PMID: 

Chronic Dis Transl Med. 2018 Dec ;4(4):211-224. Epub 2018 Dec 18. PMID: 30603740

Abstract Title: 

Tomato lycopene prevention of alcoholic fatty liver disease and hepatocellular carcinoma development.

Abstract: 

Alcoholic liver disease (ALD) is a major cause of morbidity and mortality worldwide. The incidence of hepatocellular carcinoma (HCC) is increasing in the United States, and chronic, excessive alcohol consumption is responsible for 32%-45% of all the liver cancer cases in the United States. Avoidance of chronic or excessive alcohol intake is the best protection against alcohol-related liver injury; however, the social presence and addictive power of alcohol are strong. Induction of the cytochrome P450 2E1 (CYP2E1) enzyme by chronic and excessive alcohol intake is known to play a role in the pathogenesis of ALD. High intake of tomatoes, rich in the carotenoid lycopene, is associated with a decreased risk of chronic disease. The review will overview the prevention of ALD and HCC through dietary tomato rich in lycopene as an effective intervention strategy and the crucial role of CYP2E1 induction as a molecular target. The review also indicates a need for caution among individuals consuming both alcohol and high dose lycopene as a dietary supplement.

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PMID: 

Neuroimmunomodulation. 2019 ;26(2):84-92. Epub 2019 Jan 9. PMID: 30625493

Abstract Title: 

Anti-Inflammatory Effect of Lycopene on Experimental Spinal Cord Ischemia Injury via Cyclooxygenase-2 Suppression.

Abstract: 

OBJECTIVE: Spinal cord ischemia/reperfusion injury (SCII) is a devastating complication following thoracoabdominal aortic surgeries, often leading to severe neurological deficits. We sought to examine the effects of lycopene, a naturally existing carotenoid with anti-inflammatory properties, in the treatment against SCII.METHODS: Rats were assigned into four treatment groups: Sham (sham operation), SCII (SCII-induction), LY25, and LY50 (lycopene treatment at 25 or 50 mg/kg following SCII induction, respectively).RESULTS: Lycopene treatment improved the recovery of neurological functions following SCII and suppressed the neuronal cell death and neuroinflammation at 14 days after SCII. Furthermore, Western blot assay revealed that lycopene treatment attenuated the SCII-induced increase in the protein levels of cyclooxygenase-2 (COX-2), nuclear factor-κB, and activate protein-1, as well as the reduction of heme oxygenase-1.CONCLUSION: Lycopene exerted neuroprotective functions in SCII and inhibited SCII-elicited neuroinflammation via COX-2 suppression.

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PMID: 

J Nutr Biochem. 2019 03 ;65:93-100. Epub 2018 Dec 21. PMID: 30660958

Abstract Title: 

Lycopene mitigates pulmonary emphysema induced by cigarette smoke in a murine model.

Abstract: 

Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease characterized by a non-fully reversible airflow limitation comprising chronic bronchitis and pulmonary emphysema both being induced by cigarette smoke (CS) exposure. Lycopene has shown antioxidant and anti-inflammatory properties that can prevent acute lung inflammation and emphysema. We hypothesized that administration with lycopene would repair lung damage in emphysema caused by CS exposure. Mice were administered with two different doses of lycopene (25 or 50 mg/kg/day, diluted in sunflower oil by orogastric gavage) and then exposed to 60 days of CS or not (CG). Lycopene promoted a reduction in the number of total leukocytes and it improved pulmonary emphysema. Lycopene was able to minimize redox processes by decreasing lipid peroxidation and DNA damage, and by having an increase in the activities of SOD, CAT and GSH content. Furthermore, it decreased levels of TNF-α, IFN-γ and IL-10. In addition, it was able to decrease MPO activity and nitrite content. In conclusion, our data elucidated the role of lycopene as an antioxidant and anti-inflammatory agent in mice exposed to CS.

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PMID: 

Epilepsy Res. 2019 03 ;151:1-6. Epub 2019 Jan 17. PMID: 30669043

Abstract Title: 

Protective effects of lycopene on kainic acid-induced seizures.

Abstract: 

Lycopene (LCP) is a carotenoid that protects against many diseases by alleviating oxidative stress. However, the effect of LCP on epileptic seizures has not been examined well in previous studies. In the current work, we employed kainic acid (KA) to induce experimental epileptic seizures in mice, and investigated the function of LCP during this process. We found that the onset and extent of KA-induced seizures were alleviated in LCP-pretreated mice. Nissl staining of hippocampus showed that the granule cell dispersion lesion induced by KA was improved by the LCP treatment. Additionally, we analyzed the oxidative stress levels in mice and found that LCP elevated SOD activity and suppressed MDA level in KA-induced seizures. Moreover, the expression of GABA receptors was influenced by LCP treatment. LCP suppressed the upregulation of gabrb2 and gabrb3 induced by KA, whereas it enhanced the expression of gabrb1. Results suggested that LCP plays a protective function in KA-induced seizures. Hence, it may be a potential functional food alternative for controlling and treating epileptic seizures.

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PMID: 

J Indian Soc Periodontol. 2019 Jan-Feb;23(1):25-30. PMID: 30692739

Abstract Title: 

Antioxidant therapy (lycopene and green tea extract) in periodontal disease: A promising paradigm.

Abstract: 

Background: Increased oxidative stress has emerged as one of the prime factors in the pathogenesis of periodontitis. Hence, antioxidant therapy may become a promising tool in the treatment of periodontal disease. Uric acid (UA) being a major antioxidant in saliva can be used as a marker to assess the total antioxidant capacity.Aim: The aim of the study was to investigate the influence of orally administered antioxidants (lycopene and green tea extract) on periodontal health and salivary UA levels in gingivitis patients as an adjunct to scaling and root planing (SRP).Materials and Methods: Thirty systemically healthy participants having generalized gingivitis were randomly distributed into two groups. Control group participants received full mouth oral prophylaxis, while test group participants received oral lycopene and green tea extract (CLIK) for 45 days along with complete oral prophylaxis. Plaque index (PI), sulcular bleeding index (SBI), and salivary UA levels were evaluated at baseline and 45 days after SRP. Data were analyzed with-test, using SPSS software (PASW, Windows version 18.0).Results: Both treatment groups demonstrated statistically highly significant (≤ 0.001) reduction in plaque and SBI. After treatment, a highly significant increase (≤ 0.001) in the test group and significant (≤ 0.05) increase in the control group was observed for salivary UA levels. Posttreatment comparison between test and control group delineated statistically significant results in PI (≤ 0.001), SBI (≤ 0.001), and salivary UA levels (≤ 0.01).Conclusion: Lycopene with green tea extract may prove to be a promising adjunctive prophylactic and therapeutic modality in the treatment of gingivitis patients. However, further studies are needed to evaluate the additive effect of antioxidants with routine oral prophylaxis therapy.

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PMID: 

J Cancer. 2019 ;10(2):510-521. Epub 2019 Jan 1. PMID: 30719147

Abstract Title: 

Lycopene upregulates ZO-1 and downregulates claudin-1 through autophagy inhibition in the human cutaneous squamous cell carcinoma cell line COLO-16.

Abstract: 

Lycopene, a kind of carotenoid, has been reported to have an inhibitory function on tumor cell migration. However, the potential role of lycopene in the treatment of cutaneous squamous cell carcinoma (cSCC) remains unclear. Therefore, we assessed the biological effects of lycopene in the human cSCC cell line COLO-16, human epidermal keratinocytes (HEKs) and the immortalized human keratinocyte cell line HaCaT. We found that lycopene inhibited the cell proliferation and migration of COLO-16 cells but not normal keratinocytes. In addition, lycopene upregulated the protein levels of ZO-1 in COLO-16 and HaCaT cells but not in HEKs. In contrast, lycopene upregulated the protein level of claudin-1 in HEKs but downregulated claudin-1 in COLO-16 cells. Lycopene led to a decrease in autophagic flux in COLO-16 cells in a mechanistic target of rapamycin complex 1 (MTORC1)-dependent manner. Importantly, autophagy inhibition contributed to the lycopene-induced regulation on ZO-1 and claudin-1 in COLO-16 cells. Moreover, JNK inhibitor (SP600125) and MEK inhibitor (U0126) treatment abolished the increase in phosphorylated MTOR and ribosomal protein S6 as well as the increase in ZO-1 and the decrease in claudin-1 in lycopene-treated COLO-16 cells. Gene silencing of JNK and ERK also prohibited ZO-1 upregulation and claudin-1 downregulation. In conclusion, lycopene upregulates ZO-1 expression and downregulates claudin-1 expression through the activation of ERK, JNK and MTORC1 as well as the inhibition of autophagy in human cSCC cells. Our findings demonstrate that autophagy plays a key role in lycopene-mediated pharmacological effects. This study indicates that lycopene might be a useful chemopreventive agent against cSCC.

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PMID: 

J Liposome Res. 2019 Feb 10:1-8. Epub 2019 Feb 10. PMID: 30741056

Abstract Title: 

Enhanced antitumor efficacy and attenuated cardiotoxicity of doxorubicin in combination with lycopene liposomes.

Abstract: 

The aim of this study was to evaluate whether lycopene-loaded liposomes (L-LYC) could interfere with the antitumor efficacy and cardiotoxicity of doxorubicin (DOX). L-LYC were prepared by a thin-film hydration method to overcome the instability, insolubility, and low bioavailability of lycopene. The mean diameter and morphology of the liposomes were determined by dynamic light scattering and transmission electron microscopy, respectively, and then, in vitro cytotoxicity and in vivo antitumor activity were determined to evaluate the effects of L-LYC and their combination with DOX. Finally, we evaluated whether L-LYC could decrease the DOX-induced cardiotoxicity in vivo. The results showed that the particle size of L-LYC appeared uniform, and the average diameter was approximately 160.4 nm. Compared with DOX treatment alone, the combination of L-LYC and DOX showed significantly increased cytotoxicity in vitro and decreased the tumor size in B16 melanoma-bearing mice in vivo. Furthermore, the DOX-induced cardiotoxicity was clearly relieved in combination with L-LYC. The overall findings indicated that L-LYC have a great potential for improving the therapeutic efficacy and attenuating the cardiotoxicity of the chemotherapy drug DOX.

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PMID: 

J Inorg Biochem. 2019 Apr ;193:143-151. Epub 2019 Feb 1. PMID: 30743053

Abstract Title: 

Lycopene attenuates aluminum-induced hippocampal lesions by inhibiting oxidative stress-mediated inflammation and apoptosis in the rat.

Abstract: 

Aluminum (Al) causes hippocampal lesions by oxidative stress, which is widely accepted as the primary pathogenesis of Al neurotoxicity. Lycopene (LYC), a naturally carotenoid, has received extensive attention due to its antioxidant effect. In this study, the neuroprotective effects and mechanisms of LYC against aluminum chloride (AlCl)-induced hippocampal lesions were explored. First, oral administration of LYC (4 mg/kg) alleviated AlCl-induced (150 mg/kg) cognition impairment and histopathological changes of the hippocampus in rats. Then, LYC significantly attenuated AlCl-induced oxidative stress, presenting as the reduced reactive oxygen species, malondialdehyde and 8-hydroxy-2'-deoxyguanosine levels, and increased glutathione level and superoxide dismutase activity. Moreover, LYC also protected the hippocampus from AlCl-induced apoptosis and neuroinflammation, as assessed by protein levels of p53, Bcl-2-associated X protein (Bax), B-cell lymphoma gene 2 (Bcl-2), Cytochrome c (Cyt c), cleaved caspase-3 and nuclear factor kappa B, as well as the mRNA levels of Bax, Bcl-2, tumor necrosis factor alpha, interleukin-6 and interleukin-1 beta. Finally, LYC increased nuclear factor-erythroid-2-related factor 2 (Nrf2) nuclear translocation and its downstream gene expression, including heme oxygenase-1, NAD(P)H: quinone oxidoreductase 1, glutamate cysteine ligase catalytic subunit and superoxide dismutase 1, which were involved in antioxidant, anti-apoptosis, and anti-inflammation. Overall, our findings demonstrate LYC attenuates Al-induced hippocampal lesions by inhibiting oxidative stress-mediated inflammation and apoptosis in the rat.

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PMID: 

J Nutr Biochem. 2019 Apr ;66:70-78. Epub 2019 Jan 7. PMID: 30772766

Abstract Title: 

Lycopene protects against pressure overload-induced cardiac hypertrophy by attenuating oxidative stress.

Abstract: 

Oxidative stress is considered an important pathogenic process of cardiac hypertrophy. Lycopene is a kind of carotenoid antioxidant that protects the cardiovascular system, so we hypothesized that lycopene might inhibit cardiac hypertrophy by attenuating oxidative stress. Phenylephrine and pressure overload were used to set up the hypertrophic models in vitro and in vivo respectively. Our data revealed that treatment with lycopene can significantly block pressure overload-induced cardiac hypertrophy in in vitro and in vivo studies. Further studies demonstrated that lycopene can reverse the increase in reactive oxygen species (ROS) generation during the process of hypertrophy and can retard the activation of ROS-dependent pro-hypertrophic MAPK and Akt signaling pathways. In addition, protective effects of lycopene on the permeability transition pore opening in neonatal cardiomyocytes were observed. Moreover, we demonstrated that lycopene restored impaired antioxidant response element (ARE) activity and activated ARE-driven expression of antioxidant genes. Consequently, our findings indicated that lycopene inhibited cardiac hypertrophy by suppressing ROS-dependent mechanisms.

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PMID: 

Food Funct. 2019 Apr 17 ;10(4):1974-1984. PMID: 30889234

Abstract Title: 

Lycopene inhibits hepatic stellate cell activation and modulates cellular lipid storage and signaling.

Abstract: 

Hepatic stellate cells are liver-specific perivascular cells, identified as the major source of collagen in liver fibrosis, following their activation and conversion to myofibroblast-like cells. Lycopene is a carotenoid with biological activities and protective effects described in different pathologies, but little is known about its role in liver protection. We evaluated the influence of lycopene on the cell cycle and lipid metabolism and monitored the possible pathways involved in lycopene inhibition of stellate cell activation. Lycopene induced expression of the lipocyte phenotype, with an accumulation of fat droplets in cytoplasm, with high synthesis and turnover of phospholipids and triglycerides. Cell proliferation analysis showed that lycopene reduced the growth of GRX cells. Lycopene induced an arrest in the G0/G1 phase, followed by a decrease of cells in the G2/M phase, regardless of the concentration of lycopene used. Lycopene modulated relevant signaling pathways related to cholesterol metabolism, cellular proliferation, and lipid metabolism. Also, lycopene treatment increased the expression of RXR-α, RXR-β, and PPARγ, important biomarkers of liver regeneration. These results show that lycopene was able to negatively modulate events related to the activation of hepatic stellate cells through mechanisms that involve changes in expression of cellular lipid metabolism factors, and suggest thatthis compound might provide a novel pharmacological approach for the prevention and treatment of fibrotic liver diseases.

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