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LIVER HEALTH Scientific Research

ARTICHOKE 

The Hepatocurative Effects of Cynara Scolymus L. Leaf Extract on Carbon Tetrachloride-Induced Oxidative Stress and Hepatic Injury in Rats 

Abstract 

Cynara scolymus is a pharmacologically important medicinal plant containing phenolic acids and flavonoids. Experimental studies indicate antioxidant and hepatoprotective effects of C. scolymus but there have been no studies about therapeutic effects of liver diseases yet. In the present study, hepatocurative effects of C. scolymus leaf extract on carbon tetrachloride (CCl4)-induced oxidative stress and hepatic injury in rats were investigated by serum hepatic enzyme levels, oxidative stress indicator (malondialdehyde-MDA), endogenous antioxidants, DNA fragmentation, p53, caspase 3 and histopathology. Animals were divided into six groups: control, olive oil, CCl4, C. scolymus leaf extract, recovery and curative. CCl4 was administered at a dose of 0.2 mL/kg twice daily on CCl4, recovery and curative groups. Cynara scolymus extract was given orally for 2 weeks at a dose of 1.5 g/kg after CCl4 application on the curative group. Significant decrease of serum alanine-aminotransferase (ALT) and aspartate-aminotransferase (AST) levels were determined in the curative group. MDA levels were significantly lower in the curative group. Significant increase of superoxide dismutase (SOD) and catalase (CAT) activity in the curative group was determined. In the curative group, C. scolymus leaf extract application caused the DNA % fragmentation, p53 and caspase 3 levels of liver tissues towards the normal range. Our results indicated that C. scolymus leaf extract has hepatocurative effects of on CCl4-induced oxidative stress and hepatic injury by reducing lipid peroxidation, providing affected antioxidant systems towards the normal range. It also had positive effects on the pathway of the regulatory mechanism allowing repair of DNA damage on CCl4-induced hepatotoxicity. 

Source: Emine Colak, Mehmet Cengiz Ustuner, Neslihan Tekin, Ertugrul Colak, Dilek Burukoglu, Irfan Degirmenci, and Hasan Veysi Gunes. “The hepatocurative effects of Cynara scolymus L. leaf extract on carbon tetrachloride-induced oxidative stress and hepatic injury in rats” SpringerPlus (2016):  5: 216. 

Efficacy of Artichoke Leaf Extract In Non-Alcoholic Fatty Liver Disease: A Pilot Double-Blind Randomized Controlled Trial  

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. 

Source: Yunes Panahi , Parisa Kianpour , Reza Mohtashami , Stephen L Atkin , Alexandra E Butler , Ramezan Jafari , Roghayeh Badeli , Amirhossein Sahebkar. “Efficacy of artichoke leaf extract in non-alcoholic fatty liver disease: A pilot double-blind randomized controlled trial” Phytotherapy Research (2018): 32(7):1382-1387. 

Artichoke Leaf Extract – Recent Findings Reflecting Effects on Lipid Metabolism, Liver and Gastrointestinal Tracts  

Abstract 

In various molecular, cellular and in vivo test systems, artichoke (Cynara scolymus L.) leaf extracts show antioxidative, hepatoprotective, choleretic and anti-cholestatic effects as well as inhibiting actions on cholesterol biosynthesis and LDL oxidation. Recently, active ingredients responsible for the main effects have been identified. Thus, luteolin seems to be of crucial importance for the inhibition of hepatocellular de novo cholesterol biosynthesis. The anti-dyspeptic actions ware mainly based on increased choleresis. Regarding clinical data, lipid-lowering, antiemetic, spasmolytic, choleretic and carminative effects have been described, along with good tolerance and a low incidence of side effects. Due to its specific mechanisms of action, the future use of artichoke leaf extract for the prevention of arteriosclerosis can be expected. 

Source: K Kraft. “Artichoke leaf extract – Recent findings reflecting effects on lipid metabolism, liver and gastrointestinal tracts” Phytomedicine: International Journal of Phytotherapy and Phytopharmacology (1997): 4(4):369-78. 

Increase in Choleresis By Means of Artichoke Extract  

Abstract 

The choleretic action of artichoke extract [main ingredient: cynarin (1.5-di-caffeoyl-D-quinc acid)] was investigated in a randomised placebo-controlled double-blind cross-over study (pilot study) [n = 20]. The effect of the standardized, artichoke extract: Hepar SL forte (administered as a single dose: 1.92 g, by the intraduodenal route in a solution of 50 ml of water) was studied by measuring intra-duodenal bile secretion using multi-channel probes. Thirty minutes after the test-substance was administered, a 127.3% increase in bile secretion was recorded, after 60 minutes, 151.5%, and after another 60 minutes, 94.3%, each in relation to the initial value. The relevant differences for the placebo were significant to the extent of p < 0.01 and were clinically relevant. The highest increase in the case of the placebo (139.5%) was seen after 30 minutes. At 120 and 150 minutes the volume of bile secreted under the active treatment was also significantly higher than under the placebo (p < 0.05). In the placebo group, bile secretion fell below the initial level after 3 hours. An effective period of about 120-150 minutes was regarded as satisfactory to influence enzymatic digestion and the motor function of the intestine when the test substance was given postprandially. No side effects nor changes in the laboratory parameters in connection with the experiment were observed. Results indicate that artichoke extract can be recommended for the treatment of dyspepsia, especially when the cause may be attributed to dyskinesia of the bile ducts or disorder in the assimilation of fat. 

Source: R Kirchhoff, C Beckers, G M Kirchhoff, H Trinczek-Gärtner, O Petrowicz, H J Reimann. “Increase in choleresis by means of artichoke extract” Phytomedicine: International Journal of Phytotherapy and Phytopharmacology (1994): 1(2):107-15. 

 

MILK THISTLE 

Production of the Liver-Protective Compounds Cynarin And Silymarin from Tissue Cultures of Globe Artichoke and Milk Thistle Plants  

Abstract        

The  production  of  the  useful  natural  components  form  plants  by  the  conventional methods  are  met with several problems.  The  seasonal production,  diseases,  handling  and poor storage impede offering such demand compounds to pharmaceutical factories. The main purpose  of this  work  is  to employ  different biotechnology applications  for  production  of phenolic compounds, cynarin and  silymarin from  Globe artichoke  and Milk  thistle plants respectively under in vitro conditions. Shoot tips of the two plant species were isolated from seedlings grown in vitro and then cultured on Murashige and Skoog medium supplemented with 2 mg/l Kinetin + 2 mg/l 6-benzyladenine + 0.1 mg/l Indole-3-acetic acid to get stock tissue culture materials. Calli were obtained from leaf explants using Murashige and Skoog medium + 5  mg/l 1-Naphthaleneacetic  acid + 2 

 mg/l Kinetin +  0.1 mg/l  Gibberellic acid. Supplementation of culture medium with of picloram enhanced callus growth of both plants. Addition of 3 mg/l picloram registered the best results of callus proliferation presented as growth ratio. Otherwise, accumulation enhancement of cynarin and silymarin by addition of chitosan,  and methyl jasmonate  was  investigated. It  was  found that  elicitation  of culture medium  with chitosan  and methyl  jasmonate  showed  increasing of cynarin  and silymarin contents  in  callus  cultures  of  Globe  artichoke  and  Milk  thistle  respectively.  Methyl jasmonate had more positive effect on the contents of  the interested compounds compared with chitosan. 

Source: BEKHEET S.H.; H.S.Taha; M.K.El-Bahr and A.M.M.Gabr. “Production of the liver-protective compounds cynarin and silymarin from tissue cultures of Globe artichoke and Milk thistle plants” Plant Biotechnology Dept., National Research Center (2018). 

 

TUMERIC (CURCUMIN) 

Stem Cell Therapy: Curcumin Does the Trick  

Abstract 

Curcumin is a dietary polyphenol and a bioactive phytochemical agent that possesses anti-inflammatory, antioxidant, anticancer, and chemo-preventive properties. Some of the predominant activities of stem cells include regeneration of identical cells and the ability to maintain the proliferation and multipotentiality. However, these cells could be stimulated to differentiate into specific cell types. Curcumin protects some stem cells from toxicity and can stimulate proliferation and differentiation of stem cells. In the present review, we summarize the antioxidant, stemness activity, antiaging, and neuroprotective as well as wound healing and regenerative effects of curcumin. 

Source: Simin Sharifi, Sepideh Zununi Vahed, Elham Ahmadian, Solmaz Maleki Dizaj, Atefeh Abedi, Seyed Mahdi Hosseiniyan Khatibi, Mohammad Samiei. “Stem Cell Therapy: Curcumin Does the Trick” Phytotherapy Research (2019): 33(11):2927-2937. 

Turmeric Extract and its Active Compound, Curcumin, Protect Against Chronic ccl4-Induced Liver Damage By Enhancing Antioxidation  

Abstract 

Background: Curcumin, a major active component of turmeric, has previously been reported to alleviate liver damage. Here, we investigated the mechanism by which turmeric and curcumin protect the liver against carbon tetrachloride (CCl4)-induced injury in rats. We hypothesized that turmeric extract and curcumin protect the liver from CCl4-induced liver injury by reducing oxidative stress, inhibiting lipid peroxidation, and increasing glutathione peroxidase activation. 

Methods: Chronic hepatic stress was induced by a single intraperitoneal injection of CCl4 (0.1 ml/kg body weight) into rats. Turmeric extracts and curcumin were administered once a day for 4 weeks at three dose levels (100, 200, and 300 mg/kg/day). We performed ALT and AST also measured of total lipid, triglyceride, cholesterol levels, and lipid peroxidation. 

Result: We found that turmeric extract and curcumin significantly protect against liver injury by decreasing the activities of serum aspartate aminotransferase and alanine aminotransferase and by improving the hepatic glutathione content, leading to a reduced level of lipid peroxidase. 

Conclusions: Our data suggest that turmeric extract and curcumin protect the liver from chronic CCl4-induced injury in rats by suppressing hepatic oxidative stress. Therefore, turmeric extract and curcumin are potential therapeutic antioxidant agents for the treatment of hepatic disease. 

Source: Hwa-Young Lee, Seung-Wook Kim, Geum-Hwa Lee, Min-Kyung Choi, Han-Wool Jung, Young-Jun Kim, Ho-Jeong Kwon and Han-Jung Chae. “Turmeric extract and its active compound curcumin, protect against chronic CCl4-induced liver damage by enhancing antioxidation” BMC Complementary  and Alternative Medicine (2016): 16:316. 

 

BEET 

Beetroot Juice Protects Against N-Nitrosodiethylamine-Induced Liver Injury in Rats  

Abstract 

Red beetroot, a common ingredient of diet, is a rich source of a specific class of antioxidants, betalains. Our previous studies have shown the protective role of beetroot juice against carcinogen induced oxidative stress in rats. The aim of this study was to examine the effect of long term feeding (28 days) with beetroot juice on phase I and phase II enzymes, DNA damage and liver injury induced by hepatocarcinogenic N-nitrosodiethylamine (NDEA). Long term feeding with beetroot juice decreased the activities of enzymatic markers of cytochrome P450, CYP1A1/1A2 and CYP2E1. NDEA treatment also reduced the activities of these enzymes, but increased the activity of CYP2B. Moreover, combined treatment with beetroot juice and NDEA enhanced significantly CYP2B only. Modulation of P450 enzyme activities was accompanied by changes in the relevant proteins levels. Increased level and activity of NQO1 was the most significant change among phase II enzymes. Beetroot juice reduced the DNA damage increased as the result of NDEA treatment, as well as the biomarkers of liver injury. Collectively, these results confirm the protective effect of beetroot juice against oxidative damage shown in our previous studies and indicate that metabolic alterations induced by beetroot feeding may protect against liver damage. 

Source: Violetta Krajka-Kuźniak , Hanna Szaefer, Ewa Ignatowicz, Teresa Adamska, Wanda Baer-Dubowska. “Beetroot juice protects against N-nitrosodiethylamine-induced liver injury in rats” Food and Chemical Toxicology (2012): Vol. 50, Issue 6, pp. 2027-2033. 

Liver-Protecting Effects of Table Beet (Beta Vulgaris Var. Rubra) During Ischemia-Reperfusion 

Abstract 

Objective: Table beet (Beta vulgaris var. rubra) contains important bioactive agents (betaine and polyphenols), which have a wide range of physiologic effects. Because nutritive antioxidants may reduce the occurrence of complications and postoperative mortality, dietary intake of polyphenols and vitamins before surgery may greatly contribute to the survival of patients. Our aim was to determine the liver-protecting properties of bioactive substances of table beet in a model of ischemia-reperfusion injury of the rat. 

Methods: Wistar rats were divided into two groups: non-treated (n = 24) and fed with table beet (n = 8). For 10 days the second group was treated with lyophilized table beet (2 g/kg body weight daily) mixed into the rat chow. Hepatic ischemia was maintained for 45 min, followed by 15 min of reperfusion. Ischemia-reperfusion was carried out on animals from both groups. Chemiluminescent intensity, H-donating ability, reducing power, free SH group concentration, Randox-total antioxidant status, glutathione peroxidase, and superoxide dismutase activities were determined by luminometry and spectrophotometry. Fatty acid (Shimadzu GC) and metal ion (inductively coupled plasma optical emission spectrometry) concentrations were observed in the liver. 

Results: As a result of feeding, global parameters (H-donating ability, reducing power, free SH group concentration) and enzymatic antioxidants (glutathione peroxidase and superoxide dismutase) of the liver were found to increase significantly, which indicated that the treatment had a positive effect on its redox state. The increase found in zinc and copper content may protect the hepatocytes against oxidative stress because these elements are required for the function of superoxide dismutase enzymes. In the table beet group the concentration of short-chain fatty acids decreased, whereas that of long-chain fatty acids increased. The changes in metal element and fatty acid concentrations confirmed that these elements have an essential function in cellular pathways. 

Conclusion: It may be stated that a natural antioxidant-rich diet has a positive effect on redox homeostasis during hepatic ischemia-reperfusion. 

Source: László Váli , Eva Stefanovits-Bányai, Klára Szentmihályi, Hedvig Fébel, Eva Sárdi, Andrea Lugasi, Ibolya Kocsis, Anna Blázovics. “ Liver-protecting effects of table beet (Beta vulgaris var. rubra) during ischemia-reperfusion” Nutrition (2007): Vol. 23, Issue 2, pp. 172-178. 

Beet Stalks and Leaves (Beta vulgaris L.) Protect Against High-Fat Diet-Induced Oxidative Damage in the Liver in Mice  

Abstract 

 Some flavonoids identified in beet stalks can help the antioxidant endogenous defenses during a chronic inflammation process. The current study investigates the effect of polyphenols present in beet stalks and leaves on liver oxidative damage in mice fed a high-fat diet (HF). The control (CT) or HF diet groups were supplemented with dehydrated beet stalks and leaves (SL) or beet stalk and leaf ethanolic extract (EX). In terms of Vitexin-rhaminoside equivalents (VRE), EX groups received ~5.91 mg of VRE·100 g−1 diet, while the SL groups received ~3.07 mg VRE·100 g−1 diet. After 8 weeks, we evaluated fasting blood glucose; cholesterol, hepatic Malondialdehyde (MDA) levels and hepatic Glutathione (GSH), Glutathione peroxidase (GPx), Glutathione reductase (GR) and Superoxide dismutase (SOD) activity. Dehydrated beet stalks and leaves (HFSL) attenuated the deleterious effects of a HF diet on lipid metabolism, reduced fasting blood glucose levels, ameliorated cholesterol levels and reduced GPx and GR activities (p < 0.05) compared to the HF group. However; the addition of ethanolic extract from beet stalks and leaves was unable (p > 0.05) to prevent the liver damage caused by HF diet in mice. The presence of flavonoids, such as Vitexin derivatives in beet stalks and leaves can help the liver damage induced by HF diet. 

Source: Isabela M. Lorizola, Cibele P. B. Furlan, Mariana Portovedo, Marciane Milanski, Patrícia B. Botelho, Rosângela M. N. Bezerra, Beatriz R. Sumere, Maurício A. Rostagno, and  Caroline D. Capitani. “Beet Stalks and Leaves (Beta vulgaris L.) Protect Against High-Fat Diet-Induced Oxidative Damage in the Liver in Mice” Nutrients (2018): 10(7): 872.  

 

DANDELION 

The Physiological Effects of Dandelion (Taraxacum Officinale) in Type 2 Diabetes 

Abstract 

 The tremendous rise in the economic burden of type 2 diabetes (T2D) has prompted a search for alternative and less expensive medicines. Dandelion offers a compelling profile of bioactive components with potential anti-diabetic properties. The Taraxacum genus from the Asteraceae family is found in the temperate zone of the Northern hemisphere. It is available in several areas around the world. In many countries, it is used as food and in some countries as therapeutics for the control and treatment of T2D. The anti-diabetic properties of dandelion are attributed to bioactive chemical components; these include chicoric acid, taraxasterol (TS), chlorogenic acid, and sesquiterpene lactones. Studies have outlined the useful pharmacological profile of dandelion for the treatment of an array of diseases, although little attention has been paid to the effects of its bioactive components on T2D to date. This review recapitulates previous work on dandelion and its potential for the treatment and prevention of T2D, highlighting its anti-diabetic properties, the structures of its chemical components, and their potential mechanisms of action in T2D. Although initial research appears promising, data on the cellular impact of dandelion are limited, necessitating further work on clonal β-cell lines (INS-1E), α-cell lines, and human skeletal cell lines for better identification of the active components that could be of use in the control and treatment of T2D. In fact, extensive in-vitro, in-vivo, and clinical research is required to investigate further the pharmacological, physiological, and biochemical mechanisms underlying the effects of dandelion-derived compounds on T2D. 

Source: Fonyuy E. Wirngo, Max N. Lambert, and  Per B. Jeppesen. “The Physiological Effects of Dandelion (Taraxacum Officinale) in Type 2 Diabetes” The Review of Diabetic Studies (2016): 13(2-3): 113–131.  

Dandelion Leaf Extract Protects Against Liver Injury Induced By Methionine- and Choline-Deficient Diet in Mice  

Abstract 

We investigated the hepatoprotective effects of the extract of dandelion leaves (EDL) on a murine model of methionine- and choline-deficient (MCD) diet-induced nonalcoholic steatohepatitis (NASH). C57BL/6 mice were fed for 4 weeks with one of the following diets: control diet (Cont), MCD diet (MCD), MCD diet supplemented with EDL at 200 mg/kg body weight·daily (MCD+D200), and MCD diet supplemented with EDL at 500 mg/kg body weight·daily (MCD+D500). Hepatic function was assessed by evaluating the following parameters: liver histology; plasma levels of alanine aminotransferase (ALT), triglyceride (TG), malondialdehyde (MDA), and reduced glutathione (GSH); expression levels of TNF-α and IL-6; and levels of caspase-3 and pJNK/JNK protein. Histopathological evaluations revealed that addition of EDL to the MCD diet dampens the severity of the clinical signs of NASH. Moreover, EDL led to a significant decrease in the serum levels of ALT, hepatic TG, and MDA, and in the expression levels of TNF-α, and IL-6; on the contrary, the levels of reduced GSH increased. At the post-transcriptional level, EDL significantly decreased the activation of procaspase-3 to active caspase-3, and the phosphorylation of JNK. These results suggest that the beneficial effects of EDL on NASH are mainly due to its antioxidant and anti-inflammatory activities. 

Source: Munkhtugs Davaatseren , Haeng Jeon Hur, Hye Jeong Yang, Jin-Taek Hwang, Jae Ho Park, Hyun-Jin Kim, Myung-Sunny Kim, Min Jung Kim, Dae Young Kwon, Mi Jeong Sung. “Dandelion leaf extract protects against liver injury induced by methionine- and choline-deficient diet in mice” Journal of Medicinal Food (2013): 16(1):26-33. 

Taraxacum Official (Dandelion) Leaf Extract Alleviates High-Fat Diet-Induced Nonalcoholic Fatty Liver  

Abstract 

The purpose of this study is to determine the protective effect of Taraxacum official (dandelion) leaf extract (DLE) on high-fat-diet (HFD)-induced hepatic steatosis, and elucidate the molecular mechanisms behind its effects. To determine the hepatoprotective effect of DLE, we fed C57BL/6 mice with normal chow diet (NCD), high-fat diet (HFD), HFD supplemented with 2g/kg DLE DLE (DL), and HFD supplemented with 5 g/kg DLE (DH). We found that the HFD supplemented by DLE dramatically reduced hepatic lipid accumulation compared to HFD alone. Body and liver weights of the DL and DH groups were significantly lesser than those of the HFD group, and DLE supplementation dramatically suppressed triglyceride (TG), total cholesterol (TC), insulin, fasting glucose level in serum, and Homeostatic Model Assessment Insulin Resistance (HOMA-IR) induced by HFD. In addition, DLE treatment significantly increased activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) in liver and muscle protein. DLE significantly suppressed lipid accumulation in the liver, reduced insulin resistance, and lipid in HFD-fed C57BL/6 mice via the AMPK pathway. These results indicate that the DLE may represent a promising approach for the prevention and treatment of obesity-related nonalcoholic fatty liver disease. 

Source: Munkhtugs Davaatseren , Haeng Jeon Hur, Hye Jeong Yang, Jin-Taek Hwang, Jae Ho Park, Hyun-Jin Kim, Min Jung Kim, Dae Young Kwon, Mi Jeong Sung. “Taraxacum official (dandelion) leaf extract alleviates high-fat diet-induced nonalcoholic fatty liver” Food and Chemical Toxicology (2013): 58:30-6. 

 

GINGER 

Ginger Supplementation in Non-Alcoholic Fatty Liver Disease: A Randomized, Double-Blind, Placebo-Controlled Pilot Study  

Abstract 

Background: 

Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide. The pathogenesis of this disease is closely associated with obesity and insulin resistance. Ginger can have hypolipidemic and antioxidant effects, and act as an insulin sensitizer. 

Objectives: 

The aim of this study was to evaluate the effects of ginger supplementation in NAFLD management. 

Patients and Methods: 

In a randomized, double-blind, placebo-controlled clinical trial, 44 patients with NAFLD were assigned to take either two grams per day of a ginger supplement or the identical placebo, for 12 weeks. In both groups, patients were advised to follow a modified diet and physical activity program. The metabolic parameters and indicators of liver damage were measured at study baseline and after the 12 week intervention. 

Results: 

Ginger supplementation resulted in a significant reduction in alanine aminotransferase, γ-glutamyl transferase, inflammatory cytokines, as well as the insulin resistance index and hepatic steatosis grade in comparison to the placebo. We did not find any significant effect of taking ginger supplements on hepatic fibrosis and aspartate aminotransferase. 

Conclusions: 

Twelve weeks of two grams of ginger supplementation showed beneficial effects on some NAFLD characteristics. Further studies are recommended to assess the long-term supplementation effects. 

Source: Mehran Rahimlou, Zahra Yari, Azita Hekmatdoost, Seyed Moayed Alavian, and  Seyed Ali Keshavarz. “Ginger Supplementation in Non-alcoholic Fatty Liver Disease: A Randomized, Double-Blind, Placebo-Controlled Pilot Study” Hepatitis Monthly (2016): 16(1): e34897.  

Effect of Ginger Powder Supplementation in Patients with Non-Alcoholic Fatty Liver Disease: A Randomized Clinical Trial  

Abstract 

Background Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver disorders. The main causes of NAFLD are associated with insulin resistance, severe lipid metabolism disorders, oxidative stress and inflammation. Previous studies have reported that ginger has positive metabolic results. 

Aim The aim of this study was to determine the effect of ginger powder supplement on lipid profiles, insulin resistance, liver enzymes, inflammatory cytokines and antioxidant status in patients with NAFLD. 

Methods In this randomized clinical trial, 46 people with NAFLD were parted into two groups and subjected to the ginger or placebo capsules (3 capsules daily, each containing 500 mg of ginger or wheat flour) over 12 weeks. All patients received a diet with balanced energy and physical activity during the intervention period. Liver ultrasonography, anthropometric indices and biochemical parameters were measured before and after intervention. 

Results No significant difference was found between the two groups in the baseline variables at the beginning of the study. At the end of the study, serum levels of alanine aminotransferase (ALT), total cholesterol, low-density lipoprotein (LDL-C), fasting blood glucose, and insulin resistance index (HOMA), C-reactive protein (hs-CRP), and fetuin-A in the group receiving a ginger supplement significantly decreased compared to placebo. However, there was no significant difference between the two groups in body weight, fasting insulin, HDL-C, triglyceride, adiponectin, alpha-tumor necrosis factor (TNF-α), total antioxidant capacity (TAC), gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST), fatty liver index (FLI), fatty liver grade and blood pressure. 

Conclusion The ginger supplement may be used as a complementary therapy along with existing therapies to reduce insulin resistance, liver enzymes and inflammation in patients with non-alcoholic fatty liver. 

Source: Roya Rafie, Seyed Ahmad Hosseini, Eskandar Hajiani, Amal Saki Malehi, and  Seyed Ali Mard. “Effect of Ginger Powder Supplementation in Patients with Non-Alcoholic Fatty Liver Disease: A Randomized Clinical Trial” Clinical and Experimental Gastroenterology (2020): 13: 35–45.  

Potential Efficacy of Ginger as a Natural Supplement for Nonalcoholic Fatty Liver Disease 

Abstract 

 Non-alcoholic 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 anti-dyslipidemic 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.  

Source: Amirhossein Sahebkar. “Potential efficacy of ginger as a natural supplement for nonalcoholic fatty liver disease”  World Journal of Gastroenterology (2011): 17(2): 271–272.  

 

ALFALFA 

The Effects of Aqueous Extract of Alfalfa on Blood Glucose And Lipids in Alloxan-Induced Diabetic Rats  

Abstract  

Diabetes is a common metabolic disorder that is specified by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. The use of nonpharmacological treatments (herbal agents) is a new approach in the management of diabetes. The aim of this study was to investigate the effect of aqueous extract of alfalfa on blood glucose and serum lipids in alloxan-induced diabetic rats. In this study, 32 female rats (210–250 g) were used which were divided randomly into 4 groups including intact control group, diabetic control group, and 2 diabetic groups which received 250 and 500 mg/kg doses of aqueous extract of alfalfa, respectively. In the diabetic groups, alloxan-monohydrate was injected peritoneally to create diabetic condition. The two last groups orally received aqueous extract of alfalfa for 21 days. At the end of experiment, sugar, cholesterol, triglycerides, high-density and low-density lipoprotein, and aspartate aminotransferase (ALT) and alanine aminotransferase (AST) levels were measured in the samples. Consumption of aqueous alfalfa extract significantly reduced glucose, cholesterol, triglycerides, and low-density lipoprotein (LDL) levels in the diabetic rats but enhanced high-density lipoprotein (HDL) levels. ALT and AST liver enzyme levels were also reduced in blood. Histological examination showed that the aqueous alfalfa extract caused reconstruction of damaged liver and enhanced Langerhans islets’ diameter in pancreas. Therefore, all signs of diabetes were improved by oral administration of alfalfa in defined dose. 

Source: Esmaiel Amraie,  Masome Khosravi Farsani,  Leila Sadeghi,  Tayaba Naim Khan,  Vahid Yousefi Babadi,  and Zohrab Adavi. “The effects of aqueous extract of alfalfa on blood glucose and lipids in alloxan-induced diabetic rats” Interventional Medicine and Applied Science (2015): 7(3): 124–128.  

Interactions of alfalfa plant and sprout saponins with cholesterol in vitro and in cholesterol-fed rats  

Abstract 

The in vitro interactions of saponins from alfalfa plant and alfalfa sprouts with cholesterol and the effects of alfalfa plant and sprout and saponin-free alfalfa plant on diet-induced liver cholesterol accumulation, bile acid excretion, and jejunal and colonic morphology were examined. Cholesterol-saponin interactions have been suggested as mechanisms for the observed hypocholesterolemic effects of alfalfa as well as the changes in intestinal morphology. Alfalfa plant saponins bound significant quantities of cholesterol both from ethanol solution and from micellar suspension. Alfalfa sprout saponins interacted with cholesterol to a lesser but significant extent. Sprout saponins also inhibited growth of Trichoderma viride significantly, another measure of saponin-cholesterol interaction. Bile acid adsorption was greatest for alfalfa plant and was not reduced by removal of saponins from the plant material. The ability of alfalfa to reduce liver cholesterol accumulation in cholesterol-fed rats was enhanced by removal of saponins and alfalfa sprouts did not prevent accumulation. Removal of saponins from alfalfa reduced the changes in intestinal morphology previously reported, but interaction with membrane cholesterol did not appear to be the cause of this effect of saponins. Saponin-cholesterol interaction is an important part of the hypocholesterolemic action of alfalfa but interaction of bile acids with other components of alfalfa may be of equal importance. 

Source: J A Story, S L LePage, M S Petro, L G West, M M Cassidy, F G Lightfoot, G V Vahouny. “Interactions of alfalfa plant and sprout saponins with cholesterol in vitro and in cholesterol-fed rats” The American Journal and Clinical Nutrition (1984): 39(6):917-29. 

The Regulation of Alfalfa Saponin Extract on Key Genes Involved in Hepatic Cholesterol Metabolism in Hyperlipidemic Rats  

Abstract 

 To investigate the cholesterol-lowering effects of alfalfa saponin extract (ASE) and its regulation mechanism on some key genes involved in cholesterol metabolism, 40 healthy 7 weeks old male Sprague Dawley (SD) rats were randomly divided into four groups with 10 rats in each group: control group, hyperlipidemic group, ASE treatment group, ASE prevention group. The body weight gain, relative liver weight and serum lipid 1evels of rats were determined. Total cholesterol (TC) and total bile acids (TBA) levels in liver and feces were also measured. Furthermore, the activity and mRNA expressions of Hmgcr, Acat2, Cyp7a1 and Ldlr were investigated. The results showed the following: (1) The abnormal serum lipid levels in hyperlipidemic rats were ameliorated by ASE administration (both ASE prevention group and treatment group) (P<0.05). (2) Both ASE administration to hyperlipidemic rats significantly reduced liver TC and increased liver TBA level (P<0.05). TC and TBA levels in feces of hyperlipidemic rats were remarkably elevated by both ASE administration (P<0.05). (3) mRNA expressions of Hmgcr and Acat2 in the liver of hyperlipidemic rats were remarkably down-regulated (P<0.05), as well as mRNA expressions of Cyp7a1 and Ldlr were dramatically up-regulated by both ASE administration (P<0.05). The activities of these enzymes also paralleled the observed changes in mRNA levels. (4) There was no significant difference between ASE treatment and ASE prevention group for most parameters evaluated. Our present study indicated that ASE had cholesterol-lowering effects. The possible mechanism could be attributed to (1) the down-regulation of Hmgcr and Acat2, as well as up-regulation of Cyp7a1 and Ldlr in the liver of hyperlipidemic rats, which was involved in cholesterol biosynthesis, uptake, and efflux pathway; (2) the increase in excretion of cholesterol. The findings in our study suggested ASE had great potential usefulness as a natural agent for treating hyperlipidemia. 

Source: Yinghua Shi,  Rui Guo, Xianke Wang, Dedi Yuan, Senhao Zhang, Jie Wang, Xuebing Yan, and  Chengzhang Wang. “The Regulation of Alfalfa Saponin Extract on Key Genes Involved in Hepatic Cholesterol Metabolism in Hyperlipidemic Rats” PLoS One (2014): 9(2): e88282.

 

L-CYSTEINE 

The Effect of N-Acetyl-L-Cysteine (NAC) on Liver Toxicity and Clinical Outcome After Hematopoietic Stem Cell Transplantation 

Abstract 

Busulphan (Bu) is a myeloablative drug used for conditioning prior to hematopoietic stem cell transplantation. Bu is predominantly metabolized through glutathione conjugation, a reaction that consumes the hepatic glutathione. N-acetyl-l-cysteine (NAC) is a glutathione precursor used in the treatment of acetaminophen hepatotoxicity. NAC does not interfere with the busulphan myeloablative effect. We investigated the effect of NAC concomitant treatment during busulphan conditioning on the liver enzymes as well as the clinical outcome. Prophylactic NAC treatment was given to 54 patients upon the start of busulphan conditioning. These patients were compared with 54 historical matched controls who did not receive NAC treatment. In patients treated with NAC, aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) were significantly (P < 0.05) decreased after conditioning compared to their start values. Within the NAC-group, liver enzymes were normalized in those patients (30%) who had significantly high start values. No significant decrease in enzyme levels was observed in the control group. Furthermore, NAC affected neither Bu kinetics nor clinical outcome (sinusoidal obstruction syndrome incidence, graft-versus-host disease and/or graft failure). In conclusion: NAC is a potential prophylactic treatment for hepatotoxicity during busulphan conditioning. NAC therapy did not alter busulphan kinetics or affect clinical outcome. 

Source: Ibrahim El-Serafi, Mats Remberger, Ahmed El-Serafi, Fadwa Benkessou, Wenyi Zheng, Eva Martell, Per Ljungman, Jonas Mattsson, and  Moustapha Hassan. “The effect of N-acetyl-l-cysteine (NAC) on liver toxicity and clinical outcome after hematopoietic stem cell transplantation” Scientific Reports (2018): 8: 8293.     

Therapeutic Effects of N-Acetyl-L-Cysteine on Liver Damage Induced by Long-Term ccl4 Administration  

Abstract 

N-acetyl-L-cysteine (NAC) is a drug routinely used in several health problems, e.g. liver damage. There is some information emerged on its negative effects in certain situations. The aim of our study was to examine its ability to influence liver damage induced by long-term burden. We induced liver damage by CCl4 (10 weeks) and monitored the impact of parallel NAC administration (daily 150 mg/kg of b.w.) on liver morphology and some biochemical parameters (triacylglycerols, cholesterol, alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, bile acids, proteins, albumins and cholinesterase). NAC significantly decreased levels of bile acids and bilirubin in plasma and triacylglycerols in liver, all of them elevated by impairment with CCl4. Reduction of cholesterol induced by CCl4 was completely recovered in the presence of NAC as indicated by its elevation to control levels. NAC administration did not improve the histological parameters. Together with protective effects of NAC, we found also its deleterious properties: parallel administration of CCl4 and NAC increased triacylglycerols, ALT and AST activity and significantly increased plasma cholinesterase activity. We have observed nonsignificantly increased percentage of liver tissue fibrosis. Our results have shown that NAC administered simultaneously with liver damaging agent CCl4, exhibits not only protective, but also deleterious effects as indicated by several biochemical parameters. 

Source: Oľga Otrubová , Ladislav Turecký, Oľga Uličná, Pavol Janega, Ján Luha, Jana Muchová. “Therapeutic effects of N-acetyl-L-cysteine on liver damage induced by long-term CCl4 administration” General Physiology and Biophysics (2018): Vol. 37, No. 1, p. 23-31.      

N-Acetylcysteine Improves Liver Function in Patients with Non-Alcoholic Fatty Liver Disease  

Abstract 

Background and Aims Non-alcoholic fatty liver change is a common disease of the liver in which oxidative stress plays a basic role. Studies are largely focused on protecting the liver by means of anti-oxidative material. The aim of this study is to evaluate the role of N- acetylcysteine in the process of liver injury. 

Methods Thirty patients with non-alcoholic fatty liver steatosis were randomly selected to receive either N-acetylcysteine or vitamin C. Liver function tests (alanine aminotransfrase, aspartate aminotransfrase and alkaline phosphatase) were measured as well as the grade of steatosis, the pattern of its echogenicity, the span of the liver and the spleen and the portal vein diameter before the intervention. Patients were followed up using the same method of evaluation repeated in the first, second and third months. 

Results The mean age (SD) was 40.1(12.4) in patients receiving NAC and 46(10.4) years in patients receiving vitamin C (P = 0.137). NAC resulted in a significant decrease of serum alanine aminotransfrase after three months, compared to vitamin C. This effect was independent of the grade of steatosis in the initial diagnosis. NAC was able to significantly decrease the span of the spleen. 

Conclusions N-acetyl-cysteine can improve liver function in patients with non-alcoholic fatty liver disease. Better results may be achievable in a longer follow up. 

Source: Manouchehr Khoshbaten, Akbar Aliasgarzadeh, Koorosh Masnadi, Mohammad K Tarzamani, Sara Farhang, Hosain Babaei, Javad Kiani, Maryam Zaare, and  Farzad Najafipoor. “N-Acetylcysteine Improves Liver Function in Patients with Non-Alcoholic Fatty Liver Disease” Hepatitis Monthly (2010): 10(1): 12–16.  

 

LIVER BIOLOGY 

Correlation of Fatty Liver and Abdominal Fat Distribution Using a Simple Fat Computed Tomography Protocol  

Abstract 

Aim: To evaluate the relationship between hepatic fat infiltration and abdominal fat volume by using computed tomography (CT). 

Methods: Three hundred and six patients who visited our obesity clinic between November 2007 and April 2008 underwent fat protocol CT scans. The age range of the patients was 19 to 79 years and the mean age was 49 years. The male to female ratio was 116:190. Liver and spleen attenuation measurements were taken with three regions of interests (ROIs) from the liver and two ROIs from the spleen. Hepatic attenuation indices (HAIs) were measured as follows: (1) hepatic parenchymal attenuation (CTLP); (2) liver to spleen attenuation ratio (LS ratio); and (3) difference between hepatic and splenic attenuation (LSdif). Abdominal fat volume was measured using a 3 mm slice CT scan starting at the level of the umbilicus and was automatically calculated by a workstation. Abdominal fat was classified into total fat (TF), visceral fat (VF), and subcutaneous fat (SF). We used a bivariate correlation method to assess the relationship between the three HAIs and TF, VF, and SF. 

Results: There were significant negative correlations between CTLP, LS ratio, and LSdif with TF, VF, and SF, respectively. The CTLP showed a strong negative correlation with TF and VF (r = -0.415 and -0.434, respectively, P < 0.001). The correlation between CTLP and SF was less significant (r = -0.313, P < 0.001). 

Conclusion: Fatty infiltration of the liver was correlated with amount of abdominal fat and VF was more strongly associated with fatty liver than SF. 

Source: Seonah Jang, Chang Hee Lee, Kyung Mook Choi, Jongmee Lee, Jae Woong Choi, Kyeong Ah Kim, and Cheol Min Park. “Correlation of fatty liver and abdominal fat distribution using a simple fat computed tomography protocol” World Journal of Gastroenterology (2011):  17(28): 3335–3341. 

Therapeutic Correction of Liver and Biliary Tract Pathology Among Adolescents with Obesity  

Abstract   

Background. The purpose of the study is to evaluate the efficacy of hepatoprotectors in comprehensive treatment of adolescents with obesity, non-alcoholic fatty liver disease and dysfunctional disorders of the biliary tract (DDBT). Materials and methods. The study involved 80 adolescents with obesity and insulin resistance aged 10 to 18 years. Biochemical research and ultrasound investigation of the hepatobiliary system were conducted in all the patients. The metformin was used for all the patients in the treatment of obesity. According to the results of examination, all patients were divided into two groups: 1st group — patients with clinical and ultrasound signs of DDBT, who received artichoke extract preparations; 2nd group — patients with clinical and ultrasound signs of DDBT and biliary sludge, in whom ursodeoxycholic acid (UDCA) preparations were used. Control examinations were conducted after treatment and after the sixth month. Results. Adolescents with obesity complained of increased appetite, abdominal pain and dyspepsia. Pain in the right upper quadrant and signs of atherogenic dyslipidemia were determined in these patients. According to the ultrasound investigation, signs of steatohepatosis were found in one-third of patients. Improvement of contractile function of the gallbladder and decrease of steatohepatosis symptoms were more significant in those patients received artichoke extract preparations than in the comparison group. Homogenization of the bile decrease in the signs of steatosis and hypotonia of the gallbladder were more significant in patients, who received UDCA preparations, than in the comparison group. Conclusions. The prescription of the artichoke extract preparations for the period of 1.5–2 months is reasonable for adolescents with obesity and hypotonia of the gallbladder. The administration of the UDCA preparations for the period of 2–3 months is reasonable in case of clinical signs of DDBT and biliary sludge presence. The positive effect of treatment after 6 months was observed only in patients, who were motivated to change their lifestyle. 

Source: L.K. Parkhomenko, L.A. Strashok, A.V. Yeshchenko, E.M. Zavelya, M.Yu. Isakova, M.A. Khomenko. “Therapeutic correction of liver and biliary tract pathology among adolescents with obesity” Directory of Open Access Journals (2017): 12(3):319-323. 

Cognitive Changes and Brain Volume Reduction in Patients with Non-alcoholic Fatty Liver Disease 

Abstract 

Studies of psychological condition of patients suffering from non-alcoholic fatty liver disease are rather equivocal about the results: while some claim that NAFLD patients suffer from anxiety and depression more than non-NAFLD controls, others do not withstand those findings. Lower cognitive potentials have also been reported, both in patient related and in animal model-based investigations, and correlated with assessed brain tissue changes. We hypothesized that NAFLD, as a condition, affects the brain tissue and, subsequently, the cognitive state. So we compared findings in 40 NAFLD positive and 36 NAFLD negative patients and correlated their brain tissue volumes with the results of Montreal Cognitive Assessment (MoCA) test. Binomial logistic regression verified the influence of NAFLD state leading to lower cognitive potentials: odds ratio 0.096; 95% confidence interval (CI) 0.032–0.289; p < 0.001. Patients with NAFLD had a greater risk to suffer from the cognitive impairment and depression: RR = 3.9; 95% CI 1.815–8.381; p = 0.0005 and RR = 1.65; 95% CI 1.16–2.36; p = 0.006. NAFLD significantly influenced the cognitive deficit and tissue volume reduction and patients suffering from NAFLD had about four times higher risk of having a cognitive impairment. 

Source: Branka Filipović, Olivera Marković, Vesna Đurić, and Branislav Filipović. “Cognitive Changes and Brain Volume Reduction in Patients with Non-alcoholic Fatty Liver Disease” Canadian Journal of Gastroenterology and Hepatology (2018): 9638797. 

Fructose and Sugar: A Major Mediator of Nonalcoholic Fatty Liver Disease  

Abstract 

Non-alcoholic Fatty Liver Disease (NAFLD) is the hepatic manifestation of metabolic syndrome, and its rising prevalence parallels the rise in obesity and diabetes. Historically thought to result from overnutrition and sedentary lifestyle, recent evidence suggests that diets high in sugar (from sucrose and/or high fructose corn syrup (HFCS)) not only increases the risk for NAFLD, but also, non-alcoholic steatohepatitis (NASH). Here we review the experimental and clinical evidence that fructose precipitates fat accumulation in the liver, due to both increased lipogenesis and impaired fat oxidation. Recent evidence suggests that the predisposition to fatty liver is linked with metabolism of fructose by fructokinase C, resulting in ATP consumption, nucleotide turnover and uric acid generation that mediate fat accumulation. Alterations in gut permeability, microbiome, and associated endotoxemia contributes to the risk of NAFLD and NASH. Early clinical studies suggest that reducing sugary beverages and total fructose intake, especially from added sugars, may have a significant benefit on reducing hepatic fat accumulation. We suggest larger, more definitive trials to determine if lowering sugar/HFCS intake, and/or blocking uric acid generation, may help reduce NAFLD and its downstream complications of cirrhosis and chronic liver disease. 

Source: Thomas Jensen, Manal F. Abdelmalek, Shelby Sullivan, Kristen J. Nadeau, Melanie Green, Carlos Roncal, Takahiko Nakagawa, Masanari Kuwabara, Yuka Sato, Duk-Hee Kang, Dean R. Tolan, Laura G Sanchez-Lozada, Hugo R. Rosen, Miguel A. Lanaspa, Anna Mae Diehl, and Richard J Johnson. “Fructose and Sugar: A Major Mediator of Non-alcoholic Fatty Liver Disease” Journal of Hepatology (2018): 68(5): 1063–1075. 

Stem Cells and Liver Regeneration  

Abstract 

One of the defining features of the liver is the capacity to maintain a constant size despite injury. Although the precise molecular signals involved in the maintenance of liver size are not completely known, it is clear that the liver delicately balances regeneration with overgrowth. Mammals, for example, can survive surgical removal of up to 75% of the total liver mass. Within 1 week after liver resection, the total number of liver cells is restored. Moreover, liver overgrowth can be induced by a variety of signals, including hepatocyte growth factor or peroxisome proliferators; the liver quickly returns to its normal size when the proliferative signal is removed. The extent to which liver stem cells mediate liver regeneration has been hotly debated. One of the primary reasons for this controversy is the use of multiple definitions for the hepatic stem cell. Definitions for the liver stem cell include the following: (1) cells responsible for normal tissue turnover, (2) cells that give rise to regeneration after partial hepatectomy, (3) cells responsible for progenitor-dependent regeneration, (4) cells that produce hepatocyte and bile duct epithelial phenotypes in vitro, and (5) transplantable liver-repopulating cells. This review will consider liver stem cells in the context of each definition. 

Source: Andrew W Duncan, Craig Dorrell, Markus Grompe. “Stem cells and liver regeneration” Gatroenterology (2009): 137(2):466-81. 

 

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