always affected farming efficiency. Since July 1, 2020, China has completely banned the use of antibiotics in animal feed. Inflammatory responses caused by various non-virulent pathogens have severely restricted farming efficiency, and healthy farming has become a new development trend. Echinacea, a natural plant, is not only safe and stable, but also has the advantages of being multi-component, multi-functional and multi-targeted. In the future, it can be developed into an additive that replaces antibiotics in animal feed.

2.3 Antibacterial, antiviral and antitumor effects

Caffeic acid derivatives are the main antibacterial active ingredients in Echinacea. They can inhibit the growth of Staphylococcus aureus, Pseudomonas aeruginosa and Acinetobacter Baumannii, and have a particularly strong inhibitory effect on methicillin-resistant Staphylococcus aureus (minimum inhibitory concentration of 0.7 mg/mL). Echinacea polysaccharides can improve the body's resistance to infections such as Escherichia coli and Salmonella, and have potential application value in regulating intestinal microecology [8]. In addition, echinacea extract can show a synergistic effect when combined with antibacterial drugs (enrofloxacin, gentamicin, clindamycin, doxycycline, ceftriaxone), and can reduce the amount of antibacterial drugs used. With the introduction of corresponding national policies on “anti-bacterial drug bans and restrictions”, traditional Chinese veterinary medicine will play an increasingly important role. There are currently four new veterinary drug certificates for Echinacea that have been applied for, which fully demonstrates the value of Echinacea in clinical applications.

Studies have shown that Echinacea can inhibit hyaluronidase activity, effectively prevent the spread of viral receptors on the surface of living cells, and at the same time stimulate the body's immune system and improve its antiviral ability. Currently, it is known that Echinacea extract is effective against paramyxoviruses, influenza viruses, coronaviruses, herpesviruses, respiratory syncytial virus, vesicular stomatitis virus and poliovirus infections. In addition, Echinacea in combination with etravirine has a good effect on HIV [9]. Currently, the prevention and control of infectious diseases in livestock and poultry in China is a serious situation, with frequent outbreaks of old and new diseases, serious cross-infection, and mostly hidden clinical manifestations. Therefore, traditional Chinese veterinary medicine can be used in combination in areas where Western medicine is weak. In the future, the role and mechanism of the combined application of echinacea and Western medicine can be explored.

Echinacea can activate macrophages, increase tumor necrosis factor, increase interferon and interleukin indexes, enhance the phagocytic function of macrophages, and thus kill tumor cells. Studies have shown that Echinacea can significantly improve the growth and migration of tumors induced by hepatocellular carcinoma in vivo and in vitro. In addition, the anti-cancer activity of Echinacea is related to its flavonoid content, the biosynthesis and metabolism of phenylalanine and tyrosine, etc., and it can be safely used in combination with docetaxel in the treatment of cancer [10]. Livestock and poultry tumor diseases With the continuous increase in the development of animal husbandry, traditional Chinese veterinary medicine has attracted more and more attention in the prevention and treatment of tumor diseases. Studies have shown that Echinacea can induce differentiation of cancer cells, and has the effect of inhibiting cancer cell invasion, metastasis, signal transduction and reversing tumor drug resistance. In the future, Echinacea can be developed into an anticancer synergist and anticancer pain medication.

2.4 Antioxidant capacity

It has been found in the application process that Echinacea not only has good immune activity and antibacterial, anti-inflammatory and antiviral effects, but also has a strong antioxidant effect. The antioxidant activity of different organs of Echinacea purpurea in order is flowers, leaves, underground parts and peduncle. Antioxidant activity is significantly positively correlated with the content of Echinacea purpurea extract [11]. The antioxidant components of Echinacea purpurea are mainly polyphenols and polysaccharides. Both components can eliminate free radicals in the body or protect the body from excessive free radical oxidation by regulating enzyme activity. Echinacoside can improve the antioxidant capacity of yaks grazing in high-altitude areas. It can also provide good protection for intestinal cells under oxidative stress conditions, and has the potential to be used as an intestinal antioxidant.

3 Application prospects

3.1 Use as a feed additive

In the production of livestock and poultry, adverse external environments and inadequate feeding management can induce a variety of symptoms in pigs, such as diarrhea, coughing and growth arrest. Therefore, it is necessary to study the effect of Echinacea extract on pigs of different breeds and the optimal dosage. Scientists added Echinacea to the feed and carried out relevant experiments, and the results showed that: (1) Adding 1.5% Echinacea compound ultrafine powder to the sow's diet can significantly improve the growth performance and immune function of suckling pigs. 2. Adding 1.5% Echinacea compound ultrafine powder to the diet of weaned piglets that have received basic immunization can promote antibody production, prolong the time that antibodies remain in the body, improve the quality of the weaned piglet diet, reduce the feed-to-meat ratio, and improve immune function. ③Adding 1.8% Echinacea powder to the diet of nursery pigs can improve their growth performance, immune function and disease resistance [12]. Currently, Echinacea powder is widely used in clinical practice. Adding 0.1% Echinacea powder to the feed of sows throughout the entire period can improve their production performance and lactation ability. When piglets are stressed during weaning and group transfer, adding 0.1% Echinacea powder to the feed can help improve their resistance. Adding 0.2% Echinacea powder to the feed can assist in the treatment of various viral diseases.

Li Xiuju et al. studied the effect of a combination of Echinacea extract, oregano oil and peony seed meal polypeptide on the growth performance of broilers [13]. It was found that adding 2.0% of the combination of Echinacea extract, oregano oil and peony seed meal polypeptide to the diet significantly increased the average daily weight gain and feed conversion ratio of broilers and reduced mortality. Adding 0.4% Echinacea to the feed significantly increased the final weight, average daily weight gain, half-clean and full-clean rate, thymus index, bursa index, immunoglobulin (M and G) and NDV antibody titer of broilers. Although there was no significant difference in body weight among different strains, the weight gain rate showed a significant upward trend with increasing age. In addition, 1.0% and 1.5% Echinacea purpurea can significantly increase the feed intake and egg production of laying hens and reduce the feed-to-egg ratio under high temperature conditions. In actual production, 0.1% echinacea powder or echinacea solution is often used for mixed feeding or mixed drinking for 5 to 7 days, which significantly improves the immune protection effect, immune organ index and growth performance of broilers.

Awad Awad et al. studied the effect of Echinacea pur ‐ purea (EP) powder on the summer performance and reproductive performance of ducklings. The results showed that after adding EP powder, significant changes occurred in egg shell quality, egg production rate, feed consumption and feed conversion rate. The egg production rate and hatchability were highest with 0.25% EP added, followed by 0.5%; the hemoglobin, erythrocytes, white blood cells and lymphocytes were higher than those in the control group, and heterophil rate and H/L showed a downward trend compared with the control group; all serum components except total protein and alanine aminotransferase (ALT) enzyme were significantly changed [14]. Adding 0.25% EP to the diet improved the productive performance, reproductive performance, blood lipids and antioxidant status of ducks reared in summer, and has good application value.

Jia Qinghui et al. studied the effects of Echinacea compound ultrafine powder on the production performance and immune function of weaned ferrets and found that the addition of 1.0% and 1.5% compound ultrafine powder can increase the average feed intake and daily weight gain of weaned ferrets and reduce the feed conversion ratio; the serum IgA, IgM, and IgG levels are all increased, and the activity of total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) in the serum were significantly higher than those in the control group [15]. Adding 1% Echinacea compound ultrafine powder to the basal diet can improve the production performance, immune function and antioxidant capacity of weaned mink, providing a theoretical basis for the further development of herbal additives.

Xing Lei et al. studied the application effect of Echinacea compound ultrafine powder in puppy diets. The results showed that adding 0.50% and 0.75% Echinacea powder can increase the average daily weight gain of puppies; after 30 days of continuous use, the serum IgG, IgM, IgA, and IFN-γ levels were significantly higher than those of the control group [16]. Adding 0.50% or 0.75% Echinacea compound ultrafine powder to the basic diet can significantly improve the growth performance and immune function of puppies, which may be a future direction for the application of Echinacea.

3.2 Used as an immune modulator

Echinacoside has an immunomodulatory effect on yaks grazing in high-altitude areas. Echinacoside capsules can significantly increase the white blood cell and hemoglobin levels in yak blood, enhance the yak's adaptability to the low-oxygen environment at high altitudes, improve the body's immunity, and play an anti-inflammatory role. Seckin Cuneyt et al. studied the immunomodulatory effect of Echinacea in calves. The results showed that the levels of total IgG, γ-interferon, IL-1-β, IL-4 and TNF-α gene mRNA were significantly increased from 0 to 9 days after administration [17].

Scientists measured the lysozyme activity and antibody levels in the serum to explore the regulatory effect of Echinacea powder on the humoral immune system of broilers. The results showed that the index of the central immune organ of broilers in the Echinacea compound group was significantly higher, which is of great clinical significance. Behboodi Hamid Reza et al. conducted a study on peppermint, Echinacea and thyme and found that Echinacea and prebiotic mixtures have a certain promoting effect on the production performance, immune response, blood indicators and serum biochemical indicators of broilers, revealing the immunomodulatory effect of Echinacea [18]. Medicines that are currently used as products (such as Echinacea dispersible tablets) can significantly improve the specific and non-specific immune capabilities of broiler chickens and promote their growth and development. Echinacea oral liquid can simultaneously improve the indices of humoral and cellular immunity and regulate the immunity of chickens.

3.3 Application in disease prevention and treatment

Abdelfattah H. Eladl et al. studied the effect of IMU (a commercial product based on echinacea and black cumin) on the stress response of chickens vaccinated against H9N2 avian influenza virus (AIV-H9N2) with dexamethasone (VAC). The results showed that IMU significantly increased the protection rate after challenge, enhanced the HI antibody titer and heterophilic phagocytic activity, reduced the stress caused by dexamethasone, and lowered the viral titer. Oral administration of IMU can enhance the immune response after AI-H9N2 vaccination and reduce the pathogenicity of chickens infected with stress [19]. In addition, Echinacea can reduce the damage to the immune organs of chicks caused by the highly pathogenic infectious bursal disease virus and has a significant protective effect on chicks infected with the highly pathogenic IBDV.

Luo Junfeng et al. studied the antibody titer of echinacea granules (involving Newcastle disease and avian influenza) and its performance in terms of production performance and efficiency. Adding 1 kg and 2 kg of echinacea granules can both enhance stimulation of the immune system and improve antibacterial and antiviral capabilities, thereby improving the survival rate and production performance of chickens [20]. Echinacea extract has a significant immunostimulatory effect on Newcastle disease vaccine in chickens, which can increase the titer of serum antibodies, promote lymphocyte proliferation in peripheral blood, immune organ index and protection rate against virus challenge, and have a certain effect on weight gain and feed conversion ratio.

Compared with the group treated with levamisole hydrochloride and astragalus polysaccharide, the effect is more significant. Echinacea injection has no toxic effect on chicken embryos, can increase the survival rate of NDV-infected chicken embryos and reduce the HA titer of NDV-infected chicken embryos, and is promising as an effective control drug against Newcastle disease virus infection. In addition, Echinacea solution can be used to raise the antibody titer and prolong the peak antibody time after chicken vaccination. It is often used as an adjuvant treatment for mild influenza, atypical Newcastle disease and infectious bursal disease, and has an immune enhancing effect on Newcastle disease freeze-dried vaccine.

Studies have found that Echinacea can significantly improve the antibody levels and growth performance of piglets after injection with the PRRSV vaccine. Echinacea has a good effect against porcine epidemic diarrhea in vitro, and may mainly play a role in the adsorption stage of PEDV proliferation. Adding Echinacea ultrafine powder to the diet can significantly increase the antibody level of pseudorabies. In China, Echinacea and its related preparations are approved for the adjuvant treatment of swine viral diseases and to enhance the immune effect of vaccines. For example, Echinacea powder is approved for the adjuvant treatment of swine nameless fever, influenza and circovirus disease; Echinacea root powder and particles are approved for enhancing the immune effect of the inactivated vaccine for swine blue ear disease and swine plague vaccine. Explanation: The immune-enhancing effect of Echinacea is gradually being recognized in disease prevention and control, and it can be used in the future to treat and prevent more viral diseases.

4 Conclusion

In summary, Echinacea extract has the property of enhancing the body's immunity and can also work even in the case of immunosuppression. Therefore, it can become a new therapeutic drug and raw material for stimulating the immune system to deal with problems such as hyperactive or damaged immune systems. Green farming and antibiotic-free farming have become the trend in the development of animal husbandry. In the future, Echinacea may be developed into a livestock and poultry health product and natural antibiotic, and become a widely used Chinese medicinal herb in the livestock and poultry industry and feed additives.

References

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