Lycopene: What Is It Good For?

Tomatoes are neutral in nature, with a sweet, sour, slightly cold taste. They enter the liver, stomach and lung meridians and have the effects of strengthening the stomach and promoting digestion, clearing away heat and detoxifying, cooling the blood and calming the liver, generating body fluid to quench thirst, nourishing the blood and improving appetite [1]. Lycopene is the main pigment in tomatoes and is a kind of carotenoid. It is a fat-soluble functional pigment that is considered to have extremely high nutritional value. This pigment is widely found in the ripe red plant fruits of tomatoes, carrots, watermelons, papayas, guavas, etc., with the highest content in tomatoes [2].

Lycopene has the molecular formula C40H56 and is a straight-chain hydrocarbon. It is considered to be one of the plant-based nutrients with the strongest antioxidant capacity discovered so far, as it contains 11 conjugated double bonds and 2 non-conjugated double bonds in its molecular structure. Studies have found that lycopene has a good health-promoting effect in many aspects, such as anti-oxidation, protecting the nervous system, delaying aging, inhibiting tumors, reducing cardiovascular disease, liver damage, improving human immunity and delaying osteoporosis. It is a new type of functional natural pigment with great development prospects [3-5]. Research on the functional and health-promoting effects of lycopene has always been a research hotspot in the field of pharmaceutical and healthcare nutrition food development. Therefore, this paper reviews the latest research progress in recent years, with a view to providing a reference for the development of follow-up research and new pharmaceutical and healthcare products.

1 The health benefits of lycopene

1.1 Antioxidant effects

Traditional Chinese medicine has a long history and has accumulated a wealth of health preservation measures and methods. Recent studies have shown that the aging of the human body, cancer and the occurrence of various chronic diseases are often related to superoxide and free radicals in the body. As the human body ages, cell metabolism decreases, and some external physical damage factors cause the accumulation of free radicals produced by the body's metabolism. Free radicals have strong oxidizing power, which can cause peroxidation of unsaturated lipids in biological membranes, forming lipid peroxides and producing the metabolic product malondialdehyde. The latter polymerizes and cross-links with proteins, peptides or lipids to terminate normal metabolism, thereby causing degenerative changes in the aging process [7].

Lycopene powder is a polyunsaturated hydrocarbon with the highest antioxidant capacity. It can remove free radicals in the body through physical and chemical means, inhibit the occurrence of lipid peroxidation, maintain normal cell metabolism, and prevent and delay aging. Luojinfeng et al. [8] found that lycopene can play an important role in delaying aging by scavenging free radicals, enhancing the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and reducing the content of malondialdehyde (MDA). Peng Liang et al. [9] investigated the antioxidant effect of lycopene on the human body. The serum MDA levels of volunteers in the test and control groups were 4.06 nmoL·mL-1 and 3.61 nmoL·mL-1, respectively, decreased by 11.03%; SOD activity was 90.7 U·mL-1 and 96.7 U·mL-1, respectively, an increase of 6.80%; GSH-Px activity was 122.6 NU·mL-1 and 136.9 NU·mL-1, an increase of 11.74%, indicating that lycopene has a significant antioxidant effect on the human body. Zheng et al. [10] explored the intervention effect of lycopene on the oxidative stress state induced by intravenous iron in hemodialysis (hemodialysis, MHD) patients, and found that lycopene can significantly reduce this oxidative stress state. HU et al. [11] evaluated the antioxidant effect of lycopene on mitochondrial dysfunction and apoptosis after T10 contusion spinal cord injury in rats, and found that lycopene can improve the total antioxidant capacity of spinal cord injury patients and has a certain neuroprotective effect on spinal cord injury.

YONAR et al. [12] studied the ameliorative effect of lycopene on trichlorfon-induced toxicity in carp by assessing hematological parameters and oxidant/antioxidant status. They found that the addition of lycopene helped to eliminate trichlorfon toxicity by altering the hematological status and antioxidant status of the fish. A study on the ameliorative effect of lycopene (LYC) and/or resveratrol (RES) on nano-zinc oxide toxicity in Nile tilapia showed that treatment with LYC and/or RES can effectively alleviate the oxidative stress caused by nano-zinc oxide (ZnONP), thanks to their good antioxidant activity [13]. In vivo studies have found that lycopene can inhibit the increase in white blood cells, lipid peroxidation and DNA damage induced by cigarette smoke (CS), and can reduce superoxide dismutase and catalase activity, inhibit the production of tumor necrosis factor-α, and reduce interferon-γ and interleukin-10 levels. all of which indicate that lycopene exerts good antioxidant and anti-inflammatory effects in a model of short-term exposure to cigarette smoke [14].

YANG et al. [15] found that lycopene can regulate the redox status of human retinal pigment epithelial cells through nuclear factor 2-related factors (Nrf2), inhibit intercellular adhesion molecule (ICAM-1) expression and nuclear factor (NF-κB) activation. Increased oxidative stress and inflammation may play an important role in the high mortality rate of patients with metabolic syndrome. Studies have shown that higher serum lycopene concentrations are significantly associated with a lower risk of death in patients with metabolic syndrome [16], which may be due to lycopene intake reducing oxidative stress and inflammation. RASHEED et al. [17] investigated the protective effect of lycopene on oxidative stress (OS) in acute kidney injury (AKI), found that lycopene can alleviate and prevent AKI by regulating OS and lipid peroxidation, and is a natural ingredient that can prevent nephrotoxicity caused by nephrotoxic drugs such as diclofenac.

1.2 Prevention of neurological diseases

Studies have shown that lycopene may play a role in the prevention and treatment of diseases related to the central nervous system, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, cerebral ischemia and epilepsy, through its antioxidant, anti-inflammatory and anti-proliferative activities. Lycopene can also improve the cognitive and memory abilities of rodents under different pathological conditions. In addition, lycopene can prevent neurotoxicity caused by monosodium glutamate, trimethyl tin, methyl mercury, tert-butyl hydroperoxide and cadmium. In some special cases, such as ethanol addiction and the dyskinesia of the mouth and face caused by haloperidol, lycopene has shown particular therapeutic effects. The mechanism is mainly neuroprotective effects such as inhibiting oxidative stress and neuroinflammation, neuroprotective effects such as inhibiting neuronal apoptosis and restoring mitochondrial function [18]. ZHANG et al. [19] experimentally found that lycopene can reduce lipopolysaccharide-induced inflammation and depressive-like behavior in animals. Lycopene was found to reduce neurocyte damage in the hippocampal CA1 region, inhibit the expression of IL-1 β and HO-1 induced by lipopolysaccharide in the hippocampus, and lower the levels of IL-6 and TNF- α in the plasma. Lycopene has therapeutic potential for learning and memory impairments in rats fed a high-fat diet [20].

Oxidative stress is involved in the pathogenesis and progression of Alzheimer's disease (AD) and its early stage, mild cognitive impairment. In traditional Chinese medicine, Pueraria root and ginseng are often used in combination to treat AD. In patients treated with this combination, the activity of superoxide dismutase (SOD) in the heart, liver and brain is significantly increased, the level of serum lipid peroxides is reduced, and cognitive function is effectively improved [21]. More and more studies have shown that inhibiting oxidative stress may effectively improve the symptoms of AD. Patients with Alzheimer's disease (AD) have a lower concentration of lycopene in the body. Lycopene has been confirmed to have strong antioxidant capacity, can reduce oxidative stress, and has been found to have neuroprotective effects in several Alzheimer's disease models.

He Yuan et al. [22] recruited 56 elderly patients with mild cognitive impairment to carry out a population intervention experiment with lycopene. The results showed that the lycopene group had a very significant increase in basic cognitive ability test scores (P < 0.05); at the same time, homocysteine and interleukin-6 levels were significantly reduced (P < 0.05), suggesting that lycopene intervention can enhance the cognitive function of elderly people with mild cognitive impairment. Some studies have found that lycopene can downregulate the expression of β-amyloid precursor protein in cells overexpressing the human β-amyloid precursor protein gene (APPsw), and cannot change the endogenous levels of reactive oxygen species and apoptosis in APPsw cells, but can prevent oxidative stress caused by H2O2 and copper-induced damage to APPsw cells [23].

YU et al. [24] found that supplementation with lycopene or lycopene/vitamin E can significantly improve memory deficits. The combination of lycopene and vitamin E antioxidants works in a synergistic manner and has a significant impact on preventing oxidative stress in proteinopathies. LIU et al. [25] studied the protective effect of lycopene on inflammation caused by β-amyloid in rats and found that lycopene can significantly improve cognitive impairment and reduce inflammatory damage by blocking the activation of NF-κB p65 and TLR4 expression and the production of cytokines, thereby confirming its role in reducing β-amyloid deposition in hippocampal tissue. CAO et al. [26] found that lycopene can reduce aluminum-induced damage by inhibiting oxidative stress-mediated inflammatory responses and apoptosis of rat hippocampal cells. MORSY et al. [27] found that lycopene produced a neuroprotective effect on the hippocampal body of rats poisoned by bisphenol A. The mechanism is that lycopene activates the MAPK/ERK pathway through its antioxidant effect, inhibits neuronal apoptosis, and improves learning and cognitive memory in mice.

1.3 Antitumor effect

Tumors are one of the diseases with the highest mortality rate. Currently, surgery, radiotherapy and chemotherapy are mainly used in combination with traditional Chinese medicine treatment based on syndrome differentiation to give different traditional Chinese medicine treatments. Clinical studies have found that many Chinese medicinal materials (ginseng, astragalus, wolfberry, etc.) have good anti-tumor effects. The mechanism is that the plant polysaccharides in the medicinal materials achieve anti-tumor effects by inhibiting cell proliferation, inducing apoptosis, blocking the cell cycle, anti-new blood vessel formation, and regulating the immune system [28]. Clinical studies have shown that lycopene, due to its strong antioxidant capacity, can block gene mutations in human cells caused by external mutagens, inhibit the proliferation of cancer cells, and accelerate apoptosis of cancer cells. Therefore, lycopene has a preventive and inhibitory effect on various tumors such as gastric cancer, ovarian cancer, skin cancer, lung cancer, liver cancer, and prostate cancer [29-39].

Lycopene inhibits the expression of oncogenes and the excessive proliferation of Helicobacter pylori-infected gastric epithelial cells by inhibiting the activation of Janus kinase 1 (Jak1)/signal transducer and activator of transcription 3 (Stat3) and Wnt/β-catenin signaling in gastric epithelial cells mediated by reactive oxygen species [29].  XU et al. [30] treated an ovarian cancer cell SKOV3 culture with lycopene, and found that the proliferation rate of SKOV3 cells was significantly reduced (P < 0.05), while the apoptosis rate was significantly increased (P < 0.05). Among these, up-regulating Bax expression and down-regulating Bcl-2 expression are the main ways to induce apoptosis. Bi S. Y. et al. [31] found that the human skin squamous cell carcinoma cell line COLO16 cells were treated with lycopene, and cell viability was significantly reduced. Epidermal growth factor receptor protein activation was inhibited, and the expression of glucocorticoid receptors was shown to be upregulated. However, this effect may be specific to certain tumour cells. KAREN et al. [32] found that dietary lycopene can significantly inhibit UV-induced epidermal hyperplasia and carcinogenesis.

Wang Guigang et al. [33] found in in vitro and in vivo cell experiments that lycopene has a certain inhibitory effect on the growth of non-small cell lung cancer cells in vitro and the growth of lung cancer xenografts in vivo. The mechanism may be related to lycopene blocking the cell cycle and promoting apoptosis of lung cancer cells. STICE et al. [34] found that lycopene is an effective intervention strategy and the key role of CYP2E1 induction as a molecular target, which can prevent alcoholic liver disease and hepatocellular carcinoma. Chai Xuzhe et al. [35] found that lycopene can increase the sensitivity of human osteosarcoma MG-63 cells to cisplatin, and the mechanism may be related to lycopene's ability to block the cell cycle and regulate the expression of apoptosis-related genes and proteins.

Prostate cancer is the most common cancer and the leading cause of death from cancer among men in Europe and the United States. In recent years, the incidence of prostate cancer in China has been on the rise. Abnormalities in glutathione S-transferase P1 are thought to be one of the important factors in the development of prostate cancer. Studies have found that lycopene can induce the expression of the GSTP1 gene in DU145 cells through the Nrf2/ARE pathway, thereby exerting a protective effect on prostate health [36]. TJAHJODJATI et al. found that lycopene can stimulate mitochondrial pro-apoptotic factors through endogenous pathways, increase apoptosis, inhibit insulin-like growth factors, and ultimately inhibit the development of cancer cells, thereby assisting in the treatment of prostate cancer [37]. High-dose lycopene propolis capsules can reduce the prostate index and prostate hyperplasia rate in rats with prostatic hyperplasia (P < 0.05), and increase the activity of superoxide dismutase (SOD) in the tissue (P < 0.05), thereby improving experimental prostatic hyperplasia [38]. Lycopene also alleviates testicular damage caused by benzopyrene by inhibiting oxidative stress and apoptosis, and alleviating gap junction dysfunction in testicular support cells [39].

1.4 Prevention of cardiovascular and cerebrovascular diseases

Cardiovascular and cerebrovascular diseases are collectively referred to as cardiovascular diseases and cerebrovascular diseases, and seriously threaten the health of middle-aged and elderly people. Traditional Chinese medicinal materials such as Danshen can significantly enhance myocardial SOD activity, remove excessive oxygen free radicals in the heart muscle, reduce free radical damage to mitochondria, and protect the cardiovascular system [40]. A growing number of studies have shown that lycopene also has potential cardioprotective effects and significant benefits in maintaining cardiovascular function and health [41]. PETYAEV et al. [42] applied lycopene to a clinical trial of patients with coronary artery disease. The subjects were supplemented with 7 mg of lycopene per day. After 2 and 4 weeks of the trial, the serum lycopene level in the body increased by 2.9 times and 4.3 times, respectively. Lycopene caused a 3-fold decrease in the body's IgG to Chlamydia pneumoniae, a decrease in markers of oxidative damage to inflammation, and a 5-fold decrease in oxidized low-density lipoprotein, revealing the antioxidant and anti-inflammatory functions of lycopene and demonstrating the positive effect of lycopene on the cardiovascular system.

Wen Yixian et al. [43] found through experiments that lycopene mainly reduces the production of oxidized low-density lipoprotein by affecting blood cholesterol levels, thereby reducing its damage to the vascular endothelium and maintaining the permeability of the blood-brain barrier. Indirectly, it reduces the activity of astrocytes, inhibits the phosphorylation of brain P38 protein, and reduces the secretion of interleukin, tumor necrosis factor, and nitric oxide, to exert cerebrovascular and neuronal protective effects. TREGGIARI et al. [44] studied the effects of lycopene on human umbilical vein endothelial cells by testing cell migration in vitro and found that lycopene inhibited vascular endothelial growth factor-A (VEGFA)-induced cell migration and reduced Akt phosphorylation. Lycopene administration can significantly block cardiac hypertrophy caused by pressure overload. The mechanism is that lycopene can reverse the increase in reactive oxygen species (ROS) during the hypertrophy process and delay the activation of ROS-dependent hypertrophic MAPK and Akt signaling pathways. In addition, it was observed in experiments that lycopene has a protective effect on the opening of the permeability transition pore in neonatal cardiomyocytes [45].

Lycopene can improve the damage caused by angiotensin II to vascular superoxide anions (assessed in the aorta), lipid peroxidation and antioxidant enzyme activity (measured in plasma and liver, respectively), significantly reduce the development of hypertension, and prevent cardiovascular remodeling caused by angiotensin II, but had no effect on rats with normal blood pressure [46]. SEVAL et al. [47] studied the protective effect of lycopene on aflatoxin B1 poisoning of the kidneys and heart in rats and found that the plasma urea and creatinine levels of aflatoxin B1-treated rats were elevated, while the sodium concentration was reduced. Lycopene had a protective effect against aflatoxin-induced nephrotoxicity and cardiotoxicity. Studies have found that serum uric acid plays an important role in the renin-angiotensin-aldosterone system as an intermediary between overweight/obesity and hypertension. Lycopene, as a natural antioxidant, can effectively inhibit the activity of angiotensin-converting enzyme and reduce angiotensin-ii-induced oxidative stress. Therefore, there is a significant negative correlation between serum lycopene and hypertension [48].

Lycopene can also correct lipopolysaccharide-induced oxidative stress and hypertriglyceridemia by downregulating the expression of proprotein convertase subtilisin/kexin type 9 (PCSK-9) and increasing lipoprotein lipase activity [49]. Yang Yanhui et al. [50] selected 34 hyperlipidemia patients to explore the effect of lycopene on blood lipid levels in vivo. After taking the medicine (Lycopene capsules), the levels of total cholesterol (TC) and triglycerides (TG) in the test group were significantly lower than those in the control group (P < 0.05). After taking the medicine, the levels of TC and TG in the test group were significantly lower than those before taking the medicine (P < 0.05), suggesting that lycopene has a certain effect of lowering blood lipids. SULTAN et al. [51] first discovered the molecular mechanism of the lipid-lowering activity of lycopene, that is, lycopene treatment can significantly down-regulate the expression of PCSK-9 and HMGR in the liver, and significantly up-regulate the expression of the LDL receptor in the liver. In addition, lycopene can also improve the expression of PCSK-9 under inflammatory stimulation by inhibiting the expression of inflammatory markers.

1.5 Inhibits osteoporosis

Osteoporosis is a metabolic bone disease characterized by decreased bone density. Destruction of bone microstructure and changes in non-collagenous substances in bone lead to a higher risk of fracture. This is most common in postmenopausal women. The mechanism by which the antihypertensive formula Taiping Shenghui Fang prevents osteoporosis is by increasing bone density, promoting bone formation and inhibiting bone resorption, i.e. by regulating the dual effects of osteoblasts and osteoclasts to achieve the effect of preventing osteoporosis [52]. Recent studies have shown that lycopene can also regulate bone metabolism levels in the body and has potential protective effects against bone loss.

Rong Hui et al. [53] found that lycopene administration can inhibit the occurrence of osteoporosis by reducing oxidative stress on osteoblast proliferation, differentiation and mineralization. COSTA-RODRIGUES et al. [54] found that lycopene can promote the anabolic state of bone metabolism, stimulate osteoblast proliferation and differentiation, and inhibit osteoclastogenesis, thereby improving the health of bone tissue. ARDAWI et al. [55] used lycopene administration in ovariectomized (OVX) osteoporosis rats and observed that lycopene can inhibit OVX-induced bone turnover and restore bone strength and microstructure by downregulating osteoclast differentiation and upregulating osteoblast and glutathione peroxidase ( GPx), catalase (CAT) and SOD activity, which restores bone strength and microstructure and suppresses the development of osteoporosis.

LIU et al. [56] studied the effect of lycopene on the type of skeletal muscle fibres in vivo and in vitro and found that lycopene can affect the activity of metabolic enzymes in muscle fibres, promote the expression of slow contraction fibres, enhancing mitochondrial respiratory capacity, and potentially exerting a beneficial effect on skeletal muscle metabolism by influencing the type of muscle fiber through oxidation. KIRIŞÇI M et al. [57] studied the effect of lycopene on acute ischemia-reperfusion injury (I/R) in rat hindlimb skeletal muscle, and found that lycopene treatment significantly reduced the levels of malondialdehyde and ischemic modified albumin in serum and tissue, suggesting that lycopene has protective activity against skeletal muscle cells in rats with I/R injury model.

2 Conclusion

Oxidative stress in the human body is considered to be one of the main causes of a range of diseases. Lycopene has strong antioxidant properties and is believed to be able to prevent and treat neurological diseases, inhibit the proliferation of tumor cells, prevent cardiovascular and cerebrovascular diseases, and inhibit osteoporosis and other related diseases by scavenging free radicals in the body and limiting or preventing active oxygen-induced DNA, lipid, and protein damage. Although some progress has been made in understanding the mechanism by which lycopene prevents various diseases, it is not yet clear, and further research and discussion is needed. There are also relatively few clinical trials on humans. It is believed that with continued research, lycopene will show even broader application prospects in the field of medicine and health products.

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