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ORIGINAL ARTICLE
Year : 2020  |  Volume : 33  |  Issue : 1  |  Page : 196-204

Protective effect of caffeine and curcumin versus silymarin on nonalcoholic steatohepatitis in rats


1 Department of Clinical Pharmacology, Faulty of Medicine, Menoufia University, Shebin El-Kom, Egypt
2 Department of Pathology, Faulty of Medicine, Menoufia University, Shebin El-Kom, Egypt
3 Department of Biochemistry, Faulty of Medicine, Menoufia University, Shebin El-Kom, Egypt
4 Department of Clinical Pharmacology, Faulty of Medicine, Mansoura University, Mansoura, Egypt

Date of Submission26-Aug-2018
Date of Decision01-Oct-2018
Date of Acceptance10-Oct-2018
Date of Web Publication25-Mar-2020

Correspondence Address:
Ghada A Hegazy
Shebin El-Kom, Shebin El-Kom
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_253_18

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  Abstract 

Objective
To compare between the effect of curcumin, caffeine with silymarin on an animal model of nonalcoholic steatohepatitis induced by a high-fat and high-sucrose (HFHS) diet.
Background
Nonalcoholic fatty liver disease is recognized as the most common cause of chronic liver disease. Pro-inflammatory and anti-inflammatory cytokines play a part in the pathogenesis of nonalcoholic fatty liver disease, oxidative stress, and insulin resistance.
Materials and methods
Fifty male albino rats were divided into five groups: control group; group B receives a HFHS diet for 16 weeks; group C receives a HFHS diet for 16 weeks and was treated by silymarin in the last 8 weeks; group D receives a HFHS diet for 16 weeks and was treated with curcumin in the last 8 weeks; and group E receives a HFHS diet for 16 weeks and was treated with caffeine in the last 8 weeks.
Results
The HFHS group shows a significant increase in body weight, insulin, tumor necrosis factor α, malonaldehyde, total cholesterol, and triglycerides; compared with the control group, silymarin-treated, curcumin-treated, and caffeine-treated groups show a significant decrease in these parameters.
Conclusion
Silymarin-treated, curcumin-treated, and caffeine-treated groups show a significant protection against HFHS (western) diet-induced nonalcoholic steatohepatitis.

Keywords: caffeine, curcumin, nonalcoholic steatohepatitis, silymarin, tumor necrosis factor α


How to cite this article:
El-Desoky F, Gaber AE, Holah NS, S. Radwan EE, Daba MY, Yassin AA, Hegazy GA. Protective effect of caffeine and curcumin versus silymarin on nonalcoholic steatohepatitis in rats. Menoufia Med J 2020;33:196-204

How to cite this URL:
El-Desoky F, Gaber AE, Holah NS, S. Radwan EE, Daba MY, Yassin AA, Hegazy GA. Protective effect of caffeine and curcumin versus silymarin on nonalcoholic steatohepatitis in rats. Menoufia Med J [serial online] 2020 [cited 2020 Mar 30];33:196-204. Available from: http://www.mmj.eg.net/text.asp?2020/33/1/196/281282




  Introduction Top


Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. It is found in obese people with high-fat diets and sedentary lifestyles. NAFLD comprises a spectrum of hepatic abnormalities in the liver that ranges from a simple intrahepatic accumulation of fat (steatosis) to different degrees of necrotic inflammation [nonalcoholic steatohepatitis (NASH)][1].

NAFLD is a slowly progressive disease but fibrosis rapidly progresses in 20% of cases. NASH is accompanied with an increased mortality ratio compared with the general population[2].

NAFLD is a condition of a 'two-hit' process of pathogenesis since 1998 when Day and James first proposed this hypothesis Dumas ME et al.[3].

The first-hit hepatic triglyceride accumulation increases susceptibility of the liver to injury mediated by the second hits because of inflammatory cytokines/adipokines, oxidative stress, and mitochondrial dysfunction, and lead to steatohepatitis and fibrosis[4].

A third-hit has been added to reflect inadequate hepatocyte proliferation. In the healthy liver, cell death stimulates replication of mature hepatocytes which replace dead cells and reconstitute normal tissue function[5].

However oxidative stress is a central feature of NAFLD pathogenesis by inhibition of the replication of mature hepatocytes which results in expansion of the hepatic progenitor cells. These cells can differentiate into hepatocyte-like cells, and both oval cell and intermediate hepatocyte-like cell numbers are strongly correlated with fibrosis stage, suggesting that accumulation of hepatocyte loss promotes both accumulation of progenitor cells and their differentiation toward hepatocytes and activation of these cells has also been implicated in hepatocellular carcinogenesis[6].

According to Charlton and colleagues a high-fat high-fructose diet was compared with the high-fat diet; both diets give the characters of the metabolic syndrome with obesity, insulin resistance, and steatosis. However, a high-fat diet was associated with minimal inflammation, and there was no increase in fibrosis. High-fat high-fructose diet demonstrated steatohepatitis with pronounced hepatocellular ballooning and progressive fibrosis with high similarities to the human NASH histological findings, and increased expression of genes involved with fibrosis, inflammation, endoplasmic reticulum stress, and lipoapoptosis[7].

The aim of this study was to compare the protective effect of caffeine and curcumin versus silymarin on NASH induced by a high-fat high-sucrose (HFHS) diet in rats.


  Materials and Methods Top


Materials

Curcumin and caffeine (Sigma Aldrich, St. Louis, Missouri, United States), silymarin tablets 140 mg (SEDICO, 6th of October City, Egypt), sucrose, casein, corn starch, anhydrous milk fat, vitamins and minerals mix, cellulose, LD methionine, calcium carbonate (Cornel Lab. Co., Cairo, Egypt ), rat insulin kits (DRG Instruments GmbH, Frauenbergstraße 18, 35039 Marburg, Germany), Rat tumor necrosis factor α (TNF-α) enzyme-linked immunosorbent assay kits, reagents for enzymatic calorimetric determination of malonaldehyde (MDA), reagents for enzymatic calorimetric determination of glutathione (GSH), reagents for measurement of serum aspartate aminotransferase (AST) and reagents for measurement of serum alanine aminotransferase (ALT) by colorimetric method (Biodiagnostic, 29 El-Tahrer St., Dokki, Giza, Egypt), reagents for enzymatic calorimetric determination of cholesterol, and reagents for enzymatic calorimetric determination of glucose (Spinreact, Coloma, 7, 17176 Vall D'En Bas (la), Girona, Spain).

Animals

Fifty male albino rats, weighing 150–200 g were used; they have acclimatized for 1 week prior to the experiment in a fully ventilated room at room temperature. Rats had free access to water and diet. Rats were divided into five main groups: each group consists of 10 rats:

Group A: normal chow diet for 16 weeks and receives corn oil orally for last 8 weeks

Group B: receives a HFHS diet orally for 16 weeks (21% anhydrous milk fat, 34.1% sucrose, 15% corn starch, 19.5% casein, 0.15% cholesterol, 5% cellulose, 0.4% calcium carbonate, 0.3% DL-methionine, 3.5% mineral mix, and 1% vitamin mix) and receives corn oil in the last 8 weeks[8]

Group C: receives a HFHS diet orally for 16 weeks and silymarin (100 mg/kg) in corn oil orally in the last 8 weeks[9]

Group D: receives a HFHS diet orally for 16 weeks and curcumin (10 mg/kg/day) orally in corn oil in the last 8 weeks[10]

Group E: receives a HFHS diet orally for 16 weeks and caffeine 50 mg/kg/day in corn oil orally in the last 8 weeks[11].

Methods and procedures

Body weight was measured at the beginning and the end of the study and then the rats were anaesthetized with diethyl ether and venous blood samples were collected by heparinized capillary tubes from the retro-orbital plexus of rats.

The samples were incubated at 37°C until blood clotted and then centrifuged at 4000 rpm for 10 min for separation of serum which could be stored at −80°C till used for the measurement of serum TNF-α, insulin, glucose, hepatic triglycerides, total cholesterol, ALT, AST, MDA, and reduced GSH.

Statistical analysis

Data are expressed as mean ± SEM. Analysis of variance with post hoc two comparisons are used to evaluate the differences between various experimental and control groups. P values less than 0.05 were considered significant.


  Results Top


Final body weight and liver weight

There was significant increase in final body weight and liver weight in group B (HFHS) compared with group A (control) (291.17 ± 60.11 vs. 150.50 ± 24.98, P1≤ 0.05) (13.62 ± 0.81 vs. 4.00 ± 0.88, P1≤ 0.05, respectively) [Table 1].
Table 1: Effect of silymarin, curcumin, and caffeine on final body weight, final liver weight, fasting blood glucose, serum insulin, total cholesterol, and triglycerides

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Final body weight and liver weight of group C (silymarin-treated group), group D (curcumin-treated group), and group E (caffeine-treated group) were significantly decreased compared with group B (HFHS) (190.33 ± 45.88 vs. 291.17 ± 60.11, P2≤ 0.05; 181.83 ± 38.81 vs. 291.17 ± 60.11, P2≤ 0.05; and 156.17 ± 25.49 vs. 291.17 ± 60.11; P2≤ 0.05) (5.72 ± 1.16 vs. 13.62 ± 0.81, P2≤ 0.05; 4.30 ± 0.69 vs. 13.62 ± 0.81, P2≤ 0.05; and 5.85 ± 1.47 vs. 13.62 ± 0.81, P2≤ 0.05, respectively).

Also, there was no significant change in final body weight and liver weight between group D and group E compared with group C (181.83 ± 38.81 vs. 190.33 ± 45.88, P3≥ 0.05 and 156.17 ± 25.49 vs. 190.33 ± 45.88, P3≥ 0.05) (4.30 ± 0.69 vs. 5.72 ± 1.16, P3≥ 0.05; 5.85 ± 1.47 vs. 5.72 ± 1.16, P3≥ 0.05, respectively).

There was no significant change in final body weight and liver weight between group E compared with group D (156.17 ± 25.49 vs. 181.83 ± 38.81, P4≥ 0.05) (5.85 ± 1.47 vs. 4.30 ± 0.69, P4≥ 0.05, respectively).

Fasting blood glucose and serum insulin [Table 1].

There was significant increase in fasting blood glucose in group B compared with group A (166.17 ± 8.25 vs. 91.17 ± 83.33 ± 1.36, P1≤ 0.05 and 106.00 ± 2.93 vs. 25.67 ± 1.83, P1≤ 0.05, respectively).

Fasting blood glucose and serum insulin of group C, group D, and group E were significantly decreased compared with group B (HFHS) (90.00 ± 2.21 vs. 166.17 ± 8.25, P2 ≤0.05; 84.67 ± 1.91 vs. 166.17 ± 8.25, P2≤ 0.05; and 89.33 ± 2.61 vs. 166.17 ± 8.25, P2≤ 0.05 and 28.83 ± 2.73 vs. 106.00 ± 2.93, P2 ≤0.05; 27.00 ± 1.67 vs. 106.00 ± 2.93, P2≤ 0.05; and 28.17 ± 1.35 vs. 106.00 ± 2.93, P2 ≤0.05, respectively).

Also, there was no significant change in fasting blood glucose and serum insulin between group D and group E compared with group C (84.67 ± 1.91 vs. 90.00 ± 2.21, P3≥ 0.05; and 89.33 ± 2.61 vs. 90.00 ± 2.21, P3≥ 0.05 and 27.00 ± 1.67 vs. 28.83 ± 2.73, P3≥ 0.05 and 28.17 ± 1.35 vs. 28.83 ± 2.73, P3≥ 0.05, respectively).

Also, there was no significant change in fasting blood glucose and serum insulin in group E compared with D (89.33 ± 2.61 vs. 84.67 ± 1.91, P4≥ 0.05 and 28.17 ± 1.35 vs. 27.00 ± 1.67, P4≥ 0.05, respectively).

Total cholesterol and triglycerides [Table 1].

There was significant increase in total cholesterol and triglycerides in group B compared with group A (152.17 ± 12.86 vs. 47.33 ± 5.16, P1≤ 0.05 and 164.33 ± 11.02 vs. 69.50 ± 6.09, P1≤ 0.05, respectively).

Total cholesterol and triglycerides of group C, group D, and group E were significantly decreased compared with group B (53.50 ± 22.85 vs. 152.17 ± 12.86, P2≤ 0.05; 71.83 ± 8.01 vs. 152.17 ± 12.86, P2≤ 0.05 and 100.00 ± 8.07 vs. 152.17 ± 12.86, P2≤ 0.05 and 82.50 ± 11.36 vs. 164.33 ± 11.02, P2≤ 0.05; 84.17 ± 11.51 vs. 164.33 ± 11.02, P2≤ 0.05, and 164.33 ± 11.02, P2≤ 0.05, respectively).

There was no significant change in total cholesterol between group D compared with group C (71.83 ± 8.01 vs. 55.50 ± 27.89, P3≥ 0.05) and there was a significant increase in total cholesterol between group E compared with group C (65.67 ± 22.53 vs. 53.50 ± 22.85, P3≤ 0.05).

And there was no significant change in serum triglycerides between group D and group E in comparison with group C (84.17 ± 11.51 vs. 82.50 ± 11.36, P3≥ 0.05 and 65.67 ± 22.53 vs. 82.50 ± 11.36, P3≥ 0.05, respectively).

Also, there was a significant decrease in total cholesterol between group E compared with group D (100.00 ± 8.07 vs. 71.83 ± 8.01, P4≤ 0.05). But there was no significant change in serum triglycerides between group E compared with group D (84.67 ± 9.97 vs. 84.17 ± 11.51, P4≥ 0.05).

Serum AST and ALT [Table 2].
Table 2: Effect of silymarin, curcumin, and caffeine on aspartate aminotransferase, alanine aminotransferase, liver tissue tumor necrosis factor α, liver tissue glutathione, and liver tissue malonaldehyde

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There was significant increase in serum AST and ALT in group B compared with group A (215.33 ± 84.25 vs. 24.83 ± 4.96, P1≤ 0.05 and 188.17 ± 72.62 vs. 16.33 ± 1.63, P1≤ 0.05, respectively).

Serum AST and ALT of group C, group E, and group D was significantly decreased compared with group B (88.83 ± 4.83 vs. 215.33 ± 84.25, P2≤ 0.05; 86.67 ± 9.52 vs. 215.33 ± 84.25, P2≤ 0.05 and 62.67 ± 15.12 vs. 215.33 ± 84.25, P2≤ 0.05 and 30.17 ± 3.87 vs. 188.17 ± 72.62, P2≤ 0.05; 34.83 ± 7.47 vs. 188.17 ± 72.62, P2≤ 0.05; and 23.33 ± 8.98 vs. 188.17 ± 72.62, P2≤ 0.05, respectively).

Also there was no significant change in serum AST and ALT between group D and group E compared with group C (86.67 ± 9.52 vs. 88.83 ± 4.83, P3≥ 0.05; and 65.67 ± 22.53 vs. 82.50 ± 11.36, P3≥ 0.05 and 34.83 ± 7.47 vs. 30.17 ± 3.87, P3≥ 0.05; and 23.33 ± 8.98 vs. 30.17 ± 3.87, P3≥ 0.05, respectively).

Also there was no significant change in serum AST and ALT between group E compared with group D (62.67 ± 15.12 vs. 86.67 ± 9.52, P4≥ 0.05 and 23.33 ± 8.98 vs. 34.83 ± 7.47, P4≥ 0.05).

TNF-α [Table 2].

There was significant increase in liver tissue TNF-α in group B compared with group A (54.06 ± 1.91 vs. 11.08 ± 0.84, P1≤ 0.05).

Liver TNF-α of group C, group D, and group E was significantly decreased compared with group B (25.51 ± 1.54 vs. 54.06 ± 1.91, P2≤ 0.05; 25.31 ± 1.14 vs. 54.06 ± 1.91, P2≤ 0.05; and 25.75 ± 1.94 vs. 54.06 ± 1.91, P2≤ 0.05, respectively).

Also, there was no significant change in liver TNF-α between group D and group E compared with group C (25.31 ± 1.14 vs. 25.51 ± 1.54, P3≥ 0.05 and 25.75 ± 1.94 vs. 25.51 ± 1.54, P3≥ 0.05, respectively).

Also there was no significant increase in liver TNF-α between group E compared with group D (25.75 ± 1.94 vs. 25.31 ± 1.14, P4≥ 0.05).

Liver tissue reduced GSH [Table 2].

There was significant decrease in liver tissue in group B compared with group A (248.33 ± 4.24 vs. 463.83 ± 3.83, P1≤ 0.05).

Liver tissue reduced GSH of group C, group D, and group E which was significantly increased compared with group B (429.17 ± 9.54 vs. 248.33 ± 4.24, P2≤ 0.05; 372.17 ± 8.51 vs. 248.33 ± 4.24, P2≤ 0.05 and 365.17 ± 6.11 vs. 248.33 ± 4.24, P2≤ 0.05, respectively).

There was significant decrease in liver tissue reduced GSH between group D and group E compared with group C (372.17 ± 8.51 vs. 429.17 ± 9.54, P3≤ 0.05 and 365.17 ± 6.11 vs. 429.17 ± 9.54, P3≤ 0.05).

There was no significant change in liver tissue reduced GSH in group D compared with group E (372.17 ± 8.51 vs. 365.17 ± 6.11, P4≥ 0.05).

Liver tissue MDA [Table 2].

There was significant increase in liver tissue MDA in group B compared with group A (48.27 ± 0.56 vs. 13.90 ± 0.20, P1≤ 0.05).

Liver tissue MDA of group C, group D, and group E was significantly decreased compared with group B (14.63 ± 0.43 vs. 48.27 ± 0.56, P2≤ 0.05; 16.20 ± 1.00 vs. 48.27 ± 0.56, P2≤ 0.05 and 14.80 ± 0.34 vs. 48.27 ± 0.56, P2≤ 0.05, respectively).

Also, there was no significant change in liver tissue MDA between group D and group E compared with group C (16.20 ± 1.00 vs. 14.63 ± 0.43, P3≥ 0.05 and 14.80 ± 0.34 vs. 14.63 ± 0.43, P3≥ 0.05, respectively).

Also, there was no significant change in liver tissue MDA between group D compared with group E (16.20 ± 1.00 vs. 365.17 ± 6.11, P4≥ 0.05).

Interpretation of pathological results.

Regarding apoptosis there was a highly statistically significant difference between group B and control group A and other groups as the highest apoptosis was in the disease group (21.00 ± 1.81) as the lowest apoptosis was in group D (curcumin) and group E (10.83 ± 1.17 and 9.80 ± 0.66, respectively.

More over there was a highly statistically significant difference between the disease group and other groups regarding steatosis, as the lowest steatosis was in group D (35.17 ± 3.22) [Table 3] and [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5] .
Table 3: Effect of silymarin, curcumin, and caffeine on apoptosis (OHPF) and steatosis

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Figure 1: Section in liver in group A (control group) showing normal liver architecture [normal hepatocytes (blue arrow) and central vein (yellow arrow)]. Hematoxylin and eosin, ×200.

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Figure 2: Section in liver in group B (diseased group) showing marked portal inflammation (blue arrow), parenchymal lipogranuloma (yellow arrow), and ballooning of the hepatocytes (red arrow). Hematoxylin and eosin, ×200.

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Figure 3: Section in liver of group C showing normal liver architecture with improved hepatocytic stiatosis and ballooning and showed minimal lobular inflammation (red arrow). Hematoxylin and eosin, ×200.

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Figure 4: Section in liver of group C showing improved hepatocytic stiatosis. ballooning and lobular inflammation. Hematoxylin and eosin, ×400.

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Figure 5: Section in liver of group E showing normal liver architecture with improved hepatocytic stiatosis and ballooning and showed minimal lobular inflammation (arrow). Hematoxylin and eosin, ×200.

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  Discussion Top


NAFLD is the most common liver disease in children and adults, and is a hepatic manifestation of obesity and metabolic syndrome[12].

Although insulin resistance, oxidative stress, lipid peroxidation, and cytokine production including adipokines and innate immunity are likely involved in the pathogenesis of NASH, the dietary mechanisms causing NASH are less well understood, while total caloric intake may play a role in NAFLD[13].

Some epidemiological studies implicate diets higher in saturated fat. However, NAFLD is also strongly associated with the ingestion of fructose, especially from sweetened beverages[14].

The two major sources of fructose are sucrose (table sugar) which consists of 50% fructose and 50% glucose (a disaccharide of glucose and fructose) and high fructose corn syrup, which has a varying fructose content, from 42% in pastries to 55–65% in fountain drinks[15].

The administration of fructose rapidly causes hepatic steatosis in experimental animals. Hepatic steatosis can even be induced in calorically restricted rats, provided the diet is high in sucrose (40%)[16].

According to the current study, the silymarin-treated group showed a significant reduction in body and liver weights, fasting blood glucose, serum insulin, total cholesterol, triglycerides, also showed antioxidant properities as it reduced MDA significantly; anti-inflammatory effect as it reduced the pro-inflammatory cytokine TNF-α and a significant improvement in histopathological finding compared with the HFHS diet group. These results are in agreement with most studies carried on the effect of silymarin on NASH, so silymarin is clinically used as a hepatoprotector to treat liver injuries[17].

In the current study, curcumin shows a significant decrease in final body weight and liver weight in group D curcumin-treated group compared with group B HFHS and this result is in agreement with Moradi et al.[18], who reported that curcumin increases glucose uptake by the skeletal muscle mediated by improving the expressions of glucose transporter 4 (GLUT4) through the phospholipase C–phosphoinositide-3-kinase pathway. Thus Curcuma longa increases calories consumption by enhancing glucose utilization by muscles which helps in the management of obesity and also it is beneficial for the treatment of obesity by inhibiting adipogenesis as well as activating lipolysis.

In the current study, it was found that the curcumin-treated group D showed a significant decrease in blood glucose and insulin level in comparison with HFHS group B and these results are in agreement with Ghorbani et al.[19], who explained these results as curcumin can reduce blood glucose level by reduction in hepatic glucose production and glycogen synthesis and stimulation of glucose uptake by increasing GLUT4, GLUT2, and GLUT3 gene expression, increasing activation of AMP kinase (AMPK), promoting peroxisome proliferator activator receptor gamma ligand binding activity suppressing hyperglycemia-induced inflammatory state, stimulation of insulin secretion from pancreatic tissues, and improvement in pancreatic cell function.

Total cholesterol and triglycerides were significantly decreased in the curcumin-treated group D compared with the HFHS diet group B and this was in agreement with Kim and Kim[20] who explained this result that cholesterol may bind to curcumin and be excreted; curcumin mediated increase in fecal excretion of cholesterol and bile acid and it was suggested that curcumin may prevent the absorption of cholesterol and lipids by disrupting micelle formation and promote fecal excretion of total steroids and bile acids.

Pro-inflammatory cytokine TNF-α production is significantly decreased in the curcumin-treated group D in comparison to the HFHS group B and this result was explained by studies that have supported findings that LPS is one of the major inducers of TNF-α in macrophages and monocytes and that curcumin can downregulate the expression of TNF-α. Also curcumin could affect TNF expression by affecting the methylation of TNF promoter[21].

Curcumin attenuated oxidative stress markers in the current study as it significantly decreases the MDA level, increased GSH level in the curcumin-treated group D in comparison with the HFHS group B; the previous result was explained by that curcumin can directly interact with superoxide anion and hydrogen peroxide (H2O2) and inhibit oxidative stress even more than that of vitamin E, which is an oxygen-radical scavenger[22].

Caffeine-treated group E in the current study showed a significant decrease in blood glucose and insulin level compared with the HFHS diet group B and this result was in agreement with Paiva et al.[23], who found that caffeine has been shown to have such biological functions as acting as an adenosine receptor antagonist, activating AMPK in the skeletal muscle and protecting pancreatic beta-cells against streptozotocin toxicity; AMPK reduces liver glucose production and enhances glucose capture in the skeletal muscle, presenting an important role in glucose homeostasis.

Total cholesterol and hepatic triglycerides were significantly decreased in caffeine-treated group E in comparison with the HFHS group B and this result was in agreement with Quan et al.[24], who explained these results with regard to the molecular mechanism of caffeine alleviating hepatic lipid accumulation and the expression of genes associated with lipid metabolism as it causes downregulation of transcription factor sterol regulatory element-binding protein, which controls lipogenesis transcriptionally.

The pro-inflammatory cytokine TNF-α was significantly decreased in the caffeine-treated group E compared with the HFHS diet group B and this result was in agreement with Chavez-Valdez et al.[25] who explained the mechanisms by which caffiene decreases TNF-α secretion by activated human cord blood monocytes lipoprotein lipase via angiotensin receptor 1 blockade; the mechanisms may involve not only nonspecific angiotensin receptor blockade, but also inhibition of phosphodiasterase 4 and alteration in toll-like receptor expression.

Caffeine-treated group E showed a significant decrease in MDA, and a significant increase in GSH in comparison with the HFHS diet group B and this result was explained by Corrêa et al.[26] by reducing or eliminating reactive oxygen species.

It was observed that the degree of hepatic injury including steatosis, cytological ballooning, and lobular inflammation was attenuated in the silymarin-treated group compared with the high-fat-treated group and this result was in agreement with Yao et al.[27].

Also the curcumin-treated group D showed attenuation of histological findings of NASH such as steatosis, degree of ballooning, apoptosis, lobar, and portal inflammation and decreased grade of inflammation and these findings were in agreement with Mandy et al.[28].

Caffeine-treated group E showed a significant decrease in steatosis, apoptosis, degree of ballooning, lobar, and portal inflammation and grade of fibrosis and these results were in agreement with Huafeng et al.[29].


  Conclusion Top


Silymarin, curcumin, and caffeine showed an improvement in HFHS diet-induced NASH.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

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