Study on Lycopene Antioxidant

Lycopene is a non-cyclized isomer of β-carotene. It is a natural pigment found in plants, mainly in the ripe fruit of nightshade plants in the Solanaceae family, giving tomatoes and their products their red color. Lycopene has the strongest antioxidant activity of all carotenoids. Lycopene is very effective in controlling degenerative diseases, preventing cardiovascular disease, prostate cancer, digestive tract cancer, skin cancer, reducing the risk of pancreatic cancer and uterine cancer, and preventing the formation of harmful cholesterol.

Blum et al. [1] found that lycopene can reduce the formation of foam cells induced by oxidatively modified low-density lipoproteins by reducing lipid synthesis and downregulating scavenger receptor activity and expression. Lycopene has strong antioxidant and anti-inflammatory abilities. For example, adding lycopene to the feed can significantly increase the expression levels of NFE2L2 and HMOX-1 genes in the liver of quails through the protein kinase B/signal pathway [2]. The author reviews the mechanisms of lycopene's antioxidant, anti-inflammatory, anticancer, hypoglycemic and anti-cardiovascular disease effects, as well as its effects on animal production, health and product quality, with a view to providing a reference for the application of lycopene in animal production.

1 Mechanism of action of lycopene

1.1 Antioxidant effect

Lycopene powder is an antioxidant that can inhibit the production of hydrogen peroxide, nitrogen dioxide and hydroxyl radicals, thereby exerting an antioxidant effect and protecting DNA, proteins and lipids from oxidative damage. Research on the mechanism of lycopene's antioxidant effect has found that in fluorine-induced oxidative stress in mouse cells, lycopene in combination with VE can reduce the activation of c-Jun N-terminal ki-nase (JNK) in the mitogen-activated protein kinase (MAPK) pathway and extracellular regulated protein kinase (ERK), thereby protecting DNA, proteins and lipids from oxidative damage. MAPK) pathway, by reducing the phosphorylation levels of c-Jun N-terminal ki-nase (JNK) and extracellular regulated protein kinases (ERK), it downregulates the expression levels of pro-apoptotic genes such as caspase-3, the expression levels of pro-apoptotic genes such as caspase-9 and Bax genes, reducing the cell aggregation and toxicity caused by fluoride poisoning, and increasing the expression levels of antioxidant enzymes glutathione peroxidase (GPX), superoxide dismutase (SOD) and the anti-apoptotic gene B-cell lymphoma-2 (Bcl-2). The expression levels of SOD and the anti-apoptotic gene B-cell lymphoma-2 (Bcl-2) were reduced, thereby alleviating the oxidative stress induced by fluorine poisoning [3]. In the oxidative and biochemical stress responses of mice cells caused by carbofuran, the addition of lycopene 18 mg/ (kg·BW) can significantly increase the cell albumin, protein and lipid content, increase serum acetylcholinesterase, catalase (catalase, CAT), SOD and glutathione (glutathione, GSH) activity, and significantly reduce the oxidative stress and biochemical stress caused by carbofuran [4].

In lipopolysaccharide (LPS)-induced oxidative stress, lycopene can improve LPS-induced oxidative stress by increasing SOD and GPX activity, down-regulating plasma inflammatory factor levels and inflammatory mediator expression [5]. Tomato lycopene at a dose of 50 mg/(kg·BW) per day can improve the D-galactose activity and histopathological damage in the hippocampus of CD-1 male mice with cognitive deficits, restore the amount of brain-derived neurotrophic factor (BDNF), significantly increased the mRNA expression of heme oxygenase-1 (HO-1) and NADPH quinineoxidoreductase -1 (NQO-1), downstream of the nuclear factor-E2-related factor 2 (Nrf2) pathway, in the serum of D-galactose-treated mice, and significantly reduced the tumor necrosis factor-alpha (TNF-α) level. reductase-1 (NADPH quinineoxidoreductase-1, NQO-1) mRNA expression, significantly reducing tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) mRNA expression. IL-1β) mRNA expression. Lycopene also reduces oxidative damage to neurons by activating Nrf2 or by translocating and inactivating nuclear factor κB (NF-κB) [6]. In addition, lycopene can relieve oxidative stress induced by amyloid β-protein (Aβ) and inhibit mitochondrial-mediated apoptosis. The mechanism is that lycopene inhibits the release of cytochrome C (Cyt C) and the activation of caspase-3, promotes the opening of the mitochondrial membrane permeability transition pore, effectively restore the amount of ATP in neurons, enhance mitochondrial activity, prevent DNA damage and increase the level of mitochondrial transcription factor A (MTFA) [7].

In oxidative stress-induced acute pancreatitis (AP), the addition of lycopene (50 mg/kg) can significantly reduce the serum myeloperoxidase (POD), α-amylase, and lipase activities, as well as TNF-α and nitric oxide (NO) levels, downregulate the expression of inducible nitric oxide synthase (iNOS) gene, enhance pancreatic GSH activity, and significantly improve AP [3]. NO) levels, downregulate the expression of inducible nitric oxide synthase (iNOS) gene (iNOS), enhance pancreatic GSH activity, and significantly improve AP [3]. Lycopene can significantly reduce the concentration of malondi- aldehyde (MDA), total sialic acid, and DNA fragments in the serum of rats with colitis, increase the activity of antioxidant enzymes, and prevent the occurrence of colitis [8]. Lycopene also has an antioxidant effect on the kidneys. Lycopene and rosmarinic acid, when used together, can significantly reduce gentamicin-induced nephrotoxicity in rats, including blood urea nitrogen, serum creatinine, MDA, autophagy marker protein, proapoptotic protein Bax and iNOS levels, and significantly increase SOD, GSH, GPX activity and anti-apoptotic protein Bcl-2 expression levels, relieving oxidative stress in the kidneys [9].

Another study showed that lycopene, as an antioxidant, can reduce oxidative stress in the kidney by inhibiting hepatocyte nuclear factor-1α (hepatocyte nuclear factor-1α, HNF-1α), reducing the affinity of low-density lipoprotein (LDL) receptors and the expression of sterol regulatory element binding protein-2 (SREBP-2), downregulates the expression of proprotein convertase subtilisin/kexin type (PCSK), a proprotein convertase, reduces the binding ability of apolipoprotein C II (APO C II) and lipoprotein lipase (LPL), regulates the concentration of total glutathione (tGSH) and CAT, inhibits protein carbonylation, and thus inhibits oxidative stress-induced hepatotoxicity. Lycopene can also significantly improve the cognitive deficits of P301L transgenic mice by significantly reducing the levels of MDA, GPX activity, and Thr231/Ser235, Ser262, and Ser396 phosphorylation [4].

1.2 Anti-inflammatory and anticancer effects

Inflammation is a local response to tissue damage in a particular part of the body, characterized by swelling, fever and pain. Increasing the intake of anti-inflammatory ingredients can prevent the occurrence of non-communicable diseases. Lycopene has been shown to have anti-inflammatory effects. During acute inflammation, immune cells clear pathogens through various pathways. During persistent or repeated inflammatory responses, immune cells exert anti-inflammatory effects by secreting cytokines to impair the function of macrophages. The onset and progression of many non-communicable diseases, including heart disease, neurological diseases and type 2 diabetes, are related to or affected by inflammation. When the body is in a state of balance, the function of inflammation is to eliminate the primary factors that cause cell damage, to dispose of necrotic cells and damaged tissues caused by damage and inflammation, and to initiate tissue repair. Acute inflammation is one of the key survival mechanisms of all higher vertebrates. If acute inflammation is not resolved, it may lead to chronic inflammation. Chronic inflammation is not part of the body's self-repair process and may trigger a destructive process. Damaged tissues release pro-inflammatory cytokines and other biological inflammation mediators into the body's circulation, converting tissue-based low-grade inflammation into systemic inflammation.

In addition, autoimmune diseases and long-term exposure to irritants can also lead to systemic inflammation. Although the inflammatory response process depends on the exact nature of the initial stimulus and its location in the body – for example, bacterial pathogens trigger toll-like receptors (TLR) and viral infections trigger type I interferons – they all have a common pro-inflammatory mechanism. Cell surface pattern recognition receptors (PRRs) recognise harmful stimuli, activate inflammatory signalling pathways, release inflammatory markers and recruit inflammatory cells. Inflammation activates intracellular signaling pathways, which subsequently activate the production of inflammatory mediators. Inflammatory stimuli mainly include microbial products and cytokines such as IL-1β, interleukin-6 (IL-6), and TNF-α, which mediate inflammation through interactions with TLR, IL-1β receptor (IL-1R), IL-6 receptor ( IL-6R) and TNF receptors.

Activation of these receptors triggers important intracellular signal pathways, including the MAPK, NF-κB, Nrf2, Janus kinase (JAK), signal transducer and activator of transcription (STAT) pathways. Lycopene has been shown to inhibit the binding ability of the inflammatory signaling pathway NF-κB and stress protein-1 (SP1), and to reduce the expression of the insulin-like growth factor-1 receptor (IGF-1R) and the concentration of reactive oxygen species (ROS) in SK-Hep-1 cells. Lycopene can inhibit obesity, inflammatory response and related metabolic disorders induced by high-fat diet in mice. The mechanism is that lycopene inactivates the NF-κB signaling pathway by reducing the phosphorylation of p65 and IκB, which act as regulators of the NF-κB pathway. This effect can be regarded as the anti-inflammatory effect of lycopene [10].

The anti-inflammatory effect of lycopene can also be observed in colorectal cancer cells by inactivating the NF-κB signaling pathway. Lycopene inhibits the expression of pro-inflammatory factors TNF-α, IL-1β, IL-6 and cyclooxygenase (COX) and iNOS by inhibiting the activation of NF-κB and JNK [11]. The consumption of tomatoes or lycopene is negatively correlated with the incidence of colorectal and rectal cancer in a dose-dependent manner. The mechanism is that lycopene exerts an anti-intestinal cancer effect by inhibiting the proliferation of colon cancer cells. After treating colorectal cancer cells with 12 μmol/L lycopene, found that the proportion of colorectal cancer cells undergoing late apoptosis or necrosis was higher than that of colorectal cancer cells undergoing early apoptosis. It was also found that lycopene significantly reduced the expression of various pro-inflammatory mediators such as IL-1β and TNF-a, as well as the activity of the pro-inflammatory enzyme COX-2 [12].

Studies have found that lycopene has a good anti-inflammatory effect in the process of colon cancer [13]. For example, lycopene consumption of 300 μg/d can reduce the inflammatory response and the activity of inflammatory markers in rats with induced colitis. The mechanism is that lycopene intake reduces the expression of downstream genes in the MAPK signaling pathway, thereby reducing the risk of colorectal cancer [14]. There are currently a large number of systematic reviews on the effects of lycopene on different diseases, such as prostate cancer and bladder cancer, cardiovascular risk and metabolic syndrome. These reviews of the anti-inflammatory ability of lycopene are somewhat lacking, and it is not clearly stated whether the differences between lycopene-source varieties and the different lycopene contents have an effect on the anti-inflammatory ability. For in vivo studies, it is not only necessary to focus on the intake of lycopene, but also to actually measure the concentration of lycopene circulating in the blood plasma or serum to understand the effect of lycopene on human health. Experimental studies are still needed on the role of lycopene in immune system regulation.

1.3 Hypoglycemic effect

The incidence of type 2 diabetes mellitus (T2DM) is gradually increasing with the improvement of living standards and changes in eating habits. At present, certain specific components of vegetables and functional foods have been shown to have a good therapeutic effect on T2DM. Therefore, dietary intervention may be an important strategy for the prevention and treatment of T2DM. In diabetic patients, a high-fat diet and streptozotocin lead to insulin dysfunction and a decrease in secretion capacity, resulting in impaired glucose and lipid metabolism. Lipid metabolism disorders and pancreatic damage in the body lead to lipid peroxidation and the production of free radicals, increasing the formation of advanced glycation end products, which in turn damage various organs [15-16].

The above processes are all involved in oxidized low density lipoprotein (Ox-LDL), indicating that Ox-LDL can accelerate the development of T2DM. The beneficial effect of lycopene in diabetes is related to its strong antioxidant capacity. Lycopene reduces endothelial dysfunction by reducing Ox-LDL-induced oxidative stress. In addition, lycopene intake can lower glucose levels, increase insulin levels, and improve insulin dysfunction in T2DM patients, reduce the harmful effects of T2DM on the body, and improve liver steatosis [15-18]. In summary, plasma lycopene levels are negatively correlated with the incidence of T2DM, and lycopene is considered to have potential anti-diabetic effects.

1.4 Anti-cardiovascular disease effects

Cardiovascular and cerebrovascular diseases (CVD) can be divided into congenital CVD and acquired CVD according to their causes. Congenital CVD includes ventricular septal defects, stenosis of the main artery, etc., which may be related to heredity; acquired CVD includes chronic valvular disease, dilated cardiomyopathy, etc. CVD is one of the main reasons for the decline in animal growth performance and productivity, and the increase in culling rates. Epidemiological studies have found that the Mediterranean countries have a lower CVD mortality rate than Western Europe and the United States. This may be related to the Mediterranean diet culture, which includes a lot of fruit and vegetables. The Mediterranean diet often includes tomatoes, which has prompted many researchers to look for a link between lycopene and CVD. Epidemiological studies have provided important evidence supporting the direct and effective role of lycopene in preventing CVD.

Recent studies have shown a negative correlation between lycopene intake and the incidence of myocardial infarction, angina pectoris and coronary artery insufficiency [19-20]. Many researchers have reported lower lycopene levels in the plasma of patients with hypertension, myocardial infarction, stroke and atherosclerosis. In studies on how lycopene intake affects cardiovascular disease, multiple repeatable experiments have highlighted that lycopene intake can normalize coronary endothelial-type iNOS activity and NO levels, inhibit the mevalonate pathway of cholesterol biosynthesis, and improve endothelial function. In different animal models of CVD, lycopene intake can reduce inflammatory damage and improve the ability of lipoprotein profiles and their conversion [21-23]. Lycopene treatment can reduce cholesterol levels, carotid intima-media thickness and plasma oxidative damage markers, increase high-density lipoprotein (HDL), and significantly relieve postprandial oxidative stress. The above studies all suggest the intervention effect of lycopene in cardiovascular disease. However, in modern medicine, whether lycopene has an effect on CVD is still a controversial topic that requires further well-designed clinical studies.

2 Application of lycopene in animal production

2.1 Effect of lycopene on animal health

Free radicals in animals are in a dynamic balance between production and removal. In current intensive animal production, free radicals are formed in large quantities under conditions of stress, rapid growth, high fertility and intensive metabolism in livestock farming, resulting in excess free radicals in the body that cannot be removed, causing oxidative stress in animals, resulting in chronic damage to the body and reducing the animal's resistance to disease. The discovery that lycopene can inactivate singlet oxygen molecules is of great significance, and the role of lycopene in health and disease is attracting increasing attention. At the same time, it has a positive effect on the application of antioxidants in the diet.

Hu Minyu [24] found that lycopene can prevent the biosynthesis of cholesterol, increase the level of high density lipoprotein cholesterol (HDL-C), and at the same time have a positive effect on modifying the formation of foam cells induced by LDL. This study shows that the intake of certain antioxidants by the body can reduce the concentration of active free radicals, control the production of free radicals by reducing the efficiency of the extended stage in the free radical chain reaction, or work by inhibiting the production of free radical initiators. Therefore, antioxidants play an important role in maintaining normal body functions and maintaining good health. Currently, improving animal health by adding antioxidants to feed has become an important nutritional control method.

Studies on pigs have shown that β-carotene can significantly increase the relative expression of the chemokine (C-C motif) ligand 25 [chemokine (C-C motif) ligand 25, CCL25] gene (CCL25), promote the secretion of antibodies by piglet epithelial cells, reduce the expression of pro-inflammatory cytokines, enhancing the piglets' immunity and antioxidant and anti-inflammatory abilities [25]. Beta-carotene can increase the content of beta-carotene in the sow's feces during the late stages of pregnancy, while also increasing the concentration of serum immunoglobulin A (IGA) and immunoglobulins such as colostrum IgM, IgA and IgG, enhances the immune function of sows [26] and improves the birth weight and individual weight of piglets [27]. Beta-carotene can significantly reduce the MDA level in the intestines of weaned piglets, enhance the activities of GSH-Px and SOD, and dose-dependently inhibit the phosphorylation levels of JNK and p38MRK, indicating that β-carotene can relieve the endoplasmic reticulum stress response and apoptosis in the intestines of weaned piglets, exert an anti-inflammatory effect, and reduce weaning stress damage [28].

A number of studies have found that lycopene can increase the feed intake, feed conversion efficiency and carcass weight of poultry, increase the content of VC, VE and VA in poultry serum, reduce the content of cysteine and MDA in serum and internal organs, and increase the content of HDL. Sahin et al. [29] showed that feeding different doses of lycopene supplements (50, 100, 200 mg/kg diet) can increase the live weight and feed conversion rate of Japanese geese under heat stress (34 °C) and increase the activity of antioxidant enzymes in the body [28-35]. Lycopene may also play an important role in the antioxidant defense system of poultry.

Sevcikova et al. [35] showed that lycopene supplementation can alleviate oxidative stress and improve the antioxidant capacity of Japanese quails under high temperature stress. After laying hens consume a diet containing lycopene, lycopene not only has a positive effect on the immune system of laying hens, but also stores in the egg yolk and plays a beneficial role in the human body [36]. In addition, lycopene can also improve lipid metabolism and lipid distribution in chickens [37]. Adding lycopene to the feed can significantly increase the expression of the NFE2L2 and HMOX-1 genes in the quail liver through the protein kinase B ( PKB) signal pathway significantly increased the expression of NFE2L2 and HMOX-1 genes in the liver of quails, improved antioxidant capacity and reduced disease incidence [38]. Beta-carotene also significantly increased the IgA content in the serum of 21-day-old and 42-day-old Hy-Line brown chickens [30].

Studies on ruminants have also found that lycopene can improve the production performance of meat goats fed a high-concentrate diet, increase the content of polyunsaturated fatty acids in lamb meat, and improve the antioxidant properties of the longissimus dorsi muscle. Adding lycopene to the feed can also improve the growth and development of meat sheep, their production performance, and the flavor and meat quality of the mutton. The mechanism may be that it relieves the oxidative stress generated during feeding by regulating the endocrine system of the meat sheep, improves thyroid function, and thus improves the animal's appetite [29]. Adding tomato pomace containing 13 g/kg lycopene to sheep feed can balance oxidative stress in sheep by inducing the transcriptional activity of genes involved in oxidative defense [39].

In summary, the addition of lycopene to animal feed can improve the immune function of livestock and poultry, enhance resistance, prevent disease, increase the stress resistance of sick animals, reduce the culling rate of livestock and poultry, and effectively reduce the economic losses caused by disease.

2.2 Effect of lycopene on the quality of animal products

The increase in the production capacity of meat-producing livestock and poultry may be accompanied by a decrease in meat quality. Oxidative stress can significantly change the palatability and nutritional properties of meat, affect muscle tissue development, reduce muscle water retention and shear force, increase drip loss and pH, increase lactic acid, phosphorus and cholesterol content, and reduce intramuscular fat, free fatty acids, muscle protein and fat content, making lipids and cholesterol prone to oxidation and producing an unpleasant odor. Adding lycopene to livestock feed not only enhances the animals' stress resistance, but also effectively improves the antioxidant capacity of the muscles, thereby improving the meat quality of the animals.

Agarwal et al. [40] compared the effects of adding lycopene to the diets of hens and their offspring on the body condition of the chicks in the first four weeks after hatching. They found that the concentration of carotenoids in the livers of chicks born to hens fed lycopene was 29 times that of chicks born to control hens, which was maintained until the seventh day after hatching. Lycopene was found to have the highest antioxidant activity among all carotenoids [40-41]. Feeding a diet rich in lycopene can significantly improve the characteristics and quality of Japanese quail meat [33] and eggs [34-35]. Beta-carotene can increase the egg production rate and average egg weight of laying hens, improve the yolk color [42], and significantly increase the early daily weight gain and tibia length of Hy-Line brown chicks, as well as improve the thymus, splenomegaly, and bursa index [43]. Studies have found that the use of β-carotene as an antioxidant can improve oocyte quality and even ovarian function, and it is speculated that β-carotene can improve animal reproductive performance [4].

Studies on ruminants have found that β-carotene can increase milk production and lactation efficiency in dairy cows, and increased the total solids, milk protein and lactose content of milk [44]. Beta-carotene can increase the slaughter rate and net meat rate of beef cattle [45], improve the saturation of meat color, and inhibit the deposition of back fat in beef cattle by inhibiting fat synthesis and promoting fat hydrolysis [46]. When lycopene is added to lamb, it is found that lamb containing lycopene products shows higher storage stability, good taste, more desirable color and more health-promoting effects [47]. Bloukas et al. [41] added naturally-derived lycopene to a variety of meats and found that lycopene can effectively inhibit the oxidation of muscle fat, improve muscle water retention, reduce muscle drip loss, stabilize meat color, and significantly improve the flavor and color of meat products.

In summary, adding lycopene to animal feed can significantly improve the quality and flavor of livestock and poultry meat, enhance the antioxidant capacity of livestock products, and improve the nutritional value of livestock products.

3 Summary and outlook

Lycopene powder has the potential to prevent a variety of heart, liver, bone, skin, and neurological and reproductive system diseases, as well as to fight oxidation, inflammation, cancer, and diabetes. As research standards and technology improve, the research and application of lycopene in animal production is also gradually increasing. Lycopene not only improves animal performance and health, but also improves meat quality and the quality of livestock products. However, the mechanism of action is not fully understood and further research is needed, especially on gene expression and signal pathways. In addition, the effective dose of this functional food supplement needs to be further studied, and its application in animal production needs to be further explored.

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