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Abstract

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide and is potentially treatable, though there are few therapeutic agents available. Artichoke leaf extract (ALE) has shown potential as a hepatoprotective agent. This study sought to determine if ALE had therapeutic utility in patients with established NAFLD. In this randomized double-blind placebo-controlled parallel-group trial, 100 subjects with ultrasound-diagnosed NAFLD were randomized to either ALE 600 mg daily or placebo for a 2-month period. NAFLD response was assessed by liver ultrasound and serological markers including the aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio and AST to platelet ratio index (APRI) score. Ninety patients completed the study (49 ALE and 41 placebo) with no side effects reported. ALE treatment compared with placebo: Doppler sonography showed increased hepatic vein flow (p < .001), reduced portal vein diameter (p < .001) and liver size (p < .001), reduction in serum ALT (p < .001) and AST (p < .001) levels, improvement in AST/ALT ratio and APRI scores (p < .01), and reduction in total bilirubin. ALE supplementation reduced total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and triglyceride concentrations (p = .01). This study has shown beneficial effects of ALE supplementation on both ultrasound liver parameters and liver serum parameters (ALT, AST, APRI ratio, and total bilirubin) in patients with NAFLD.

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... Artichoke can have protective effects against NAFLD by reducing the production of reactive oxygen species [13], lipid peroxidation [9], and protein oxidation and increasing the activity of glutathione peroxidase [14]. Some in vitro, animal, and human studies evaluated the potential antioxidant effect of artichoke on hepatocytes [15][16][17][18]. In a study conducted by Panahi et al. [17], treatment with artichoke leaf extract (ALE) significantly lowered aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and improved AST/ALT ratio compared with the placebo group. ...
... Some in vitro, animal, and human studies evaluated the potential antioxidant effect of artichoke on hepatocytes [15][16][17][18]. In a study conducted by Panahi et al. [17], treatment with artichoke leaf extract (ALE) significantly lowered aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and improved AST/ALT ratio compared with the placebo group. However, Fallah Huseini et al. [19] did not find any significant effects on ALT and AST for ALE group in comparison with the control group. ...
... The p values less than 0.05 were considered to be statistically significant. [27] 2000 L L L L L L 2. Roghani-Dehkordi and Kamkhah [30] 2009 L L L L L L 3. Fallah Huseini et al. [19] 2012 L L L L S L 4. Rangboo et al. [29] 2016 L L S L L L 5. Panahi et al. [17] 2018 L L L L L L 6. Musolino et a. [28] 2020 L L L L L L 7. Rondanelli et al. [31] 2020 L L L L L L L, Low risk of bias; H, High risk of bias; S, Some concerns. ...
Article
Studies examining the effect of artichoke on liver enzymes have reported inconsistent results. This systematic review and meta-analysis aimed to assess the effects of artichoke administration on the liver enzymes. PubMed, Embase, the Cochrane Library, and Scopus databases were searched for articles published up to January 2022. Standardized mean difference (Hedges' g) were analyzed using a random-effects model. Heterogeneity, publication bias, and sensitivity analysis were assessed for the liver enzymes. Pooled analysis of seven randomized controlled trials (RCTs) suggested that the artichoke administration has an effect on both alanine aminotransferase (ALT) (Hedges' g, -1.08; 95% confidence interval [CI], -1.76 to -0.40; p = 0.002), and aspartate aminotransferase (AST) (Hedges' g, -1.02; 95% CI, -1.76 to -0.28; p = 0.007). Greater effects on ALT were detected in trials that lasted ≤8 weeks. Also, greater effects on AST were detected in trials using > 500 mg artichoke. Overall, this meta-analysis demonstrated artichoke supplementation decreased ALT and AST.
... Artichoke's leaves contain polyphenolic compounds, prebiotics (inulin), minerals, ascorbic acids, and folate [13]. Its leaf extract is rich in dietary fibers and antioxidant components [14], proposing the extract as beneficial in the control of HTN. Based on an experimental study, artichoke leaf extract also increases endothelial nitric oxide synthase (eNOS) gene expression and nitric oxide (NO) production in cultured human vascular endothelial cells and enhances endothelium-dependent vasodilation in mice aorta [15]. ...
... The current evidence is relatively limited and non-conclusive and only a few studies have reported that the supplementation of artichoke and artichoke products have a promising effect on controlling blood pressure [9][10][11][12]. While these findings are not supported by other studies [14,16,17]. A recent meta-analysis indicated that artichoke supplementation did not affect blood pressure. ...
... Of these articles, 10 were excluded because of the following reasons: irrelevant (n = 3), has no placebo-controlled group (n = 1), complex intervention (n = 1), without sufficient data for outcomes (n = 2), and conference abstracts (n = 3). Finally, 7 studies met all our inclusion criteria [9][10][11][12]14,16,17]. ...
Article
Full-text available
Despite controversies, no earlier study has systematically summarized findings from earlier studies on the effect of artichoke supplementation on blood pressure. Therefore, current systematic review and meta-analysis was done on the effect of artichoke supplementation on systolic blood pressure (SBP) and diastolic blood pressure (DBP) in adults. Five databases were searched from inception to January 2022 using relevant keywords. All randomized clinical trials investigating the impact of oral artichoke supplementation on any of the blood pressure parameters including SBP or/and DBP were included. Out of 1,507 citations, 7 trials that enrolled 472 subjects were included. Artichoke supplementation resulted in significant reduction in SBP (weighted mean difference [WMD], −2.01 mmHg; 95% confidence interval [CI], −3.78, −0.24; p = 0.026) and DBP (WMD, −1.45 mmHg; 95% CI, −2.81, −0.08; p = 0.038). Greater effects on SBP were detected in trials using ≤ 500 mg artichoke, lasted > 8 weeks, participants aged < 50 years' old and sample size ≤ 70. There was also a similar impact of artichoke on DBP. However, significant non-linear associations were found between artichoke supplementation dosage and study duration with both SBP (for dosage: p non-linearity = 0.002, for duration: p non-linearity = 0.016) and DBP (for dosage: p non-linearity = 0.005, for duration: p non-linearity = 0.003). We found a significant reduction in both SBP and DBP following artichoke supplementation in adults. It could be proposed as a hypotensive supplement in hypertension management.
... [38][39][40] The mean -SD for the change (within each group) was readily available in two studies. 41,42 The included studies were conducted between 2016 and 2019 and recruited a total of 333 NAFLD patients. The treatment period ranged from 4 to 24 weeks with a median of 8 weeks (interquartile range 8-16 weeks) while the average treatment period was 12 weeks. ...
... The reduction in HDL was higher in the ALE compared with the placebo group as reported by Panahi. 41 The reduction was not signicantly different between groups in three studies and only Radchenko et al. showed that ALE had a benecial effect on HDL. 40 Two studies did not report a statistically signicant difference in the D LDL levels between both the intervention and control groups. ...
... Doppler sonography showed signicant increased hepatic vein ow, reduced portal diameter, and liver size when NAFLD patients were treated with ALE. 41 Color Doppler ultrasound (US) of carotid arteries and US assessment of endothelial function revealed that the atherosclerotic markers carotid intima-media thickness and ow-mediated silation value were improved signicantly in NAFLD subgroups. 38 ...
Article
Nonalcoholic fatty liver disease (NAFLD) is a major chronic liver disease that can lead to liver cirrhosis, liver cancer, and death. Artichoke leaf extract (ALE) is well known in folk medicine for its hepatoprotective effect. Till recent times, no sufficient data from randomized clinical trials (RCTs) exist to support such use. This meta-analysis summarizes evidence from recent RCTs that evaluated ALE in NAFLD patients. Electronic databases were searched for RCTs that used ALE in NAFLD patients. The random-effects model was used to pool effect sizes (standardized change score). Data synthesis from five RCTs (333 patients) showed that ALE resulted in a significant reduction in alanine aminotransferase (standardized mean difference [SMD]: 1.1; 95% confidence interval [CI], 0.79-1.73; P < .001) and aspartate aminotransferase levels (SMD: 1.01; 95% CI, 0.52-1.51; P < .001) compared with the control group. ALE also resulted in a significant reduction in total cholesterol (SMD: 0.98; 95% CI, 0.53-1.43; P = .004), low-density lipoprotein (SMD: 0.96; 95% CI, 0.3-1.62; P < .001) and triglycerides (SMD: 0.95; 95% CI, 0.58-1.32; P < .001). The current review provides evidence from RCTs to support the use of ALE as a hepatoprotective agent in NAFLD patients. The study was registered on the PROSPERO database with the Registration No. CRD42020182502 (https://www.crd.york.ac.uk/prospero).
... After full-text review, four more studies were excluded due to the following reasons: irrelevant outcomes (n = 2), without sufficient data (n = 1), and review paper (n = 1). Finally, a total of 14 RCTs was included for the final systematic review and meta-analysis (Bundy, Walker, Middleton, Wallis, & Simpson, 2008;Englisch et al., 2000;Fallah Huseini, Kianbakht, & Heshmat, 2012;Gatmiri et al., 2019;Panahi et al., 2018;Rangboo et al., 2016;Rezazadeh et al., 2019;Khatereh Rezazadeh, Rezazadeh, & Ebrahimi-Mameghani, 2018;Roghani-Dehkordi & Kamkhah, 2009;Rondanelli et al., 2013;Rondanelli, Giacosa, Orsini, Opizzi, & Villani, 2011;Rondanelli et al., 2014;Rondanelli et al., 2020;Skarpanska-Stejnborn et al., 2008). ...
... The general characteristics of the 14 eligible trials are summarized in Table 1 (Englisch et al., 2000), and UK (Bundy et al., 2008). Apart from two studies that were exclusively conducted among men (Roghani-Dehkordi & Kamkhah, 2009;Skarpanska-Stejnborn et al., 2008), other studies were among both genders (Bundy et al., 2008;Englisch et al., 2000;Fallah Huseini et al., 2012;Gatmiri et al., 2019;Panahi et al., 2018;Rangboo et al., 2016;Rezazadeh et al., 2019;Rezazadeh, Aliashrafi, et al., 2018;Rondanelli et al., 2011;Rondanelli et al., 2013;Rondanelli et al., 2014;Rondanelli et al., 2020). All included RCTs utilized a parallel-group design. ...
... All included RCTs utilized a parallel-group design. The included studies had recruited subjects with hypercholesterolemia (Bundy et al., 2008;Englisch et al., 2000;Rondanelli et al., 2013), hypercholesterolemia with type 2 diabetes (Fallah Huseini et al., 2012), NASH (Rangboo et al., 2016), hypertension (Roghani-Dehkordi & Kamkhah, 2009), overweight and obesity with impaired fasting glucose (IFG) (Rondanelli et al., 2014;Rondanelli et al., 2020), NAFLD (Panahi et al., 2018), chronic kidney disease (Gatmiri et al., 2019), hypertriglyceridemia (Rezazadeh et al., 2019), metabolic syndrome (Rezazadeh, Aliashrafi, et al., 2018;, and nonhypercholestrolemic rowers (Skarpanska-Stejnborn et al., 2008). Artichoke was administered in varying doses from 50 to 2,700 mg/day for a duration of 5-12 weeks. ...
Article
Accumulating evidence regarding the effect of artichoke on lipid profile is equivocal. We updated a previous meta‐analysis on the effect of artichoke extract supplementation on lipid profile and performed dose–response analysis. We searched PubMed, Scopus, Web of Science, and Cochrane Library from inception to June 2021 using relevant keywords. Papers from identified articles were collected. Two researchers rated the certainty in the estimates using the GRADE approach. Combining 15 effect sizes from 14 studies based on the random‐effects analysis, we found that artichoke significantly reduced TG (weighed mean difference [WMD]: −17.01 mg/dl, 95% CI: −23.88, −10.13, p = .011), TC (WMD: −17.01 mg/dl, 95% CI: −23.88, −10.13, p < .001), and LDL‐C (WMD: −17.48 mg/dl, 95%CI: −25.44, −9.53, p < .001). No significant effect of artichoke on HDL‐C level was detected (WMD: 0.78 mg/dl, 95%CI: −0.93, 2.49, p = .371). Combining the two effect sizes revealed that artichoke juice supplementation significantly reduced TG (WMD: −3.34 mg/dl, 95%CI: −5.51, −1.17, p = .003), TC (WMD: −18.04 mg/dl, 95%CI: −20.30, −15.78, p < .001), LDL‐C (WMD: −1.75 mg/dl, 95%CI: −3.02, −0.48, p = .007), and HDL‐C levels (WMD: −4.21 mg/dl, 95%CI: −5.49, −2.93, p < .001). In conclusion, we found that artichoke supplementation may favor CVD prevention by acting in improving the lipid profile.
... 11 Whilst a study conducted in NAFLD patients revealed that artichoke leaf extract supplementation substantially decreased ALT and AST levels, in comparison with the placebo group. 14 However, contrary to the positive findings reported above, Roghani-Dehkordi and Kamkhah reported no significant increases in AST levels after artichoke leaf juice supplementation. 15 Although some previous clinical trials have advocated the positive effects of artichoke on liver enzymes, the overarching results of previous studies are equivocal. ...
... to 70 years. The selected articles were conducted on NAFLD, 11,14,25 hypertensive, 15 11,14,15,24,25 Germany, 23 Italy, 22 and France, 21 respectively. The dose of artichoke ranged from 100 mg/day to 2700 mg/day, and the duration of administration varied from 4 to 12 weeks. ...
... to 70 years. The selected articles were conducted on NAFLD, 11,14,25 hypertensive, 15 11,14,15,24,25 Germany, 23 Italy, 22 and France, 21 respectively. The dose of artichoke ranged from 100 mg/day to 2700 mg/day, and the duration of administration varied from 4 to 12 weeks. ...
Article
Objective A systematic review and meta-analysis was conducted to summarize studies conducted on the effects of artichoke supplementation on liver enzymes. Methods Suitable studies were detected by searching online databases, including Medline, Embase, Cochrane Library, and Scopus databases, until 05 June 2021. As liver enzymes were reported in different units, standardized mean differences (SMD) were used and data were pooled using a random-effects model. Heterogeneity, publication bias, and sensitivity analysis were also assessed. Results Pooled analysis, of eight clinical trials, revealed that artichoke supplementation significantly reduced the concentration of aspartate aminotransferase (AST) (P=0.001) and alanine transaminase (ALT) (; P = 0.016), in comparison with placebo. Subgroup analysis suggested that artichoke administration significantly reduces AST and ALT in patients with non-alcoholic fatty liver disease (P=0.003 for AST and P<0.001 for ALT), and ALT among overweight/obese subjects (P=0.025). Conclusions Artichoke supplementation elicited significant reductions in liver enzymes, especially among patients with non-alcoholic fatty liver disease.
... In healthy hypercholesterolemic adults, ALE treatment (1280 mg daily for 12 weeks) decreases plasma total cholesterol by 4.2% [9]. In patients with diagnosed NAFLD, ALE treatment (600 mg daily for 9 weeks) reduces liver size, serum total cholesterol and triglyceride concentrations [10]. In a rat model of a high-fat diet, ALE limits hepatic disorders by reducing the fatty liver deposition in the hepatic lobule [11]. ...
... At the cellular level, we found that: (1) ALE metabolites exert hepatoprotective properties in human hepatocytes by counteracting a fatty acid-induced lipotoxic stress that is commonly observed in hypercholesterolemia [9] and steatohepatitis [10]; (2) ALE metabolites limit adipogenic differentiation and hypertrophy, a cellular feature of obesity and metabolic syndrome [23]; (3) finally, ALE metabolites protect chondrocyte from an IL-1β stimulation that mimics osteo-arthritis inflammatory environment [14]. ...
... These doses of 400 mg/kg/day in rats and 1.6 g/kg/day in mice for 10 to 56 days correspond to 8 to 15 g/day in humans according to the metabolic weight conversion table. In humans, the average dose for a chronic exposure is around 1.8 g, ranging from 250 to 3200 mg for 5 to 12 weeks (250 [46]; 1200 [9,22]; 600 [10]; 1800 [23,47]; 3200 mg [48]). ...
Article
Full-text available
The aging of our population is accompanied by an increased prevalence of chronic diseases. Among those, liver, joint and adipose tissue-related pathologies have a major socio-economic impact. They share common origins as they result from a dysregulation of the inflammatory and metabolic status. Plant-derived nutrients and especially polyphenols, exert a large range of beneficial effects in the prevention of chronic diseases but require clinically validated approaches for optimized care management. In this study, we designed an innovative clinical approach considering the metabolites produced by the digestive tract following the ingestion of an artichoke leaf extract. Human serum, enriched with metabolites deriving from the extract, was collected and incubated with human hepatocytes, human primary chondrocytes and adipocytes to determine the biological activity of the extract. Changes in cellular behavior demonstrated that the artichoke leaf extract protects hepatocytes from lipotoxic stress, prevents adipocytes differentiation and hyperplasia, and exerts chondroprotective properties in an inflammatory context. These data validate the beneficial health properties of an artichoke leaf extract at the clinical level and provide both insights and further evidence that plant-derived nutrients and especially polyphenols from artichoke may represent a relevant alternative for nutritional strategies addressing chronic disease issues.
... Clinical trials suggest that extracts from artichoke may have healing properties to treat several diseases, such as non-alcoholic fatty liver disease (NAFLD) 21,22 , hypocholesteremia 23 , metabolic syndrome 24,25 , and hypertension 19,26 . However, the outcomes of clinical trials have been varied concerning the effects of artichoke on BP. ...
... After evaluating the full text of the remaining 21 studies, 11 articles did not meet the inclusion criteria. Overall, eight eligible clinical trials with eight intervention arms were selected for our analysis 19,[21][22][23][24][26][27][28] . Two articles were excluded J o u r n a l P r e -p r o o f 8 from quantitative assessment 33,34 because they used the same study population as another study 24 . ...
... The mean age of subjects among included articles was from 35 to 58 years. These RCTs were carried out in NAFLD patients 21,22 , nonalcoholic steatohepatitis patients 27 , hypertensive patients 19,26 , type 2 diabetics 28 , hypercholesterolemic patients 23 , and metabolic syndrome participants 24 . All included studies used a parallel study design. ...
Article
Full-text available
Purpose Clinical trials considering the effects of artichoke supplementation on blood pressure have yielded different and contradictory outcomes. Thus, a systematic review and meta-analysis were performed to assess effects of artichoke administration on blood pressure. Methods Related studies were detected by searching the Cochrane Library, PubMed, Embase and Scopus databases up to 15 March 2020. Weighted Mean Differences (WMD) were pooled using a random-effects model. Heterogeneity, sensitivity analyses, and publication bias were evaluated using standard methods. Results Pooled analysis of eight randomized controlled trials revealed that artichoke supplementation did not have an effect on systolic blood pressure (SBP), (WMD: -0.77 mmHg, 95% CI: -2.76 to 1.22) or diastolic blood pressure (DBP) (WMD: -0.11 mmHg, 95% CI: -1.72 to 1.50) when compared to the placebo group. However, subgroup analyses based on health status suggested that artichoke administration among hypertensive patients may significantly reduce SBP (WMD: -3.19 mmHg, 95% CI: -3.32 to -3.06) and DBP (WMD: -2.33 mmHg, 95% CI: -2.23 to -2.43), but no such reduction was found in NAFLD patients. Furthermore, our results indicated that artichoke supplementation for 12 weeks led to a significantly decreased DBP (WMD: -2.33 mmHg, 95% CI: -2.43 to -2.23), but 8 weeks of intervention did not (WMD: 0.80 mmHg, 95% CI: -1.06 to 2.66). Conclusion Artichoke supplementation may potentially lead to SBP and DBP reduction in hypertensive patients. In addition, artichoke supplementation for 12 weeks may significantly improve DBP.
... Finally, 10 clinical trials with 10 interventions arms were selected in our ultimate analysis. 15,17,[22][23][24][25][26][27][28][29] One article was excluded by quantitative assessment, 30 because it used the same population as another study. 25 ...
... The average age of individuals ranged from 38 to 58 years. The studies on overweight individuals, 27,28 NAFLD patients, 23,29 nonalcoholic steatohepatitis patients, 24 hypertensive patients, 15,26 type 2 diabetes, 22 hypercholesterolemic 17 and metabolic syndrome participants 25 were included. The clinical trials were released between the period from 2009 to 2019. ...
... The clinical trials were released between the period from 2009 to 2019. The studies were carried out in Iran, 15,[23][24][25][26]29 Italy 17,27,28 and Korea. 22 The dose of artichoke ranged from 100 mg/day to 19.45 g/day. ...
Article
Full-text available
Background Studies on the efficacy of artichoke administration on anthropometric indices gave different outcomes. Hence, a systematic review and dose-response meta-analysis were accomplished to understand the effects of artichoke administration on anthropometric indices. Methods Related clinical trials were found by searching in PubMed, Embase, the Cochrane Library and Scopus databases up to 29 February 2020. Weighted Mean Differences (WMD) were analyzed using a random-effects model. Heterogeneity, publication bias and sensitivity analysis were assessed for anthropometric indices. Results Pooled analysis of 10 randomized controlled trials (RCTs) suggested that the artichoke administration has effect on waist circumference (WMD: -1.11 cm, 95 % CI: -2.08 to - 0.14), as opposed to the other anthropometric indices including weight (WMD: -0.62 kg, 95 % CI: -1.86 to 0.61) or BMI (WMD: -0.12, 95 % CI: -0.43 to 0.20). However, the analysis of the subgroups according to the health status showed that artichoke supplementation in hypertensive patients significantly reduced weight (WMD: -2.34 kg, 95 % CI: -3.11 to -1.57) but not the other indicators (WMD: -0.06 kg, 95 % CI: 0.78 to 0.67). Conclusions The artichoke supplementation has effect on the waist circumference, but not on the other anthropometric indices. For establishment of more accurate conclusion more studies with longer administration duration are need to be done.
... Artichoke is related to the traditional Mediterranean diet style, as is a well-known plant in the Mediterranean countries. 11 Artichoke's leaves contain polyphenolic compounds, prebiotic (inulin), minerals, ascorbic acids and vitamin B9. 11 Its leaf extract is rich in dietary fibers and antioxidant components, 12 proposing the extract as beneficial in the control of the glycemic indices. 13 The probiotics found in the artichoke seems to lower the glycemic index. ...
... 14 Although, artichoke and artichoke products supplementation appears to be a safe alternative for the glycemic control, the current evidence relatively limited and non-conclusive. 4,6,[12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] A few studies have reported that the supplementation of artichoke and artichoke products have a promising effect on controlling the glycemic indices. 13,14,16,18 In contrast, others did not confirm such effects. ...
... The detailed process of the search strategy is presented in Fig. 1. Finally, 9 full RCTs articles, with nine intervention arms were selected for the present metaanalysis [12][13][14]16,17,19,22,[24][25][26] . Two articles were excluded by quantitative assessment 18,23 because the study used the same population with another study. ...
Article
Objectives Cynara scolymus L. (common artichoke) and its products have been considered as potential phytotherapeutic agents for various conditions, such as cardiovascular, hepatic and gastric diseases, among others. Until now, the effects of artichoke and artichoke products administration on glycemic indices have not been sufficiently appraised. The present study evaluated the effects of artichoke and artichoke products administration on the glycemic indices. Methods Clinical trials were identified in the Cochrane Library, PubMed, Embase and Scopus databases; to infinity until 15 March 2020. Weighted mean differences (WMD) were pooled using a random-effects model. Heterogeneity, sensitivity analysis and publication bias were reported using standard methods. Results Pooled analysis of nine Randomized controlled trials (RCTs), demonstrated that the administration of artichoke and artichoke products led to a significant reduced fasting blood sugar (FBS) (WMD: -5.28 mg/dl, 95% CI: -8.95, -1.61; p = 0.005). However, other glycemic indeces including fasting insulin (WMD: -0.45 μIU/dL, 95% CI: -1.14, 0.25; p = 0.20), HOMA-IR (MD: -0.25, 95% CI: -0.57, 0.07; p = 0.12) or Hemoglobin A1c (HbA1c) (WMD: -0.09, 95% CI: -0.20, 0.02; p = 0.09) did not alter after the administration of artichoke and artichoke products. A subgroup analysis comparing the kind of intervention, revealed that just the supplementation of artichoke and artichoke products, in a noco-supplementation form, was efficacy for the reduction of Homeostatic model assessment of insulin resistance (HOMA-IR) (WMD: -0.52, 95% CI: -0.85, -0.19; p = 0.002) Conclusions The supplementation of artichoke and artichoke products can significantly reduce the FBS concentrations in humans. Moreover, these outcomes suggested that just the supplementation of artichoke and artichoke products is more effective in the reduction of HOMA-IR levels than the co-supplementation form. However, additional clinical trials with longer study periods are necessitated to obtain a robust conclusion for producing new guidelines as part of a healthy diet.
... Many natural bioactive components isolated from fruits, vegetables, and fish or produced by microorganisms could be promising agents capable of reversing NAFLD [11,12]. In particular, some studies suggested that ω-3 polyunsaturated fatty acids (PUFAs) [12,13]; curcumin [12,14]; bergamot polyphenol fraction (BPF) [15,16]; artichoke leaf extract [15][16][17][18]; black seed oil of Nigella sativa [19]; and the standardised fraction "Picroliv" of the root of Picrorhiza kurroa [20,21] have anti-oxidant, anti-inflammatory, hypolipidemic and hypoglycemic proprieties [22,23]. Moreover, they can also reduce hepatic steatosis and other liver injury, both in preclinical and clinical studies [12][13][14][15][16][17][18][19][20][21]. ...
... In particular, some studies suggested that ω-3 polyunsaturated fatty acids (PUFAs) [12,13]; curcumin [12,14]; bergamot polyphenol fraction (BPF) [15,16]; artichoke leaf extract [15][16][17][18]; black seed oil of Nigella sativa [19]; and the standardised fraction "Picroliv" of the root of Picrorhiza kurroa [20,21] have anti-oxidant, anti-inflammatory, hypolipidemic and hypoglycemic proprieties [22,23]. Moreover, they can also reduce hepatic steatosis and other liver injury, both in preclinical and clinical studies [12][13][14][15][16][17][18][19][20][21]. Many other natural compound are reported to have beneficial effects on NAFLD, including indole-3-carbinol (I3C) found in cruciferous vegetables [24][25][26]; silymarin [12,27,28] and silybin [29,30] isolated from milk thistle; luteolin found in fruits, vegetables, and natural herbs [31,32] astaxanthin produced by microalgae [33] and many others [34][35][36][37][38][39][40]. ...
Article
Full-text available
Background Currently, there is no approved medication for non-alcoholic fatty liver disease management. Pre-clinical and clinical studies showed that several bioactive molecules in plants or foods (i.e., curcumin complex, bergamot polyphenol fraction, artichoke leaf extract, black seed oil, concentrate fish oil, picroliv root, glutathione, S -adenosyl- l -methionine and other natural ingredients) have been associated with improved fatty liver disease. Starting from these evidences, our purpose was to evaluate the effects of a novel combination of abovementioned nutraceuticals as a treatment for adults with fatty liver disease. Methods A total of 140 participants with liver steatosis were enrolled in a randomized, double-blind, placebo controlled clinical trial. The intervention group received six softgel capsules daily of a nutraceutical (namely Livogen Plus®) containing a combination of natural bioactive components for 12 weeks. The control group received six softgel capsules daily of a placebo containing maltodextrin for 12 weeks. The primary outcome measure was the change in liver fat content (CAP score). CAP score, by transient elastography, serum glucose, lipids, transaminases, and cytokines were measured at baseline and after intervention. Results After adjustment for confounding variables (i.e., CAP score and triglyceride at baseline, and changes of serum γGT, and vegetable and animal proteins, cholesterol intake at the follow-up), we found a greater CAP score reduction in the nutraceutical group rather than placebo (− 34 ± 5 dB/m vs. − 20 ± 5 dB/m, respectively; p = 0.045). The CAP score reduction (%) was even greater in those with aged 60 or less, low baseline HDL-C, AST reduction as well as in men. Conclusion Our results showed that a new combination of bioactive molecules as nutraceutical was safe and effective in reducing liver fat content over 12 weeks in individuals with hepatic steatosis. Trial registration ISRCTN, ISRCTN70887063. Registered 03 August 2021—retrospectively registered, https://doi.org/10.1186/ISRCTN70887063
... These include Silybum marianum (L.) Gaertn. and Cynara cardunculus L. [6][7][8] Brazil hosts 15-20 % of the world's biodiversity, [9] and is estimated to have up to 45,000 plant species, many of them with potential medicinal use. [10] In this context, Brazilian 'caboclos' and communities from rural areas are important sources of ethnobotanical knowledge associated with phytotherapy, established over many years of empirical experimentation involving a mixture of European, African and indigenous practices relating to the use of plants belonging to the native flora. ...
... Out of all the species documented, 56.4 % (153) are native to the Brazilian flora, accounting for 292 citations, spread across 108 genera belonging to 54 botanical families ( Table 1). Fabaceae and Asteraceae were the most dominant families, with 18 and 16 species, respectively, followed by Apocynaceae (8) and Solanaceae (7). The relatively high number of species belonging to the Fabaceae and Asteraceae families is consistent with previous ethnobotanical studies performed in Brazil, [17,18] and might be explained by their great abundance and accessibility. ...
Article
Ethnobotanical studies have established that the folk use of plants for hepatobiliary disorders is very common in Brazil. This review aimed to compile, describe and discuss the main native Brazilian medicinal plants used as hepatoprotective agents listed on 25 books by authors from various regions in the country. Based on the 153 species found, a comprehensive analysis of the most relevant scientific studies is presented, including Piper umbellatum , Echinodorus macrophyllus , Fevillea trilobata and Achyrocline satureioides. Some medicinal plants share both a large number of citations and scientific evidence to corroborate their hepatoprotective effects, including Solanum paniculatum , Baccharis crispa and Phillanthus niruri , which could be of interest to develop new phytomedicines. Additionally, some active ingredients are indicated as being responsible for the liver protective effects described, particularly phenolic compounds (flavonoids, coumestans and lignans).
... Panizzi and Scarpati (1965) reported that caffeoylquinic derivatives (cynarin) were responsible for stimulating biliary secretion. Panahi et al. (2018) reported that artichoke leaf extract supplementation had beneficial effects on both ultrasound liver parameters and liver serum parameters of human patients. Also, Chang et al. (2014) reported that 10% Jerusalem artichoke (H. ...
... In the present study, although there was no statistical difference in body redness (a*) between the groups, a positive inclination was recorded in this parameter in the B40 AS group. Significantly increased skin brightness of the fish could be oriented by the ameliorative effects of globe artichoke on the liver (Chang et al. 2014;Heidarian, Jafari-Dehkordi, and Seidkhani-Nahal 2011;Panahi et al. 2018). Although there have been experiments on the application of dietary herbal remedies on the liver improvement of fish (Huang et al. 2018;Jia et al. 2019;Liao et al. 2020;Naiel, Ismael, and Shehata 2019;Owatari et al. 2018;Sun et al. 2019;Xiao et al. 2017;Xiong et al. 2019), there was a lack of data about evaluating skin-related parameters connected to liver metabolism. ...
Article
The present study aimed to evaluate the possible effects of a natural hepatomodulator on growth; some biological, blood, and color parameters; body; cost analysis; and liver histology of rainbow trout. A commercial rainbow trout diet was used for the control group, and 500 mg kg⁻¹ of commercial additive was used for the treatment group. The experiment was carried out for 12 weeks. At the end of the experiment, there was no significant effect on growth or biological and some blood parameters (P > 0.05); however, significant skin brightness changes (P < .05) were observed on the fish. Also, liver sections of the fish fed with the control diet showed a high proportion of lipid accumulation on hepatic parenchyma compared to fish that were fed treated diets. These results showed that application of commercial artichoke extract to rainbow trout diets might have positive effects on outer skin colorization and liver fat accumulation.
... These beneficial effects were maintained even when we stratified subjects according to the presence and degree of NAFLD. Our findings are in accord with recently published data of a pilot trial, in which an improvement of anthropometric variables after artichoke leaf extract supplementation in NAFLD subjects was present [28]. Other preclinical and clinical studies have demonstrated several health-promoting properties of extracts of Cynara spp., such as hypoglycemic, hypocholesterolemic, hypotriglyceridemic, other than antioxidant and hepatoprotective actions [11]. ...
... Artichoke leaf extract has been proven, also, for its anti-inflammatory effects in non-alcoholic steatohepatitis induced in animal models [43]. In addition, compounds derived from artichoke, too, have been previously described to act in the anti-inflammatory process, even in subjects with NAFLD [15,28]. These hepatoprotective effects may be surely ascribed to the antioxidant effects of phenols present in artichoke leaves. ...
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The objective was to evaluate the effects of 6 months of supplementation with Altilix ® , containing chlorogenic acid and its derivatives, and luteolin and its derivatives, on cardiovascular risk and hepatic markers in subjects with metabolic syndrome (MetS). A randomized, double-blind, placebo-controlled study was performed in 100 subjects with MetS with a follow-up period of 6 months; 50 subjects were randomized to Altilix ® (26 men and 24 women, mean age 63 ± 8 years) and the other 50 to placebo (28 men and 22 women, mean age 63 ± 11 years). Anthropometric, cardiometabolic, and hepatic parameters were assessed at baseline and at the end of follow-up. Carotid intima-media thickness and endothelial function were assessed by doppler ultrasound and by flow-mediated dilation of the brachial artery, respectively. The presence and degree of non-alcoholic fatty liver disease (NAFLD) was assessed by the fatty liver index (FLI), and subjects were divided into three subgroups: (1) without NAFLD; (2) with borderline NAFLD; and (3) with NAFLD. After 6 months of Altilix ® supplementation, we found a significant improvement vs. placebo in most of the evaluated parameters, including body weight (−2.40% (95% CI −3.79, −1.01); p < 0.001), waist circumference (−2.76% (95% CI −4.55, −0.96); p = 0.003), HbA1c (−0.95% (95% CI −1.22, −0.67); p < 0.001), plasma lipids, FLI (−21.83% (95% CI −27.39, −16.27); p < 0.001), hepatic transaminases, flow-mediated dilation (10.56% (95% CI 5.00, 16.12); p < 0.001), and carotid intima-media thickness (−39.48% (95% CI −47.98, −30.97); p < 0.001). Further, the improvement in cardiometabolic variables was independent of the degree of hepatic steatosis. Altilix ® supplementation improved hepatic and Nutrients 2019, 11, 2580 2 of 17 cardio-metabolic parameters in MetS subjects. Altilix ® supplementation was a beneficial approach in the management of hepatic and cardiometabolic alterations in MetS subjects.
... Evidence currently available shows that artichoke administration can improve lipid profile in patients with hypercholesterolemia, me- tabolic syndrome, overweight, type 2 diabetes mellitus, non-alcoholic fatty liver disease and non-alcoholic steatohepatitis [18][19][20][21][22][23][24][25][26][27][28][29]. The main effects of artichoke administration on lipid profile are related to the observed reductions in LDL, TC and TG serum levels. ...
... Regarding HDL, no strong evi- dence for its increased serum levels could be found. At the same time as the studies of Nazni et al. and Rondanelli et al. [24,29] identified in- creased HDL levels within the range of 8-9 mg/dL, the study of Panahi et al [25] observed decreased levels, in the range of 4.7 mg/dL (Table 1). ...
... This supplement could also be used in statin-intolerant individuals [190], for its hepatoprotective activity, which is demonstrated by its reduction of elevated serum ALT activity. A few cases of minor and transient gastrointestinal effects (mainly abdominal discomfort) have been reported [191]. Even though the artichoke leaf extract could represent an adjuvant in the regulation of lipid profile and liver levels of AST and ALT in NAFLD patients, long-term RCTs are still missing and needed to confirm both the safety and efficacy of this nutraceutical. ...
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Non-Alcoholic Fatty Liver Disease (NAFLD) is a common condition affecting around 10-25% of the general adult population, 15% of children, and even >50% of individuals who have type 2 diabetes mellitus. It is a major cause of liver-related morbidity, and cardiovascular (CV) mortality is a common cause of death. In addition to being the initial step of irreversible alterations of the liver parenchyma causing cirrhosis, about 1/6 of those who develop NASH are at risk also developing CV disease (CVD). More recently the acronym MAFLD (Metabolic Associated Fatty Liver Disease) has been preferred by many European and US specialists, providing a clearer message on the metabolic etiology of the disease. The suggestions for the management of NAFLD are like those recommended by guidelines for CVD prevention. In this context, the general approach is to prescribe physical activity and dietary changes the effect weight loss. Lifestyle change in the NAFLD patient has been supplemented in some by the use of nutraceuticals, but the evidence based for these remains uncertain. The aim of this Position Paper was to summarize the clinical evidence relating to the effect of nutraceuticals on NAFLD-related parameters. Our reading of the data is that whilst many nutraceuticals have been studied in relation to NAFLD, none have sufficient evidence to recommend their routine use; robust trials are required to appropriately address efficacy and safety.
... At the same time, another study examined the protective effects of artichoke leaf extract on the liver of NAFLD patients: in this study, subjects suffering from NAFLD were treated with 600 mg/day of artichoke leaf extract for a period of two months. Patients who were given artichoke extract showed reduction of total cholesterol, low-density lipoprotein cholesterol, triglyceride concentrations, liver enzymes and total bilirubin compared to the control group [113]. Lee et al. evaluated the effect of artichoke leaf extract in two experimental models: in vivo on the livers of mice with NAFLD induced as a result of high fat/high fructose diet; in vitro on HepG2 liver cells in which oxidative stress was induced following treatment with H2O2. ...
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Non-alcoholic fatty liver disease (NAFLD) is considered one of the leading causes of liver-related morbidity and mortality. NAFLD is a cluster of liver disorders that includes the accumulation of fat in the liver, insulin resistance, diffuse steatosis, lobular inflammation, fibrosis, cirrhosis and, in the latter stages, liver cancer. Due to the complexity of the disease and the multifactorial basis for the development of liver dysfunction, there is currently no unique drug treatment for NAFLD and the pharmacological options are inconclusive. In recent years, natural products have been studied for their potential beneficial effect in both preventing and treating fatty liver and its consequences in both local and systemic effects related to NAFLD. In particular, bergamot polyphenolic fraction (BPF), which is rich in natural polyphenols, and Cynara cardunculus wild type (which contains large quantities of sesquiterpenes, caffeic acid derivatives and luteolin) have both been investigated in both pre-clinical settings and clinical studies showing their effect in counteracting NAFLD-related health issues. In the present review we summarize the experimental and clinical evidence on the effect of BPF and Cynara extract alone or in their combination product (Bergacyn®) in NAFLD. In particular, data reported show that both extracts may synergize in counteracting the pathophysiological basis of NAFLD by inhibiting lipid accumulation in liver cells, oxidative stress and inflammation subsequent to liver syeatosis and, in the latter stages, liver fibrosis and tissue degeneration. Moreover, due to its powerful vasoprotective effect, the combination of BPF and Cynara extract (Bergacyn®) leads to improved endothelial dysfunction and cardioprotective response in both animal models of NAFLD, in veterinary medicine and in humans. Thus, supplementation with BPF and Cynara Cardunculus extract and their combination product (Bergacyn®) represent a novel and potentially useful approach in preventing and treating NAFLD-associated complications.
... These findings were consistent with previous research findings. Panahi et al. reported that supplementation with 600 mg of artichoke leaf extract for 2 months significantly decreased serum levels of ALT and AST, improved AST/ALT ratio and APRI scores, and reduced total bilirubin compared to the placebo [26]. Another study conducted by Tang et al. has highlighted a protective effect of artichoke components against acute alcoholinduced liver injury in mice, by showing that an artichoke ethanolic extract significantly decreased AST and ALT in the injured liver. ...
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Pre-obesity is a condition that predisposes to the risk of developing obesity, cardiovascular diseases (CVD), and diabetes. Our previous study demonstrated that a Cynara cardunculus (L.) based nutraceutical named Altilix® (Bionap, Italy), containing chlorogenic acid and luteolin extracts, was able to improve several hepatic and cardio-metabolic parameters. Given this background, we conducted a post-hoc analysis of the Altilix® study in order to analyze the supplement’s effects in the subgroup of pre-obesity subjects on anthropometry (weight and waist circumference), glucose metabolism (HbA1C, HOMA-IR, and HOMA-β), lipid profile (total cholesterol, triglycerides, LDL-cholesterol and HDL-cholesterol), hepatic functionality (FLI, AST, ALT and AST/ALT), carotid-media thickness (CIMT) and endothelial function (FMD). Fifty subjects from the original study cohort (which consisted of 100 subjects) were chosen with BMI ≥ 25 and < 30 kg/m2. All subjects received the Altilix® supplement (150 mg/day) or placebo using a computer-based random allocation system. After six months of treatment Altilix® significantly reduced body weight, glycemic, and lipid parameters (total cholesterol, triglycerides, LDL-cholesterol) and improved hepatic functionality, CIMT, and FMD. In conclusion, these results confirm that Altilix® supplementation has a significant effect on cardiometabolic parameters not only in obese subjects but also in pre-obesity subjects.
... Table 4]. However, these results changed with the simultaneous use of aerobic exercise and natural products as follows: the effect of aerobic exercise and [74] natural products on the reduction of AST levels was obtained at -1.55 (CI95%: -2.85 to -0.24), ALT: -2.03 (CI95%: -3.70 to -0.36), GGT: -0.43 (CI95%: -1.24 to 0.38), and ALP: -0.04 (CI95%: -0.84 to 0.76). ...
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Background: Nonalcoholic fatty liver is the most common chronic liver disease. Regarding the side effects of synthetic medicines and the variety of natural products in Iran climate, the present study aimed to investigate the effect of medicinal plants and natural products on liver enzymes in patients with non-alcoholic fatty liver disease in Iran using meta-analysis. Methods: To extract the intended studies, internal and external databases, including SID, Magiran, IranDoc, PubMed, Scopus, Web of Science, Embase, Cochrane, and Clinical Trial Registration System of Clinical trial.gov, the ISRCTN system, as well as Clinical Trial Registration System affiliated to the World Health Organization were searched. The obtained data were analyzed in STATA.14 software. A P value less than 0.05 was considered statistically significant. Results: A total of 44 rstudies were reviewed with a sample size of 1298 participant; they were published in the period from 2009 to 2018, silymarin had the highest effect on the reduction of AST (SMD = -2.68), cinnamon excreted the most profound effect on ALT (SMD = -2.69). In addition, cinnamon had the highest effect on gamma-glutamyl transferase (GGT) (SMD:-3.17), and curcumin had the highest effect on alkaline phosphatase (ALP) (SMD = -1.88). In the lipid profile, the effect of medicinal herbs and natural products on lowering total cholesterol and LDL was statistically significant. In the glycemic profile, the effect of medicinal plants and natural products on the reduction of fasting blood sugar, insulin, and hemoglobin A1c levels was statistically significant. Conclusions: As evidenced by the obtained results, the highest effect of using natural products was observed in the reduction of GGT, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels, respectively; nonetheless, the effect of natural products on ALP reduction was not statistically significant.
... Studies have shown increased liver weight within 10 and 15 weeks of obesity induction [43]. In contrast, ultrasound findings demonstrated significant improvement in NASH severity in 81.6% of patients treated with artichoke extract (600 mg/day) versus placebo as well as a significant reduction in liver damage markers such as alanine aminotransferase and aspartate aminotransferase [44]. ...
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This study aimed to evaluate the effect of Cynara cardunculus leaf ethanol extract on inflammatory and oxidative stress parameters in the hypothalamus, prefrontal cortex, hippocampus, striatum, cerebral cortex and liver of high-fat diet-induced obese mice. Food intake, body weight, visceral fat weight, and liver weight were also evaluated. Male Swiss mice were divided into control (low-fat purified diet) and obese (high-fat purified diet) groups. After 6 weeks, mice were divided into control + saline, control + C. cardunculus leaf ethanol extract, obese + saline, obese + C. cardunculus leaf ethanol extract. Cynara cardunculus leaf ethanol extract (1600 mg/kg/day) or saline was administered orally for 4 weeks. Brain structures (hypothalamus, hippocampus, prefrontal cortex, striatum and cerebral cortex) and liver were removed. Treatment with C. cardunculus leaf ethanol extract did not affect body weight but did reduce visceral fat. Obesity can cause inflammation and oxidative stress and increase the activity of antioxidant enzymes in brain structures. Treatment with ethanolic extract of C. cardunculus leaves partially reversed the changes in inflammatory damage parameters and oxidative damage parameters and attenuated changes in the antioxidant defense. The C. cardunculus leaf ethanol extract benefited from the brains of obese animals by partially reversing the changes caused by the consumption of a high-fat diet and the consequent obesity. These results corroborate those of studies indicating that the C. cardunculus leaf ethanol extract can contribute to the treatment of obesity.
... 5 The increasing incidence of NAFLD has been related to a dramatic change in dietary habits, notably an increase in consumption of fat and simple carbohydrates. 6 Rapidly increasing urbanization, mechanization and economic development of Africa and the world at large have resulted in a dietary transition from a traditional to a modernized diet (food in which the quality has been affected). Similarly, Ethiopia is also undergoing an epidemiologic transition mainly driven by demographic and lifestyle changes that promotes enormous changes in diets. ...
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Introduction: Nonalcoholic fatty liver disease (NAFLD) is the most prevalent disease due to a dramatic change in dietary habits, especially an increase in consumption of fat and carbohydrates in deep-fried foods. Objective: The objective was to evaluate the effect of hydromethanolic seed extract of Lepidium sativum on deep-fried palm oil diet induced NAFLDon male mice. Methods: An experimental study design was conducted. Twenty-four male mice aged 8 to 10 weeks, weighing 32-42 g were divided into four groups. The four groups were divided into two controls and two treatments. Mice in normal control (C0) were administered only with the basal diet whereas negative control (C1) provided only with the deep-fried palm oil diet. The treatment groups T1, and T2 were administered with deep-fried palm oil diet and HMSELS at dose of 200 and 400 mg/kg/day, respectively for 28 days. Then on day 29, the mice were fasted overnight, anaesthetized and sacrificed by cervical dislocation after blood was taken by cardiac puncture for liver function tests while liver tissues were taken for histopathology investigation. Results: The serum ALT and total bilirubin showed significant decrement whereas the serum albumin levels showed significant increment in T2 group. However, serum AST and ALP levels were decreased significantly in both T1 and T2 groups. Besides, the T2 group liver sections of mice were showed better effect of HMSELS on restoring the damaged liver histopathology almost toward normal. Conclusion: The HMSELS at a dose of 400 mg/kg/day (T2) was more effective on the liver function tests and liver histopathology that altered by feeding deep-fried palm oil diet. The good protective effect of HMSELS against deep-fried palm oil diet-induced NAFLD might be due to its antioxidant content.
... Many studies have shown that artichoke leaf extract (ALE), rich in phenolic compounds and caffeic acid derivatives, provides a hepatoprotective effect by significantly preventing oxidative damage in hepatocyte membranes. It has been reported in many studies in the literature that ALE exhibits both nephroprotective and hepatoprotective properties in paracetamol and cadmium-induced toxicity [4][5][6][7] . ...
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Objective: The aim of this study was to evaluate the hepatoprotective effect and mechanism of action of artichoke leaf extract in hepatic ischemia/reperfusion injury. Methods: Rats were divided into three groups such as sham, control, and artichoke leaf extract groups. Antioxidant enzyme activities and biochemical parameters were examined from the tissue and serum obtained from the subjects. Histopathological findings were scored semiquantitatively. Results: Statistically, the antioxidant activity was highest in the artichoke leaf extract group, the difference in biochemical parameters and C-reactive protein was significant compared with the control group, and the histopathological positive effects were found to be significantly higher. Conclusions: As a result, artichoke leaf extract had a hepatoprotective effect and that this effect was related to the antioxidant and anti-inflammatory effects of artichoke.
... A doubleblind clinical trial in patients with non-alcoholic liver injury confirmed the results of preclinical studies. Patients receiving ALE 600 mg daily for 2 months had an increased hepatic vein flow, reduced portal vein diameter, and improved lipid and hepatic enzyme profiles (Panahi et al., 2018). Another trial investigated the efficacy of a standardized ALE in patients with chronic Hep C infection (Huber et al., 2009). ...
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Humans used plants for thousand of years as food, drugs, or fuel to keep homes warm. People commonly used fruits and roots, and other parts of the plant were often wasted. This review aims to discuss the potential of rational stem-to-stern use of three highly versatile and valuable plants with hepatoprotective properties. Milk thistle ( Silybum marianum L. Gaertn.), artichoke ( Cynara cardunculus ), and chicory ( Cichorium intybus L.) have well-characterized hepatoprotective properties. These plants have been chosen since liver diseases are significant diseases of concern worldwide, and all parts of plants can be potentially utilized. Artichoke and chicory are commonly used as food or dietary supplements and less often as phytodrugs. Various dietary supplements and phytodrugs prepared from milk thistle (MT) fruits/seeds are well-known to consumers as remedies supporting liver functions. However, using these plants as functional food, farm animal feed, is not well-described in the literature. We also discuss bioactive constituents present in various parts of these plants, their pharmacological properties. Distinct parts of MT, artichoke, and chicory can be used to prepare remedies and food for humans and animals. Unused plant parts are potentially wasted. To achieve waste-free use of these and many other plants, the scientific community needs to analyze the complex use of plants and propose strategies for waste-free technologies. The government must stimulate companies to utilize by-products. Another problem associated with plant use as a food or source of phytodrug is the overharvesting of wild plants. Consequently, there is a need to use more active cultivation techniques for plants.
... The LC/MS analysis revealed metabolic signatures by regulating sixteen metabolites and altering two metabolic pathways (nicotinate and nicotinamide metabolism, fatty acid metabolism). ALT and AST are traditional liver markers, and the elevated serum levels indicated clear liver injury (26)(27)(28). In this study, serum AST and ALT levels increased between TI and CI after operation, but the augments of serum AST (P=0.01) and ALT (P=0.01) ...
Article
Background: Liver cancer as the main leading cancer has caused heavy burdens globally. The prognosis of liver cancer is closely related with postoperative nutrition support. Corn oligopeptides (COPs) are protein hydrolysates produced by enzymatic treatments, which have shown potential bioactivities, such as inhibiting angiotensin I-converting enzyme, resisting lipid peroxidation and anti-oxidant. However, the correlation between COPs and liver cancer patients is still unknown and the potential mechanism of COPs on liver cancer is unclear as well. The aim of this study was to assess effects of 7-day intervention of COPs after surgery on liver function and serum metabolic profiles of liver cancer patients. Methods: Patients were assigned into COPs intervention group (n=50) and control group (n=91) for 7 days. Investigations were scheduled at 1st day and 7th day after liver resection surgery respectively, mainly including anthropometric, biochemical indexes and liquid chromatography-mass spectrometry (LC/MS) analysis. Results: Seven-day supplementation of COPs on early post-surgery liver cancer patients down-regulated levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin and up-regulated prothrombin time activity and prealbumin levels. LC/MS analysis revealed metabolic signatures including regulation of 16 metabolites, which was closely related with two metabolic pathways (nicotinate and nicotinamide metabolism, fatty acid metabolism). Conclusions: COPs supplementation has displayed the potentials on alleviating the injury of liver function and it may be due to regulation of fatty acid metabolism, nicotinate and nicotinamide metabolism, lipid peroxidation and anti-inflammatory action. More researches are warranted in future to confirm the exact mechanisms.
... 34 Over the centuries, many populations have incorporated artichokes into their culture and food habits because of their efficacy and safety. 35 Pre-and clinical studies show that artichoke bud extract (ABE) has potential as a lipidlowering and hepatoprotective agent 36,37 due to the presence of powerful antioxidants. For instance, animal experiments indicated that these extracts elevate superoxide dismutase, catalase, glutathione, and glutathione peroxidase activities in the liver and lower the contents of malondialdehyde in the liver and plasma. ...
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Hypertension adversely affects the quality of life in humans across modern society. Studies have attributed increased reactive oxygen species production to the pathophysiology of hypertension. So far, a specific drug to control the disease perfectly has not been developed. However, artichoke, an edible vegetable, plays an essential role in treating many diseases due to its potent antioxidant activities. The objective of this study is to evaluate the effect of artichoke bud extract (ABE) on heart tissue metabolomics of hypertensive rats. Spontaneously hypertensive rats and Wistar–Kyoto (WKY) rats were divided into six groups, then exposed to different doses comprising ABE, Enalapril Maleate, or 1% carboxylmethyl cellulose for 4 weeks. Their blood pressures were recorded at 0, 2, 3, and 4 weeks after the start of the test period. Thereafter, all rats were anesthetized, and blood was collected from their cardiac apexes. Then, we measured the levels for 15 kinds of serum biochemical parameters. An established orthogonal partial least square-discriminant analysis model completed the metabolomic analysis. Hypertensive rats in the ABE group exhibited well-controlled blood pressure, relative to those in the model group. Specifically, artichoke significantly lowered serum levels for total protein (TP), albumin (ALB), and uric acid (UA) in the hypertensive rats. This effect involved the action of eight metabolites, including guanine, 1-methylnicotinamide, p-aminobenzoic acid, NAD, NADH, uridine 5′-monophosphate, adenosine monophosphate, and methylmalonic acid. Collectively, these findings suggest that ABE may play a role in affecting oxidative stress and purine, nicotinate, and nicotinamide metabolism.
... Many plants have important roles in human health care. There are some plants that are consumed habitually by humans and that have been proven as hepatoprotective capacity, for example, artichoke [7][8][9], milk thistle [10,11], grapefruit, and chamomile [12,13]. ...
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Background In spite of the huge advances in recent medicine, there is no effective drug that completely protects the liver from toxic materials. This study was conducted to investigate the hepatoprotective effect of arctigenin from burdock ( Arctium lappa ) against carbon tetrachloride (CCl 4 )-induced liver injury. Results Arctigenin pre-administration reduced hepatotoxicity markers significantly as compared to CCl 4 group. In addition, both silymarin and arctigenin declined matrix metalloproteinase-2 (MMP-2) in the serum (1177 ± 176), (978 ± 135) significantly as compared to CCl 4 group (1734 ± 294). The hepatic antioxidant parameters (total glutathione, superoxide dismutase, and glutathione reductase) were significantly decreased after CCl 4 injection, an effect that has been prevented by pre-administration of both silymarin and arctigenin. Histological examinations illustrated that arctigenin reduced CCl 4 damage, where it decreased inflammation, congestion, and ballooning. Conclusions Arctigenin exerted a hepatoprotective effect against CCl 4 -induced liver damage in terms of suppressing MMP-2 and oxidative stress comparative to that of silymarin.
... There were no side effects reported with the intervention. 59 Moving to milk thistle, Silybum marianum, we also encountered a plant with a long history of traditional use as a hepatoprotectant and hepatic trophorestorative. Silymarin, a flavonoid compound found in the leaves and seeds of milk thistle, has been the subject of studies in both NAFLD and NASH patients. ...
... Los extractos de alcachofa parecen tener un efecto sobre el control de la hipercolesterolemia y otras enfermedades relacionadas, como el síndrome metabólico, el sobrepeso, la diabetes tipo II, la esteatosis hepática de varia origen (Mocelin et al., 2016;Panahi et al., 2018;Rezazadeh et al., 2018). La literatura resulta aún dispersa y se necesitan más estudios para entender correctamente los mecanismos de acción y su uso en humanos. ...
... 4,10 However, there are no efficient and accessible FDA-approved pharmacological treatments for NAFLD. 1 Therefore, good metabolic control through dietary modification and increased physical activity is always the first line of recommended treatment but it is not often fully efficacious in reversing the diseases especially at advanced stages. 6,8,11 Hence, novel treatments to control or slow the progression of NAFLD are urgently needed. It has been reported that nutraceuticals have some benefits in reducing hepatic fat, transaminase levels, inflammation and oxidative burden in NAFLD. ...
Article
Background: Nonalcoholic fatty liver disease (NAFLD) as a prevalent hepatic disease is associated with an increased risk of morbidity and mortality related to the liver and cardiovascular disease (CVD). Lifestyle modification and good metabolic control is the first line of treatment, but not always efficacious in reversing NAFLD pathogenesis. Curcumin is a dietary phytochemical with hepatoprotective activities, though its low bioavailability is considered as a major challenge for clinical applications. Therefore, in this study, in order to improve the bioavailability of curcumin, it was coadministered with piperine and we investigated the effects of this bioavailability-enhanced curcumin on serum hepatic enzymes, lipid profile, and glycemic indices in patients with NAFLD. Methods: In this randomized controlled parallel-group trial, 70 subjects with ultrasound-determined NAFLD were randomized to either 500 mg curcuminoids coadministered with 5 mg piperine daily or placebo for 12 weeks. NAFLD severity (on the basis of sonography) and hepatic function was assessed at baseline and at the study end. Results: Seventy subjects completed the study. Supplementation with curcuminoids plus piperine significantly reduced the hematocrit (P = 0.027), erythrocyte sedimentation rate (P = 0.048) and the serum concentrations of alanine aminotransferase (P = 0.035), aspartate aminotransferase (P = 0.042), alkaline phosphatase (P = 0.004), cholesterol (P < 0.016), low-density lipoprotein cholesterol (P < 0.017), Iron (P = 0.026), and Hemoglobin (P = 0.025) and increased total iron-binding capacity (P = 0.003). However, except albumin, changes in other parameters were not statistically different between groups. In addition, administration of curcuminoids plus piperine significantly improved NAFLD severity (P < 0.001), which was statistically different compared with the placebo group (P = 0.022). Also, the percentage of improved patients was marginally higher in the curcuminoids plus piperine group when compared with the placebo group (P = 0.058). Conclusion: This study suggested beneficial effects of combined curcuminoids and piperine supplementation on disease severity in patients with NAFLD.
... Эффективность артишока в лечении различных заболеваний печени доказана не только в экспериментальных, но и в клинических исследованиях. Y. Panahi и коллеги (2018), авторы рандомизированного двойного слепого исследования, рекомендовали больным неалкогольной жировой болезнью печени принимать экстракт листьев артишока в дозе 600 мг/сут (n=49) или плацебо (n=41) на протяжении двух месяцев [69]. Исследователи установили, что прием артишока сопровождался улучшением кровотока по печеночной вене (р<0,001), уменьшением диаметра портальной вены и размеров печени (во всех случаях р<0,001), снижением уровня аланинаминотрансферазы (АлАТ) и аспартатаминотрансферазы (АсАТ), нормализацией соотношения АсАТ/АлАТ (во всех случаях р<0,001), а также уменьшением уровня общего билирубина по сравнению с плацебо. ...
Article
Composition of the Engilen preparation, medicinal properties of plants that make up the preparation, indications for its prescription are analyzed in detail in the article. Particular attention is paid to the advantages of Engilen, such as: optimal doses and ratio of active ingredients, wide range of indications, effectiveness upon combined diseases of the digestive system and with the concomitant pathology of other organs and systems. The results of our own study are presented, showing the effectiveness of Engilen upon chronic acalculous cholecystitis and non-alcoholic steatohepatitis in patients with excessive body mass or obesity. In addition, an effective correction of various types of the gall-bladder dysfunction has been obtained.
... Energy sensor Activation TGFβ1-simulated phosphorylation of AKT(downregulate0 (Domitrović et al., 2009;Panahi et al., 2018;Wan and Jiang, 2018) Morin ...
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The liver is not only involved in metabolism and detoxification, but also participate in innate immune function and thus exposed to frequent target Thus, they are the frequent target of physical injury. Interestingly, liver has the unique ability to regenerate and completely recoup from most acute, non iterative situation. However, multiple conditions, including viral hepatitis, non alcoholic fatty liver disease, long term alcohol abuse and chronic use of medications can cause persistent injury in which regenerative capacity eventually becomes dysfunctional resulting in hepatic scaring and cirrhosis. Despite the recent therapeutic advances and significant development of modern medicine, hepatic diseases remain a health problem worldwide. Thus, the search for the new therapeutic agents to treat liver disease is still in demand. Many synthetic drugs have been demonstrated to be strong radical scavengers, but they are also carcinogenic and cause liver damage. Present day various hepatic problems are encountered with number of synthetic and plant based drugs. Nexavar (sorafenib) is a chemotherapeutic medication used to treat advanced renal cell carcinoma associated with several side effects. There are a few effective varieties of herbal preparation like Liv-52, silymarin and Stronger neomin phages (SNMC) against hepatic complications. Plants are the huge repository of bioactive secondary metabolites viz; phenol, flavonoid, alkaloid etc. In this review we will try to present exclusive study on phenolics with its mode of action mitigating liver associated complications. And also its future prospects as new drug lead.
... 10 Although not significant when compared with the placebo group, the positive effect of the tested nutraceutical on glycemia and transaminase levels is not to be underestimated. As a matter of fact, artichoke and berberine have well-documented positive effects on the parameters correlated to insulin resistance 11,12 and nonalcoholic hepatic steatosis, 13,14 which are per se strongly associated with the CV risk. ...
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Hypercholesterolemia represents one of the main reversible cardiovascular risk factors. In this pilot clinical trial, we have tested the short-term efficacy and safety of a new combined cholesterol-lowering nutraceutical containing artichoke dry extract and berberine at enhanced bioavailability in subjects with moderate polygenic hypercholesterolemia in primary prevention for cardiovascular disease. After 2 months of treatment, the tested nutraceutical induced a significant reduction in plasma total cholesterol (−19%), low-density lipoprotein cholesterol (−16%), non–high-density lipoprotein cholesterol (−19%) and triglyceride levels (−15%), in association with a standardized control diet. No side effect has been observed during the trial. In conclusion, on the short-term, the tested nutraceutical has been shown to be well tolerated and effective, even if not containing any statin-like compound.
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Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide. The etiology of NAFLD is highly heterogeneous, which occurs and develops under the joint action of metabolism, inflammation, genetics, environment, and gut microbiota. At present, the principal therapeutic modalities targeting NAFLD are lifestyle interventions such as weight loss through diet and exercise. At present, there is no established therapy for the treatment of NAFLD, and many therapies are associated with a variety of side effects. A great number of in vitro and in vivo experiments have indicated that there are many natural foods that have therapeutic potential for NAFLD. This review summarizes the natural foods and their mechanisms that were found in recent years, furthermore, provides further information relevant to the treatment of NAFLD.
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Abstract Background The “multiple-hit” hypothesis is currently the most widely accepted theory for non-alcoholic fatty liver disease (NAFLD) pathogenesis. The present study aimed to investigate the effects of the water extract of artichoke (WEA) on NAFLD and its underlying mechanism. Methods Rats were fed a high-fat diet (HFD) for 8 weeks to induce NAFLD and then treated with WEA at three doses (0.4, 0.8, and 1.6 g/kg body weight, BW) for 8 weeks. At the end of the intervention, serum biochemical parameters, hepatic antioxidant capacity, hepatic levels of pro-inflammatory cytokines, liver histopathology, hepatic inflammatory gene and lipid metabolism gene expression, and Akt and p-Akt (S473) protein levels were determined. Results The body weight, liver weight, liver triglyceride (TG) and serum levels of TG, total cholesterol, low-density lipoprotein cholesterol, alanine aminotransferase, aspartate aminotransferase, glucose, and insulin were all significantly reduced in the WEA-treated groups (0.8 and 1.6 g/kg BW) compared with the HFD group (P
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Background and Purpose: Non-alcoholic fatty liver disease is the most common liver disease that is progressing and affects more than a quarter of the world's population. In this regard, researchers believe that exercise and herbal medicines with anti-lipid and antioxidant properties can be beneficial as supplementary therapy. Therefore, the aim of this study was to examine the effects of eight weeks aerobic training and artichoke distillate consumption on liver fat and serum levels of liver enzymes in women with non-alcoholic fatty liver. Materials and Methods: For this purpose, 24 obese or overweight volunteer women with non-alcoholic fatty liver with the mean age of 39.9±3.8 years, and mean weight of 75.4±12.1 kg, were randomly assigned into three groups of eight subjects: artichoke, aerobic, and control. Subjects in the aerobic group performed three sessions of aerobic exercises per week for eight weeks. The aerobic training program included 30 minutes of running with an intensity of 11 on the Borg scale rating of perceived exertion during the first week. Training duration increased to 45 minutes and the intensity increased to 13 from the fifth week of the aerobic training program, according to the principle of progressive overload. Subjects in the artichoke group received 180¬cc of the artichoke distillate per day (60cc after each meal). The control group performed no intervention during the study period. Blood sample and ultrasound sonography of the liver were performed 48 hours before and after the intervention to measure serum levels of Alanine Aminotransfer-ase, Aspartate Aminotransferase, lipid profile (total cholesterol, triglycerides, low-density lipoprotein, and high-density lipoprotein), and liver fat. Results: Results showed that liver fat levels were significantly decreased within the aerobic (P = 0.034) and the artichoke (P = 0.011) groups. However, there was no significant difference between the effectiveness of the aerobic training and artichoke distillate consumption (P = 0.393). Serum levels of Alanine Aminotrans-ferase and Aspartate Aminotransferase had significant decrement within the aerobic group (P = 0.016 and P = 0.028, respectively). The levels of these enzymes had non-significant decrement within the artichoke group (P = 0.080 and P = 0.172, respectively), and significant increments within the control group (P = 0.024 and P = 0.008, respectively). There were no significant changes in the lipid profile within the groups. Conclusion: Performing three sessions of aerobic training with moderate intensity per week for eight weeks or consumption of 60cc artichoke distillate after each meal could reduce the levels of liver fat in obese or overweight women with non-alcoholic fatty liver. In addition, these patients can use aerobic training to reduce the liver enzymes and the artichoke distillate to prevent the increase of these enzymes. However , artichoke distillate consumption or moderate-intensity aerobic training could not lead to improvement of the liver fat levels in two months, without following a healthy diet regimen or other medical treatments.
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The liver is one of the most important organs in the human body with crucial functions such as metabolism, secretion, storage, and detoxification. Due to the liver’s vital duties, hepatic diseases are among the most important health problems because they can cause various complications and also may result in death. Plants have traditionally been used to treat and prevent liver diseases as well as many other diseases for centuries. Today, phytotherapeutic approaches have become popular because of the side effects of existing drugs used in therapy, and the number of research studies in this field has increased considerably. The results obtained from in vivo and in vitro studies are remarkable. Studies conducted with different extracts of many traditional plants have shown that these plants have promising hepatoprotective effects. Although different pathways and mechanisms were mentioned, the plants’ curative effects have been mostly associated with their antioxidant activities. The available data clearly demonstrate the healing power of herbal products in hepatic disorders. However, in order to make these herbals/herbal products usable in treatment, they need to be standardized and their efficacy/safety should be supported by detailed biochemical and clinical studies.
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Cynara cardunculus L. with its three botanical varieties are presented as potential food and drug resources. Its young flower heads are commonly consumed as a principal part of different Mediterranean dishes, especially the globe artichoke, whereas its different plant parts are considered potential sources of valuable phytoconstituents, mainly polysaccharides, and polyphenols. These chemicals contribute to its nutrition, industry, and bioactivities, including hepatic-and cardiovascular protection and inflammation disorders. A holistic comparative study of artichoke phytochemicals make-up as determinants of its quality, nutritive value and health benefits is presented for its different varieties. Such reviewed evidence is an essential prerequisite for a future better selection of certain variety, and or utilization in therapeutic, food and pharmaceutical applications. The review presented few endeavors for the development of potential novel functional foods fortified with artichoke extracts and/or its bioactive which are of value and need to be more recognized commercially.
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Artichoke is a component of the Mediterranean diet. Therefore, the aim of this meta-analysis was to determine if artichoke extract supplementation affected human lipid parameters. The search included PubMed-Medline, Scopus, Web of Science and Google Scholar databases up to March 28, 2017, to identify RCTs investigating the impact of artichoke extracts on plasma lipid levels. Quantitative data synthesis was performed using a random-effects model, with weighed mean difference (WMD) and 95% confidence interval (CI) as summary statistics. Meta-analysis of data from 9 trials including 702 subjects suggested a significant decrease in plasma concentrations of total cholesterol (WMD: −17.6 mg/dL, 95%CI: −22.0, −13.3, p<0.001), Low Density Lipoprotein-Cholesterol (LDL-C; WMD: −14.9 mg/dL, 95%CI: −20.4, −9.5, p = 0.011) and triglycerides (WMD: −9.2 mg/dL, 95%CI: −16.2, −2.1, p = 0.011). No significant alteration in plasma High Density Lipoprotein-Cholesterol (HDL-C) concentrations was observed (WMD: 1.0 mg/dL, 95%CI: −1.1, 3.1, p = 0.333). A significant association between the LDL-lowering effect of artichoke and baseline LDL-C concentrations (slope: −0.170; 95%CI: −0.288, 0.051; p = 0.005) was observed. Thus, supplementation with artichoke extract was associated with a significant reduction in both total and LDL-C, and triglycerides, suggesting that supplementation may be synergistic with lipid-lowering therapy in patients with hyperlipidemia.
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Aims: To appraise the clinical and genetic evidence that low-density lipoproteins (LDLs) cause atherosclerotic cardiovascular disease (ASCVD). Methods and results: We assessed whether the association between LDL and ASCVD fulfils the criteria for causality by evaluating the totality of evidence from genetic studies, prospective epidemiologic cohort studies, Mendelian randomization studies, and randomized trials of LDL-lowering therapies. In clinical studies, plasma LDL burden is usually estimated by determination of plasma LDL cholesterol level (LDL-C). Rare genetic mutations that cause reduced LDL receptor function lead to markedly higher LDL-C and a dose-dependent increase in the risk of ASCVD, whereas rare variants leading to lower LDL-C are associated with a correspondingly lower risk of ASCVD. Separate meta-analyses of over 200 prospective cohort studies, Mendelian randomization studies, and randomized trials including more than 2 million participants with over 20 million person-years of follow-up and over 150 000 cardiovascular events demonstrate a remarkably consistent dose-dependent log-linear association between the absolute magnitude of exposure of the vasculature to LDL-C and the risk of ASCVD; and this effect appears to increase with increasing duration of exposure to LDL-C. Both the naturally randomized genetic studies and the randomized intervention trials consistently demonstrate that any mechanism of lowering plasma LDL particle concentration should reduce the risk of ASCVD events proportional to the absolute reduction in LDL-C and the cumulative duration of exposure to lower LDL-C, provided that the achieved reduction in LDL-C is concordant with the reduction in LDL particle number and that there are no competing deleterious off-target effects. Conclusion: Consistent evidence from numerous and multiple different types of clinical and genetic studies unequivocally establishes that LDL causes ASCVD.
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Background . High HDL-cholesterol (HDL-C) values are negatively correlated with cardiovascular diseases. This review analyses the effect of the supplementation with various Mediterranean diet products (artichoke, bergamot, and olive oil) and Asian diet products (red yeast rice) on the HDL-C value in dyslipidemic subjects. Methods . A systematic review has been done involving all the English written studies published from the 1st of January 1958 to the 31st of March 2016. Results . The results of this systematic review indicate that the dietary supplementation with red yeast rice, bergamot, artichoke, and virgin olive oil has promising effects on the increase of HDL-C serum levels. The artichoke leaf extract and virgin olive oil appear to be particularly interesting, while bergamot extract needs further research and the effect of red yeast rice seems to be limited to patients with previous myocardial infarction. Conclusions . Various MediterrAsian diet products or natural extracts may represent a potential intervention treatment to raise HDL-C in dyslipidemic subjects.
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Non-alcoholic fatty liver disease (NAFLD) is a global health problem. Although many aspects of NAFLD pathogenesis have been understood, there is a paucity of effective treatments to be used as the second line when lifestyle modification is insufficient. Curcumin, a natural polyphenol from turmeric, has been shown to be effective against development of hepatic steatosis and its progression to steatohepatitis, yet these beneficial effects have not been explored in clinical practice. The aim of this study is to investigate the effects of curcumin on hepatic fat content as well as biochemical and anthropometric features of patients with NAFLD. In this randomized double-blind placebo-controlled trial, patients with ultrasonographic evidence of NAFLD were randomly assigned to receive an amorphous dispersion curcumin formulation (500 mg/day equivalent to 70-mg curcumin) or matched placebo for a period of 8 weeks. Liver fat content (assessed through ultrasonography), glycemic and lipid profile, transaminase levels, and anthropometric indices were evaluated at baseline and at the end of follow-up period. The clinical trial protocol was registered under the Iranian Registry of Clinical Trials ID: IRCT2014110511763N18. Compared with placebo, curcumin was associated with a significant reduction in liver fat content (78.9% improvement in the curcumin vs 27.5% improvement in the placebo group). There were also significant reductions in body mass index and serum levels of total cholesterol, low-density lipoprotein cholesterol, triglycerides, aspartate aminotransferase, alanine aminotransferase, glucose, and glycated hemoglobin compared with the placebo group. Curcumin was safe and well tolerated during the course of trial. Findings of the present proof-of-concept trial suggested improvement of different features of NAFLD after a short-term supplementation with curcumin. Copyright © 2016 John Wiley & Sons, Ltd.
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Jerusalem artichoke (JA) has the potential to attenuate lipid disturbances and insulin resistance (IR), but the underlying mechanisms are not well understood. In the present study, we elucidated the physiological responses and mechanisms of JA intervention with a comprehensive transcriptome analysis. Wistar rats were fed a control diet, a 60 % fructose-enriched diet (FRU), or a FRU with 10 % JA (n 6-7) for 4 weeks. An oral glucose tolerance test was carried out on day 21. Liver samples were collected for biochemical and global gene expression analyses (GeneChip® Rat Genome 230 2.0 Array, Affymetrix). Fructose feeding resulted in IR and hepatic TAG accumulation; dietary JA supplementation significantly improved these changes. Transcriptomic profiling revealed that the expression of malic enzyme 1 (Me1), associated with fatty acid synthesis; decorin (Dcn), related to fibrosis; and cytochrome P450, family 1, subfamily a, polypeptide 2 (Cyp1a2) and nicotinamide phosphoribosyltransferase (Nampt), associated with inflammation, was differentially altered by the FRU, whereas dietary JA supplementation significantly improved the expression of these genes. We established for the first time the molecular mechanisms driving the beneficial effects of JA in the prevention of type 2 diabetes and non-alcoholic fatty liver disease. We propose that 10 % JA supplementation may be beneficial for the prevention of the onset of these diseases.
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& Aims: Some patients with nonalcoholic fatty liver disease (NAFLD) develop liver-related complications and have higher mortality than other patients with NAFLD. We determined the accuracy of simple, non-invasive scoring systems in identification of patients at increased risk for liver-related complications or death. We performed a retrospective, international, multicenter cohort study of 320 patients diagnosed with NAFLD, based on liver biopsy analysis, through 2002 and followed through 2011. Patients were assigned to mild, intermediate, or high-risk groups based on cut-off values for 2 of the following: NAFLD fibrosis score, aspartate aminotransferase/platelet ratio index (APRI), FIB-4 score, and BARD score. Outcomes included liver-related complications and death or liver transplantation. We used multivariate Cox proportional hazard regression analysis to adjust for relevant variables and calculate adjusted hazard ratios (aHRs) RESULTS: During a median follow-up period of 104.8 months (range 3-317 months), 14% of patients developed liver-related events, and 13% died or underwent liver transplantation. The aHRs for liver-related events in the intermediate and high-risk groups, compared to the low-risk groups, were 7.7 (95% confidence interval [CI], 1.4-42.7) and 34.2 (95% CI, 6.5-180.1), respectively, based on NAFLD fibrosis score; 8.8 (95% CI, 1.1-67.3) and 20.9 (95% CI, 2.6-165.3) based on the APRI; and 6.2 (95% CI, 1.4-27.2) and 6.6 (95% CI, 1.4-31.1) based on the BARD score. The aHRs for death or liver transplantation in the intermediate and high-risk groups, compared to the low risk groups, were 4.2 (95% CI, 1.3-13.8) and 9.8 (95% CI, 2.7-35.3), respectively, based on the NAFLD fibrosis scores. Based on APRI and FIB-4 scores, only the high-risk group had a greater risk of death or liver transplantation (aHR, 3.1; 95% CI, 1.1-8.4 and aHR, 6.6; 95% CI, 2.3-20.4, respectively). Simple non-invasive scoring systems help identify patients with NAFLD who are at increased risk for liver-related complications or death. NAFLD fibrosis score appears to be the best indicator of patients at risk, based on hazard ratios. The results of this study require external validation.
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The aim of this study was to evaluate the effects of artichoke leaf extract (ALE) supplementation (250 mg, 2 b.i.d.) on the lipid pattern. A randomized, double-blind, placebo-controlled clinical trial was performed on 92 overweight subjects with primary mild hypercholesterolaemia for 8 weeks. Forty-six subjects were randomized to supplementation (age: 54.2 ± 6.6 years, body mass index (BMI): 25.8 ± 3.9 kg/m(2), male/female: 20/26) and 46 subjects to placebo (age: 53.8 ± 9.0 years, BMI: 24.8 ± 1.6 kg/m(2), male/female: 21/25). Verum supplementation was associated with a significant increase in mean high-density lipoprotein (HDL)-cholesterol (p < 0.001) and in mean change in HDL-cholesterol (HDL-C) (p = 0.004). A significantly decreased difference was also found for the mean change in total cholesterol (p = 0.033), low-density lipoprotein (LDL)-cholesterol (p < 0.001), total cholesterol/HDL ratio (p < 0.001) and LDL/HDL ratio (p < 0.001), when verum and placebo treatment were compared. These results indicate that ALE could play a relevant role in the management of mild hypercholesterolaemia, favouring in particular the increase in HDL-C, besides decreasing total cholesterol and LDL-cholesterol.
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Patients with nonalcoholic fatty liver disease (NAFLD) often have dyslipidemia along with other features of metabolic syndrome such as obesity, diabetes mellitus, and hypertension. The dyslipidemia in NAFLD is characterized by increased serum triglycerides, increased small, dense low-density lipoprotein (LDL nontype A) particles, and low high-density lipoprotein (HDL) cholesterol. The pathogenesis of dyslipidemia in NAFLD is not well understood, but it is likely related to hepatic overproduction of the very low-density lipoprotein particles and dysregulated clearance of lipoproteins from the circulation. There is unequivocal evidence that cardiovascular disease is the most common cause of mortality in patients with NAFLD. Aggressive treatment of dyslipidemia plays a critical role in the overall management of patients with NAFLD. Statins are the first-line agents to treat high cholesterol and their dosage should be adjusted based on achieving therapeutic targets and tolerability. Although all statins appear to be effective in improving cholesterol levels in patients with NAFLD, there is more experience with atorvastatin in patients with NAFLD; furthermore, it is the only statin to date to show a reduced cardiovascular morbidity in patients with NAFLD. The risk for serious liver injury from statins is quite rare and patients with NAFLD are not at increased risk for statin hepatotoxicity. Omega-3 fatty acids are perhaps the first choice to treat hypertriglyceridemia because of their safety, tolerability, and efficacy in improving serum triglycerides, as well as their potential to improve liver disease.
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Increased prevalence of abnormal aminotransferase levels and/or ultrasonographic evidence of hepatic steatosis (HS) have been found in women with polycystic ovary syndrome (PCOS). However, factors associated with non-alcoholic fatty liver disease (NAFLD) in PCOS are still under investigation. The aim of this case-control study was to investigate the presence of NAFLD and to assess factors associated with this condition in PCOS patients. A prospective study of 57 premenopausal PCOS patients and 60 age- and weight-matched control women, with a history of no or minimal alcohol consumption was conducted. Anthropometric variables, biochemical and hormonal parameters were determined and NAFLD was evaluated by abdominal ultrasonography and biochemical testing, after excluding causes of secondary liver disease. Insulin resistance was assessed by homeostasis model assessment of insulin resistance (HOMA-IR) and free androgen index (FAI) was calculated. PCOS patients had an increased prevalence of HS [21/57 patients (36.8%) versus 12/60 controls (20.0%), P < 0.05] and abnormal (> or =40 IU/l) serum aminotransferase levels [13/57 patients (22.8%) versus 2/60 controls (3.3%), P < 0.01] than controls. All patients and controls with metabolic syndrome had HS. Factors associated with HS were PCOS diagnosis, older age, increased BMI, waist circumference (WC), HOMA-IR and FAI values and decreased high-density lipid cholesterol and sex hormone binding globulin levels. PCOS patients had an OR of 3.55 (95% CI: 1.02-5.35) for HS versus controls, after adjustment for age, BMI and WC. NAFLD is common in PCOS patients and increased androgen bioavailability may be implicated, in combination with metabolic abnormalities. Liver evaluation is proposed in PCOS patients, especially in those with metabolic syndrome.
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Chronic hepatitis C (CHC) is one of the most important causes of chronic liver disease in the world, potentially resulting in cirrhosis, hepatocellular carcinoma, and the need for liver transplantation. Liver biopsy is currently performed before therapy indication. Although, it is the golden standard there are many reasons to avoid or delay the procedure. APRI Score is an easy, low cost and practice alternative method which was described as an alternative for assessing structural changes in chronic hepatitis C (CHC). The rationale of this study was to observe the accuracy of APRI Score in comparison to liver biopsy in 400 patients divided into two groups of 200 carriers (Validation and Experimental groups respectively) selected at random or according to liver fibrosis staging (METAVIR). The ROC curves showed a concordance among these two methods of 92% and 88.5% when 1.05 was the cut off (F3 and F4), and 87% and 83%, on 0.75 cut offs (F2-F4). The discordance in advanced fibrosis staging (F3 and F4) was only 16 (8%) and 22 (11%) out of 200 patients in the experimental and validation groups, respectively. In 26 (13%) out of 200 patients in the experimental group and 34 (17%) out of 200 patients in the validation group, there was discordance between APRI Score and liver biopsy in moderate and advanced fibrosis (F2-F4). In conclusion APRI is a serological marker that has satisfactory sensitivity and specificity together with a high predictive value and it can be useful either in the absence of a biopsy or to reduce the frequency with which biopsies need to be carried out to monitor the evolution of chronic hepatitis C and the right moment for treatment indication.
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Non-alcoholic fatty liver disease (NAFLD) is a major cause of liver diseases, and is closely related to metabolic syndrome and its related conditions, diabetes mellitus and dyslipidemia. On the other hand, NAFLD as a multisystem disease increases the risk of several chronic diseases include type 2 diabetes mellitus, cardiovascular disease (CVD), and chronic kidney disease. The main objective was to review the efficacy of bioactive natural compounds assessed by clinical trials. Search literature using four databases (PubMed, EBSCO, Web of Science, and Ovid Medline) to review publications that focused on the impact of bioactive natural compounds in NAFLD treatment. Due to the lack of effective pharmacological treatments available for NAFLD, lifestyle modifications such as following a healthy diet, vigorous physical activity, and weight reduction remain the first line of treatment for NAFLD. However, due to the poor adherence to this type of treatment, especially for long-term weight loss diets some of which may have harmful effects on the liver, finding novel therapeutic agents for NAFLD treatment and/or preventing NAFLD progression has garnered significant interest. Although the therapeutic agents of NAFLD treatment have been reviewed previously, to date, no summary has been conducted of clinical trials examining the effects of herbal compounds on NAFLD-related biomarkers. This review highlights the beneficial role of herbal bioactives and medicinal plants in NAFLD treatment, particularly as complementary to a healthy lifestyle. All natural products described in this review seem to have some benefits to improve oxidative stress, cellular inflammation and insulin-resistance, which always remain as the "primum movens" of NAFLD pathogenesis.
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Objective Non-alcoholic fatty liver disease (NAFLD) is a common liver disease characterized by excess lipid deposition in the hepatic tissue and subsequent oxidative and inflammatory damage. Curcumin is a dietary polyphenol with lipid-modifying, antioxidant and anti-inflammatory properties. This study aimed to evaluate the efficacy and safety of supplementation with phytosomal curcumin in subjects with NAFLD. Methods Patients diagnosed with NAFLD (grades 1–3 according to liver ultrasonography) were randomly assigned to the curcumin (phytosomal form; 1 000 mg/day in 2 divided doses) (n=50) or placebo group (n=52) for a period of 8 weeks. All patients received dietary and lifestyle advises before the start of trial. Anthropometric measurements, hepatic enzymes, and liver ultrasonography were assessed at baseline and after 8 weeks of follow-up. Results 87 subjects (n=44 and 43 in the curcumin and control group, respectively) completed the trial. Supplementation with curcumin was associated with a reduction in body mass index (−0.99±1.25 vs. − 0.15±1.31 in the curcumin and placebo groups, respectively; p=0.003) and waist circumference (−1.74±2.58 vs. −0.23±3.49 in the curcumin and placebo groups, respectively; p=0.024). Ultrasonographic findings were improved in 75.0% of subjects in the curcumin group, while the rate of improvement in the control group was 4.7% (p<0.001). Serum levels of aspartate aminotransferase and alanine aminotransferase were reduced by the end of trial in the curcumin group (p<0.001) but elevated in the control group (p<0.001). Curcumin was safe and well tolerated during the course of trial. Conclusion Short-term supplementation with curcumin improves liver fat and transaminase levels in patients with NAFLD.
Article
At present, there is no evidence based pathway to stratify risk of chronic liver disease in a general population setting. Non-invasive tests of liver fibrosis may provide a mechanism for earlier diagnosis. These tests have been extensively validated in the hospital setting but their performance in a general population setting is unclear. We performed a systematic review of non-invasive tests used to stratify patients at risk of clinically significant liver disease in a general population setting and report the prevalence of chronic liver disease as defined by these tests. We systematically searched EMBASE, MEDLINE, Web of Science, reference lists from the original studies and recent conference proceedings. All study designs were considered. Nineteen studies were identified, utilising eleven non-invasive tests. Only transient elastography and Fibrotest were compared against histological end-points. The prevalence of liver fibrosis varied between 0.7% and 25.7%. More focussed stratification for advanced liver fibrosis (0.9%-2%) or cirrhosis (0.1%-1.7%) narrowed estimates of prevalence. Studies targeting patients with liver disease risk factors such as hazardous alcohol use or type 2 diabetes reported higher prevalence of advanced liver fibrosis (0%-27.9%) and cirrhosis (2.4%-4%). Validated non-invasive tests of liver fibrosis consistently detected otherwise unrecognised liver disease in the general population. Studies targeting risk factors found cirrhosis in 2.4 to 4 % of their target populations. Reliance on abnormal liver function tests will miss the majority of patients with significant liver injury. New pathways to stratify chronic liver, using non-invasive markers of liver fibrosis, are needed in the general population setting.
Article
Large-scale epidemiological studies firmly established the association between low plasma levels of high-density lipoprotein-cholesterol (HDL-C) and elevated risk of cardiovascular disease. This relationship is thought to reflect the key biological function of HDL, which involves reverse cholesterol transport from the arterial wall to the liver for further excretion from the body. Other aspects of the cardioprotective HDL functionality include antioxidative, anti-inflammatory, anti-apoptotic, anti-thrombotic, vasodilatory, anti-infectious and anti-diabetic activities. Over the last decades, wide interest in HDL as an athero- and cardioprotective particle has resulted in the development of HDL-C raising as a therapeutic approach to reduce cardiovascular risk. Several strategies to increase circulating HDL-C concentrations were developed that primarily included use of niacin and fibrates as potent HDL-C raising agents. In the statin era, inhibition of cholesteryl ester transfer protein, infusion of artificially reconstituted HDL and administration of apolipoprotein A-I mimetics were established as other approaches to raise HDL-C. More recently, novel strategies targeting HDL metabolism, such as upregulation of apolipoprotein A-I production by the liver, were added to the list of HDL therapeutics. This review summarises current knowledge of HDL-targeting therapies and discusses perspectives of their use.
Article
Nonalcoholic fatty liver disease (NAFLD) is the most common type of liver disease. NAFLD is considered a multifactorial disease and a clinically relevant hepatic manifestation of metabolic syndrome. NAFLD is often accompanied by a constellation of metabolic and non-metabolic alterations, like dyslipidemia, insulin resistance in the liver and peripheral tissues, inflammation and oxidative stress; therefore, treatment of NAFLD should be directed at correcting all of these disturbances. The natural polyphenol curcumin has been the subject of increasing research for the treatment of NAFLD due to its lipid-modifying, antioxidant, anti-inflammatory, insulin-sensitizing, anti-steatotic, and anti-fibrotic properties. The therapeutic efficacy of curcumin has been demonstrated in several experimental models of NAFLD, however, clinical evidence is still scarce. The present review summarizes the current knowledge on the impact of curcumin supplementation on different biochemical and histopathological features of NAFLD.
Article
Given the high prevalence and rising incidence of non-alcoholic fatty liver disease (NAFLD), the absence of approved therapies is striking. Although the mainstay of treatment of NAFLD is weight loss, it is hard to maintain, prompting the need for pharmacotherapy as well. A greater understanding of disease pathogenesis in recent years was followed by development of new classes of medications, as well as potential repurposing of currently available agents. NAFLD therapies target four main pathways. The dominant approach is targeting hepatic fat accumulation and the resultant metabolic stress. Medications in this group include peroxisome proliferator-activator receptor agonists (eg, pioglitazone, elafibranor, saroglitazar), medications targeting the bile acid-farnesoid X receptor axis (obeticholic acid), inhibitors of de novo lipogenesis (aramchol, NDI-010976), incretins (liraglutide) and fibroblast growth factor (FGF)-21 or FGF-19 analogues. A second approach is targeting the oxidative stress, inflammation and injury that follow the metabolic stress. Medications from this group include antioxidants (vitamin E), medications with a target in the tumour necrosis factor α pathway (emricasan, pentoxifylline) and immune modulators (amlexanox, cenicriviroc). A third group has a target in the gut, including antiobesity agents such as orlistat or gut microbiome modulators (IMM-124e, faecal microbial transplant, solithromycin). Finally, as the ongoing injury leads to fibrosis, the harbinger of liver-related morbidity and mortality, antifibrotics (simtuzumab and GR-MD-02) will be an important element of therapy. It is very likely that in the next few years several medications will be available to clinicians treating patients with NAFLD across the entire spectrum of disease.
Article
Background: Non-alcoholic fatty liver disease (NAFLD) is one of the most common hepatic diseases in the general adult population. Dyslipidemia, hyperuricemia and insulin resistance are common risk factors and accompanying features of NAFLD. Curcumin is a dietary natural product with beneficial metabolic effects relevant to the treatment of NAFLD. Aim: To assess the effects of curcumin on metabolic profile in subjects with NAFLD. Methods: Patients diagnosed with NAFLD (grades 1-3; according to liver sonography) were randomly assigned to curcumin (1000 mg/day in two divided doses) (n=50) or control (n=52) group for a period of 8 weeks. All patients received dietary and lifestyle advises before the start of trial. Anthropometric measurements, lipid profile, glucose, insulin, glycated hemoglobin, and uric acid concentrations were measured at baseline and after 8 weeks of follow-up. Results: Eighty-seven subjects (n=44 and 43 in the curcumin and control group, respectively) completed the trial. Supplementation with curcumin was associated with a reduction in serum levels of total cholesterol (p<0.001), LDL-C (p<0.001), triglycerides (p<0.001), non-HDL-C (p<0.001) and uric acid (p<0.001); while serum levels of HDL-C and glucose control parameters remained unaltered. Curcumin was safe and well tolerated during this study. Conclusion: Results of the present trial suggest that curcumin supplementation reduces serum lipids and uric acid concentrations in patients with NAFLD.
Article
Artichoke (Cynara scolymus) leaf extract was one of the few herbal remedies which the clinical and experimental trials have complemented each other. Both experimental and clinical effects have been verified through extensive biomedical herbal remedy research. Specifically, antioxidant, choleretic, hepatoprotective, bile-enhancing and lipid-lowering effects have been demonstrated, which corresponded with its historical use. Ongoing research seems to indicate that artichoke indeed have medicinal qualities. Most significant appears to be its beneficial effect on the liver. In animal studies, liquid extracts of the roots and leaves of artichoke have demonstrated an ability to protect the liver, with possibly even to help liver cells regenerate. Although research is not yet conclusive, scientists were optimistic that its long-standing use in humans for digestive and bowel problems was indeed justified. It may also play a role in lowering cholesterol and thus help to prevent heart disease. Boiled wild artichoke reduced postprandial glycemic and insulinemic responses in normal subjects but has no effect on metabolic syndrome patients. This article intended to review the wide ranging pharmacological effects of artichoke leaf extract.
Article
Background/aims: To investigate the advantage of Chlorella vulgaris supplementation as an adjunctive therapy in patients with non-alcoholic fatty liver disease (NAFLD). Methodology: In a randomized, open-label clinical trial, 76 individuals with NAFLD were randomly assigned to: 1) Chlorella group (n=33), receiving C. vulgaris extract (1200 mg/day) + metformin (750 mg/ day) + vitamin E (200 mg/day) for 3 months, or 2) Metformin group (n=43), receiving metformin (1250 mg/ day) + vitamin E (200 mg/day) for 3 months. Weight, body mass index (BMI), homeostasis model assessment of insulin resistance (HOMA-IR) index as well as serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), insulin, total and direct bilirubin, fasting blood sugar (FBS), glycated hemoglobin (HbA1c), uric acid, albumin and lipid profile were evaluated at baseline and at the end of trial. Results: Weight and BMI were decreased in both groups. Serum ALT, AST, triglycerides, uric acid, HbA1c and HOMA-IR index were reduced only in the Chlorella group whereas significant changes in total cholesterol, LDL, HDL and FBS were only observed in the metformin group. There were also borderline significant reductions in insulin and FBS in the Chlorella group. Conclusions: The findings of the present trial indicated that addition of C. vulgaris extract to the therapeutic regimen of NAFLD including metformin and vitamin E, is associated with favorable effects on serum levels of transaminases, triglycerides as well as insulin sensitivity. Therefore, C. vulgaris extract might be a promising hepatoprotective supplement for patients with NAFLD.
Article
Several studies investigated the effect of pioglitazone and rosiglitazone on aminotransferases and liver histology in adults with NASH. In an early uncontrolled open-label study117 in 22 subjects with biopsy-proven NASH, rosiglitazone improved aminotransferases and hepatic steatosis, ballooning and inflammation scores, but not fibrosis. But in a subsequent RCT, Ratziu et al.118 observed that rosiglitazone improved aminotransferases and hepatic steatosis, but not necroinflammation or fibrosis and its two-year open-label extension phase also showed similar results.119 Belfort et al.120 conducted a RCT of pioglitazone (45 mg/day) in patients with NASH who had impaired glucose tolerance or T2DM. Although there was a significant weight gain (2.5 ± 0.5 kg) with pioglitazone, it significantly improved aminotransferases, steatosis, ballooning, and inflammation. The NAS improved with pioglitazone in 73% compared to 24% of placebo-treated patients (P
Article
A study was conducted in hamsters to determine if artichoke leaf extract (ALE) could lower plasma total and non-HDL cholesterol by increasing fecal excretion of neutral bile acids and sterols. Sixty-four Golden Syrian hamsters (8 week old) were fed control diet or a similar diet containing ALE (4.5 g/kg diet) for 6 weeks. No significant changes for total cholesterol, HDL, non-HDL cholesterol triglycerides or fecal neutral sterols and bile acids were found after 21 days for ALE-fed animals compared with controls. But after 42 days, ALE-fed male hamsters had significantly lower total cholesterol (15%), non-HDL cholesterol (30%) and triglycerides (22%) and female hamsters fed ALE showed reductions of 15% for total cholesterol, 29% for non-HDL cholesterol and 29% for triglycerides compared with controls. Total neutral sterol and bile acids concentrations increased significantly by 50% and 53% in fecal samples of ALE fed males, and 82.4% and 25% in ALE fed females compared with controls. The ALE lowered hamster plasma cholesterol levels by a mechanism involving the greater excretion of fecal bile acids and neutral sterols after feeding for 42 days.
Article
Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases and its prevalence is likely to reach epidemic proportions. According to the "two-stage hypothesis" proposed for the pathophysiology of NAFLD, insulin resistance, oxidative stress and pro-inflammatory cytokines are among the key promoters of the disease. Here, ginger has been hypothesized to prevent NAFLD or blunt its progression via several mechanisms, such as sensitizing insulin effects, activating peroxisome proliferator-activated receptor γ which induces adiponectin and down-regulates pro-inflammatory cytokines, changing the balance between adiponectin and tumor necrosis factor-α in favor of adiponectin, promoting considerable antioxidant effects and antidyslipidemic properties, and reducing hepatic triglyceride content which can prevent steatosis. The aforementioned mechanisms imply that ginger possesses interesting potentials for serving as a natural supplement for the prevention and treatment of NAFLD. Therefore, conducting trials to explore its benefits in clinical practice is greatly recommended.
Article
Non-alcoholic fatty liver disease (NAFLD), the most common liver disorder in the Western world, is a clinico-histopathological entity in which excessive triglyceride accumulation in the liver occurs. Non-alcoholic steatohepatitis (NASH) represents the necroinflammatory form, which can lead to advanced liver fibrosis, cirrhosis, and hepatocellular carcinoma. The pathogenesis of NAFLD/NASH is complex but increased visceral adiposity plus insulin resistance with increased free fatty acids release play an initial key role for the onset and perpetuation of liver steatosis. Further events in the liver include oxidative stress and lipid peroxidation, decreased antioxidant defences, early mitochondrial dysfunction, iron accumulation, unbalance of adipose-derived adipokines with a chronic proinflammatory status, and gut-derived microbial adducts. New gene polymorphisms increasing the risk of fatty liver, namely APOC3 and PNPLA3, have been lately identified allowing further insights into the pathogenesis of this condition. In our review pathophysiological, genetic, and essential diagnostic and therapeutic aspects of NAFLD are examined with future trends in this field highlighted.
Article
We develop the idea of using data from the first 'few' patients entered in a clinical trial to estimate the final trial size needed to have specified power for rejecting H0 in favour of H1 if a real difference exists. When comparing means derived from Normally distributed data, there is no important effect on test size, power or expected trial size, provided that a minimum of about 20 degrees of freedom are used to estimate residual variance. Relative advantages and disadvantages of using larger internal pilot studies are presented. These revolve around crude expectations of the final study size, recruitment rate, duration of follow-up and practical constraints on the ability to prevent the circulation of unblinded randomization codes to investigators and those involved in editing and checking data.
Article
High-dose aqueous extracts from artichoke leaves were found to inhibit cholesterol biosynthesis from (14)C-acetate rather moderately in HepG2 cells in contrast to primary cultured rat hepatocytes in which the inhibition was stronger. Preincubation of the extracts with several glycohydrolases revealed that pretreatment with beta-glucosidase considerably reinforced the inhibition. A significant reduction of acetate incorporation was found above extract concentrations of 0.01 mg/mL and at 0.2 mg/mL almost 60% inhibition was observed. Cytotoxic effects detected by the MTT-assay were restricted to higher concentrations of the extracts with and without beta-glucosidase pretreatment. Since cynaroside represents a major glucoside in artichoke extracts, both cynaroside and its aglycone luteolin were tested. It could be demonstrated that cynaroside is indeed one of the targets of beta-glucosidase and that the liberated luteolin is responsible for the inhibitory effect. Direct measurements of beta-glucosidase activity in rat hepatocytes and HepG2 cells revealed that endogenous enzyme activity in hepatocytes may be sufficient to convert cynaroside to its aglycone, while in HepG2 cells this may not be the case. These findings emphasize the importance of beta-glucosidase-dependent liberation of luteolin for the ability of artichoke extracts to inhibit hepatic cholesterol biosynthesis.
Article
We aimed to define nonalcoholic steatohepatitis (NASH) histopathological change over time and to correlate changes with clinical characteristics. We retrieved nonalcoholic fatty liver cases from our histopathology database covering 1985 to 2001. We also identified patients in clinic with NASH on biopsy >1 yr prior. All patients were evaluated and clinical data obtained in clinic. Those patients qualifying for NASH therapeutic trials underwent liver biopsy pretreatment. One pathologist (S.T.) read all slides using a NASH grading and staging system. A total of 22 patients had repeat biopsies a mean of 5.7 yr (range 1.4-15.7 yr) after the first biopsy. Nine were women, nine had diabetes, 11 had hypertension, and 14 had hyperlipidemia. Mean body mass index was 33.8 kg/m(2) (range 26.5-48.6 yr). Mean age was 50.6 yr (range 33-64 yr). Ten patients (45%) had fibrosis stage 1 or 2, and two patients (9%) had bridging fibrosis or cirrhosis (stage 3 or 4) on first biopsy. Seven (32%) had increases in fibrosis score. Four patients (18%) had decreases in fibrosis score. The percentage of patients with stage 3 or 4 increased from 9% to 18%. In two patients the disease progressed rapidly (fibrosis scores from 1 to 3 in 1.4 yr and from 2 to 4 in 2.6 yr). Only serum AST at last biopsy correlated with histological change, being higher in those with disease progression. Three patients progressed from steatosis to steatohepatitis with fibrosis. NASH has a variable histological course. However, one third of patients have fibrosis progression, and one third of these have rapid progression to advanced fibrosis. Histological progression correlated with higher serum AST but no other clinical factors. Steatosis alone may progress to NASH with fibrosis.
Article
Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease that can progress to cirrhosis and hepatocellular carcinoma. NAFLD has been associated with obesity and other features of the metabolic syndrome, including insulin resistance, impaired glucose tolerance, and dyslipidemia. As a result, and with a lack of other effective treatments, weight loss achieved through lifestyle modifications (diet and exercise) has been promoted as the standard treatment. However, there is very little empiric evidence to support the effectiveness of weight loss for NAFLD. This article reviews the current literature on the effects of weight loss achieved through lifestyle modification or medications on NAFLD. To date, there have been no randomized controlled trials of weight loss interventions on hepatic pathology. Only three published trials (N = 89 subjects), which include a comparison group, have been published. These studies suggest improvement in liver enzymes and/or hepatic pathology; however, direct between group comparisons are lacking. Four small, nonrandomized studies (N = 59 subjects) have evaluated the effect of weight loss achieved with medications (4 of orlistat, 1 of sibutramine) on NAFLD. These suggest some improvement in liver enzymes and histopathology. Finally, a brief review of observational studies on the association between NAFLD pathology or liver enzymes and diet composition suggests a possible role for the manipulation of macronutrients and/or micronutrients in NAFLD treatment. In summary, there is little empiric evidence to support the role of weight loss achieved through lifestyle modification or medication in the treatment of NAFLD. Rigorously conducted, randomized controlled trials are needed in this area.
Article
This document presents the official position of the American Association for the Study of Liver Diseases (AASLD) on the application of serum alanine aminotransferase (ALT) activity, based upon an analysis of the currently available scientific data. Its authorship was selected by the Public Policy Committee. The document is fully endorsed by the AASLD Governing Board.
The natural history of nonalcoholic fatty liver disease: A clinical histopathological study
  • Harrison
A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C
  • Wai