Liver 360
CLINICAL STUDIES ON THE FOLLOWING INGREDIENTS:
Vitamin D3 (as cholecalciferol)
Vitamin D and non-alcoholic fatty liver disease: a meta-analysis of randomized controlled trials
Abstract
The results of randomized controlled trials (RCTs) investigating supplemental vitamin D on aminotransferases and cardio-metabolic risk factors in subjects with non-alcoholic fatty liver disease (NAFLD) have been inconsistent. The present study aimed to quantitatively evaluate whether supplementation with vitamin D has beneficial effects in treatment of NAFLD. A systematical literature search was performed with Cochrane Library, PubMed, Scopus databases and Web of Science up to June 2020. The mean changes in alanine aminotransferase (ALT), aspartate aminotransferase (AST), fasting glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), and triglyceride (TAG) were calculated as standard mean difference (SMD) using a random-effects model. Pre-specified subgroup and univariate meta-regression analyses were performed to identify the sources of heterogeneity. Ten trials with a total of 544 NAFLD subjects were included for data synthesis. The summary estimates indicated that supplemental vitamin D significantly reduced the levels of serum/plasma fasting glucose (-0.22; 95%CI: -0.39, -0.04), insulin (-0.68; 95%CI: -1.22, -0.14) and HOMA-IR (-1.32; 95%CI: -2.30, -0.34), and marginally reduced the ALT (-0.18; 95%CI: -0.39, 0.04) and TAG (-10.38; 95%CI: -21.09, 0.34) levels. However, the pooled effect did not support that supplemental vitamin D was beneficial for concentrations of AST, TC, HDL-C and LDL-C. The present study provides substantial evidence that supplemental vitamin D has favorable effects on glycemic control and insulin sensitivity in NAFLD patients. Vitamin D could be as an adjuvant pharmacotherapy of NAFLD.
Source: Guo XF, Wang C, Yang T, Li S, Li KL, Li D. Vitamin D and non-alcoholic fatty liver disease: a meta-analysis of randomized controlled trials. Food Funct. 2020 Sep 23;11(9):7389-7399. doi: 10.1039/d0fo01095b. PMID: 32966467.
Efficacy of vitamin D supplementation on adult patients with non-alcoholic fatty liver disease: a single-center experience
Abstract
Aim: The aim of this study was to determine the efficacy of a 6-month intramuscular vitamin D supplementation in improving the liver parameters in adult patients with non-alcoholic fatty liver disease (NAFLD).
Background: The association between vitamin D level and NAFLD has not been determined.
Methods: A single-blinded non-randomized controlled trial was conducted in 80 NAFLD patients assigned to receive a monthly single intramuscular dose of 200,000 IU cholecalciferol/vitamin D3 (n= 40), or placebo (n= 40) for six months. Transient elastography for the measurement of controlled attenuation parameter (CAP) and liver stiffness measurements (LSM), as well as fibrosis 4 score (FIB4) and NAFLD fibrosis score (NFS) were performed.
Results: The mean serum 25(OH)D was significantly increased after six months of vitamin D treatment (16.31±10.23 Vs 39.37±11.99 ng/ml). In the vitamin D group, most vitamin D deficiency patients (70% deficiency, 10% insufficiency, and 20% sufficiency) had changed to be sufficient (7.5% deficiency, 5% insufficiency, and 87.5% sufficiency). On the other hand, the values of CAP (311.9±42.2 dB/m) and LSM (6.8±2 kPa) had significantly reduced after six months of supplementation (287.0 ±44.3dB/m and 6.1 ±1.1 kPa, respectively) with significantly higher mean CAP and LSM change from baseline in vitamin D group compared to the placebo group. Furthermore, the ALT and AST levels were significantly improved in Vitamin D group compared to the placebo group (P < 0.05). Multivariate regression analysis showed that lower serum 25(OH)D level was the only significant predictor for NAFLD (OR=0.89, p=0.001) in this study.
Conclusion: A monthly single intramuscular dose of 200,000 IU cholecalciferol is effective in improving the laboratory and fibroscan parameters of the liver disease in NAFLD patients, which confirm a significant relationship between vitamin D deficiency and the risk of NAFLD.
Source: Gad AI, Elmedames MR, Abdelhai AR, Marei AM, Abdel-Ghani HA. Efficacy of vitamin D supplementation on adult patients with non-alcoholic fatty liver disease: a single-center experience. Gastroenterol Hepatol Bed Bench. 2021 Winter;14(1):44-52. PMID: 33868609; PMCID: PMC8035533.
Effect of vitamin D3 supplementation on hepatic lipid dysregulation associated with autophagy regulatory AMPK/Akt-mTOR signaling in type 2 diabetic mice
Abstract
Vitamin D3 has been reported to protect liver against non-alcoholic fatty liver disease (NAFLD) by attenuating hepatic lipid dysregulation in type 2 diabetes mellitus (T2DM). However, the mechanism of vitamin D3 on hepatic lipid metabolism-associated autophagy in hyperglycemia-induced NAFLD remains yet to be exactly elucidated. C57BL/6J mice were intraperitoneally injected with 30 mg/kg of streptozotocin and fed a high-fat diet for induction of diabetes. All mice were administered with vehicle or vitamin D3 (300 ng/kg or 600 ng/kg) by oral gavage for 12 weeks. Histological demonstrations of the hepatic tissues were obtained by H&E staining and the protein levels related to lipid metabolism and autophagy signaling were analyzed by Western blot. Treatment with vitamin D3 improved insulin resistance, liver damage, and plasma lipid profiles, and decreased hepatic lipid content in the diabetic mice. Moreover, vitamin D3 administration ameliorated hepatic lipid dysregulation by downregulating lipogenesis and upregulating lipid oxidation under diabetic condition. Importantly, vitamin D3 treatment induced autophagy by activating AMP-activated protein kinase (AMPK), inactivating Akt and ultimately blocking mammalian target of rapamycin (mTOR) activation in the T2DM mice. Additionally, vitamin D3 was found to be effective in anti-apoptosis and anti-fibrosis in the liver of diabetic mice. The results suggested that vitamin D3 may ameliorate hepatic lipid dysregulation by activating autophagy regulatory AMPK/Akt-mTOR signaling in T2DM, providing insights into its beneficial effects on NAFLD in type 2 diabetic patients.
Source: Lim H, Lee H, Lim Y. Effect of vitamin D3supplementation on hepatic lipid dysregulation associated with autophagy regulatory AMPK/Akt-mTOR signaling in type 2 diabetic mice. Exp Biol Med (Maywood). 2021 May;246(10):1139-1147. doi: 10.1177/1535370220987524. Epub 2021 Feb 4. PMID: 33541129; PMCID: PMC8142114.
Turmeric (root)
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 Root (Beta vulgaris)
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.
Glycine
Glycine-based treatment ameliorates NAFLD by modulating fatty acid oxidation, glutathione synthesis, and the gut microbiome.
Abstract
Nonalcoholic fatty liver disease (NAFLD) including nonalcoholic steatohepatitis (NASH) has reached epidemic proportions with no pharmacological therapy approved. Lower circulating glycine is consistently reported in patients with NAFLD, but the causes for reduced glycine, its role as a causative factor, and its therapeutic potential remain unclear. We performed transcriptomics in livers from humans and mice with NAFLD and found suppression of glycine biosynthetic genes, primarily alanine-glyoxylate aminotransferase 1 (AGXT1). Genetic (Agxt1 -/- mice) and dietary approaches to limit glycine availability resulted in exacerbated diet-induced hyperlipidemia and steatohepatitis, with suppressed mitochondrial/peroxisomal fatty acid β-oxidation (FAO) and enhanced inflammation as the underlying pathways. We explored glycine-based compounds with dual lipid/glucose-lowering properties as potential therapies for NAFLD and identified a tripeptide (Gly-Gly-L-Leu, DT-109) that improved body composition and lowered circulating glucose, lipids, transaminases, proinflammatory cytokines, and steatohepatitis in mice with established NASH induced by a high-fat, cholesterol, and fructose diet. We applied metagenomics, transcriptomics, and metabolomics to explore the underlying mechanisms. The bacterial genus Clostridium sensu stricto was markedly increased in mice with NASH and decreased after DT-109 treatment. DT-109 induced hepatic FAO pathways, lowered lipotoxicity, and stimulated de novo glutathione synthesis. In turn, inflammatory infiltration and hepatic fibrosis were attenuated via suppression of NF-κB target genes and TGFβ/SMAD signaling. Unlike its effects on the gut microbiome, DT-109 stimulated FAO and glutathione synthesis independent of NASH. In conclusion, impaired glycine metabolism may play a causative role in NAFLD. Glycine-based treatment attenuates experimental NAFLD by stimulating hepatic FAO and glutathione synthesis, thus warranting clinical evaluation.
Source: Rom O, Liu Y, Liu Z, Zhao Y, Wu J, Ghrayeb A, Villacorta L, Fan Y, Chang L, Wang L, Liu C, Yang D, Song J, Rech JC, Guo Y, Wang H, Zhao G, Liang W, Koike Y, Lu H, Koike T, Hayek T, Pennathur S, Xi C, Wen B, Sun D, Garcia-Barrio MT, Aviram M, Gottlieb E, Mor I, Liu W, Zhang J, Chen YE. Glycine-based treatment ameliorates NAFLD by modulating fatty acid oxidation, glutathione synthesis, and the gut microbiome. Sci Transl Med. 2020 Dec 2;12(572):eaaz2841. doi: 10.1126/scitranslmed.aaz2841. PMID: 33268508; PMCID: PMC7982985.
Glycine prevents hepatic fibrosis by preventing the accumulation of collagen in rats with alcoholic liver injury
Abstract
We studied the effect of administering glycine, a non-essential amino acid, on liver collagen content and its characteristics in experimental hepatotoxic Wistar rats. All the rats were fed standard pellet diet. Hepatotoxicity was induced by orally administering ethanol (7.9 g kg(-1)) for 30 days. Control rats were given isocaloric glucose solution. Glycine was administered subsequently at a dose of 0.6 g kg(-1) po every day, along with alcohol for the next 30 days. Alcohol administration significantly elevated the levels of liver hydroxyproline and total collagen content, cross-linked fluorescence, shrinkage temperature and lipid peroxidation, whereas it significantly decreased the solubility of liver collagen as compared with the control rats. Simultaneous glycine supplementation to alcohol-fed rats significantly reduced the levels of liver hydroxyproline and total collagen content, cross-linked fluorescence, shrinkage temperature and lipid peroxidation and enhanced the solubility of liver collagen as compared with the unsupplemented alcohol-fed rats. In conclusion, administration of glycine had a positive influence both on the quantitative and qualitative properties of hepatic collagen in alcoholic liver injury.
Source: Senthilkumar R, Nalini N. Glycine prevents hepatic fibrosis by preventing the accumulation of collagen in rats with alcoholic liver injury. Pol J Pharmacol. 2004 Jan-Feb;56(1):121-8. PMID: 15047986.
Glycine as a therapeutic immuno-nutrient for alcoholic liver disease
Abstract
Activation of Kupffer cells by gut-derived endotoxin is an important factor in ethanol hepatotoxicity. Further, it was shown that ethanol modulates both the expression and activity of several intracellular signaling molecules and transcription factors in Kupffer cells and chronic ethanol treatment enhances Kupffer cell sensitivity to endotoxin. These findings suggest that inhibition of Kupffer cell activation is effective for clinical application in alcoholic hepatitis. Recently, accumulating lines of evidence suggest a possibility that glycine is useful as an immuno-modulating amino acid. It has been shown that a diet containing glycine improved survival in endotoxin shock by preventing Kupffer cell activation. Glycine most likely prevents the LPS-induced elevation of intracellular Ca concentration in Kupffer cells, thereby minimizing LPS receptor signaling and cytokine production. Indeed, glycine prevents alcohol-induced liver injury in a long-term enteral ethanol feeding rats (Tsukamoto-French) by decreasing production of TNF-alpha in the liver. Moreover, glycine is protective against apoptosis of sinusoidal endothelial cells (SECs) that is one of the initial events in the development of liver injury. On the other hand, epidemiologic data have identified chronic alcohol consumption as a significant risk factor for carcinogenesis. Interestingly, glycine inhibits growth of tumor in vivo most likely because of the inhibition of angiogenesis. It was shown that the inhibitory effect of glycine on growth and migration of endothelial cells is due to activation of a glycine-gated Cl channel. It is hypothesized that the opening of this anion channel hyperpolarizes the cell membrane, blocks influx of Ca through voltage-dependent Ca channel, thereby blunting growth factor-mediated signaling. Therefore, glycine can be used not only for treatment of alcoholic hepatitis, but also for chemoprevention and treatment of hepatocellular carcinoma in alcoholic cirrhosis. Taken together, it is concluded that glycine is a potent therapeutic immuno-nutrient for various kinds of chronic liver diseases including alcoholic liver disease (ALD).
Source: Yamashina S, Ikejima K, Enomoto N, Takei Y, Sato N. Glycine as a therapeutic immuno-nutrient for alcoholic liver disease. Alcohol Clin Exp Res. 2005 Nov;29(11 Suppl):162S-5S. doi: 10.1097/01.alc.0000189281.82523.6c. PMID: 16344603.
Dandelion Powder (root)
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.
Milk Thistle Extract (seed)(silymarin)
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).
Artichoke Extract (Cynara scolymus)
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.
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.
Ginger (root)
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.
Organic Alfalfa (leaf)
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: Amraie E, Farsani MK, Sadeghi L, Khan TN, Babadi VY, Adavi Z. The effects of aqueous extract of alfalfa on blood glucose and lipids in alloxan-induced diabetic rats. Interv Med Appl Sci. 2015 Sep;7(3):124-8. doi: 10.1556/1646.7.2015.3.7. Epub 2015 Sep 28. PMID: 26525173; PMCID: PMC4609025.
The Antioxidant Properties of Alfalfa (Medicago sativa L.) and Its Biochemical, Antioxidant, Anti-Inflammatory, and Pathological Effects on Nicotine-Induced Oxidative Stress in the Rat Liver
Abstract
Medicago sativa Linn or alfalfa is a tonic plant rich in proteins, vitamins, and minerals that is used to treat many diseases due to its pharmacological properties such as anti-inflammatory and antioxidant activities. So, the aim of this study was to evaluate the efficacy of alfalfa methanolic extract (AME) on the prevention of liver damage caused by nicotine. The total phenols, flavonoids levels, and the free radical scavenging activity of its extract (IC50) were measured. In this study, 30 Wistar rats were randomly divided into 5 groups as control (untreated), N (nicotine only), T1, T2, and T3 (nicotine + AME 100, 250, and 500 mg/kg/day, respectively). AME (orally) and nicotine (intraperitoneal injection, 0.5 mg/kg/day) were then administered for 21 days. Weight gain, the liver-to-body weight ratio, liver functional enzymes, and the lipid profile were measured. Moreover, we evaluated oxidative stress, proinflammatory parameters, and histopathological changes in the liver. Total phenols, flavonoids, and IC50 were determined as 51.68 ± 0.62 mg GAE/g, 18.55 ± 1.01 mg QE/g, and 350.91 ± 16.46 μg/ml, respectively. Nicotine changed the measured parameters to abnormal. AME increased weight gain, the liver-to-body weight ratio, and enzymatic antioxidant levels and decreased malondialdehyde, liver functional enzymes, and proinflammatory cytokine levels. The lipid profile and histopathological changes have also been improved by AME in a dose-dependent manner. The results showed that AME in a dose-dependent manner by improving the inflammation and oxidative damage could improve the liver damage caused by nicotine.
Source: Raeeszadeh M, Beheshtipour J, Jamali R, Akbari A. The Antioxidant Properties of Alfalfa (Medicago sativa L.) and Its Biochemical, Antioxidant, Anti-Inflammatory, and Pathological Effects on Nicotine-Induced Oxidative Stress in the Rat Liver. Oxid Med Cell Longev. 2022 Mar 26;2022:2691577. doi: 10.1155/2022/2691577. PMID: 35378828; PMCID: PMC8976666.
BioPerine TM (Piperine) & Turmeric (Curcumin)
Curcumin and Piperine Combination for the Treatment of Patients with Non-alcoholic Fatty Liver Disease: A Double-Blind Randomized Placebo-Controlled Trial
Abstract
Background: Experimental and clinical studies have revealed that curcumin may be an effective therapy for non-alcoholic fatty liver disease (NAFLD). Hence, the aim of this study was to assess the effect of curcumin plus piperine administration on NAFLD.
Methods: Adults 18-65 years-old diagnosed with NAFLD by liver sonography were randomly allocated to curcumin (500 mg/day) or placebo groups for 2 months. All participants received both dietary and exercise advice. Anthropometric and biochemical measurements as well as hepatic ultrasound were performed at baseline and final conditions.
Results: Seventy-nine participants were recruited and randomly allocated into the curcumin (n = 39) or placebo (n = 40) groups. There were no significant differences between placebo and curcumin groups for demographic and clinical characteristics and NAFLD grade at baseline. After the treatment period, the curcumin group exhibited lower alkaline phosphatase (-16.2 ± 22.8 versus -6.0 ± 22.5 mg/dL, p = 0.04) concentrations and severity of NAFLD compared with the placebo group (p = 0.04).
Conclusion: Results of this clinical trial suggest that short-term treatment with curcumin plus piperine administration improves NAFLD severity.
Source: Mirhafez SR, Dehabeh M, Hariri M, Farimani AR, Movahedi A, Naderan RD, Jamialahmadi T, Simental-Mendía LE, Sahebkar A. Curcumin and Piperine Combination for the Treatment of Patients with Non-alcoholic Fatty Liver Disease: A Double-Blind Randomized Placebo-Controlled Trial. Adv Exp Med Biol. 2021;1328:11-19. doi: 10.1007/978-3-030-73234-9_2. PMID: 34981468.
An updated meta-analysis of effects of curcumin on metabolic dysfunction-associated fatty liver disease based on available evidence from Iran and Thailand
Abstract
Metabolic dysfunction-associated fatty liver disease (MAFLD) is a common cause of chronic liver disease and can progress to nonalcoholic steatohepatitis and cirrhosis. This study aims to summarize the evidence for the effects of curcumin on MAFLD progression. Studies were identified from Medline and Scopus databases until April 2022. Systematic reviews and meta-analyses (SRMA) and randomized controlled trials (RCT) were selected based on pre-specified criteria. Three reviewers independently extracted data and assessed quality of included studies. Of the 427 identified records, 6 SRMAs and 16 RCTs were included in the analysis. Very high overlap was observed among SRMAs with corrected covered area of 21.9%. From an updated meta-analysis, curcumin demonstrated significant improvement in aspartate and alanine aminotransferase with pooled mean difference [95% confidence interval (CI)] of −3.90 (−5.97, −1.82) and −5.61 (−9.37, −1.85) units/L, respectively. Resolution and improvement of hepatic steatosis was higher in curcumin than control group with pooled relative risk (95% CI) of 3.53 (2.01, 6.22) and 3.41 (1.36, 8.56), respectively. Curcumin supplementation also led to lower fasting blood sugar, body mass index, and total cholesterol. Further trials should be conducted to assess the effect of curcumin on liver histology, especially regarding non-invasive hepatic fibrosis and steatosis.
Source: Lukkunaprasit T, Tansawet A, Boonmanunt S, Sobhonslidsuk A, McKay GJ, Attia J, Thakkinstian A. An updated meta-analysis of effects of curcumin on metabolic dysfunction-associated fatty liver disease based on available evidence from Iran and Thailand. Sci Rep. 2023 Apr 10;13(1):5824. doi: 10.1038/s41598-023-33023-3. PMID: 37037891; PMCID: PMC10086025.
BioPerine TM (Piperine)
Piperine attenuates cardiovascular, liver and metabolic changes in high carbohydrate, high fat-fed rats
Abstract
Black pepper is used worldwide to enhance food flavor. We investigated dietary supplementation with piperine, the active principle of black pepper, to high carbohydrate, high fat (HCHF) diet-fed rats as a model of human metabolic syndrome. Rats were fed with either HCHF diet (carbohydrate, 52%; fat, 24%; 25% fructose in drinking water) or cornstarch (CS) diet for a total of 16 weeks. Diets of the treatment groups (CS + piperine and HCHF + piperine) were supplemented with piperine for the last 8 weeks of this protocol. After 16 weeks, rats fed with HCHF diet developed hypertension, elevated oxidative stress and inflammation-induced cardiac changes (infiltration of inflammatory cells in heart, increase in count and degranulation of mast cells in heart, cardiac fibrosis and increase in ventricular stiffness), reduced responsiveness of aortic rings, impaired glucose tolerance, abdominal obesity together with liver fibrosis, fat deposition and increased plasma liver enzymes. Supplementation with piperine (375 mg/kg food; approximately 30 mg/kg/day) in HCHF-fed rats normalized blood pressure, improved glucose tolerance and reactivity of aortic rings, reduced plasma parameters of oxidative stress and inflammation, attenuated cardiac and hepatic inflammatory cell infiltration and fibrosis and improved liver function. These changes clearly suggest that piperine reduces symptoms of human metabolic syndrome in HCHF-fed rats by reducing inflammation and oxidative stress.
Source: Diwan V, Poudyal H, Brown L. Piperine attenuates cardiovascular, liver and metabolic changes in high carbohydrate, high fat-fed rats. Cell Biochem Biophys. 2013 Nov;67(2):297-304. doi: 10.1007/s12013-011-9306-1. PMID: 22038304.
Inulin
Inulin Improves Diet-Induced Hepatic Steatosis and Increases Intestinal Akkermansia Genus Level
Abstract
Hepatic steatosis is characterized by triglyceride accumulation within hepatocytes in response to a high calorie intake, and it may be related to intestinal microbiota disturbances. The prebiotic inulin is a naturally occurring polysaccharide with a high dietary fiber content. Here, we evaluate the effect of inulin on the intestinal microbiota in a non-alcoholic fatty liver disease model. Mice exposed to a standard rodent diet or a fat-enriched diet, were supplemented or not, with inulin. Liver histology was evaluated with oil red O and H&E staining and the intestinal microbiota was determined in mice fecal samples by 16S rRNA sequencing. Inulin treatment effectively prevents liver steatosis in the fat-enriched diet group. We also observed that inulin re-shaped the intestinal microbiota at the phylum level, were Verrucomicrobia genus significantly increased in the fat-diet group; specifically, we observed that Akkermansia muciniphila increased by 5-fold with inulin supplementation. The family Prevotellaceae was also significantly increased in the fat-diet group. Overall, we propose that inulin supplementation in liver steatosis-affected animals, promotes a remodeling in the intestinal microbiota composition, which might regulate lipid metabolism, thus contributing to tackling liver steatosis.
Source: Escalona-Nández I, Juárez-Hernández E, Chávez-Tapia NC, Uribe M, Barbero-Becerra VJ. Inulin Improves Diet-Induced Hepatic Steatosis and Increases Intestinal Akkermansia Genus Level. Int J Mol Sci. 2022 Jan 17;23(2):991. doi: 10.3390/ijms23020991. PMID: 35055177; PMCID: PMC8782000.
Inulin alleviates inflammation of alcoholic liver disease via SCFAs-inducing suppression of M1 and facilitation of M2 macrophages in mice
Abstract
Background: Alcoholic liver disease (ALD) presents one of the leading causes of cirrhosis worldwide. We have demonstrated that inulin alleviates ALD in mice. However, the exact role of hepatic macrophages in effects of inulin on ALD remains largely unclear.
Methods: In vivo, mice were divided into 4 groups: pair-fed (PF) group (PF/CON), alcohol-fed (AF) group (AF/CON), PF with inulin (INU) group (PF/INU) and AF with INU group (AF/INU). Each group was fed modified Lieber-DeCarli liquid diet with or without alcohol. In vitro, RAW264.7 cell lines were polarized to M1 macrophage (Mψ) or M2 Mψ subsets with lipopolysaccharide (LPS) or interleukin-4 (IL-4) stimulation, respectively. The effects of propionate, butyrate and valeric on macrophage M1/M2 were investigated.
Results: The contents of propionate, butyrate and valeric were significantly increased in AF/INU group compared with that in the AF/CON group. M1 Mψ, inducible nitric oxide synthase (iNOS) and tumor necrosis factor-α (TNF-α) in AF/INU group were significantly lower than those in AF/CON group. In contrast, M2 Mψ, arginase-1 (Arg-1), and interleukin-10 (IL-10) were notably increased in AF/INU group. In vitro, sodium propionate, sodium butyrate and sodium valerate can suppress M1 Mψ and increase M2 Mψ polarization.
Conclusion: In ALD, inulin ameliorates the inflammation via SCFAs-inducing suppression of M1 and facilitation of M2 Mψ, which may potentially contribute to the control of the disease.
Source: Wang Z, Zhang X, Zhu L, Yang X, He F, Wang T, Bao T, Lu H, Wang H, Yang S. Inulin alleviates inflammation of alcoholic liver disease via SCFAs-inducing suppression of M1 and facilitation of M2 macrophages in mice. Int Immunopharmacol. 2020 Jan;78:106062. doi: 10.1016/j.intimp.2019.106062. Epub 2019 Dec 9. PMID: 31830621.
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