The Impact of Plant Extracts on the immune function of animals
The Impact of Plant Extracts on the Immune System
Recent trends and developments in the area of animal nutrition have been characterized by an increasing interest in the potential impact of plants, herbs and spices on the immune function of animals (Table 1). The prohibited use of antibiotic growth enhancers since the beginning of the year 2006 necessitates to consider alternatives that may help to support the immune function and health status of farm animals (Bosi and Trevisi 2006). The maintenance of optimal immune functions is an important prerequisite for the production of healthy food from animal origin.
Table 1. Plants that have been tested with regards to the immune system
(Barker Benfield 2005)
Problems occur especially in young animals, for instance in piglets around weaning (Stokes et al. 2004). The importance of nutrients for the maintenance of optimal immune functions has been considered in the past mainly regarding the role of macro- and micronutrients for the defence mechanisms.
Protein level, specific immuno-active peptides (Coffey and Cromwell 2001; Valenti and Antonini 2005), amino acid intake (Chandrakant et al. 2006), dietary fat level and source and the levels and the intake of digestible or fermentable carbohydrates are important cornerstones for the maintenance of adequate immune functions (Plat and Mensink 2005; Watzl et al. 2005). Minerals, trace elements and vitamins have been shown to affect the innate and adaptive defence mechanisms (Chandrakant et al. 2006). Several “newer” feed additives have been shown to affect the cellular and humoral immunity.
Probiotics are increasingly used not mainly due to a growth promoting potential but due to their stabilizing effects on digestive processes (Taras et al. 2006). During the past years the interest in the potential use of phytogenic feed additives has considerably increased. Herbs, spices or in general botanicals can have a measurable impact on the function and reactivity of the immune system (Craig 1999). Research activities have been intensified in the last years, however, the understanding of the specific mode of action and the functional aspects of phytogenic additives still need much more in depth studies. This overview focuses on the potential role of herbal feed ingredients in the nutrition of farm animals with special regards to the immune system. In general, the explanatory power of many studies is rather limited due to the use of blends of different phytogenic feed additives, making it difficult to assess the individual effects. In addition, more research is warranted on the effects on intestinal physiology, microbiology and immunology. The understanding of gut physiology and disorders will allow to provide a better basis for adequate dietary options (Lalles et al. 2004). Mechanisms for the interaction of plants with the host’s immune system maybe related to intestinal and extraintestinal effects. Intestinal effects may be explained by effects on the microflora or by direct interaction with the gut immune system.
Effects of plant extracts on the intestinal microbial community
Due to the variety of active ingredients there is no typical reaction of the immune system to ingested plant materials. They may act due to the gross composition or due to substances that are secondary plant metabolites occurring in minor concentrations but that may have considerable potential to affect immune functions. The gastrointestinal tract is the primary organ coming that is exposed to botanical ingredients.
Effects on the immune function can be mediated either by alterations of the composition of the gastrointestinal microflora or by direct effects on the gut associated or general immune system. The significance of a “balanced” intestinal microecology for the health and well being of animals and humans has been recognized since long time and has also some impact in the immune function of the host. The intestinal microecology is a complex system that is important for the stability of the digestive processes, the prevention of the entry and colonization of pathogens and the development of the adaptive immune system (Smulikowska 2006). Evidence for the effectiveness of botanicals is given by clinical and physiological studies. Several field observations in pigs indicated that botanicals may affect the occurrence, severity and duration of post weaning diarrhoea in large scale production units. Products are available with several plant extracts with antibacterial active compounds.
Oregano leaves or juice is probably the most frequent ingredient for pig diets (Ken and Bilkei 2003; Sads and Bilkei 2003; Tedesco et al. 2005). The mechanisms by which the active compounds interact with the intestinal microflora are not well characterized. However, in vitro studies demonstrated effectiveness of the essential oils against pathogenic Escherichia coli (Hammer et al. 1999). Effectiveness of plants and extracts may differ considerably depending on the test system. In vitro studies tend to indicate more frequently positive effects of herbs or spices against pathogenic bacteria compared to in vivo trials (Jugl Chizzola et al. 2005; Hagmuller et al. 2006).
In vivo effects are often less clear, but faecal coliform counts were lower in post-weaning in pigs on 0.75 % of a herbal extract containing cinnamon, thyme and oregano (Namkung et al. 2004). Effects on the metabolic activity of the gastrointestinal microflora have also been reported for chicken, however, more in vivo studies are needed to confirm the results (Guo et al. 2003).
Effects of plants and plant extracts on the immune system
Only limited evidence is available considering the potential impact of plant extracts or botanicals with the intestinal or general immune system. The difficulty in such trials is the choice of parameters and the model.
Some study protocols chose vaccination trials, others used healthy animals or pathogen challenge trials. In vaccination trials, a dry extract prepared from Panax ginseng containing ginsenosides was shown to act as adjuvant inducing higher antibody titres in guinea pigs (Rivera et al. 2003). In a rat model of chronic Pseudomonas aeruginosa pneumonia ginseng extracts induced an activation of Th-1 type of cellular immunity and down-regulation of humoral immunity after parenteral application (Song et al. 1998). Aloe vera acemannan, a beta -(1,4)-acetylated mannan, can be an effective adjuvant in vaccination against some avian viral diseases in chicken (Djeraba and Quere 2000). Boswellic acids from B. serrata, after oral administration of 50-200 mg/kg inhibited the expression of the 24 h delayed type hypersensitivity reaction and primary humoral response to sheep red blood cells in mice (Sharma et al. 1996). Prolonged oral administration for 21 d increased the body weight, total leukocyte counts and humoral antibody titres of rats.
Several studies have been published in ruminants. Cows receiving 300 g/day/animal of whole-plant Echinacea purpurea meal with 1.26% of caffeic acid from the 10th day before the expected calving date had higher concentrations of gamma immunoglobulins after 3 weeks (Dymnicka et al. 2004). The extract of brown seaweed, Ascophyllum nodosum, enhanced monocyte oxidative burst in leukocytes from lambs during heat stress.
Phagocytic activity, and red and white blood cell glutathione peroxidase increased when lambs were ingesting supplemented feed (Saker et al. 2004).
Rosmarinus officinalis as feed supplement induced a reduction in mammary gland infections in goats (Savoini et al. 2003). Thuja occidentalis alone or in combination with Echinacea purpurea affected post vaccination reactions in goats and in vitro reactivity of bovine leukocytes (Schuberth et al. 2002; Grossi et al. 2004).
Ascophyllum nodosum seaweed extract was also tested in monogastric animals. Young pigs were subjected to enteric disease challenge with Salmonella typhimurium. Salmonella infection was accompanied by an acute phase response with increased rectal temperature and diminished feed intake.
Effects of the dietary supplement were noted with regards to growth performance, however, the immune response was not affected in the presence or absence of microbial challenge. In vitro results indicated some activation of porcine alveolar macrophages to higher PGE2 secretion (Turner et al. 2002). In another trial with Salmonella challenge a Quillaja saponaria extract had only small effects in weanling piglets with regards to growth performance and immune function (Turner et al. 2002). The dietary supplementation of a commercial preparation of plant extracts did not different growth rates in piglets compared to groups supplemented with colistin or carbadox. Total leukocyte counts were significantly higher in piglets treated with plant extracts than antibiotic-treated animals, and total neutrophils and lymphocytes were higher in plant extract-treated piglets than in colistin-treated ones. The shedding of haemolytic E. coli in the faeces of animals in the three treatment groups was not different (Savoini et al. 2002)
Oregano is a common ingredient of herbal feed additives and is often used in combination with several other herbs or spices. Only few studies are available using oregano as single supplement. Weaner piglets fed 1000 ppm of an oregano supplement had higher weight gain and lower disease incidence compared to the not supplemented control animals (Sads and Bilkei 2003).
In growth-retarded growing-finishing pigs fed a diet with 3000 ppm commercial oregano feed additive containing 60 g carvacrol and 55 g thymol/ kg improved daily gain and feed conversion rate and reduced mortality. The lymphocyte differentiation antigens CD4, CD8, MHC class II and the non- T/non-B cells in the peripheral blood and the proportion of CD4+CD8+ double-positive T lymphocytes in peripheral blood and mesenteric lymph nodes were higher in the treated animals (Walter and Bilkei 2004). A herbal extract with a blend of cinnamon, thyme and oregano did not have significant effects on the serum concentrations of immunoglobulin G in pigs (Namkung et al. 2004).
In prefarrowing and lactation diets of sows under field conditions 1000 ppm oregano as dried leaf and flower of Origanum vulgare, enriched with 500 g/kg of cold-pressed essential oils of O. vulgare, reduced sow mortality rate, culling rate during lactation and increased farrowing rate and piglet health (Allan and Bilkei 2005).
Oregano seems to be promising as an alternative to ionophore antibiotics for protection against E. tenella infection in broilers (Giannenas et al. 2004). Supplementation with ground oregano could reduce the adverse effects of E. tenella infection, as judged by the increased body weights and improved feed conversion rates.
Few studies are available on other plants or plant constituents on the immune function. Other species than ruminants, pigs and broilers have been rarely considered. A study in piglets on the interactive effects of beta -glucans obtained from Astragalus membranaceus and Escherichia coli lipopolysaccharide challenge did not indicate any effects on weight gain and feed conversion ratio. At an inclusion level of 500 mg/kg, glucans decreased the release of inflammatory cytokine and corticosteroids and increased the lymphocyte proliferation response of weanling piglets via enhanced IL-2 bioactivity (Mao et al. 2005).
Echinacea purpurea did not affect growth performance, weight loss, blood picture, plasma enzymes, and colostrum composition in sows or the performance of piglets. Several studies with piglets could demonstrate that post vaccination swine erysipelas antibodies increased in the treated groups indicating some immune stimulating efficiency. Feed conversion rate was more favourable in treated piglets (Maass et al. 2005).
Quillaja saponaria extract had some effects on serum immunoglobulin concentrations and growth rate in piglets, however, the results were not uniform and subjected to effects by birth weight. Lower birth weights and pigs with limited intake of colostrum immunoglobulins might be candidates for the oral administration of the saponin (Garcia et al. 2004).
Use of Echinacea is popular in horses, although data on effectiveness or safety are scarce. In a double-blind, placebo-controlled, cross-over trial with 8 horses the treatment with Echinacea increased phagocytic ability of neutrophils, increased peripheral lymphocyte counts and seemed to have stimulated neutrophil migration into the tissues. Some effects were also noted on the peripheral red blood cells, the concentration of haemoglobin and packed cell volume (O’Neill et al. 2002). Water extracts of Calendula officinalis and Melissa officinalis were administered orally to broilers between 10-21 d of age, before a challenge with inactivated Salmonella enteritidis on day 41. Cellular immune reactions against salmonella were modified in C. officinalis-treated birds (Barbour et al. 2004).
Conclusion and expectations
Plants and plant extracts have the potential to influence immune function in farm and companion animals. The current situation is characterized by a lack of well controlled studies fulfilling the requirements that would allow a comprehensive assessment of the effects on the immune system. A major flaw of many studies is the study design, especially the use of blends that do not allow a conclusion on the efficacy of individual plants. Further research work in that field is urgently warranted.
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1 Institut für Tierernährung am Fachbereich Veterinärmedizin an der Freien Universität Berlin, Germany
2 Institut für Ernährung, Veterinärmedizinische Universität Wien, Austria
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