Prevention and Treatment of NAFLD with Traditional Chinese Medicine Monomers by Regulating AMPK Pathway： A Review / 中国实验方剂学杂志

Non-alcoholic fatty liver disease （NAFLD） is a chronic liver disease with complex and diverse pathogenesis， and there is no effective treatment or specific drugs for its clinical treatment. In recent years， its incidence has been on the rise， and it has become the earnest expectation of medical researchers in China and abroad that related patients could be treated. AMP-activated protein kinase （AMPK） functions to regulate cellular energy homeostasis and mitochondrial homeostasis. When activated， it has a good intervention effect on NAFLD progression with lipid metabolism disorders and mitochondrial homeostasis disorders. For NAFLD， the activation of AMPK can inhibit the production of new lipogenesis in the liver， promote the oxidation of fatty acids in the liver， and enhance the mitochondrial function of adipose tissues. As a key target of metabolic diseases， AMPK can also improve apoptosis， liver fibrosis， autophagy， and inflammation. Traditional Chinese medicine （TCM） is good at treating diseases from multiple targets and multiple pathways and is also commonly used in the treatment of chronic liver disease in clinical practice. A large number of in vitro and in vivo experimental studies on NAFLD have shown that TCM monomers have good prospects for the treatment of NAFLD through the AMPK signaling pathway， including glycosides， phenols， alkaloids， flavonoids， quinones， terpenoids， and lignans， which are natural activators of AMPK. This study reviewed the research progress on TCM monomers in regulating the AMPK pathway to prevent and treat NAFLD， providing a broader perspective for TCM treatment of NAFLD.

Mechanisms of cholesterol metabolism imbalance in a PA-induced non-alcoholic fatty liver disease cell model / 中国药科大学学报

@#Liver cholesterol metabolism disorder plays an important role in the development of non-alcoholic fatty liver disease (NAFLD).In order to reveal the molecular mechanism of cholesterol homeostasis imbalance induced by saturated fatty acids, HepG2 cells were stimulated with palmitic acid (PA).Lipids accumulation was analyzed by Oil Red O staining, intracellular triglyceride and cholesterol quantification.The level of genes and proteins related to cholesterol homeostasis was measured by RT-qPCR and western blotting.Additionally, intracellular bile acids and mitochondrial oxysterols were detected by LC-MS/MS.The results demonstrated that intracellular lipids such as TG and TC were significantly increased in the model with PA stimulation.Although no significant difference was detected in genes related to cholesterol synthesis and uptake, the protein expression of ABCG5 and LXRα were significantly down-regulated, indicating a decrease in cholesterol efflux.Meanwhile, the gene expression of STARD1 and CYP7B1, which are responsible for bile acid alternative synthesis, were markedly enhanced, along with a significant increase of cholesterol and 27-OHC in mitochondria and CDCA in cells.These results suggested that PA overload may disrupt cholesterol homeostasis by inhibiting cholesterol efflux and promoting bile acids synthesis.

Assessment of chronic kidney disease in patients with non-alcoholic fatty liver disease (NAFLD); A single center experience

Background: Non-alcoholic fatty liver disease (NAFLD) represents a considerable percentage of chronic liver diseases worldwide. The liver is not the only organ affected by NAFLD but also affects other organs such as the cardiovascular system and the kidney. In recent decades, there has been a growing body of evidence linking NAFLD to kidney function. So, the current study aims to assess the percentage of chronic kidney disease (CKD) in NAFLD patients and its link to different stages of hepatic fibrosis. Patients and Methods: A case-control study evaluated 62 non-alcoholic fatty liver disease patients and a control group of 38 volunteers with apparently healthy livers (normal echo pattern by ultrasound). All participants underwent serum creatinine measurement, albumin creatinine ratio in urine, calculation of estimated glomerular filtration rate (eGFR), abdominal ultrasound, and fibroScan examination. Results: The authors showed that the percentage of patients with chronic kidney diseases (patients with GFR less than 60 ml or micro-albuminuria) were significantly higher among NAFLD groups than in healthy controls. There was a significant positive correlation between the albumin creatinine ratio and subcutaneous fat thickness, BMI, and steatosis degrees. The estimated glomerular filtration rate (eGFR) and the age of the patients had a significant negative correlation. In comparison, the eGFR and AST levels had a significant positive correlation. Conclusions: Our results showed that NAFLD substantially raises the risk of getting CKD

Efecto del extracto hidroalcohólico de la planta Lampaya medicinalis Phil. (Verbenaceae) sobre la esteatosis inducida in vitro en hepatocitos humanos / Effect of the hydroalcoholic extract of the plant Lampaya medicinalis Phil. (Verbenaceae) on in vitro-induced steatosis in human hepatocytes

INTRODUCCIÓN: La enfermedad del hígado graso no alcohólico (EHGNA) es la forma más común de enfermedad hepática. A nivel celular se caracteriza por la acumulación de triglicéridos (TG) en forma de gotas lipídicas (GL) dando lugar a esteatosis e inflamación. Entre los factores relevantes para la síntesis de TG se encuentran las enzimas DGAT1/2 que catalizan la etapa final de la síntesis de TG, y la proteína FABP4 que transporta lípidos intracelulares y se expresa en modelos de enfermedad hepática dependiente de obesidad. Por otra parte, TNF-α es una reconocida citoquina involucrada en el proceso inflamatorio en la EHGNA. La medicina popular del norte de Chile ha utilizado la planta Lampaya medicinalis Phil. (Verbenaceae) para el tratamiento de algunas enfermedades inflamatorias. OBJETIVO: Evaluar el efecto de un extracto hidroalcóholico de lampaya (EHL) sobre la esteatosis y expresión de marcadores de inflamación en hepatocitos tratados con ácidos grasos. Diseño experimental: Estudio in vitro en cultivos de la línea celular humana HepG2 tratadas con ácido oleico (AO) y ácido palmítico (AP). MÉTODOS: Se incubó hepatocitos HepG2 con AO/AP por 24 horas en presencia o no de EHL. Se evaluó la presencia de GL y el contenido de TG intracelulares por Oil Red O y Nile Red, respectivamente. La expresión de DGAT1/2, FABP4 y TNF-α fue evaluada por qPCR. RESULTADOS: Los hepatocitos tratados con AO/AP mostraron un aumento en las GL y TG, así como una mayor expresión de DGAT2 en comparación al control. El cotratamiento con EHL revirtió los efectos inducidos por AO/AP. CONCLUSIONES: EHL revierte el incremento en las GL, TG y en la expresión de DGAT2 inducido por AO/AP en células HepG2. Estos hallazgos sugieren un efecto hepatoprotector de la Lampaya contra la esteatosis, y apoyarían su uso complementario en el tratamiento de patologías con componente inflamatorio como la EHGNA.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease. At the cellular level, it is characterized by the accumulation of triglycerides (TG) in the form of lipid droplets (LD), which leads to steatosis and inflammation. Among relevant factors for TG synthesis are the enzymes DGAT1/2 catalyzing the final stage of TG synthesis, and the protein FABP4 which transports intracellular lipids and is expressed in cell models of obesity-dependent liver disease. Additionally, TNF-α is a cytokine involved in the inflammatory process associated to NAFDL. Lampaya medicinalis Phil. (Verbenaceae) is a plant used in folk medicine in northern Chile to treat some inflammatory diseases. OBJECTIVE: To evaluate the effect of the hydroalcoholic extract of lampaya (HEL) on steatosis and the expression of inflammatory markers in hepatocytes treated with fatty acids. Study design: In vitro study in cultures of the human HepG2 cell line treated with oleic acid (OA) and palmitic acid (PA). METHODS: HepG2 hepatocytes were incubated with OA/PA for 24 hours in the presence and absence of HEL. The formation of LD and the accumulation of intracellular TG were assessed by Oil Red O and Nile Red, respectively. The expression of DGAT1/2, FABP4 and TNF-α was assessed by qPCR. RESULTS: The treatment with OA/PA increased the levels of LD and TG as well as the expression of DGAT2 in HepG2 hepatocytes compared to control cells. HEL cotreatment counteracted OA/PA-induced effects. CONCLUSIONS: HEL prevents the increase in LD and TG levels and DGAT2 expression induced by OA/PA in HepG2 cells. These findings suggest that lampaya may have a protective effect against hepatic steatosis, which would support its complementary use in the treatment of pathologies associated with inflammation, such as NAFLD.

Molecular Mechanism Analysis of Jiangtang Xiaozhi Tablets in Treatment of NAFLD / 中国实验方剂学杂志

Objective:To explore the molecular mechanism of Jiangtang Xiaozhi tablets （JTXZT） in the treatment of non-alcoholic fatty liver disease （NAFLD） by means of network pharmacology and molecular docking. Method:With the help of traditional Chinese medicine （TCM） Systems Pharmacology Database and Analysis Platform （TCMSP）， TCMs Integrated Database （TCMID）， Encyclopedia of TCM （ETCM） and Bioinformatics Analysis Tool for Molecular Mechanism of TCM （BATMAN-TCM）， the chemical compositions of medicinal materials in JTXZT were obtained， the compound targets were predicted in SwissTargetPrediction database and STITCH database. The targets of NAFLD were searched by The Human Gene Database （GeneCards）， Online Mendelian Inheritance in Man （OMIM）， Therapeutic Target Database （TTD） and DisGeNET， and intersection analysis was performed with the targets of the active ingredients to obtain the targets of JTXZT for treatment of NAFLD. Based on STRING 11.0 database， the protein-protein interaction （PPI） network of therapeutic targets was constructed， and the enrichment analysis of therapeutic targets was carried out by DAVID 6.8. Finally， the interaction characteristics of key components and core therapeutic targets of JTXZT for treatment of NAFLD were verified based on molecular docking. Result:The key components of JTXZT for treatment of NAFLD were quercetin， luteolin， kaempferol， berberine， isorhamnetin， betulinic acid， oleanolic acid， ursolic acid. formononetin and hexitol， and the core targets of JTXZT for treatment of NAFLD were mitogen-activated protein kinase 1 （MAPK1）， Jun proto-oncogene， activator protein-1 （AP-1） transcription factor subunit （JUN）， MAPK3， protein kinase B1 （AKT1 or Akt1）， tumor protein p53 （TP53）， E1A binding protein p300 （EP300）， Fos proto-oncogene， AP-1 transcription factor subunit （FOS）， tumor necrosis factor （TNF），amyloid beta precursor protein （APP） and cytochrome P450 family 2 subfamily E member 1 （CYP2E1）. Biological function and pathway enrichment analysis showed that JTXZT mainly through xenobiotic metabolic process， oxidation-reduction process， cholesterol metabolic process and other biological processes， regulating phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway， MAPK signaling pathway， NAFLD and insulin signaling pathway to play a role in the treatment of NAFLD. The results of molecular docking showed that the active components of JTXZT had a good affinity with the core targets of JTXZT for the treatment of NAFLD. Conclusion:JTXZT treats NAFLD through multiple active components， multiple key targets and multiple action pathways.

An Exploration on Mechanisms of Treating Different Diseases with Same Method of Qinggan Huayu Granules in Treating NAFLD and Liver Cancer Based on Network Pharmacology / 中国实验方剂学杂志

Objective:To reveal the effective components， targets and possible mechanisms of Qinggan Huayu granules in the treatment of non-alcoholic fatty liver disease （NAFLD） and liver cancer based on network pharmacology and experimental verification， and to provide a basis for its rational interpretation of treating different diseases with same method for NAFLD and liver cancer. Method:Based on databases of traditional Chinese medicine and disease， the network pharmacology was used to screen main active compounds and potential targets of Qinggan Huayu granules for NAFLD and liver cancer. STRING 11.0 was used to analyze the interaction between potential targets. The core targets were selected from the interaction targets by cytoHubba plug-in. The gene ontology （GO） function and the Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were performed on the target by Metascape database. At the same time， <italic>in vitro</italic> experiments were conducted to validate the effect of kaempferol， one of the main active ingredients of Qinggan Huayu granules， on hepatocellular carcinoma cell model and NAFLD cell model. Result:A total of 43 potential targets of Qinggan Huayu granules for for NAFLD and liver cancer were screened， corresponding to 136 active ingredients in 8 herbal medicines. Through enrichment analysis of potential targets， there were 20 biological processes， 13 molecular functions， 9 cellular components and 15 signaling pathways. Qinggan Huayu granules regulated biological behaviors of tumors related to liver cancer and NAFLD （such as apoptosis inhibition and oxidative stress） mainly through kaempferol， quercetin， luteolin and other active ingredients for Caspase-3 （CASP3）， tumor protein p53 （TP53）， vascular endothelial growth factor A （VEGFA） and other hub genes. <italic>In vitro</italic> experiments revealed that kaempferol could inhibit cell proliferation in a dose-dependent manner in hepatocellular carcinoma cell model. And kaempferol could modulate the levels of malondialdehyde （MDA） and glutathione peroxidase （GPx）， which were the molecular markers of oxidative stress of NAFLD cell model. Kaempfero also regulated the expression level of CASP3 in hepatocellular carcinoma cell model and NAFLD cell model. Conclusion:The main mechanism of Qinggan Huayu granules in treating liver cancer and NAFLD with concept of treating different diseases with same method is related to systematic synergy effect of multiple compounds （represented by quercetin， luteolin and kaempferol）， multiple targets （represented by VEGFA， TP53 and CASP3） and multiple signaling pathways （represented by oxidative stress and cell apoptosis）.

Effect of Yinchenhao Tang on Type 2 Diabetes Mellitus Complicated with Non-alcoholic Fatty Liver Disease in MKR Mice / 中国实验方剂学杂志

Objective:To investigate the action mechanism of Yinchenhao Tang against type 2 diabetes mellitus （T2DM） complicated with non-alcoholic fatty liver disease （NAFLD） in MKR mice. Method:Forty eight-week-old MKR mice were fed a high-fat diet for eight weeks and then divided into the model group，original Yinchenhao Tang （17.16 g·kg^-1） group，Yinchenhao Tang group at a specified dose （4.68 g·kg^-1） in teaching materials，and positive drug ［metformin + simvastatin， （65+2.6）×10^-3 g·kg^-1］ group. Another 10 MKR mice of the same age were classified into the blank group and 10 FVB mice into the normal group. After eight weeks of intragastric administration in each group，the liver wet weight，oral glucose tolerance test （OGTT），serum inflammatory factors interleukin-6 （IL-6） and tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>），and changes in blood lipid and liver function were determined. Hematoxylin-eosin （HE） staining was conducted for observing the morphological changes in liver tissue under a transmission electron microscope，followed by the detection of Toll-like receptor 4 （TLR4），myeloid differentiation factor 88 （MyD88），and nuclear transcription factor-<italic>κ</italic>B （NF-<italic>κ</italic>B） protein expression by Western blot. Result:Compared with the model group，the medication groups exhibited significantly reduced liver wet weight index （<italic>P</italic><0.01），improved OGTT result （<italic>P</italic><0.05），and down-regulated serum IL-6 and TNF-<italic>α</italic> levels （<italic>P</italic><0.01）. In terms of morphological changes，Yinchenhao Tang protected the hepatocyte structure and alleviated hepatocyte steatosis. Moreover， Yinchenhao Tang obviously down-regulated the protein expression levels of TLR4，MyD88，and NF-<italic>κ</italic>B in liver tissue of MKR mice with T2DM combined with NAFLD （<italic>P</italic><0.05），and the down-regulation of TLR4 and NF-<italic>κ</italic>B in the original Yinchenhao Tang group was better than that in the Yinchenhao Tang group at a specified dose in teaching materials （<italic>P</italic><0.05）. Conclusion:Yinchenhao Tang is able to reduce inflammatory factor levels and down-regulate TLR4，MyD88，and NF-<italic>κ</italic>B expression in liver tissue to relieve the pathological liver injury and interfere with T2DM combined with NAFLD of MKR mice. It exerts a certain liver-protective effect by lowering the blood lipids and delaying the hepatic inflammation.

Prevalence of Non-Alcoholic Fatty Liver with Gall Stones Disease in Himalayan Population

Non-Alcoholic Fatty Liver Disease (NAFLD) is the hepatic pandemic of the 21st century. It is the amassing of fats in the hepatic tissue without significant alcohol intake that results in hepatic steatosis. Patients with gall bladder stones may have associated NAFLD as these ailments share similar factors like obesity, hypertriglyceridemia and diabetes mellitus. However, few, if any, reports are available about the association of NAFLD with gallstones in the hilly population. Hence, this study was conducted to find out the prevalence of NAFLD in patients with gall bladder stone disease.METHODSThis study was done in the Department of Surgery, Indira Gandhi Medical College, Shimla, from June 2017 to May 2019. A total of 300 patients of ultrasound proven gall bladder stones was studied for NAFLD by Fibroscan (transient elastography). Transient elastography (TE) is a noninvasive method that has been shown to be useful for the detection of liver steatosis and fibrosis. NAFLD was diagnosed based on the value of CAP (Controlled Attenuation Parameter) & degree of fibrosis was assessed based on liver stiffness measurement (LSM) value on TE. Steatosis was graded as S0, S1, S2, and S3 while fibrosis was graded as F0-F1, F1, F2, F3, and cirrhosis. Minimum cut-off CAP value for diagnosing NAFLD was 214 dB/m & significant fibrosis was taken with LSM value >7.5 kPa.RESULTSPatients of gall stone disease showed significant liver steatosis, suggestive of NAFLD in 189 patients (63%), based on CAP value; however, 111 patients (37%) did not have significant steatosis. In patients with NAFLD, 57 (30%) had mild steatosis (s1) while 39 (20.53%) & 24 (12.63%) had moderate (s2) and severe (s3) steatosis respectively. Similarity, 72 (24%) patients had significant fibrosis while 228 (76%) patients had no to insignificant fibrosis on TE, 51 (17%) patients had moderate fibrosis, while 14 (4.5%) and 8 (2.5%) patients had severe fibrosis & cirrhosis respectively.CONCLUSIONSHigh prevalence of NAFLD in patients of gall stone disease was observed. Most of the patients had mild NAFLD i.e. grade S1 steatosis & in addition, fibrosis was present in 24% patients of NAFLD with gall stone disease.

Prescription for NAFLD Based on Relationship Between Intestinal Microecology and Spleen-stomach's Ascending and Descending Theory / 中国实验方剂学杂志

Non-alcoholic fatty liver disease (NAFLD) is a kind of metabolic stress liver injury, which has become one of most common chronic liver diseases in China and even world. Therefore, the occurrence and development of NAFLD and its prevention and treatment have been attracted more and more attention. The disturbance of intestinal microecology, especially intestinal flora, is one of important factors leading to NAFLD. The syndrome traceability, etiology and pathogenesis of nafld in traditional Chinese medicine (TCM) are related to imbalance of spleen-stomach's ascending and descending. The effect of NAFLD treatment depends on spleen-stomach's ascending and descending. The intestinal tract is main part for realizing spleen-stomach function according to principle of TCM. Intestinal flora is a regulation factor affecting host metabolism, which is consistent with biological connotation of TCM principle of spleen-stomach's ascending and descending. Because spleen-stomach's ascending and descending disorder is consistent with symptoms of intestinal flora imbalance, intestinal flora is closely related to spleen-stomach's ascending and descending in TCM. Based on modern intestinal micro-ecosystem, this paper expounds theoretical basis for treatment of NAFLD based on relationship between spleen-stomach's ascending and descending in TCM, and on that basis, ideas of prescription and medication for NAFLD were put forward, mainly including: invigorating spleen and replenishing Qi and ascending clearity, regulating Qi-flowing and regulating stomach and descending turbidity, resolving phlegm, activating blood circulation and dissipating accumulation, and dominant role in coordinating spleen-stomach's ascending and descending and intestinal microecology is highlighted in treatment of NAFLD. Soothing liver and regulating Qi, dispersing and descending lung-Qi, ascending clearity and descending turbidity, and warming and activating kidney-Yang, synergistic factors for onset of NAFLD were taken into account to promote spleen-stomach's ascending and descending functions, and therapeutic effect shall be considered from perspective of intestinal microecology. After retention enema with Chinese herbs, transporting function of large intestine might be activated to help stomach-Qi descending and coordinate spleen-stomach's ascending and descending, and intestinal microecological mechanism of drug delivery channel intervening NAFLD may be studied based on 16s rDNA gene pathway. With deepening of research on intestinal flora, relationship between it and spleen-stomach's ascending and descending and NAFLD will be further revealed, which not only inherits China's long history of applying spleen-stomach's ascending and descending to treat liver diseases, but also expand perspective of regulating intestinal microecolog(intestinal flora) in treatment of NAFLD.

Effect of Betulic Acid on RAGE/NF-κB/iNOS Signaling Pathway Expression in Steatosis Cell / 中国实验方剂学杂志

Objective::To investigate the effect of betulic acid(BA) on steatosis LO2 cells. Method::LO2 cells were intervened with BA at different gradient concentrations (0, 10, 20, 40, 80, 160, 250 μmol·L-1) for 24 hours. methyl thiazolyl tetrazolium(MTT) staining was used to observed cell viability to determine the final concentration of BA. The cells were divided into control, model, dimethylsulfoxide (DMSO) and BA groups, as well as BA groups intervened with low, middle and high concentrations. First, model, DMSO and BA group's cells were cultured in 10% Lipid Mix 1 medium for 24 hours to establish a nonalcoholic fatty liver model. Then, DMSO group and low, medium and high-concentration groups were separately cultured with 0.1%DMSO medium and 20, 40, 80 μmol·L-1 BA medium for 24 hours. And control and model groups were cultured in drug-free medium for 24 hours. Oil red O staining and Nile red staining were used to observe the intracellular lipid droplets. Immunofluorescence was used to detect the protein expression of inducible nitric oxide synthase (iNOS). Western blot was used to detect the protein expression levels of receptor for advanced glycation end-products (RAGE), nuclear factor κB p65 (NF-κB p55) and iNOS. Result::BA within the concentration of 80 μmol·L-1 had no significant toxicity on LO2 cells. Compared with control group, the intracellular lipid droplets were significantly increased in the model group, and the expressions of oxidative stress-related proteins RAGE, NF-κB p65 and iNOS also increased significantly(P<0.05). Compared with model group, the intracellular lipid droplets in DMSO group were similar to those in model group, with no significant difference in the three protein expressions between the two groups. However, the intracellular lipid droplets deposition in the BA group was significantly decreased. And the expressions of RAGE, NF-κB p65 and iNOS proteins in high-concentration BA group were significantly decreased(P<0.05, P<0.01). Conclusion::BA can significantly improve the intracellular fat deposition in LO2 cells, which was probably related to the inhibition of the expressions of oxidative stress-related proteins RAGE, NF-κB p65 and iNOS.

Research status of liver transplantation in the treatment of non-alcoholic fatty liver disease / 器官移植

Liver transplantation is the most effective means to treat the related end-stage liver disease caused by non-alcoholic fatty liver disease (NAFLD). But the recurrence rate of NAFLD after liver transplantation is very high due to the affection of obesity, metabolic syndrome and other adverse factors. In recent years, liver transplantation for NAFLD related end-stage liver disease has made some progress both in China and abroad. This article reviews the research progress of NAFLD and liver transplantation for NAFLD.

Non-alcoholic fatty liver disease in general paediatric population - associated factors and screening by Ultrasonography

Background: Ultrasonography(USG) is an easily available and non-invasive method for screening the general paediatric population for prevalence of non-alcoholic fatty liver disease (NAFLD).Methods: This was a cross-sectional descriptive study conducted in the Paediatric Out Patient Department on 100 randomly selected children of school going age group (5-15 years). A detailed history regarding diet and lifestyle, anthropometric measurements of the children like height, weight , BMI and waist ' hip ratio and blood pressure was correlated with USG of general paediatric population.Results: There were 4 cases of NAFLD of which one case was of normal weight. The study shows that the mean weight of normal population was 33.36 kgs. while the mean weight of children with fatty liver was 56.38 kgs. The mean value of systolic and diastolic blood pressure in normal population is 98.46 mmHg and 57.48 mmHg respectively while in that of children with NAFLD, it was 119.00 mmHg and 78.50 mmHg respectively. Among the dietary factors, increased intake of non-veg food, fast food, soft drinks and decreased intake of eggs and fish food is seen in children with NAFLD. Children with decreased physical activity also showed to have increased NAFLD.Conclusions: As NAFLD is seen even in children with normal weight, all children of general pediatric population can be screened for NAFLD by an easily available and non-invasive method like USG for an early intervention to prevent morbidity associated with NAFLD.

Hepatic Steatosis, its Complication and Correlation with Risk Factor and Management

Liver detoxifies the various metabolic products inside thebody and converts toxic substance to less toxic by differentphases of detoxification reaction. It play broad-spectrumrole (synthetic, storage, metabolic, protective secretary andExcretory). Sedentary life style, Unhygienic food, adulteratedfood, high dose of alcohol, fatty diet adversely affect the normalfunctioning of liver. Fatty Liver Disease refers to a reversiblecondition in which there is accumulation of triglyceride fatinto intra-cytoplasmic Vacuole. If fatty liver is not treatable attime then it goes to various stages (NAFLD, NASH, Fibrosis,Cirrhosis and Hepatocellular Carcinoma). Diet and aerobicexercise plays an important role in management of Liverdisease. The present article focused on fatty liver disease ismanageable at earlier stage by spreading awareness programamong the individual.

Non-alcoholic fatty liver disease associated with hepatocellular carcinoma: An increasing concern

Hepatocellular carcinoma (HCC) is the sixth most common cancer in world and third largest cause of cancer-related deaths. The last few decades have witnessed the emergence of non-viral causes of HCC, the most important being non-alcoholic fatty liver disease (NAFLD). NAFLD ranges from simple steatosis in the absence of excessive alcohol intake to non-alcoholic steatohepatitis (NASH) with or without cirrhosis. About 3-15 per cent of the obese patients with NASH progress to cirrhosis and about 4-27 per cent of NASH with cirrhosis patients transform to HCC. It is also known that HCC can develop de novo in patients with NASH without the presence of cirrhosis. Yearly cumulative incidence of NASH-related HCC is low (2.6%) compared to four per cent of viral-HCC. NAFLD has been associated with risk factors such as metabolic syndrome, insulin resistance, altered gut flora and persistent inflammation. Due to alarming rise in metabolic diseases, both in the developing as well as the developed world, it is expected that the incidence of NAFLD/NASH-HCC would rise manifold in future. No definite guidelines have been drawn for surveillance and management of NAFLD/NASH-associated HCC. It is thus important to discuss the entity of HCC in NAFLD at length with special focus on its epidemiology, risk factors, pathophysiology, diagnosis, clinical presentation and prevention.

Etiology of fatty liver – Cause and effectiveness

Background: The incidence of fatty liver in India is estimated to be around 9-32% with higher incidence in diabetics, obese and dyslipidemic patients. The incidence is increasing with the noninvasive investigation of ultra-sound abdomen and greater awareness of patients opting for Master Health Checkups. Aim of the study: The aim of the study was to analyze the causative factor of fatty liver and their relative incidence in the patients who reported to out-patient clinic with Master Health Checkup details. Materials and Methods: The analysis was performed as an out-patient procedure by scrutinizing the master health checkup results. Interview technique was used to collect information on a predesigned protocol. The patients with ultrasound abdomen report revealing fatty liver were all taken up for the study which included both male and female patients. Results: The main cause for alcoholic fatty liver was consumption of alcohol. There was a positive history of alcohol intake in 43 patients out of 122 patients studied (35%). The remaining percentage comes under Non Alcoholic Fatty Liver Disease (NAFLD) and the various causes include obesity (91%) Dydlipidemia (96%), Diabetes Mellitus (47.5%). Hypothyroidism was present in 3 patients and 5 patients had no other specific risk factors probably belonging to idiopathic group. Conclusions: Males constitute 71% and females 29%, out of 122 patients studied with fatty liver. The causes are alcohol (35%), obesity (91%), dyslipidaemia (96%), diabetes mellitus (47.5%) were found in this study.

Deranged Liver Enzymes in Type 2 Diabetes Mellitus Subjects in a Tertiary Malaysian Hospital

@#Introduction: The prevalence of diabetes mellitus (DM) in Malaysia is drastically increasing. Subjects with DM are more likely to have deranged liver function tests (LFT). This study aimed to determine the prevalence of abnormal liver enzymes [(alanine aminotransferase (ALT) and alkaline phosphatase (ALP)] and its associated factors among type 2 DM (T2DM) subjects visiting a referral diabetic clinic in a tertiary government hospital. Methods: This retrospective, cross-sectional study included electronic data of 300 T2DM subjects ≥18 years old in the outpatient specialist clinic from January 2011 to December 2014. Statistical analysis was performed using SPSS version 22. Results: The study population at large included Malays, of age >60 years with comparable gender percentage. Most subjects had long-standing DM, poor glycaemic control and were on treatment. The prevalence of abnormal ALT and ALP was 27.3% and 13%; with 90.2% and 97.4% having mild ALT and ALP elevations, respectively. Significant associations noted for age, body mass index (BMI) and duration of T2DM for ALT whereas for ALP, anti-diabetic medication was significant between groups of normal and abnormal levels. Deranged liver enzymes were associated significantly with dyslipidaemia. Conclusion: Our study on the crude prevalence of raised liver enzymes may help identify T2DM patients at increased risk of non-alcoholic fatty liver disease (NAFLD). Modification of metabolic risk factors, such as weight loss, control of dyslipidaemia rather than just tighter glycaemic control should be emphasised to reduce morbidity and mortality. Liver enzymes remain a simple and non- invasive marker of liver pathology in daily medical practice

Clinical profile and factors associated with Non-Alcoholic Fatty Liver Disease (NAFLD) among overweight and obese children: A prospective study

@#<p style="text-align: justify;"><strong>INTRODUCTION:</strong> In the past decades, the prevalence of childhood overweight and obesity has increased worldwide. Childhood obesity has been associated with wide range of serious health complications and increased risk of premature adult illnesses. Non-alcoholic Fatty Liver Disease (NAFLD) was of concern because of limited data among children. The study aims to determine the prevalence and demographic /clinical factors associated with NAFLD among overweight and obese children.</p><p style="text-align: justify;"><strong>METHODOLOGY:</strong> The study was a cross-sectional study among overweight and obese participants aged 2-18 years old. A total of 96 subjects were included. Frequencies and percentages of clinical characteristics were determined. Chi-square, linear correlation and logistic regression analysis for different factors were performed.</p><p style="text-align: justify;"><strong>RESULTS:</strong> Among the 92 subjects, 26 (28%) were overweight while 66 (72%) were obese. The M:F ratio was 1.8:1 and majority belonged to 6-10 years old (44%). As to socioeconomic class, the rity (59%) were from the low-income group. The overall prevalence of NAFLD among overweight and obese subjects was 29.3%. None of the clinical factors (age, gender, socioeconomic status, BMI, waist circumference, actual caloric intake, and dietary fat consumption) were significantly associated with NAFLD. Analysis of biochemical factors revealed that alanine aminotransferase, aspartate aminotransferase, serum triglycerides and total cholesterol were found to be associated with NAFLD. Among which AST and ALT were identified predictors of NAFLD.</p><p style="text-align: justify;"><strong>CONCLUSION:</strong> There was high prevalence of NAFLD among overweight and obese children. Screening among the pediatric population may aid on early identification and prevent its progression. ALT, AST, serum triglycerides and total cholesterol were independently related wih NAFLD. AST and ALT were identified predictors of NAFLD.</p>

Action mechanism of Jiangzhi Ligan Decoction in treatment of non-alcoholic fatty liver disease based on network pharmacology / 中草药

Objective: To characterize the “multi-components, multi-targets, and multi-pathways” mechanism of Jiangzhi Ligan Decoction on non-alcoholic fatty liver disease (NAFLD) using network pharmacology technology. Methods: Data regarding natural molecules of Jiangzhi Ligan Decoction, targets of NAFLD, and interactions between natural molecules and NAFLD targets were screened. Network pharmacology of the interactions between natural molecules and NAFLD targets were established using Cytoscape software. The biological process and the signaling pathway of the putative targets were analyzed using ClueGO. Results: The network analysis indicated that 82 active ingredients and 53 NAFLD related targets were screened in Jiangzhi Ligan Decoction, which was involved in regulation of insulin resistance, oxidative stress, inflammation, PI3K/Akt signaling pathway, inflammasome signaling pathway, IL-10 signaling pathway, and T cell signaling pathway. Conclusion: This study provides an important basis for further study on the pharmacological mechanism of Jiangzhi Ligan Decoction in the treatment of non-alcoholic fatty liver disease.

Effect of gentiopicroside on AMPKα signaling pathway of rats with non-alcoholic fatty liver disease / 中草药

Objective To investigate the therapeutic effect of gentiopicroside has a on rats with non-alcoholic fatty liver disease (NAFLD) induced by high-fat and high-sucrose diet, and explore its mechanism. Methods After 10 d adaptive feeding, 60 male SD rats were randomly divided into the normal group, model group, gentiopicroside low, medium, high dose treatment groups, and positive drug polyeno phosphoryl choline (PPC) intervention group. Except for the normal group, the rats in other groups were received a high fat and glucose diet for 12 weeks to establish NAFLD model; After model successfully established, gentiopicroside low, medium, and high dosetreatment groups were given 50, 100, and 200 mg/(kg•d) gentiopicroside, PPC group was ig given 23 mg/(kg•d) PPC, and 500 μL/(kg•d) saline was given to the normal and model groups. After treated for eight weeks, the rats were sacrificed, and the serum was collected from rats to detect the liver function, blood lipid, serum oxidation, antioxidant capacity, and inflammatory factors. HE staining was used to observe pathological changes of liver. In addition, western blotting and qRT-PCR were used to detect the expression of AMPKα and p-AMPKα. Results HE staining showed that the size of liver cells in the normal group was uniform and the nuclei were evenly distributed, there were obvious vacuoles and a certain inflammatory reaction in the model group. Compared with the model group, gentiopicroside treatment group and PPC group (especially the gentiopicroside middle and high dose group) had a significant improvement, but there were still some differences compared with the normal group; Compared with the normal group, the AST, ALT, HDL-C, LDL-C, MDA, IL-1, and IL-6 in the model group were significantly increased (P 0.05); The results of Western blotting and qRT-PCR showed that compared with the normal group, the expression of p-AMPKα protein and AMPKα mRNA in the model group was significantly decreased (P<0.05). After gentiopicroside and PPC administration, they were significantly increased (P<0.05), and gentiopicroside groups showed a significant dose-dependent manner, and the middle dose and high dose of gentiopicroside groups were better than the PPC group (P<0.05), while the expression of AMPKα protein has no significant difference in each group (P<0.05). Conclusion The NAFLD rats showed a obvious hepatic fat infiltration and dyslipidemia, the liver function index and inflammatory factors levels were elevated, and the anti-oxidant capacity was decreased. Gentiopicroside significantly improved above symptoms, which may be associated with the increased expression of p-AMPKα in liver tissue of NAFLD rats by gentiopicroside.

Ethanol extract of Allium fistulosum inhibits development of non-alcoholic fatty liver disease

BACKGROUND/OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease and is closely associated with metabolic syndrome. In the present study, we observed the effect of ethanol extract of Allium fistulosum (EAF) on NAFLD and have suggested the possibility of using EAF as a natural product for application in the development of a treatment for NAFLD. MATERIALS/METHODS: The preventive effect on hepatic lipid accumulation was estimated by using an oleic acid (OA)-induced NAFLD model in vitro and a Western diet (high-fat high-sucrose; WD)-induced obese mouse model. Animals were divided into three groups (n = 7): normal diet group (ND), WD group, and WD plus 1% EAF group. RESULTS: EAF reduced OA-stimulated lipid accumulation in HepG2 cells in the absence of cellular cytotoxicity and significantly blocked transcriptional activation of sterol regulatory element-binding protein 1 and fatty acid synthase genes. Subsequently, we investigated these effects in vivo in mice fed either ND or WD in the presence or absence of EAF supplementation. In comparison to the ND controls, the WD-fed mice exhibited increases in body weight, liver weight, epididymal fat weight, and accumulation of fat in hepatocytes, and these effects were significantly attenuated by EAF supplementation. CONCLUSIONS: Allium fistulosum attenuates the development of NAFLD, and EAF elicits anti-lipogenic activity in liver. Therefore, EAF represents a promising candidate for use in the development of novel therapeutic drugs or drug combinations for the prevention and treatment of NAFLD.