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Objective: To compare the effect on insulin absorption intra-nasally of Acanthophyllum squarrosum (ASQ) compared with Acanthophyllum saponaria (ASA) and sodium cholate (NAC), which have proven pro-absorptive effects.
Methods: The formulation used in this study contained 2IU insulin (per rat), 1% carboxymethylcellulose (CMC) and a pro-absorptive agent at the same concentration. We assessed the hypoglycaemic effect of each formulation in 5 rats in the fasting state.
Results: There was no significant difference in the pro-absorptive effects of ASQ, ASA, and NAC. Blood glucose levels 2 hours after administration of insulin, given as a percentage of baseline glucose concentration, were as follows for the three formulations used: ASQ: 36.78±11.06%, ASA: 27.46±2.39%, and NAC: 39.94±14.93%. Conclusion: Acanthophyllum squarrosum has a significant pro-absorptive effect, comparable to that to Acanthophyllum saponaria.

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 Alterations in carbohydrate metabolism are frequently observed in cirrhosis. We conducted this study to define the prevalence of diabetes mellitus (DM) and impaired glucose tolerance (IGT) in patients with chronic liver disease (CLD), and explore the factors that may be potentially associated with the development of DM in these patients.
Methods: From October 2002 to March 2003, 185 consecutive patients with CLD, who referred to "Tehran Hepatitis Center", were enrolled into the study. Fasting plasma glucose and two-hour plasma glucose were measured in patients' sera. DM and IGT were diagnosed according to latest American Diabetes Association criteria.
Results: The subjects included 42 inactive HBV carriers, 102 patients with HBV or HCV chronic hepatitis, and 41 cirrhotic patients. Mean age was 43.8±12.0 years ranging between 22 to 84 years. DM and IGT were diagnosed in 40 (21.6%) and 21(11.4%) patients, respectively. Univariate analysis showed that age (P=0.000), CLD status (P=0.000), history of hypertension (P=0.007), family history of DM (P=0.000), and body mass index (BMI) (P=0.009) were associated with DM. Using Multivariate analysis, age (P=0.01), family history of DM (P=0.0001), chronic hepatitis (0.0004), and cirrhosis (P=0.0004) remained as the factors independently associated with DM. When patients with cirrhosis and chronic hepatitis were analyzed separately, higher Child-Pugh's score in cirrhosis (P=0.04) and older age (P=0.04), higher fibrosis score (P=0.04), and higher BMI (P=0.003) in patients with chronic hepatitis were found to be associated with higher prevalence of DM. Conclusion: Our findings indicated that patients with cirrhosis and chronic hepatitis are at risk of developing DM. Older age, sever liver disease, and obesity were associated with development of DM.

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Background: The liver plays a main role in the production and metabolism of lipoproteins, and then impaired lipid metabolism is often seen in patients with liver cirrhosis and chronic hepatitis (CH). As a result, plasma lipid levels could be as useful indicators of liver function and patient's prognosis especially in liver cirrhosis.
Methods: We measured the lipoprotein levels in 77 consecutive patients with liver cirrhosis and CH. 47 men (61%) and 30 women (39%) with mean age 43years (SD=16.4) and mean BMI 26(SD=4.2) have been recruited as patients group. Child score and MELD scale was determined in patients group. The control group was age and sex matched with patients group.
Results: In case group, the levels of HDL LDL, TG, and total cholesterol were significantly lower than control group (p <0.0001). In patients with cirrhosis, the levels of LDL, HDL and total cholesterol were progressively lower when comparing patients in Child class A with patients in class C (p<0.0001).This difference was more significant in LDL and total cholesterol and between upper Child scores ,similarly decreasing in LDL, HDL ,and total cholesterol level was observed when MELD score increased (P<0.0001).
Conclusion: There is a correlation between plasma lipid levels and liver function, so it may be mentioned as an accessible and reliable indicator of liver function in cirrhotic and CH patients.

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Background: Existing studies show that a poor diet has an effect on the progression of non-alcoholic fatty liver disease (NAFLD). The aim of the present study was to systematically summarize the results of studies on the relationship between dietary intakes and NAFLD. Methods: A review of Scopus, PubMed, Cochrane Library, Magiran, Medlib and SID databases and theses in the National Library of the Islamic Republic of Iran was conducted to identify epidemiological studies concerning NAFLD, food groups and dietary patterns. Cross-sectional, case-control and cohort studies with documented in English were selected for this systematic review. Duplication, topic, type of study, study population, variables examined and quality of data reporting of articles were evaluated. Results: Of 2128 articles found in the initial search, 33 were reviewed in full-text of these 6 articles were included in the systematic review. The literature review showed patients with NAFLD consumed more red meat, fats and sweets and less whole grains, fruits and vegetables. The Western dietary pattern was positively associated with the risk of NAFLD and adherence to the Mediterranean diet was negatively correlated to hepatic steatosis. Conclusion: The results of the systematic review indicate that different dietary intakes may be associated with development of NAFLD and its related factors. Due to limited research documented on this topic, further prospective studies are recommended.

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Background: Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease is increasing in adults and children worldwide. Obesity, insulin resistance or diabetes type II, hyperlipidemia and hypertriglyceridemia plays a major role in the epidemiology of this disease. Cytokeratin 18 (CK-18) the major intermediate filament protein in the liver is a marker of increased hepatocyte apoptosis. The aim of this study was to determinate CK-18 level as a marker of hepatocyte apoptosis and paraoxonase as a biochemical marker for lipid peroxidation.

Methods: This case–control study was done on 51 subjects with confirmed NAFLD by ultrasound and 30 healthy individuals. CK-18 is proposed as a biomarker alternative cell death. The serum was used for measurement of the apoptosis-associated neo-epitope in the C-terminal domain of CK-18 by the M30-Apoptosense ELISA kit. The M30 detection antibody recognizes a neo-epitope mapped to positions 387 to 396 of CK18, so called CK18-Asp396 that is only revealed after caspase cleavage of the protein and is postulated as a selective biomarker of apoptosis. Serum PON1 activity was assayed using a synthetic substrate. Paraoxon substrate (diethyl-p nitrophenylphosphate), was deliberated using the increase of absorbance at 412 nm at 37 ◦C. 

Results: There were significant differences regarding serum cytokeratin 18 (p=0.005), paraoxonase activity (p=0.03), triglycerides (p=0.04) and low-density lipoprotein (p=0.04) between NAFLD and healthy subjects. Between CK-18 and paraoxonase with the early stages of fatty liver disease are associated.

Conclusion: This study suggests that serum levels of cytokeratin 18 can be useful in predicting non-alcoholic fatty liver disease. Paraoxonase activity (PON1) should be considered a biochemical marker of lipid peroxidation and the need for follow-up in patients with NAFLD

Keywords: Non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), Cytokeratin 18 (CK-18), Paraoxonases

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Background: Diabetes produces free radicals and damages the liver. The aim of this study was to investigate the effects of Rosmarinus Officinalis leaf hydroalcoholic extract on histopathology and enzymes activity of liver in alloxan induced diabetic rats.
Methods: In this study, 50 adult male Wistar rats weighing 200 to 250 grams, were divided randomly into 5 groups of 10; non-diabetic control, diabetic control and 3 experimental groups (diabetic rats treated with the dosage of 50mg/kg, 100mg/kg and 200mg/kg rosemary leaf extract intraperitoneally for 14 days).
Diabetes was induced in rats by intraperitoneal injection of a single dose 120 mg/kg alloxan was done. At the end of the treatment period, blood samples were taken from the left ventricular heart of mice and aspartate aminotransferase (AST / SGOT), alanine aminotransferase (ALT / SGPT) and alkaline phosphatase (ALP) in serum were measured. Immediately liver was removed and histological samples were fixed in 10% formalin and then stained with hematoxylin-eosin technique (H & E).
Results: In diabetic rats, unlike control mice, the liver enzymes (AST, ALT and ALP) increases, because of damage of liver tissue (p<0.01).
The level of liver enzymes (AST, ALT and ALP) in rats treated with doses 50mg/kg, 100mg/kg and 200mg/kg of rosemary leaf extract showed a significant reduction in these enzymes compared to control diabetes (p<0.01).
Conclusion: Histological studies showed reduced inflammation in the liver lobule and the port in the experimental groups. The third experimental group had greatest impact on reducing liver inflammation and space ports showed lobule. Histologically, tissue changes were in line with biochemical changes.
The effects of Rosmarinus Officinalis leaf hydroalcoholic extract because of its high antioxidant properties, reduce free radicals and inflammation of the liver damage caused by diabetes by inhibiting the enzyme is reduced.

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Background: Hypoglycaemic effects of Galega officinalis and  silver nanoparticles are established. In the present study, the effects of silver nanoparticles synthetized by Galega officinalis extract were investigated on gene expression of TNF-α, IL-6 and serum levels of liver enzymes in diabetes type 2.
Methods: In the present study 20 male Wistar rats in 4 group(n= 5 in each group) weighing 180- 200 gr were used. Control or nikotinamid and stroptozotosin induced diabetic rats receieved intraperitoneal injection of saline or 2/5mg/Kg silver nanoparticles synthetized by Galega officinalis extract or chemichal method for 14 days respectively. One day after the last injections, serum samples and adipose tissue were collected. Mean serum concentration of glucose, urea, creatinine, alanine amino transferase(ALT), and aspartate amino transferase(AST) were determined by spectrophotometry. Mean relative gene expression of TNF-α and IL-6 were determined by method of real time PCR.
Results: Mean serum levels of ALT and AST enzymes, glucose, urea significantly decreased in diabetic rats receiving chemichal or green silver naoparticles compared to diabetic group. Mean relative gene expression of TNF-α and IL-6 significantly decreased in diabetic rats receiving chemichal or green silver naoparticles compared to diabetic ones.
Conclusion: Both chemical and green synthetized silver nanoparticles may prevent hepatocyes damages and they may improve insulin resistance in diabetes type 2 partly via decresing pro- inflammatory factors.

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Background: Over the years type 2 diabetes, in addition to causing irreversible effects on various parts of the body, also causes liver dysfunction and increases the risk of heart failure, but due to the lack of physical symptoms, less attention has been paid. So, the aim of this study was to determine the effect of 8 weeks of endurance training on diabetic indexes and myocardial GLUT4 and liver enzymes of type 2 diabetic rats.
Methods: A total number of 24 rats (220±20) were divided randomly into three groups; 1-Non-diabetic Control group (NC, n=8). 2-Diabetic Control group (D, n=8) To induce type 2 diabetes, high-fat diets were given to rats for two weeks, then streptozotocin (Aldrich company) at a dose of 37 mg / kg in citrate buffer M0.1 (PH4.5) after 6 hours of intraperitoneal fasting was injected, For the healthy control group, the same amount of buffer was injected. Also, aerobic exercise groups ran 5 times a week and 8 weeks on a motorized treadmill. Diabetic index’s, myocardial GLUT4 (Western blotting) and liver enzymes (ELISA) of rats were measured.
Results: Endurance training significantly decreased fasting blood glucose, insulin resistance index (both P= 0.00). It also caused a significant increase in insulin (P= 0.01) and insulin sensitivity index (P= 0.00) compared to the diabetic control group. On the other hand, the amount of GLUT4 in the training group increased significantly (P= 0.01). The results also showed that in comparison with the diabetic control group, ALT and AST did not increase significantly in diabetics with endurance training (P= 0.30, P= 0.5, respectively).
Conclusion: Based on the results, it seems that endurance training significantly increases the level of GLUT4 in the heart and significantly decreased diabetic parameters such as fasting glucose, HOMA-IR index and liver enzymes.

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Background: Inflammation plays a critical role in the promotion of hepatocyte damage and liver fibrosis. In recent years the protective role of exercise and royal jelly (RJ), has been suggested for metabolic and inflammatory disorders. In this study, we aimed to evaluate the effects of aerobic training (AT) and RJ on pro-inflammatory markers in a rat's model of a high-fat diet (HFD).
Methods: In this experimental study, 45 male rats were randomly divided into five groups (Each group: n=9): Normal Diet (ND), High-Fat Diet (HFD), High-Fat Diet +Training (HFDT), High-Fat Diet + Royal Jelly (HFDRJ), and High-Fat Diet +Training + Royal Jelly (HFDTRJ). The supplement groups received 100 mg of royal jelly (kg/body weight) diluted in distilled water orally during the intervention period. The aerobic exercise program included treadmill running with an intensity of 50-60% oxygen consumption (VO2max), 5 days/week for 8 weeks.
Results: HFD increased hepatic NF-κB (p=0.006), TNF-α (p=0.0001) and IL-1β (p=0.0001). AT, RJ as well as the combination of AT with RJ decreased NF-κB, TNF-α and IL-1β (p≤0.05). Decrease in NF-κB, TNF-α and IL-1β were significant in HFDTRJ group compared to HFDT and HFDRJ groups (p≤0.05).
Conclusion: The combination of AT and RJ may decrease inflammatory markers and improve HFD-induced hepatic steatosis by reducing the expression of NF-κB, TNF-α, and IL-1β.

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Background: Non-alcoholic fatty liver disease (NAFLD) is a pathological syndrome associated with increased serum levels of liver enzymes. The purpose of this study was to investigate the impact of exercise training on liver enzymes (ALT, AST, and GGT) and liver fat content in adults with NAFLD.
Methods: The PubMed, Web of Science, SID, Magiran, and Google scholar databases were searched until February 2022 for English and Persian articles. Meta-analyses were performed to compare the impact of exercise training on liver function in patients with fatty liver. SMD and 95% confidence interval (95% CI) were calculated using effect models. Also, the I2 test was used to determine heterogeneity, and the Funnel plot and Egger tests at a significant level of 0.1 were used to determine publication bias.
Results: The results of meta-analysis of 36 studies with 1602 patient with NAFLD, showed that exercise training caused a significant decrease in ALT enzyme [SMD=-0.73, (95% CI: -0.51 to -0.95), p=0.001], AST enzyme [SMD=-0.61, (95% CI: -0.39 to -0.83), p=0.001], GTT enzyme [SMD=-0.66, (95% CI: -0.18 to -1.14), p =0.007], and intrahepatic fat [SMD=-0.58, (95% CI: -0.78 to -0.38), p=0.001].
Conclusion: The findings of the present meta-analysis show the important role of exercise training (aerobic, resistance, and combined training) in improving liver function. So, all three types of aerobic, resistance, and combined exercise are suggested as a non-drug approach to reduce liver enzymes and intrahepatic fat for adults with NAFLD.

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Background: The health and proper functioning of the endoplasmic reticulum in the liver can lead to an increase in the quality of the metabolism of liver cells. Exercise can lead to liver health by regulating liver enzymes and factors related to apoptosis pathway. Therefore, the aim of the current research is to compare the performance of the endoplasmic reticulum chaperone protein of the liver of healthy model rats with the intervention of different training sessions and starvation.
Methods: In this experimental research, 30 Wistar male rats with a weight range of 330 ± 25 grams were selected and divided into six groups: 1) control, 2) starvation, 3) 3 days of training per week, 4) 5 days of training per week, 5) starvation + 3 training days per week, 6) starvation + 5 training days per week. Training consisted of one hour of continuous running on a treadmill for 4 weeks, and starvation was performed for 14 hours when the rats were awake. Data analysis was performed using one-way analysis of variance and post hoc LSD statistical tests in SPSS version 23 software. A significance level of P≤ 0.05 was considered.
Results: Data analysis showed a significant change in the levels of liver enzymes alanine aminotransferase (ALT) and aspartate transaminase (AST) (P≤ 0.05). This change in CHOP gene expression was also significant (P≤ 0.05).
Conclusion: Aerobic training for 3 and 5 days with starvation can lead to liver health by reducing liver enzymes (AST and ALT) and cell death-related factor (CHOP) through the apoptosis pathway.

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Background: Interval exercises with high intensity and consumption of plant extracts probably have beneficial effects on inflammatory indicators. The aim of this study was to investigate the effect of eight weeks of High-Intensity Interval Training (HIIT) and the consumption of Loquat leaf extract on the serum levels of TNF-α and interleukin-18 in obese men with non-alcoholic fatty liver disease.
Methods: In this semi-experimental study, forty men with non-alcoholic fatty liver disease with body mass index (33.92 ± 1.82) with informed written consent were randomly selected and assigned into four groups: control, training, Extract, Extract + training (Each group of 10 people). Exercises were performed for eight weeks and three sessions per week for 60 minutes with intensity between 80-95% of the reserve heart rate. Two capsules of 250 mg of Loquat leaf extract were also prescribed daily. Paired t-test and analysis of covariance were used.
Results: A significant decrease in the levels of TNF-α (15.3%) and interleukin 18 (14.9%) was observed in the training + extract group (P<0.05). A significant difference was observed in the levels of TNF-α (P=0.001) and interlock 18 (P=0.001) between the groups, and these changes were more significant in the Extract + training group than in the training and extract groups.
Conclusions: It is concluded that performing intense intermittent training along with Loquat leaf extract will be able to improve TNF-α and interleukin 18 indices related to fatty liver in people with non-alcoholic fatty liver disease. However, confirmation of this hypothesis requires more research.

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Background: The Purpose of this study was to evaluate the effect of High Intensity Interval Training & Royal Jelly on expression of the genes of the hepatic miR-423-5P - FAM3A-AKt2 pathway in rats.
Methods: The statistical population was 36 male Wistar rats and reaching a weight of 193 ± 20 grams, they were subjected to a high-fat diet diet and intraperitoneal injection of 25 mg STZ. Blood sugar above 150 to 400 mg/dl was considered as a criterion to ensure that the mice had type 2 diabetes. Then divided into 4 groups (diabetic control group, intermittent exercise, Royal Jelly and exercise-Royal Jelly group). The experimental group of did HIIT with a 20 to 36 m/min. for 8 weeks. Royal jelly experimental groups consumed 100 mg/kg royal Jelly. 48 hours after the last training session, the mice were anesthetized with ether and blood was taken from the heart and tissue was removed, including liver tissue, and the tissue sample was transferred to a freezer temperature of -80. Serum glucose measurements were performed by an Auto analyzer. Insulin was measured by an ELISA kit, and the insulin resistance index was measured by formulas. The expression level of miRNA-423-5P, FAM3A and AKt genes in liver tissue was measured using Real Time-PCR method .the data, analyzed by one-way analysis of variance and Bonferroni’s post hoc and univariate and effect size. The significance level was considered to be p≥ 0.05.
Results: The findings showed that the expression of the hepatic miR-423-5P gene in the experimental groups of intermittent exercise with royal jelly and the exercise group and the gel group significantly decreased compared to the control group, and the expression of the FAM3A gene increased in the experimental groups compared to the control group. Non-significant and the expression of AKt2 gene in the training group and the training group with gel increased significantly compared to the control group, and in the gel group only compared to the control group, there was a non-significant increase, Also, there was a significant decrease in glucose in the experimental groups of HIIT exercise and HIIT- Royal jelly compared to the diabetic control group (p <0.05).Expression of the miR-423-5P gene was significantly lower in all groups compared to control, expression of mRNA FAM3 had insignificant increase and expression of mRNA AKt2 had a significant increase in groups of regular exercise and exercise with nutritional intervention. This gene had an insignificant increase of expression in the group with only nutritional intervention.
Conclusion: It seems that HIIT and royal jelly consumption, both alone and in combination, although with greater effect, can create favorable changes in the expression of Mir 4235p. FAM3A and AKt2 help to improve the condition of the liver.