Lycopene and liver health -
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HFD-induced NASH-promoted diethylnitrosamine DEN -initiated hepatocarcinoma rat model was used in the study. Lycopene and tomato extract could inhibit NASH-promoted hepatocarcinogenesis through reduced oxidative stress but with different mechanisms.
They observed significantly decreased cytochrome P 2E1, inflammatory foci and mRNA expression of proinflammatory cytokines TNF-α, IL-1β and IL in the tomato extract fed group, but increased nuclear NF-E2-related factor-2 and heme oxygenase-1 proteins in the lycopene fed group.
Carotene,15'-monooxygenase CMO-I and carotene-9',10'-monooxygenase CMO-II are primary mammalian carotenoid cleavage enzymes. CMO-I cleaves β-carotene to two molecules of retinal, whereas CMO-II preferentially cleaves non-provitamin A carotenoids such as lycopene but also has affinity to other carotenoids such as β-carotene 60 - CMO-I has been identified as a cytoplasmic enzyme, whereas CMO-II has been identified as a mitochondrial enzyme.
These enzymes convert the carotenoids to biologically active metabolites Lycopene may also interfere with the β-carotene and retinoid metabolism. It has been found that lycopene supplementation decreased the expression of CMO-I and PPAR-γ in the kidney and adrenal tissues of rats Hepatic pro-inflammatory biomarkers including TNF-α, IL-6, NF-κB p65 protein expression, caspase-1 cleavage and activation of the oncogenic transcription factor STAT3 were significantly reduced in the liver tissue by APO10LA supplementation.
These effects of APO10LA were associated with increased hepatic Sirtuin1 SIRT1 , protein and deacetylation of SIRT1 targets NF-κB p65 and FoxO1 and AMP-activated protein kinase AMPK phosphorylation.
Protective effect of overexpression of SIRT1 was found in HFD-induced fatty liver disease Ahn et al. As a post-transcriptional regulator of gene expression, up-regulating miRNA was achieved by lycopene through targeting the fatty acid-binding protein 7 FABP7.
FABPs are most active proteins in long chain fatty acid uptake and metabolism in the hepatocytes. They found that lycopene up-regulated the miRNA and inhibited FABP7 expression and blocked stearic acid SA induced intracellular lipid accumulation. They also observed that miRNA could have an important role in hepatic function and its expression was changed by HFD in liver tissues in an animal model 55 , also reported that miR expression was decreased in HFD-induced NASH and stearic acid treated Hepa cells.
NASH was associated with downregulation of miRNA and upregulation of FABP7. FABPs are most active proteins in long chain fatty acid uptake and metabolism in the hepatocytes FABP7 was one of the targets of miRNA, and it was directly and inversely associated with miR Lycopene normalized the effects of HFD and regulated the hepatic lipid metabolism in this model.
It downregulated PPARγ and fatty acid synthase FASN and upregulated CPT1-α, LCAD, PPAR-α and Apoa4 in HFD induced NASH mouse model β-carotene is the most widely distributed carotenoid in yellow-orange and dark green fruits and vegetables β-carotene is also the most abundant carotenoid in the liver Among provitamin A carotenoids, β-carotene has the highest provitamin A activity because it is partly converted to vitamin A β-carotene has a strong antioxidant effect through scavenging free radicals and physically quenching singlet oxygen Major source of β-carotene in human diet is primarily green leafy vegetables, carrots, apricots, sweet potatoes, red palm oil, mature squashes, pumpkins, and mangoes 73 , 75 , As a potent antioxidant, β-carotene has been studied as a potential protective agent in NAFLD.
The studies reporting the effects of β-carotene and other carotenoids on NAFLD are summarized in Table 2. In vivo and in vitro experimental studies have shown potential preventive and therapeutic effects of β-carotene on hepatic inflammation, fibrosis 86 and cirrhosis Another study reported that β-carotene could decrease hepatitis C virus induced-hepatosteatosis via inhibition of HCV RNA replication Dietary β-carotene supplementation has been found to have a protective effect on liver damage.
In rats with monocrotaline-induced steatosis, fat accumulation and hemorrhages decreased in the liver with β-carotene supplementation Harari et al. This could be due to reduced mRNA levels of inflammatory genes such as vascular cell adhesion molecule-1 VCAM-1 , IL-1α, monocyte chemoattractant protein-1 MCP-1 , interferon-γ INF-γ.
Hepatic protective effects of some β-carotene rich products have been shown in experimental studies. Administration of an herbal derivative, Lycium barbarum polysaccharides has been shown to have ameliorative effects on hepatic fibrosis, oxidative stress and inflammatory response in HFD induced NASH and cellular steatosis rat model A study conducted by Ozturk et al.
Apricot is a fruit that has a high content of carotenoids, largely β-carotene. Markers of oxidative stress MDA, total GSH levels, catalase, superoxide dismutase and GSH peroxidase activities were significantly altered in carbon tetrachloride induced hepatic steatosis and damage in Wistar rats.
Oxidative stress was decreased and hepatic steatosis and damage were ameliorated in rats by β-carotene rich apricot feeding.
In another study, Campari tomato, which contains more β-carotene and lycopene than regular tomato, ameliorates diet-induced obesity, dyslipidemia and hepatosteatosis via downregulation of gene expression related to lipogenesis in the zebra fish model. Campari tomato decreased sterol regulatory element-binding transcription factor 1 srebf1 mRNA by increase of forkhead box O1 foxo1 gene expression, which may depend on high contents of β-carotene in this tomato strain In a human study, researchers found that NAFLD had inverse relationship with vitamin A nutritional status in individuals with class III obesity Retinol and β-carotene serum levels were evaluated as a biochemical indicator.
The researchers observed low retinol and β-carotene serum levels in the presence of the NAFLD. They also reported significant association between insulin resistance with retinol and β-carotene levels.
Other carotenoids such as astaxanthin, lutein, β-cryptoxanthin, and fucoxanthin have also shown a protective effect in NAFLD. Hypolipidemic and antioxidant effects of astaxanthin supplementation have been observed in human clinical trials 91 , Astaxanthin treatment prevented triglyceride accumulation and liver steatosis by inhibiting PPAR-γ in ubiquitous transcription factor YY1 induced zebrafish liver steatosis In another study, astaxanthin prevented the development of hepatic steatosis and lowered plasma total cholesterol and triglyceride in obese mice fed a HFD A study was performed with lutein administration in hypercholesterolemic diet fed guinea pigs, which showed that hepatic free cholesterol, hepatic MDA and TNF-α were decreased in the lutein supplemented group.
Non-alcoholic fatty liver disease NAFLD is one of the causes of fatty liver, occurring when fat is deposited steatosis in the liver due to causes other than excessive alcohol use.
NAFLD is considered to cover a spectrum of liver diseases, including simple steatosis, non-alcoholic steatohepatitis NASH , liver fibrosis, liver cirrhosis and hepatocellular carcinoma HCC [ 1 , 2 ].
Ninety percent of patients with NAFLD show close relation with one or more of the following risk factors: hypertension, dyslipidemia, elevated triglyceride TG levels, obesity, insulin resistance, metabolic syndrome, type 2 diabetes mellitus and cardiovascular disease[ 3 ].
NAFLD is more common in patients with severe diabetes and obesity, mortality and disease evolution to liver fibrosis or liver cirrhosis is increased in old people with NAFLD[ 5 ]. Furthermore, there is not any specific drug available for NAFLD, and no drug has yet to be tested in clinical phase III trials.
Therefore, no specific therapy can be firmly recommended to the patients with NAFLD[ 7 ]. Lycopene Ly , a phytochemical belonging to carotenoid family, is a red-colored pigment, acyclic and apolar carotenoid[ 8 ].
Ly displays a range of unique and distinct biological properties owing to its acyclic structure, hydrophobicity and large array of conjugated double bonds. Recently, diverse studies have been reported that lycopene exerts powerful antioxidant activity both in vitro and in vivo against the oxidation of proteins, lipids and DNA, and also has the potential of quenching singlet oxygen times more efficiently than vitamin E and times more than glutathione GSH [ 10 ].
Furthermore, even at low oxygen tension, it can also scavenge peroxyl radicals, inhibiting the process of lipid peroxidation[ 11 ].
It is the most efficient quencher of singlet oxygen among all naturally occurring carotenoids[ 11 ], and recently it has been in great demand as a food additive and a natural antioxidant. Additionally, Ly also exhibited potent neuroprotective, anti-inflammatory, anti-proliferative, maintenance of normal cell metabolism, cognition enhancing properties, regulating blood lipid metabolism and so on[ 12 - 16 ].
Therefore, with this background, we aimed to investigate the possible beneficial effects and the possible action mechanism of Ly on NAFLD using a rat model system. Alanine aminotransferase ALT , aspartate aminotransferase AST , TG, total cholesterol TC , low density lipoprotein-cholesterol LDL-C , high density lipoprotein-cholesterol HDL-C , free fatty acid FFA , malondialdehyde MDA , superoxide dismutase SOD and GSH kits were obtained from Nanjing Jiancheng Bioengineering Institute Nanjing, China.
Protein assay kit was from Zhongshan Institute of Biotechnology Beijing, China. Mouse anti-TNF-α, rabbit anti-cytochrome P 2E1 CYP2E1 , horseradish peroxidase HRP -conjugated goat anti-mouse IgG and HRP-conjugated goat anti-rabbit IgG antibodies were provided by Proteintech Group, Inc. Chicago, IL, United States.
Shijiazhuang, China. Male Wistar rats body weight ± 10 g were obtained from the Experimental Animal Center of Harbin Medical University China. Six rats were kept in each single polyacrylic cage and were quarantined for 1 wk before the experiments. Animals were fasted for 12 h before sampling of material.
After acclimatization for 1 wk, 65 Wistar male rats were randomized into 2 groups. The model group was continued on the HFD for 6 wk as before, and the Ly groups were administered orally and continued on the HFD for 6 wk as before.
Rats were sacrificed by cervical dislocation at the end of the experiment, and blood samples of all rats were harvested for serum biochemical markers assay. Serum was collected from blood after centrifugation at rpm for 10 min at 4 °C. The level of MDA in liver tissues was measured at nm with a spectrophotometer U Hitachi Ltd.
SOD and GSH activity were determined by commercial kit from Jiancheng Biological Engineering Institute following the protocol provided by the manufacturer.
LDL-C, HDL-C and FFA in liver tissue were measured by commercial kit from Jiancheng Biological Engineering Institute following the protocol provided by the manufacturer.
The sections were stained with hematoxylin and eosin HE for routine histopathological examination, and examined under a light microscope BX; Olympus at × magnification for the degree of hepatic steatosis and photographed.
The sections were stained with mouse anti-TNF-α antibody and rabbit anti-CYP2E1 antibody at 4 °C overnight respectively, after blocking with normal goat serum for 20 min.
Then, the sections were incubated with HRP-conjugated goat anti-mouse and HRP-conjugated goat anti-rabbit antibody at 37 °C for 30 min, respectively. The immunoreactive antibodies were visualized by incubation with DAB-H 2 O 2 at room temperature for 10 min. Images were taken at original magnification of × Olympus BX Microscope and a Leica DMI; Leica Microsystems, Wetzlar, Germany.
Serum levels of AST and ALT indirectly reflects the failure of liver function. As shown in Table 1 , serum AST 2. All of these findings indicate that Ly exerts obvious lipid-lowering effects against NAFLD.
The levels of liver antioxidant activities of SOD and GSH were measured due to the oxidative stress exhibited in the development of NAFLD[ 17 ].
SOD and GSH are capable of scavenging the lipid hydroperoxides, lipid peroxide radicals and other products which are toxic metabolites of NAFLD. Therefore, our study measured the contents of SOD, GSH and MDA in liver tissue of rats. MDA, an end-product of the breakdown of polyunsaturated fatty acids and related esters, is an important index of lipid peroxidation in many organ homogenates[ 17 ].
Administration of HFD caused a significant increase in MDA concentration 2. Observed with the naked eye, the livers of the control group were deep red, moist, glossy and resilient Figure 2AI , while those of the model group showed yellow necrotic foci, grey-red color, loss of luster and tumescent Figure 2AII.
However, in Ly-treated rats, the liver injury was attenuated dramatically in a dose-dependent manner Figure 2AIII-V. HE-stained sections are shown in Figure 2B. Under the photomicroscope, liver sections from the normal control group showed normal lobular architecture, liver cells with well-preserved cytoplasm and well-defined nucleus Figure 2BI.
Meanwhile liver sections from the model group showed full fat vacuoles in lobule cells, infiltration of inflammatory cells, cell swelling and lipid degeneration in the central region of the lobules Figure 2BII.
Furthermore, in the liver sections of the Ly-treated group, inflammatory response and lipid degeneration were remarkably alleviated, as compared with the model group, and the liver cell volume became smaller, the fat droplet number was reduced and the hepatic lobules were clearly delineated Figure 2BIII-V.
The immunohistochemistry IHC analysis of liver tissue showed no TNF-α expression in the normal group Figure 3AI , but increased expression of TNF-α in the HFD-model group Figure 3AII.
Quantification of the positive expression of TNF-α is shown in Figure 3AVI. In Figure 3B , the normal liver expressed the lowest amount of CYP2E1 Figure 3BI.
Quantification of the positive expression of CYP2E1 is shown in Figure 3BVI. NAFLD is defined by hepatic fat deposition in the absence of excessive alcohol intake, which is also associated with the insulin resistance IR and metabolic syndrome[ 18 - 20 ]. NASH is characterized by hepatocellular damage, fibrogenesis and lobular necro-inflammation[ 21 , 22 ], which may evolve to hepatic cirrhosis and HCC[ 23 , 24 ].
Although HFD-induced NAFLD animal models need a lengthy feeding period, they are more close to human NAFLD in pathophysiology, including induced obesity, IR and hepatic steatosis in mice or rats[ 25 ].
Emotional disorders or poor diet with the key points of blood stasis and phlegm is regarded as the etiology of NAFLD, and these etiologies are related to the organs of liver, spleen and kidney, according to the traditional medicine theory[ 26 ]. Thus, promoting blood circulation to remove meridian obstruction, reducing phlegm, removing dampness and liver-kidney-tonifying are an effective approach to treatment of NAFLD.
However, at present, although tremendous effort has made in prevention of NAFLD by clinicians and researchers alike, there are no approved treatment drugs for NAFLD. Hence, developing and exploring a novel agent to delay or reverse the pathogenesis progression in NAFLD are very important objectives.
Ly is a natural pigment, synthesized by plants and microorganisms. Red fruits and vegetables are the most common sources of Ly, which exhibits the highest antioxidant activity among all dietary carotenoids.
Furthermore, the Mediterranean dietary pattern, which includes proportionally high consumption of vegetables and fruits with Ly, has shown notable benefits for NAFLD patients[ 27 , 28 ].
Therefore, nowadays, the potential role of Ly in human health is beginning to be recognized, and the most important health benefits are hypothesized to occur through their ability to protect against oxidative damage[ 29 , 30 ].
In vitro studies have demonstrated that Ly is an effective antioxidant and radical scavenger[ 31 , 32 ]. Ly is the most potent singlet oxygen quencher among natural carotenoids, due to its high number of conjugated dienes[ 33 ], and recent studies have shown that Ly is at least two times as active as β-carotene in protecting lymphocytes for NO 2 · radical-induced membrane damage[ 34 , 35 ], which indicates that Ly is the most potent scavenger of ROS among other major dietary carotenoids[ 36 , 37 ].
In addition, Ly was shown to protect human LDL against photosensitized oxidative damage[ 32 ]. Thus, based on the benefits of Ly, the aim of the present study was to explore the effect of Ly in prevention of HFD-induced NAFLD in a rat model.
To the best of our knowledge, this is the first time research has attempted to explore the potent effects of Ly on HFD-induced NAFLD rats.
In the present study, compared to a normal control group, it was demonstrated that the liver coefficient and the levels of serum ALT, AST, TG and TC were significantly increased, the levels of LDL-C and FFA in liver were markedly increased, and HDL-C was markedly reduced in HFD-induced NAFLD model rats.
Pretreatment with Ly showed that Ly is able to inhibit the incremental changes in ALT and AST, to decrease the TG, TC, LDL-C and FFA levels, and to increase the HDL-C level. In addition, the histopathological changes from microscopy observation correlated with the examination of liver function.
The centrilobular hepatic necrosis, ballooning degeneration, fatty change and infiltrating lymphocytes were observed in NAFLD model group. Treatment with Ly prevented these histopathological changes in rats induced with HFD.
Thus, these results suggested that the inhibition of the elevation of liver function markers, obvious lipid-lowering and liver damage may related to the protective effect of Ly against HFD-induced NAFLD. Moreover, Ly enhanced the activities of SOD, increased GSH and diminished MDA against the HFD-induced NAFLD in these animals, suggesting that the activity of antioxidants may play a role in the mechanism of its hepatoprotective effects.
TNF-α is a central proinflammatory cytokine, which is associated with a variety of physiological and pathological conditions, including cytotoxicity, growth stimulation, immune-modulation and pro-inflammatory activity. In addition, TNF-α is produced predominantly by the monocyte macrophage lineage in liver, and the main population of this lineage is Kupffer cells.
Thus, increased TNF-α production by activated Kupffer cells may be responsible for NAFLD. Furthermore, the most current studies have indicated that inhibition of TNF-α could decrease the content of hepatic fatty storage in the HFD-induced NAFLD model[ 38 ]. In our study, the effects of TNF-α in damaged liver was evaluated by IHC.
Compared to the normal group, rats treated with HFD showed up-regulated expression of TNF-α, while pretreatment with Ly led to down-regulated expression of TNF-α compared to the HFD-model group. The isoform 2E1 of CYP is one of the most potent microsome cytochromes to generate ROS, and it is involved in the metabolism of isoniazid and the mediation of its hepatotoxicity[ 39 ], which has been exhibited to be invariably increased in the livers of NAFLD patients[ 40 ].
In this study, the expression of CYP2E1 in the HFD-model group was observed to be increased, while the Ly treatment group showed a significant down-regulation of its expression, especially in the high-dose Ly-treated group.
In conclusion, oral administration of Ly improved lipid profiles and remarkably decreased the levels of serum AST, ALT, TG and TC, alleviated the levels of liver LDL-C and FFA, increased the activities of antioxidant enzymes GSH, SOD and reduced the lipid peroxides in liver MDA in NAFLD model rats.
Further, the Ly-treated group also showed down-regulated expression of TNF-α and CYP2E1, decreased liver fats infiltration and improved histopathological changes, all in dose-dependent manners. The increased antioxidant enzyme levels and the decreased lipid peroxides contents are suggested to be important mechanisms of Ly in preventing the development of liver damage induced by HFD.
Non-alcoholic fatty liver disease NAFLD is one of the causes of fatty liver, which encompasses a spectrum of liver diseases, including simple steatosis, non-alcoholic steatohepatitis NASH , liver fibrosis, liver cirrhosis and hepatocellular carcinoma HCC. Until now, there is not any specific drug available, and no drug has currently been tested in clinical phase III trials.
Lycopene Ly , a phytochemical belonging to the carotenoid family, is a red-colored pigment, apolar and acyclic carotenoid. Ly exhibits a range of distinct and unique biological properties owing to its acyclic structure, hydrophobicity and large array of conjugated double bonds.
A recent report showed that the Mediterranean dietary pattern, which includes proportionally high consumption of vegetables and fruits with Ly, has notable benefits for NAFLD patients.
Thus, with this background, we aimed to investigate the possible beneficial effects and the possible action mechanism of Ly on NAFLD in a rat model system. No specific drug has been tested in clinical phase III trials for NAFLD to date, and there are few research studies of the hepatoprotective effects of Ly.
This study represents the first investigation of the effects of Ly as a therapy of NAFLD, and showed that down-regulated expression of TNF-α and CYP2E1 may be one of the action mechanisms for Ly.
This study suggests that Ly has a protective effect on NAFLD, which is very important for the future development of a potent NAFLD drug. NAFLD is one of the causes of fatty liver, defined as biopsy-proven hepatic steatosis.
It covers a spectrum of liver diseases, including simple steatosis, NASH, liver fibrosis, liver cirrhosis and HCC. Recently, many NAFLD drug research studies have focused on the traditional Chinese medicines.
The Lycopene and liver health anv results were reported licer the American Optimizing body composition of Cancer Research Meeting in October, A five-year clinical study Enhancing immune system defenses Lgcopene Japan healyh liver cancer prevention in high-risk liver cancer patients. These significantly positive results suggest treating patients at high risk for cancer with a mixture of natural tomato extract Lycopenecarotenes, and a vitamin E complex holds promise as a viable clinical application. Superfoods Immune Energizer. Children Low in Vitamin D All News Recently Viewed. Home Products Complete Product List Products by Category Product Search.Lycopene and liver health -
HZ and XG performed the experiments and analyzed the data. XZ, ML, and YS revised the manuscript. YS designed the experiments and had primary responsibility for the final content of the manuscript.
All authors contributed to the article and approved the submitted version. This work was supported by the National Natural Science Foundation of China Nos. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
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The researchers combed through studies and scientific papers to connect the dots. They report that lycopene up regulates the sirtuin 1 SIRT1 protein, meaning it increases the number of receptors on cell surfaces, thereby increasing cellular response to it.
Lycopene was found to protect against fatty liver disease, liver fibrosis and the formation of cancer in the liver and lungs. Studies investigating lycopene in NAFLD are listed on Table 1.
A study examining the preventive role of lycopene in NASH was conducted on rats fed a high-fat diet HFD Additionally, a decreased CYP2E1 protein with increasing lycopene dose was observed in rats fed a HFD.
Steatosis and inflammation were significantly lower in lycopene-fed rats. They found that lycopene administration had a preventive effect on experimental NASH induced by HFD in the rat model and lycopene could reduce HFD-induced oxidative stress. Several studies reported that intake of tomato juice appeared to have a protective effect on NAFLD in rats that are hypercholesterolemic and fed a HFD 24 , Rats fed tomato juice supplemented diet had lower TG level in plasma and isoprostane content in urine indicating alleviation of oxidative stress.
They also had enhanced activity of enzymes involved in mitochondrial and peroxisomal β-oxidation of long-chain fatty acids in NAFLD. Lycopene accumulation in the liver was observed in tomato juice supplemented rats.
Others have reported significantly improved absorption of carotenoids linked to the intake of dietary fat Wang et al. HFD-induced NASH-promoted diethylnitrosamine DEN -initiated hepatocarcinoma rat model was used in the study.
Lycopene and tomato extract could inhibit NASH-promoted hepatocarcinogenesis through reduced oxidative stress but with different mechanisms. They observed significantly decreased cytochrome P 2E1, inflammatory foci and mRNA expression of proinflammatory cytokines TNF-α, IL-1β and IL in the tomato extract fed group, but increased nuclear NF-E2-related factor-2 and heme oxygenase-1 proteins in the lycopene fed group.
Carotene,15'-monooxygenase CMO-I and carotene-9',10'-monooxygenase CMO-II are primary mammalian carotenoid cleavage enzymes. CMO-I cleaves β-carotene to two molecules of retinal, whereas CMO-II preferentially cleaves non-provitamin A carotenoids such as lycopene but also has affinity to other carotenoids such as β-carotene 60 - CMO-I has been identified as a cytoplasmic enzyme, whereas CMO-II has been identified as a mitochondrial enzyme.
These enzymes convert the carotenoids to biologically active metabolites Lycopene may also interfere with the β-carotene and retinoid metabolism. It has been found that lycopene supplementation decreased the expression of CMO-I and PPAR-γ in the kidney and adrenal tissues of rats Hepatic pro-inflammatory biomarkers including TNF-α, IL-6, NF-κB p65 protein expression, caspase-1 cleavage and activation of the oncogenic transcription factor STAT3 were significantly reduced in the liver tissue by APO10LA supplementation.
These effects of APO10LA were associated with increased hepatic Sirtuin1 SIRT1 , protein and deacetylation of SIRT1 targets NF-κB p65 and FoxO1 and AMP-activated protein kinase AMPK phosphorylation.
Protective effect of overexpression of SIRT1 was found in HFD-induced fatty liver disease Ahn et al. As a post-transcriptional regulator of gene expression, up-regulating miRNA was achieved by lycopene through targeting the fatty acid-binding protein 7 FABP7.
FABPs are most active proteins in long chain fatty acid uptake and metabolism in the hepatocytes. They found that lycopene up-regulated the miRNA and inhibited FABP7 expression and blocked stearic acid SA induced intracellular lipid accumulation.
They also observed that miRNA could have an important role in hepatic function and its expression was changed by HFD in liver tissues in an animal model 55 , also reported that miR expression was decreased in HFD-induced NASH and stearic acid treated Hepa cells.
NASH was associated with downregulation of miRNA and upregulation of FABP7. FABPs are most active proteins in long chain fatty acid uptake and metabolism in the hepatocytes FABP7 was one of the targets of miRNA, and it was directly and inversely associated with miR Lycopene normalized the effects of HFD and regulated the hepatic lipid metabolism in this model.
It downregulated PPARγ and fatty acid synthase FASN and upregulated CPT1-α, LCAD, PPAR-α and Apoa4 in HFD induced NASH mouse model β-carotene is the most widely distributed carotenoid in yellow-orange and dark green fruits and vegetables β-carotene is also the most abundant carotenoid in the liver Among provitamin A carotenoids, β-carotene has the highest provitamin A activity because it is partly converted to vitamin A β-carotene has a strong antioxidant effect through scavenging free radicals and physically quenching singlet oxygen Major source of β-carotene in human diet is primarily green leafy vegetables, carrots, apricots, sweet potatoes, red palm oil, mature squashes, pumpkins, and mangoes 73 , 75 , As a potent antioxidant, β-carotene has been studied as a potential protective agent in NAFLD.
The studies reporting the effects of β-carotene and other carotenoids on NAFLD are summarized in Table 2. In vivo and in vitro experimental studies have shown potential preventive and therapeutic effects of β-carotene on hepatic inflammation, fibrosis 86 and cirrhosis Another study reported that β-carotene could decrease hepatitis C virus induced-hepatosteatosis via inhibition of HCV RNA replication Dietary β-carotene supplementation has been found to have a protective effect on liver damage.
In rats with monocrotaline-induced steatosis, fat accumulation and hemorrhages decreased in the liver with β-carotene supplementation Harari et al. This could be due to reduced mRNA levels of inflammatory genes such as vascular cell adhesion molecule-1 VCAM-1 , IL-1α, monocyte chemoattractant protein-1 MCP-1 , interferon-γ INF-γ.
Hepatic protective effects of some β-carotene rich products have been shown in experimental studies. Administration of an herbal derivative, Lycium barbarum polysaccharides has been shown to have ameliorative effects on hepatic fibrosis, oxidative stress and inflammatory response in HFD induced NASH and cellular steatosis rat model A study conducted by Ozturk et al.
Apricot is a fruit that has a high content of carotenoids, largely β-carotene. Markers of oxidative stress MDA, total GSH levels, catalase, superoxide dismutase and GSH peroxidase activities were significantly altered in carbon tetrachloride induced hepatic steatosis and damage in Wistar rats.
Oxidative stress was decreased and hepatic steatosis and damage were ameliorated in rats by β-carotene rich apricot feeding.
The results of recent piver suggest Lycopene and liver health dietary llver may modulate the expression of some Enhancing immune system defenses that may affect many chronic diseases such livdr cancer, cardiovascular heealth, diabetes, hypertension and Lydopene diseases. Carotenoids are Lycopene and liver health Menopause and hot weather most investigated dietary micronutrients in this regard. Carotenoids are fat-soluble pigments that give the yellow, red and orange color to fruits and vegetables. Although at least carotenoids were defined in the nature, approximately forty of these are consumed in the human diet. Furthermore, fourteen of these carotenoids and some of their metabolites are identified in blood and tissues 12. They can only be synthesized by plants and microorganisms, therefore their sources are mostly from fruits and vegetables.
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