Review of herbal medicine works in the avian species

Abstract Poultry meat consumption is increasing worldwide but the overuse of antimicrobials for prevention and treatment of diseases has increased antimicrobial resistance (AMR), triggering a major public health issue. To restrict AMR emergence, the government supports the optimization of natural products that are safe and easy to obtain with minimal side effects on poultry, humans, and the environment. Various studies have explored the potential of herbs in animal health for their antiviral, antibacterial, antifungal, antiparasitic, immunomodulatory, antioxidant, and body weight gain properties. Therefore, this study reviewed plants with potential application in avian species by summarizing and discussing the mechanisms and prophylactic/therapeutic potential of these compounds and their plant origin extracts.


Introduction
Poultry meat is consumed worldwide, but the overuse of antimicrobials to prevent and treat diseases in poultry has facilitated the emergence of antimicrobial resistance (AMR) [1]. AMR in poultry is reportedly [2] due to excessive use of antibiotics, including disease prevention programs, treatment of infections, accelerating growth, and increasing production [3]. Antibacterials are equally important drugs for treating human diseases [4]; therefore, AMR emergence in poultry requires discovering safe synthetic antibacterial substitutes.
Developing countries commonly use herbal medicines for treating various diseases [5] and herbs have become popular alternatives for poultry, as natural antibacterial and antifungal [6], antiprotozoal [7,8], antiviral [9], antioxidants, growth promoters, anti-inflammatory, and for increasing immunity and weight [10]. Herbs are potential antimicrobials due to their phenolic components (simple phenols, phenolic acids, quinones, flavones, tannins, and coumarins), terpenoids and essential oils, alkaloids and lectins, and polypeptides [11]. They are also relatively inexpensive with no harmful side effects due to simple absorption by the body. Hence, traditional remedies are widely used based on low cost, local availability, and practical application and do not require modern technology, such as refrigeration [12].
Herbs have other benefits in escalating host response to vaccination by inducing infection prevention through controllable procedures [13]. Therefore, the objective of this review is to evaluate in vivo studies on poultry as recommended references for scientists, field practitioners, and pharmaceutical manufacturers for poultry disease prevention and control.

Literature Search
We used an inductive approach to search electronic research databases and identify topics related to herbal medicine compounds or extracts that affect avian species as antiviral, antibacterial, antifungal, antiparasitic, immunomodulator, antioxidant, and body weight gain agents. We retrieved and reviewed 76 relevant articles investigating components that contribute to herbal medicine action in avian species.

Antiviral
Viruses are disease-causing agents that easily emerge, mutate, and spread, making them difficult to treat. In the poultry industry, there are several prevalent viral diseases, such as infectious bursal disease, Newcastle disease (ND), and infectious laryngotracheitis. Various vaccines are available to protect from such diseases, but most farmers prefer using herbs, as some believe that vaccination is ineffective. Further, vaccines are expensive, often have no Available at www.veterinaryworld.org/Vol.14/November-2021/8.pdf guarantee of bird safety, and are not easily accessible and occasionally noxious [14].
Yasmin et al. [15] reported that herbs, such as aloe species, Azadirachta indica (neem) and Commiphora swynnertonii (Burtt), can treat ND. However, aloe species are only effective for disease management rather than treatment, as there were no significantly different effects between treated and untreated groups. Surprisingly, neem leaf extract demonstrated anti-ND virus (NDV) properties by reducing NDV-stimulated splenocyte proliferation in mice compared with uninfected controls, while administering Burtt extract resulted in significantly lower mortality rates based on clinical symptoms and antibody titer.
Ou et al. [16] revealed that combined extracts of Rhizoma Dryopteridis crassirhizomatis and Fructus mume are effective against infectious bursal disease virus (IBDV) infection. The extract combination improved antibody levels and decreased viral load in the targeted organs. Similarly, Camellia sinensis (green tea) is effective for treating avian influenza (AIV) and inclusion body hepatitis-hydropericardium syndrome. Catechins from C. sinensis can suppress viral RNA synthesis by inhibiting endonuclease activity of RNA polymerase, thus potentially killing the virus. The interaction between catechins and viral neuraminidase proteins can prevent virus release [17,18].
Oil extract from Nigella sativa oil is suitable as adjuvants for AIV vaccines, as reviewed by Mady et al. [19]. The herbs also improved host response to vaccination. Administration of N. sativa oil on 14 days post-avian influenza vaccination stimulated lymphocyte proliferation and immunity development to 86% phagocytic percent [20]. Further, virgin coconut oil promotes T-lymphocyte production, improving T-helper cells, as well as stimulating antibody production from B-lymphocyte cells against AIV. However, a similar study shows that chicks given a 15 mL VCO/kg diet can diminish lymphocytes [21].
Tannin also has antiviral properties [22]. Latheef et al. [23] investigated the immunomodulatory activity of Withania somnifera, Tinospora cordifolia, and A. indica in chicks infected with chicken infectious anemia virus, observing that the herbs effectively resisted virus multiplication and pathogenesis. A combination of extracts of Ocimum sanctum, W. somnifera, Emblica officinalis, T. cordifolia, Mangifera indica, and Asphaltum (shilajit) was effective against AIV H9N2 and IBDV coinfection by enhancing antibody levels, thereby increasing survival rate and body weight gain, as well as reducing the viral load in the bursa of Fabricius [24]. More information about herbal plants with antiviral properties is documented in Table-1.

Antibacterial
The increasing population of bacteria resistant to antibiotics has threatened the safety of food products, such as chicken, and humans that consume them.
Many studies highlight the antibacterial properties of medicinal plants, which are as important as existing synthetic drugs. This potential has become the basis of increasing interest in choosing medicinal plants as an alternative medicine for poultry.
Tannin contained in Amla (Phyllanthus emblica) fruit powder [25] can kill bacteria by stimulating phagocytic cells [26]. Amla consumption stimulates increased lactic acid by Lactobacilli in the gut, which leads to diminished pH in the intestine to prevent coliforms from merging themselves within the intestinal mucosa and ultimately reduce tissue damage caused by failure from toxin production [27]. Salvia rosmarinus (rosemary) supplementation of the broiler diet can increase Lactobacilli counts and minimize Escherichia coli levels [28]. Similarly, Hanan [29] reported that Curcuma longa (turmeric) supplementation mitigated the viability of E. coli in the cecum, while increased Lactobacilli count affected weight gain.
Lannaon [30] found that herbal combinations of avocado leaves, guava, duhat, Eucalyptus, or tamarind trees can be a potential antibiotic for broiler chickens, which performed better than existing antibiotics. Another study by Mapatac [31] showed that administering guava decoction improved performance of broilers among other plants, namely, avocado (Persea americana) and malunggay (Moringa oleifera) leaves. However, other studies report that consumption of various parts of avocado may show effective antibacterial properties. These leaves and bark extracts contain saponins, tannins, flavonoids, and terpenoids, which are effective against E. coli and Staphylococcus aureus [32]. Further, the fruit contains defensin PaDef, which is potent in killing E. coli and S. aureus [33], and the seed contains a high phenolic compound effective against E. coli, S. aureus, and Streptococcus agalactiae [34].
Thyme also delayed the growth of E. coli [39] and S. Typhimurium [40] in vitro. The essential oil of cinnamon (Cinnamomum zeylanicum) improved antibacterial properties against foodborne bacteria, such as Klebsiella spp., E. coli, Listeria monocytogenes, and Bacillus spp. [41,42]. Moreover, Griggs and Available at www.veterinaryworld.org/Vol.14/November-2021/8.pdf Jacob [43] reported that cinnamon (C. zeylanicum) essential oil has potential natural antibiotic properties in poultry. In addition, Allium sativum, Allium cepa, and Menthe spp. can effectively reduce the growth of E. coli [44]. More information about herbal plants with antibacterial properties is documented in Table-2.

Antifungal
Aspergillus fumigatus causes frequent respiratory disease in birds called aspergillosis compared with other species, such as Aspergillus flavus, Aspergillus niger, Aspergillus Nidulans, and Aspergillus terreus [45]. Plant extracts contain phenolic compounds as potential antifungal and antiaflatoxigenic agents [46] using various mechanisms, such as inhibiting the production of aflatoxin B1, namely, syringaldehyde, sinapic acid, and acetosyringone [47], and decreasing A. flavus growth by targeting oxidative mitochondrial stress as a defense system using substances such as salicylic acid, thymol, vanillyl acetone, cinnamic acid, and vanillin [48].
The seeds and fruit extract of Carum copticum can be effective against Aspergillus spp. by inhibiting growth [56]. Further, leaf extract of Satureja bachtiarica contains thymol and γ-terpinene that can limit the growth of C. albicans, Candida krusei, and Kennedia glabrata [57]. The combination of Prosopis spicigera, Zingiber officinale, and Trachyspermum ammi are rich in alkaloids, amino acids, protein, sterols, and terpenes that are toxic toward C. albicans, C. krusei, C. tropicalis, and Candida glabrata [58]. The aromatic ring and the presence of free phenol hydroxyl of Mentha piperita and Thymus vulgaris L. formulation activity can damage fungal cell walls and membranes, such as Aspergillus, Penicillium spp., Fusarium, and Saccharomyces [59]. Similarly, oil extracts of Z. multiflora Boiss, Cinnamomum verum, and Pimpinella anisum can inhibit the growth of C. albicans, A. flavus, A. niger, and A. fumigatus [60]. The combination of Mentha arvensis, O. sanctum, and A. sativum was potent in preventing the growth of mycelial cells of A. fumigatus, Aspergillus parasiticus, and Penicillium spp. [61]. Allicin content of Allium tuncelianum is a toxigenic agent against C. albicans and Malassezia pachydermatis [62]. Similarly, the production of aflatoxin B1 of A. flavus was stopped by C. longa L. [63]. Further herbal extract studies on antifungal properties in poultry are listed in Table-3.

Antiparasitic Antiprotozoal
Antiprotozoal works by destroying the protozoa itself or inhibiting their growth and reproductive capabilities. Some commercial drugs, such as mebendazole, metronidazole, nitroimidazole dimetridazole, ornidazole, tinidazole, monensin, salinomycin, and semduramycin, have been regulated in many countries. Since then, diseases caused by protozoa has increased and resulted in economic losses.
Habibi et al. [64] observed that consumption of Nectaroscordum tripedale with diclazuril leads to improved growth performance, lesion score, the extent of bloody diarrhea, and oocyst count in individuals infected by Eimeria tenella. The herb can promote body mass gain and has previously been shown to alleviate lesion scores in birds compared with the control group.
Muthamilselvan et al. [65] evaluated other anticoccidial herbs, including Artemisia annua, pine bark, A. sativum, and C. sinensis. A. annua contains artemisinin that can stimulate reactive oxygen species to inhibit E. tenella sporulation and cell wall formation [66]. Further, sulfur content of A. sativum is effective in preventing E. tenella sporulation. Pine bark extract contains condensed tannins that influx the wall of oocytes, damage the cytoplasm, and inactivate endogenous enzymes responsible for the sporulation mechanism. Sporocytes in oocytes then turn abnormal and lead to diminished sporulation of oocytes in E. tenella, Eimeria Maxima, and Eimeria acervulina [67]. Selenium and polyphenol substances of C. sinensis are also effective anti-coccidiosis agents leveraging the same mechanism [68]. Further, previous reports show that allicin of A. sativum can effectively inhibit the sporulation of E. tenella [69]. N-3 fatty acids, flavonoids, and vernoside extracted from Linum usitatissimum [70], Ageratum conyzoides [71], and Vernonia amygdalina [72] are also potential herbs for the same parasites. A previous study reported that Carica papaya (papain) leaves [73] and saponin and betaine source plants (Cyamopsis tetragonoloba, Mesembryanthemum cordifolium, Morinda citrifolia, and Malvaviscus arboreus) lysed oocysts and protected the epithelial cells [74]. The essential oils of Origanum vulgare, olive leave extract, grape seed extract, guar, T. vulgaris, turmeric, and clove extract are also effective in destroying parasites [75]. The coccidiostat effect was also studied by Christaki et al. [76] who extracted apacox from the combination of Agrimonia eupatoria, Echinacea angustifolia, Ribes nigrum, and Cinchona succirubra, showing a coccidiostatic effect on E. tenella, despite the effect being significantly lower than the control group. Furthermore, Gefu et al. [77] showed that onion (A. cepa) is a potential antiparasitic against protozoa, such as Leishmania spp. The parasite was successfully eradicated after onion extract was administered at a 1.25 mg/mL dose [78]. The pronounced antiprotozoal activity of onion is due to the sulfur compound alliin and its ability to treat lesions caused by protozoa [79].
Histomonas meleagridis is protozoa causing high mortality and morbidity in poultry. A study by Hafez and Hauck [80] reported that essential oils combining C. verum, A. sativum, Citrus limon, and S. rosmarinus provide prophylactic effects that can diminish mortality in infected animals. The herbal properties as an antiprotozoal agent in poultry are summarized in Table-4.

Anthelmintic
The residual effects on chicken meat or eggs due to drug consumption and reducing synthetic drug use in chickens are pertinent issue, which not only causes resistance but also incurs additional residual impacts that endanger humans and the environment. Pumpkin oil (Cucurbita pepo L.) acts as an anthelmintic, as well as a natural laxative, by reducing helminth count and egg output [81,82]. Consumption of myrrh and thyme can also kill helminths, such as Trichinella spiralis [83]. Administering onion oil at Available at www.veterinaryworld.org/Vol.14/November-2021/8.pdf a concentration of 5 mg/kg/day is potent on mature worms and the cystic stage of T. spiralis, which can also enhance protective antibodies against the parasite [84]. In 2003, Zenner et al. [85] studied the influence of cinnamon oil on Trichomonas and H. meleagridis [85]. The oil contains trans-cinnamaldehyde and proanthocyanidins that promote its anthelmintic effects [86], disrupting the intestinal tissue of the parasites.
Both in vitro and in vivo studies have explored the anthelmintic activity of leaf extracts of Tephrosia vogelii and V. amygdalina against A. galli infections. The plant extracts comprise chemical elements, such as rotenoids, lactones, sesquiterpene, glycosides, tannins, and anthracenes, which all showed significant anthelmintic activity (p<0.05) against A. galli. The in vitro study demonstrated that both extracts effectively inhibited 74.7% and 63.7% of larval migration, respectively, while fecal egg counts decreased by 77.4% and 76.9%, respectively [87]. Other plants also target the same helminth. Papaya (C. papaya) extracts are effective anthelmintics against the growth of A. galli eggs due to proteolytic enzymes, such as papain, chymopapain, and lysozymes found in the latex, as well as the leaves [88]. Here, papain inhibited all developmental stages of the parasite. The study also suggested that the dust of bishkatali leaves can inhibit the development of A. galli eggs. The table below provides detailed information on various plants that act as anthelmintics in poultry (Table-5).

Lice and mice
The use of chemical insecticides may harm birds since the toxic effects directly jeopardize birds and possibly contaminate chicken meat. Jacob and Pescatore [89] proved that the aqueous extract of garlic and cinnamon oil kills lice and mice infestations in chickens, including Trichomonas, H. meleagridis, and head lice. Other herbal products effective against lice infestation in poultry include 2% aqueous solution of Pestoban [90] at a 1:30 dilution [91]. Another study showed that garlic extracts killed 96.5% of Dermanyssus gallinae infestation in layer farms [92] and mites show overall body damage under scanning electron microscope examination, including darkened leg coloring. Unfortunately, no further information exists on histopathological changes to mites induced by herbs. Pumnuan et al. [93] suggested that clove essential oil is a natural insecticide to control chicken lice (Lipeurus caponis L.), while spices such as Annona senegalensis, Tectona grandis, Securidaca longepedunculata, Indigofera hirsuta, Lophira lanceolata, Hyptis spicigera, Steganotaenia araliacea, Oxytenanthera abyssinica, Nicotiana tabacum, Jatropha curcas, Ficus exasperata, A. indica, and Parkia biglobosa are effective insecticides, with A. senegalensis being the most popular endogenous plant in controlling ectoparasites in backyard poultry [94]. Table-6 describes herbs having anti-ectoparasite properties for poultry (Table-6).

Immunomodulator
Medicinal plants contain compounds to stimulate immunity. Plant extracts have been recommended as immunomodulators due to their effects on the animal immune system related to phytochemicals, such as flavonoids, polysaccharides, lactones, alkaloids, diterpenoids, and glycosides. Many medicinal plants show less toxic side effects; hence, they are considered a safe treatment compared to synthetic therapy.
In poultry, plant extracts containing a mixture of cinnamaldehyde, carvacrol, and capsicum oleoresin as immunomodulators, showed regression of CD 40 LG, interferon (IFN)-G, and interleukin (IL)-6, indicating low inflammation, especially in the digestive tracts against avian coccidiosis caused by intestinal protozoan parasites and Eimeria spp. [95]. The overall effects were confirmed by higher levels of serum antibodies and enhanced pro-inflammatory cytokine production in the duodenum.
Another study on the role of Astragalus membranaceus as an immunomodulator showed improved immune activity in broiler chicks infected with lipopolysaccharide [96]. The study showed that the immune organ weight and IgG level increased, while liver and kidney functions improved. The plant also stimulated the growth of fecal microorganism composition. Tan and Vanitha [97] reported that Aloe vera leaves contain CARN750 that selectively stimulates immunomodulatory substances, such as cytokine and lymphocytes, while the roots and leaves of Panax ginseng are rich in saponin can effectively stimulate lymphocytes, cytokine, and IL-6 to improve macrophage performance. The herbs offered potential resistance to viral infections in birds by stimulating macrophage production, as well as T-cell-mediated immune responses and stimulating macrophages through TLR6 signaling and NF kappa B translocation, leading to cytokine production. The hematological profile also improved after synthesizing more hemoglobin in the bone marrow after hepatic cells released erythropoietic factors. In a study of 42-day-old broilers given sheep red blood cells, turmeric rhizome powder improved blood immunoglobulin A, immunoglobulin G, and immunoglobulin M levels, and minimized the monocyte ratio [98]. However, insufficient doses may fail to improve immune response [99]. Tamam et al. [100], and Das et al. [101] reported that C. verum essential oil promotes macrophages,  (Table-7).

Antioxidants
Adding Borreria latifolia to the chicken diet can help prevent lipid peroxidation [102]. The phenols act to minimize lipid peroxidation and inhibit free radicals and oxidative deterioration, which can improve chicken meat quality. Antioxidant properties have also been observed in broiler chicken meal supplemented with a mixture of bitter leaf meal and M. oleifera leaf without affecting serum biochemistry of the experimental birds [103]. Both leaves contain phytochemicals, such as flavonoid, quercetin, and phenol that can increase serum antioxidant enzymes, such as glutathione, catalase, and superoxide dismutases, and decrease lipid peroxidation. A review by Ali et al. [104] also mentioned that cinnamon was safe for poultry health and had positive environmental and economic aspects. Bravo et al. [105] demonstrated increased energy utilization and growth performance in broilers after administering a mixture of cinnamaldehyde, carvacrol, and capsicum oleoresin. The additive effect of plants supports antioxidant enzyme function of the mucosal layer cells that protect the tissue [106], suggesting the potential for plant extracts as antioxidants. The table shows herbs that act as antioxidants for poultry (Table-8).

Body Weight Gain
Administering medicinal plants in animal production health are increasing following several studies that have highlighted the additive effects of plants in improving biological development. Herbal medicines, such as white turmeric (curcumin), red ginger (zingerone), galangal (methyl-cinnamic), and garlic (allicin), are alternative treatments due to their ability to increase the viability of chickens, as indicated by a decrease in the percentage mortality and body weight gain. These plants improved digestibility and durability of treated chickens, resulting in better nutrient intake [107]. Further, a combination of A. sativum, Urtica dioica, Inula helenium, Glycyrrhiza glabra, R. officinalis, Chelidonium majus, Thymus serpyllum, Tanacetum vulgare, and Coriandrum sativum increased chicken weight gain and food conversion ratio in an anti-coccidial study [108]. This formula is rich in polyphenols that reduce the oocyst output and decrease the total lesion score, thereby improving digestibility. Naderi et al. [109] also revealed that adding 2.5 g of turmeric powder to 1 kg poultry feed significantly increased body weight gain during the starter (0-21 days) period. Including 5 g of C. longa powder in a 1 kg diet also improved growth rates of broilers. Turmeric not only increased the weight of bursa of Fabricius but also promoted the production and secretion of bile and digestive enzymes, thereby improving digestion and absorption of dietary nutrients. Another herb with the same potential is Allium hookeri root [110], which contains organosulfur compounds, proteins, volatile sulfur, prostaglandins, fructans, vitamins, and polyphenols that improved

Parts used Mode of action Agent References
Capsicum L. Capsicum Fruits Regression of CD 40 LG, IFN-G, and IL-6, indicating low inflammation, higher levels of serum antibodies and enhanced pro-inflammatory cytokine production in the duodenum Eimeria spp. [95] A. membranaceus Huangqi Leaves, roots Improved immune activity in broiler chicks infected with lipopolysaccharide The immune organ weight and IgG level increased, while the liver and kidney functions improved. The plant stimulated the growth of the fecal microorganism composition  [111]. Curcumin and turmeric can enhance body weight gain due to their effects on feed intake and improved growth [112]. Dosoky and Setzer [113] showed that curcumin acts as a stimulant, carminative, stimulates digestibility, has antimicrobial properties, and is a gastric toxicity inhibitor, while turmeric (1%) acts as an antioxidant in promoting positive feed conversion ratio [114].
Moringa stenopetala leaf meal exhibits high pepsin soluble nitrogen (82-91%), low acid detergent-insoluble protein (1-2%), and low antinutritional factors [115]. It may also contain Vitamin E [116] to improve intestinal microarchitecture and produce acidic mucin, as shown in treated chickens [117]. Cinnamon and thyme administration in a dose of 0.5%, 1% thyme, and 1% cinnamon in chickens with colibacillosis effectively decreased total aerobic bacterial count of the gastrointestinal tract and improved body performance in chickens [118]. These herbs altered cell wall permeability of bacteria and created a pore that leads to osmotic shock and leakage of the cytoplasm, resulting in cell death [119]. Another study showed that nettle or lemon balm can improve chicken body weight after 21 days of administration [120]. Nettle has anti-inflammatory properties and high flavonoid content that relaxes smooth muscles of the digestive tract and bile ducts [121]. It is also rich in antioxidants that act intracellularly [122], which could be responsible for better animal performance. The study also revealed that herbs successfully replaced antibiotic growth promoters; moreover, adding 0.1%, 0.25%, and 0.5% crude preparation of fenugreek, ginger, and turmeric in the diet-stimulated growth rates of gut layers by significantly reducing the excretion of fecal anaerobic bacteria while maintaining excretion of beneficial bacteria [123]. Abdullahi et al. [124] revealed that herbs stimulated the production of IL-2, IL-10, tumor necrosis factor, and IFN-γ, improving Ig antibody levels in serum, thereby promoting daily weight gain. The table below describes various herbs that improve body weight promoters in poultry (Table-9).

Anticancer
Recent studies on cancer have bolstered our medical understanding. Cancer occurs not only in humans but also in animals and is frequently described as cellular mutation to DNA within cells because of free radicals in the body affected by exposure to ionizing radiation and other experimental toxins [125]. In avian species, cancer is often related to viruses, namely, avian leukosis virus, Marek's disease virus, reticuloendotheliosis virus, and lymphoproliferative disease viruses [126].
Chemotherapy is considered the sole treatment for cancer. The genes inside the nucleus of cells will be damaged. Some chemotherapeutic drugs operate by splitting cells, while others aim to inhibit the process of gene replication before cell splitting. In some cases, however, chemotherapy can damage healthy cells and release a protein that supports tumor growth [127].
Herbs can be used in various ways to support cancer treatment by relieving the undesirable effects of chemotherapy, accommodating convalescence after chemo-and radio-therapeutics, promoting the conventional cancer treatment, supporting conventional treatment in some conditions, assisting in cancer prevention, strengthening immune function, and promoting various tracts influenced by cancer [128].
Grape seed proanthocyanidin extract is a polyphenolic antioxidant with pharmacological and nutraceutical benefits, including anticancer properties [129]. Proanthocyanidins can scavenge free radicals 20-fold better than other antioxidants, such as Vitamin C, Vitamin E, and β-carotene, and have potential as cancer growth inhibitors with significantly greater protection against free radicals, free radical-induced lipid peroxidation, and DNA damage [130]. Moreover, seed grape oil has previously shown antioxidant components and effectively worked as a natural antioxidant in broilers [131].
Natural killer (NK) cells known as innate immune cells can eradicate tumor cells [132] by delivering cytotoxic granules containing perforin and granzymes, which lyse target cells [133]. Ashwagandha (W. somnifera Dunal) may improve NK cell function in ovarian tumor in laying hen model to diminish occurrence and development of ovarian tumor tissue [134]. The plant has cytolytic properties to fight human tumor cell lines [135,136]. Other herbs that promote NK cells activity are found within the combination of W. somnifera, Glycyrrhiza glabra, Z. officinale, O. sanctum, and Elettaria cardamomum, which can be fortified in regular tea [137].
A formulation of dandelion root, mustard leaf, and safflower leaf can improve innate chicken immunity, including peripheral blood lymphocyte proliferation, nitric oxide production by macrophages, and free radical scavenging activity, as well as prevent chicken tumor cell development [138]. Other studies showed that safflower (Carthamus tinctorius) can augment natural immunity and medicate cancers. Safflower petals contain polysaccharides that augment splenocyte proliferation and stimulate macrophage activation, as well as significantly diminish the viability of chicken tumor cells [139].
Turmeric (C. longa Linn.) contains high levels of antioxidants and anti-inflammatory properties [140]. Daily curcumin intake produces a significant and dose-dependent reduction in spontaneous ovarian cancer occurrence and tumor growth, presenting a recommended chemopreventive strategy for ovarian cancer [141]. Various molecular mechanisms revealed that NF-kB and STAT3 signaling pathways were significantly inhibited. However, the nuclear factor erythroid 2/ Available at www.veterinaryworld.org/Vol.14/November-2021/8.pdf A. vera Aloe Leaves The polysaccharides affected the intestinal microflora and reduced intestine lesion, promoting weight gain and better performance [111] C. longa and C. aromatica

Curcumin and turmeric
Rhizomes Curcumin is a stimulant, carminative, stimulates digestibility, has antimicrobial properties, and is a gastric toxicity inhibitor, while turmeric (1%) acts as an antioxidant in promoting feed conversion ratio [112][113][114] M. stenopetala Cabbage tree Leaves The bioactive compounds improved the intestinal microarchitecture and the production of acidic mucin [115][116][117] C. verum and T. vulgaris

Cinnamon and thyme
Barks and leaves Decreased the total aerobic bacteria count of the gastrointestinal tract and improved the body performance of the chicken [118,119] U. dioica Nettle Fruits Nettle has anti-inflammatory properties and high flavonoid content that relaxed smooth muscles of the digestive tract and the bile ducts. It is also rich in antioxidants that act intracellularly that might be responsible for better animal performance [120][121][122] T. foenum-graecum Fenugreek Seeds Stimulated the growth rate of layers by significantly reduction of excretion of fecal anaerobic bacteria and no changes in excretion of beneficial bacteria. The herbs stimulated the production of IL-2, IL-10, TNF, and IFN-γ, improving the Ig antibody level in serum, thereby promoting daily weight gain  heme oxygenase 1 antioxidant pathway was stimulated by curcumin intake in a dose-dependent manner in ovarian tissue [141]. A compilation of herbs that have anticancer properties for poultry is shown in Table-10.

Conclusion
This review demonstrated that certain plants are potential medicines for avian species. Various plants present numerous advantages, including minimal side effects potentially harmless for birds, humans, and the environment, as well as limiting drug resistance and diminishing residue in chicken meat and eggs. Further studies on other medicinal plants applied to chickens are needed to explore the potential of other plants on avian health. In the future, natural products with low side effects to fight poultry disease may be possible; moreover, some possible limitations in this review can exist. More methodological work is needed to offer more medicinal plants as alternatives to synthetic drugs that are effective and safe for poultry, humans, and the environment.