Monday, May 13, 2019

Non Alcoholic Fatty Liver Disease (NAFLD) Treatment In Healthy Food Perspective

Nonalcoholic fatty liver disease (NAFLD) is a chronic condition caused by fat accumulated in the liver over time, in the absence of excessive alcohol use. The disease can be classified into the types of non-inflammatory fatty liver (NAFl) and inflammatory nonalcoholic steatohepatitis (NASH)(1).

Nonalcoholic fatty liver disease (NAFLD) is one of the major causes of cirrhosis and liver cancer.

According to world statistics, nonalcoholic fatty liver disease (NAFLD) is normally known as a disease of the Western world(2). However, due to the economic prosperity of Southeast Asian(3), the disease also was found in a large number of population in the cities, causing concerns of many scientists in the region(4)(6).

According to the joint assessment of the prevalence of non-alcoholic fatty liver disease and risk factors for advanced fibrosis and mortality in the US, led by the Stanford University School of Medicine, "The prevalence of NAFLD in the United States (U.S.) has risen from 18% in 1988–1991 to 31% in 2011–2012. Estimates of NAFLD prevalence for adults in Western countries is 20–30%, with much higher prevalence in adults with obesity (80–90%), diabetes (30–50%), and hyperlipidemia (90%)"(5).

Among the more affluent regions of China, the prevalence rate of non-alcoholic fatty liver disease (NAFLD) is approximately 15%(6). The number may decrease substantially if the poor rural populations where obesity is non-existence are also taking into account(7).

The exact causes of NAFLD aren't well understood. Some researchers suggested that certain risk factors such as long-term use of certain medications(8), genetic preposition(8), insulin resistance(8), high cholesterol(8) and triglycerides(8) in the blood, polycystic ovary syndrome(8), metabolic syndrome(8), obesity(8), and type 2 diabetes(8) are associated with the onset of the disease.

Recent studies also found that people with obstructive sleep apnea(11), underactive thyroid (hypothyroidism(10) and underactive pituitary gland (hypopituitarism) (9) also at an increased risk of the NALFD.

Some researchers suggested that unhealthy diet such as high-fat diet may also have a strong implication on NAFLD(12)(13).


Dr. Jensen VS, the lead scientist in the study high-fat diet-induced non-alcoholic fatty liver disease, wrote, "In humans and animal models, excessive intake of dietary fat, fructose, and cholesterol has been linked to the development of non-alcoholic fatty liver disease (NAFLD)"(13).

And, " Only HFr-fed rats developed dyslipidemia as characterized by higher levels of plasma triglycerides compared to all other groups (p < 0.0001). Hepatic dysfunction and inflammation was confirmed in HFD-fed rats by elevated levels of hepatic MCP-1 (p < 0.0001), TNF-alpha (p < 0.001) and plasma β-hydroxybutyrate (p < 0.0001), and in NASH-fed rats by elevated levels of hepatic MCP-1 (p < 0.01), increased hepatic macrophage infiltration (p < 0.001), and higher plasma levels of alanine aminotransferase (p < 0.0001) aspartate aminotransferase (p < 0.05), haptoglobin (p < 0.001) and TIMP-1 (p < 0.01) compared to Control"(13).

According to the statistics, in the US, over 100 million people have non-alcoholic fatty liver disease and the condition is more double over the past 20 years(14). The disease also is the most prevalent liver disease in children(14).

The prevalence rate of NAFLD is varied among different ethnic groups in the US. Dr. Rich NE, the lead scientist in the investigation of the ethnicity and NAFLD, wrote, "NAFLD prevalence was highest in Hispanics, intermediate in Whites, and lowest in Blacks, although differences between groups were smaller in high-risk cohorts (range 47.6%-55.5%) than population-based cohorts (range, 13.0%-22.9%)(15)".

And, "Among patients with NAFLD, the risk of NASH was higher in Hispanics (relative risk, 1.09; 95% CI, 0.98-1.21) and lower in Blacks (relative risk, 0.72; 95% CI, 0.60-0.87) than Whites"(15).

The progression of NAFLD and NASH led to cirrhosis, the late stage of liver scarring are well defined, as the liver tries to heal itself by halting inflammation(16), leading to symptoms of ascites(16)(18), swell esophageal varices(16)(19), hepatic encephalopathy(16)(17) and complications of liver cancer(16)(17) and liver failure(16)(17).

Most people at the early stage NAFLD are asymptomatic, however, as the disease progression into the later stage, most patients experience symptoms of right upper abdominal discomfort(20), fatigue(20), and/or malaise(20), and jaundice(20) with yellowing of the skin and eyes(20).

Most patients with NAFLD have elevated levels of liver enzymes gamma-glutamyl transferase (GGT)(21) and/or Aspartate Aminotransferase (AST)(21) to platelet ratio index (APRI) score(21), and/or Alanine Aminotransferase (ALT) (21) which are the markers used to predict the severity of liver disease including the fatty liver. A blood test is required if you suspected to have developing nonfatty liver disease.

Conventionally, as of today, there is no effective treatment of NAFLD(22)(23). Weight loss for overweight and obese patients(22) has been recommended through our the industry accompanied by the change of lifestyles(22) such as moderate exercise and reduced intake of alcohol, depending on individuals.

Patients who are hepatitis virus B and C carriers are also recommended to be vaccinated(22).

Given the nature of the nonalcoholic fatty liver disease, the search for effective treatment for NAFLD from the natural sources used over thousands of years in traditional medicine for the treatment of liver disease has been intensified(23). Many secondary metabolites, whole foods, and herbal medicine have been found to be effective in vivo, vitro and small human trials(24). However, most of them were stopped due to a simple reason. Who will spend billions to prove the thing which has no commercial values? Secondary metabolites, whole foods, and herbal medicine cannot be patented.

C. Healthy foods
Eating a healthy diet with a high in vegetables and fruits knowledged by health experts is the best way to prevent diseases including non-alcoholic fatty liver disease, particularly in older adults.

1. Olea europaea (Olive)
Olive Its fruit, is also called the olive and the source of olive oil. Olea europaea L is a small tree, belonging to the family Oleaceae, native to the coastal areas of the eastern Mediterranean Basin and south end of the Caspian Sea(98).

In the evaluation of oxidative stress induced non-alcoholic steatohepatitis (NASH) on hypertensive/NIH-corpulent rats fed a diet of AIN-93G with or without olive leaf extract (500, 1000, 2000 mg/kg diet, and control; 5 rats each) for 23 weeks, oleuropein, the active constituent of olive leaf, exhibited antioxidative stress(99) by enhancing the levels of antioxidant(99) against hepatic fat accumulation(99) in a rat model of NASH.

In other words, a diet of AIN-93G containing more than 1000 mg/kg olive leaf extract had a preventive effect on the occurrence of NASH(99) by improving the levels of thioredoxin-1 expression(99) and decreasing the levels of 4-hydroxynonenal expression(99) associated with hepatic lipid peroxidation(99) in rat with NASH.

Where overexpression of thioredoxin-1 expression is a marker of liver disease.

Based on the findings, researchers said, "olive leaf extract may help prevent NASH,... through its anti-oxidative activity.".


Also, in rats fed a cholesterol-rich diet for 16 weeks, administration of polyphenol-rich olive leaf extracts significantly lowered total cholesterol (TC)(100), triglycerides (TG)(100) and low-density lipoprotein cholesterol (LDL-C)(100) and increased the serum level of high-density lipoprotein cholesterol (HDL-C)(100).

Furthermore, administration of polyphenol-rich olive leaf extracts was found to lower the levels of thiobarbituric acid reactive substances (TBARS)(100), a byproduct of lipid peroxidation upon the injection of in liver, heart, kidneys, and aorta significantly.

Moreover, the also extracts also increased the serum antioxidant potential(100) and the hepatic CAT(100) and SOD activities(100).

Collectively, polyphenol-rich olive leaf extracts protected the liver against the onset of NASH(100) by inhibiting parameters(100) involved in the production of oxidative stress(100).


2. Punica granatum L. (Pomegranate)
Pomegranates is a fruit-bearing small tree, genus Punica, belonging to family Lythraceae, native to Iran but has been cultivated in Asian since ancient time. Pomegranate flower (PGF) has been used in traditional medicine for the treatment of hyperlipidemia, insulin resistance, and diabetes(101).

In glucose-fed hyperglycaemic and alloxan-induced diabetic rats, oral administration of its aqueous-ethanolic (50%, v/v)extracts of pomegranate led to significant lowering the blood glucose(101)with a maximum dose up to 400 mg/kg, b.w.

On on streptozotocin (STZ) induced diabetic rats, Punica granatum aqueous extract (PgAq) restored parameters of diabetes(103) including blood glucose level(103), total cholesterol (TC)(103), triglycerides (TG)(103), low-density lipoprotein cholesterol (LDL-C)(103), very low density lipoprotein (VLDL)(103), and improved antioxidant profiles(103) including glutathione-S-transferase (GST)(103), superoxide dismutase (SOD)(103) and catalase (CAT)(103).

Additionally, the extract also elevated the levels of HDL-C(103), compared to the diabetic control group.

In other words, Punica granatum aqueous extract (PgAq) processed anti-chronic diseases including NASH associated with atherogenic lipoprotein profile(103), aggravated antioxidant status(103), and impaired glucose metabolism(103).


3. Zingiber officinale (Ginger)
Ginger (Zingiber officinale) or ginger root is the genus Zingiber, belonging to the family Zingiberaceae, native to Tamil, used in traditional and Chinese medicine to treat dyspepsia, gastroparesis, constipation, edema, difficult urination, and colitis(104).


On streptozotocin (STZ)-induced type I diabetic rats, oral administration of juice of Z. officinale (4 ml kg-1, p.o. daily) for 6 weeks showed a significant increase in insulin levels(105) and a decrease in fasting glucose levels(105).


Treatment with Z. officinale also decreased serum cholesterol(105), serum triglyceride(105) and blood pressure(105) in diabetic rats.


Based on the findings, researchers said, " (The) potential antidiabetic activity of the juice of Z. officinale in type I diabetic rats, possibly involving 5-HT receptors".

In vitro, Zingiber officinale Roscoe was found to reduce the elevation of rat plasma triacylglycerol(106) levels 1 and 2 h involved in hydrolysis(106) after oral administration of a lipid emulsion containing corn oil by interfering the intestinal absorption of dietary fat.

In vivo, mice fed the high-fat diet containing 3% aqueous extract of Z. officinale Roscoe compared to controls fed the high-fat diet significantly reduced final parametrial adipose tissue weights(106) associated with fat metabolism(106).

4. Green tea
Green tea contains more amount of antioxidants than any drinks or food with the same volume, and is the leaves of Camellia sinensis, undergone minimal oxidation during processing, originated from China(107).

In male ZF rats fed a high-fat diet (HFD) for 2 wk then treated with GTP (200 mg/kg) or saline (5 mL/kg) for 8 wk, GTP intervention showed a decreased weight gain(108) and a significantly lowered visceral fat(108).

GTP treatment not only significantly reduced fasting serum insulin(108), glucose(108), and lipids levels(108), but also attenuated the levels of pro-inflammatory cytokines(108) in rats fed a high-fat diet (HFD) by regulating the pathways associated with fat metabolism(108).

Furthermore, GTP treated rats also was found with hepatic lipogenesis(108) and triglycerides outflux(108) from the liver, compared to controls.

SlimTrym®, a formulated product composed of citrus polymethoxyflavones (PMFs), green tea extract, and lychee extract administrated in male C57BL/6 mice fed a normal diet (ND), high fat diet (HFD) or HFD containing 0.1% or 0.5% SlimTrym® for 16 weeks, significantly reduced weight gain(109) and relative perigonadal(109), retroperitoneal(109), mesenteric fat weight(109) as well as the size of the adipocyte(109).

Moreover, SlimTrym® supplementation also effectively inhibited the hepatic steatosis(109) and the elevated serum levels of enzymes(109) associated with liver injury or damage, such as glutamate oxaloacetate transaminase (GOT)(109), glutamate pyruvate transaminase (GPT)(109).

Observation of the adipose tissue and liver after injection of SlimTrym®, researchers found that the formula also SlimTrym® exerted its anti-NASH(109) and obesity(109) effect by inhibiting the receptors(109) involved in lipogenesis(109) and lipid accumulation(109).

5. Wolfberry
Wolfberry is the fruit of plant Lycium barbarum of the family Solanaceae, used as a famous drug or supplement by traditional Chinese medicine for the treatment of liver and eyes problems(110).

In C57BL/6N mice by feeding with MCD diet for 6 weeks, accompanied by the 1 mg/kg Lycium barbarum polysaccharides (LBP) intragastrically fed on a daily basis with or without MCD diet lasting from the 4th to 6th week, LBP, a major bioactive constituents of wolfberry attenuated the hepatic injury(111) in a non-alcoholic steatohepatitis (NASH)(111) induced by methionine-choline-deficient (MCD)(111) in mouse model.

Additonally, LBP normalized the increased serum ALT(111) and AST levels(111), hepatic oxidative stress(111), fibrosis(111), inflammation(111), and apoptosis(111) in a mouse model fed with MCD diet.

Furthermore, LBP injection also attenuated the overexpression of proteins(111) in facilitating the production of pro-inflammatory cytokines(111) involved in lipid peroxidation(111).

Based on the findings, researchers suggested that the reduction of hepatic injury during the progression of NASH by therapeutic LBP treatment is attributed to the inhibition of proteins and protein receptor associated with proinflammation and inflammatory diseases(111), respectively.

Moreover, on a high‑fat diet (HFD)-induced NAFLD mice model and C57BL/6 mice fed a normal control diet, high‑fat diet (HFD), HFD supplemented with 2 g/kg LRE, or HFD supplemented with 5 g/kg LRE, treatment with LRE markedly decreased the levels of triglycerides(112), total cholesterol(112), aspartate aminotransferase(112) and alanine aminotransferase(112) in the serum of mice fed an HFD, and improved glucose metabolism(112) and insulin sensitivity(112) in NAFLD mice.

Also, treatment with LRE significantly decreased the expression level of proteins(112) involved in the transcriptional regulation of lipid metabolism(112), energy balance(112), and inflammation(112) in the liver tissues through enhancing the hepatic AMPK pathway(112) in preventing liver lipid accumulation and insulin resistance.

6. Garlic
Garlic, or Allium sativum, is a species in the onion genus Allium, native in Asia, Egypt, and the Mediterranean regions, used popularly in traditional and Chinese medicine in treating common cold and flu to the Plague, blood pressure cholesterol levels, natural antibiotic(113).

According to the study by the Huazhong University of Science and Technology, a traditional Chinese medicine formula including resveratrol, Lycium barbarum polysaccharides, dioscin, bergamot polyphenol fraction, capsaicin, and garlic-derived S-allylmercaptocysteine, garlic-derived S-allylmercaptocysteine, inhibit the progression of NAFLD(114) by exhibiting the liver autophagy/lipophagy(114).

In other words, the formula protected the liver against the onset of NAFLD by inhibiting insulin resistance(114), dysfunctional lipid metabolism(114), endoplasmic reticulum stress(114), oxidative stress(114), inflammation(114), and apoptosis/necrosis(114).

Furthermore, in a clinical trial including 110 subjects with NAFLD were randomly assigned to the intervention or the control group. The intervention group received two garlic tablets (containing 400 mg of garlic powder) daily while the control group received placebo tablets, 400 mg of garlic powder showed a significantly greater reduction in body weight(116) and fat mass(116) compared to controls.


7. Uncontaminated fish oil
Uncontaminated fish oil is derived from the tissues of oily fish, excluding fish which are contaminated and at the top of the food chain(117).

Fish do not actually produce omega-3 fatty acids, but instead, accumulate them from consuming microalgae that produce these fatty acids.

Compared to the 10 male Sprague-Dawley rats fed a control diet (CON), a Western-style high-fat and high-cholesterol diet (WD), or a WD diet containing fish oil (FOH) for 16 weeks respectively, researchers found that fish oil significantly ameliorated WD-induced dyslipidemia(118), transaminase elevation(118), hepatic steatosis(118), inflammatory infiltration(118), and fibrosis(118) induced by the Western diet by correcting the expression levels of genes(118) involved in fatty acid and cholesterol metabolism(118).


Additionally, fish oil also inhibited the expression levels of pro-inflammation genes(118) such as Mcp1, Socs2, Sema4a, and Cd44(118) compared to the WD group.


Collectively, researchers said, " fish oil protects against WD-induced NALFD via improving lipid metabolism and ameliorating hepatic inflammation".

In male Sprague-Dawley rats fed with a lab chow (CON), high-fat high-cholesterol diet (WD), or WD supplemented with fish oil (FOH), respectively, fish oil modification of hepatic lipid metabolism(119) and signaling transduction(119) through the alternation of hepatic miRNAs(119) including rno-miR-29c-3p, rno-miR-30d-5p, rno-miR-33-5p, rno-miR-34a, and rno-miR-328a-3p, compared to differentially expressed miRNAs (DEMs) between FOH and WD groups.

By compared to different expression of miRNAs (DEMs) between FOH and WD groups, researchers said, (The result) reveals that fish oil supplementation alters hepatic expression of miRNAs, which may contribute to fish oil amelioration of NAFLD in rats".


8. Flax seeds
The seeds of the flax plant (Linum usitatissimum) contained both omega-3 and omega-6 fatty acids.
Its oil used as a supplement generally contains 50% of the omega-3 fatty acid - alpha-linolenic acid and 25 % of the omega-6 fatty acid linolenic acid, 15 % of mainly monounsaturated oleic acid and trace amounts of palmitoleic acid and eicosenoic acid(120).


In the aged laying-hens-a novel and more physiologically relevant model of human disease induced NAFLD, supplemented with whole flaxseed (WFX) reduced steatosis(121) and hepatocellular ballooning(121).

Furthermore, the serum AST(121) associated with liver injury or damage(121) also was reduced in hens provided WFX and defatted flaxseed meal (DFM).

Compared to other group fed with fas seeds, FXO supplementation showed a greater effect in the modification of transcript abundance of genes(121) linked to NAFLD.

Based on the findings, researchers said, "These findings demonstrate the potential use of whole flaxseed for the treatment and prevention of NAFLD in humans".

In a two-arm randomized open labeled controlled clinical trial was conducted on 50 patients with non-alcoholic fatty liver disease (NAFLD), assigned to take either a lifestyle modification (LM) or LM +30 g/day brown milled flaxseed for 12 weeks, researchers found that at the end of the study,
flaxseed supplementation exhibited a significantly greater reduction on body weight(122), liver enzymes(122), insulin resistance(122), and hepatic fibrosis(122) and steatosis(122) compared to LM group.

Flaxseed supplementation also reduced the levels of hepatic markers(122) compared to the control group.

Researchers wrote in the final report, "flaxseed supplementation plus lifestyle modification is more effective than lifestyle modification alone for NAFLD management".

9. Coffee
Coffee, a popular and social beverage all over the world, particularly in the West, is a drink made from roast bean from the Coffea plant, native to tropical Africa and Madagascar. Chlorogenic acids (CGA) are the most abundant phenolic compounds in green coffee beans and in the human diet and have been suggested to mitigate several cardiometabolic risk factors(123).

In ApoE-/- mice fed an atherogenic diet without (vehicle) or with water-based standardized green coffee extract (GCE) by gavage (equivalent to 220 mg/kg of CGA) for 14 weeks, GCE showed to improve metabolic parameters(124), including fasting glucose(124), insulin resistance(124), serum leptin(124), urinary catecholamines(124), and liver triglycerides(124), without affecting the atherosclerotic lesion progression(124) or plasma lipid levels(124).

GCE also reduced weight gain(124), decreased adiposity(124), lower inflammatory infiltration(124) in adipose tissue(124), and protection against liver damage(124) and induced the shifts in favor of good gut microbiota(124), compared to vehicle group.

The levels of liver pro-inflammation cytokines(124) also were decreased by the injection of GCE.

In a study of patients with metabolic syndrome (Mets) randomly allocated to consume 400 mg GCE or placebo capsules twice per d for 8 weeks with both groups were advised to follow an energy-balanced diet, injection of GCE supplementation, significantly reduced systolic blood pressure (SBP)(125) compared with the placebo group.

Furthermore, the GCE treatment group showed a significantly reduced fasting blood glucose (FBS)(125), waist circumference(125) and insulin resistance(125) in comparison to placebo.

Based on the findings, researchers said, "GCE administration had an ameliorating effect on some of the Mets components such as high SBP, high FBS, and Mets (metabolic syndrome) main aetiological factors including insulin resistance and abdominal obesity.

10. Broccoli
Broccoli is a mustard/cabbage plant, belonging to the family Brassicaceae. The vegetable has large flower heads, usually green in color and the mass of flower heads surrounded by leaves and evolved from a wild cabbage plant on the continent of Europe(126).


On adult 5-wk-old male B6C3F1 mice received a control diet (AIN-93M) or a Western diet (high in lard and sucrose, 19% and 31%, wt:wt, respectively), with or without freeze-dried broccoli (10%, wt:wt), mice group treated with broccoli exhibited lower hepatic triglycerides(127) and NAFLD scores(127).


Additionally compared to the control group, mice group treated with broccoli decreased liver injured or damaged markers(127) and protected against liver inflammation(127) and slowed the initiation and progression of a hepatic neoplasm(127).

In the sum up, researchers said, "Long-term consumption of whole broccoli countered both NAFLD development enhanced by a Western diet and hepatic tumorigenesis induced by DEN in male B6C3F1 mice".


In mice exposed to the hepatocarcinogen diethylnitrosamine (DEN), Sulforaphane from broccoli exerted significant liver protection against NAFLD and liver cancer.

In male 15-day-old C57BL/6J mice were given DEN and placed on a Western or Western+10%Broccoli diet from the age of 4 weeks through 7 months, researchers at the end of the experiment showed that dietary broccoli decreased hepatic triacylglycerols(128), NAFLD(128), liver damage(128) and tumor necrosis factor(128) by month 5 without changing body weight(128) or relative liver weight(128), and slowing down the carcinogenesis(128), seen in 100% of mice.

In other words, broccoli, a good source of sulforaphane, is a good candidate to slow the progression of hepatic lipidosis(128).


11. Walnuts
Walnut tree is one of the Genus plants belonging to the family Juglandaceae about 30–130 ft cultivated for its nut and kernel and for the commercial purpose all over the world(129).

On male C57BL/6J mice fed a rodent chow or HFD (45% energy-derived)±walnuts (21.5% energy-derived) for 6 weeks, before injection of walnut, mice fed with HFD showed a significantly elevated fat accumulation(130).

Mice fed a rodent chow or HFD (45% energy-derived)±walnuts (21.5% energy-derived) compared to HFD group prevented HFD-mediated alteration of the levels of key proteins involved in lipid homeostasis(130) in the induction lipid accumulation in the liver(130).


Furthermore, walnut protected the liver against the overexpression of pathways in elevated oxidative stress-induced lipid peroxidation(130) as well as the proteins associated with programming liver cells apoptosis(130) caused by HFD.

Researchers based on the findings wrote, "The beneficial effects of dietary walnut likely result, at least partially, from its antioxidant ingredients and attenuating HFD-induced hepatic steatosis, nitroxidative stress and apoptosis".

Also, on male C57BL/6J mice fed either a regular rodent chow or HFD (45% energy-derived) with or without walnuts (21.5% energy-derived) for 20weeks.dietary walnuts significantly decreased the amounts of hepatic triglyceride (TG)(131)compared to HFD-fed mice.

Similar to the aforementioned results, additional walnuts significantly altered the levels of proteins(131), involved in the hepatic lipid homeostasis(131).

Moreover, in the examined the adipose tissues isolated from mice fed the HFD+walnut diets, researchers found that walnut significantly decreases levels of proinflammatory cytokines(131) compared to those significantly elevated in mice fed HFD alone without affecting the significantly alter HFD-induced peripheral glucose intolerance(131) or insulin resistance(131).

Researchers wrote in the final report, "the protective effects of walnuts against HFD-induced hepatic TG accumulation in mice are mediated, at least partially, by modulating the key proteins in hepatic lipid homeostasis and suppression of the genes related to adipose tissue inflammation and macrophage infiltration as well as prevention of adipocyte apoptosis".

12 Avocado
Avocados are a commercially valuable fruit and are cultivated in tropical climates throughout the world, it is a green-skinned, pear-shaped fruit that ripens after harvesting and native to the Caribbean, Mexico, South America, and Central America, belonging to the flowering plant family Lauraceae(132).


On male Sprague-Dawley rats fed high-cholesterol diet for four weeks to induce hypercholesterolemia, followed by the VAO (450 and 900 mg·kg-1 ·day-1 ) and simvastatin (10 mg·kg-1 ·day-1) given orally while maintaining the high-cholesterol diet for another four weeks, according to the assessment of urinary metabolomics using NMR, oral administration of VAO partially recover the metabolism dysfunction(133)) induced by hypercholesterolemia mainly via lipid, energy(133), amino acid(133), and gut microbiota(133) metabolism.

On Streptozocin-induced diabetic mice, before treatment of avocado oil, a rich source of C18, diabetic mice elicited a noticeable increase in the content of docosahexaenoic acid (DHA)(134) found in the mitochondrial peroxidizability index(134) and higher levels of lipid peroxidation(134).


Furthermore, Mitochondrial respiration(134) and activity were impaired in diabetic rats with a significant increase in reactive oxygen species (ROS) generation(134).


Additional avocado oil not only restored all the alternative parameters(134) in the diabetic mice except by the changes in mitochondrial fatty acid composition(134) but also normalized the hyperlipidemia(134).


However, avocado oil showed no effect on the prevention of hyperglycemia polyphagia(134).


Based on the findings, researchers said, " These findings might have also significant implications in the progression of NAFLD in experimental models of steatosis".

Summary
Taken altogether, phytochemicals, herbal medicines, healthy foods found in the research paper may be considered remedies for the prevention and treatment of non-alcoholic fatty liver disease, pending to large sample size and multicenter human study.

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Author Biography
Kyle J. Norton (Scholar, Master of Nutrition, All right reserved)
Health article writer and researcher; Over 10.000 articles and research papers have been written and published online, including worldwide health, ezine articles, article base, health blogs, self-growth, best before it's news, the karate GB daily, etc.,.
Named TOP 50 MEDICAL ESSAYS FOR ARTISTS & AUTHORS TO READ by Disilgold.com Named 50 of the best health Tweeters Canada - Huffington Post
Nominated for shorty award over last 4 years
Some articles have been used as references in medical research, such as international journal Pharma and Bioscience, ISSN 0975-6299.

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(24) An Overview of Herbal Products and Secondary Metabolites Used for Management of Type Two Diabetes by Ajda Ota and Nataša P. Ulrich. (PubMed)(98) Healthy #Foods - Nuts & Seeds - Olive (Olea europaea) by Kyle J. Norton
(99)Olive leaf extract prevents the spontaneous occurrence of non-alcoholic steatohepatitis in SHR/NDmcr-cp rats by Omagari K1, Kato S, Tsuneyama K, Hatta H, Sato M, Hamasaki M, Sadakane Y, Tashiro T, Fukuhara M, Miyata Y, Tamaru S, Tanaka K, Mune M. (PubMed)
(100) Hypolipidemic and antioxidant activities of oleuropein and its hydrolysis derivative-rich extracts from Chemlali olive leaves by bJemai H1, Bouaziz M, Fki I, El Feki A, Sayadi S.(PubMed)
(101) Super Foods - #Pomegranates(Punica granatum) by Kyle J. Norton
(102) Effect of Punica granatum Linn. (flowers) on blood glucose level in normal and alloxan-induced diabetic rats by Jafri MA1, Aslam M, Javed K, Singh S. (PubMed)
(103) Antidiabetic effect of Punica granatum flowers: effect on hyperlipidemia, pancreatic cells lipid peroxidation, and antioxidant enzymes in experimental diabetes by Bagri P1, Ali M, Aeri V, Bhowmik M, Sultana S. (PubMed)
(104) Popular #Herbs - #Ginger (Zingiber officinale) by Kyle J. Norton
(105) Anti-diabetic activity of Zingiber officinale in streptozotocin-induced type I diabetic rats by Akhani SP1, Vishwakarma SL, Goyal RK. (PubMed)
(106) Antiobesity Actions of Zingiber officinale Roscoe by Li-Kun Han, Xiao-Jie Gong, Shiho Kawano, and Masato Saito. (Research Gate)
(107) Healthy #Foods - Green tea - Leaves of Camellia sinensis by Kyle J. Norton
(108) Green tea polyphenols ameliorate non-alcoholic fatty liver disease through upregulating AMPK activation in high fat fed Zucker fatty rats by Tan Y1, Kim J1, Cheng J1, Ong M1, Lao WG1, Jin XL1, Lin YG1, Xiao L1, Zhu XQ1, Qu XQ. (PubMed)
(109) Combination of citrus polymethoxyflavones, green tea polyphenols, and Lychee extracts suppresses obesity and hepatic steatosis in high-fat diet induced obese mice by Pan MH1,2,3,4, Yang G1, Li S1, Li MY5, Tsai ML5, Wu JC6, Badmaev V7, Ho CT8, Lai CS. (PubMed)
(110) Super Foods - Wolfberry by Kyle J. Norton
(111) Lycium barbarum polysaccharides improve hepatic injury through NF-kappa-B and NLRP3/6 pathways in a methionine choline deficient diet steatohepatitis mouse model by Xiao J1, Wang F2, Liong EC3, So KF4, Tipoe GL. (PubMed)
(112) Lycium ruthenicum extract alleviates high-fat diet-induced nonalcoholic fatty liver disease via enhancing the AMPK signaling pathway by Lin J1, Zhang Y1, Wang X1, Wang W. (PubMed)
(113) Popular #Herbs - #Garlic (Allium sativum) by Kyle J. Norton
(114) Traditional Chinese herbal extracts inducing autophagy as a novel approach in therapy of nonalcoholic fatty liver disease by Liu C1, Liao JZ1, Li PY. (PubMed)
(116) Effect of garlic powder consumption on body composition in patients with nonalcoholic fatty liver disease: A randomized, double-blind, placebo-controlled trial by Soleimani D1, Paknahad Z2, Askari G3, Iraj B4, Feizi A. (PubMed)
(117) Superfoods - Uncontaminated Fish Oil by Kyle J. Norton
(118) Fish oil alleviated high-fat diet-induced non-alcoholic fatty liver disease via regulating hepatic lipids metabolism and metaflammation: a transcriptomic study by Yuan F1,2, Wang H3, Tian Y4, Li Q5, He L6, Li N7, Liu Z. (PubMed)
(119) Fish Oil Feeding Modulates the Expression of Hepatic microRNAs in a Western-Style Diet-Induced Nonalcoholic Fatty Liver Disease Rat Model by Wang H1, Shao Y1, Yuan F1,2, Feng H1, Li N1, Zhang H1, Wu C3, Liu Z. (PubMed)
(120) Superfoods - Flaxseed oil by Kyle J. Norton
(121) Therapeutic effect of flax-based diets on fatty liver in aged laying hens by Davis JE1, Cain J2, Small C3, Hales DB. (PubMed)
(122) Flaxseed supplementation in non-alcoholic fatty liver disease: a pilot randomized, open-labeled, controlled study by Yari Z1, Rahimlou M2, Eslamparast T1, Ebrahimi-Daryani N3, Poustchi H4, Hekmatdoost A. (PubMed)
(123) 71 Health Benefits and 28 Adverse Effects of Coffee by Kyle J. Norton
(124) Green Coffee Extract Improves Cardiometabolic Parameters and Modulates Gut Microbiota in High-Fat-Diet-Fed ApoE-/- Mice by Caro-Gómez E1, Sierra JA2, Escobar JS3, Álvarez-Quintero R4, Naranjo M5, Medina S6, Velásquez-Mejía EP7, Tabares-Guevara JH8, Jaramillo JC9, León-Varela YM10, Muñoz-Durango K11, Ramírez-Pineda JR. (PubMed)
(125) Effects of green coffee extract supplementation on anthropometric indices, glycaemic control, blood pressure, lipid profile, insulin resistance and appetite in patients with the metabolic syndrome: a randomized clinical trial by Roshan H1, Nikpayam O1, Sedaghat M2, Sohrab G. (PubMed)
(126) Healthy #Foods - Vegetables - Cabbage (Brassica oleracea) by Kyle J. Norton
(127) Dietary Broccoli Lessens Development of Fatty Liver and Liver Cancer in Mice Given Diethylnitrosamine and Fed a Western or Control Diet by Chen YJ1, Wallig MA2, Jeffery EH. (PubMed)
(128) Dietary broccoli protects against fatty liver development but not against the progression of liver cancer in mice pretreated with diethylnitrosamine by Chen YJ1, Myracle AD1, Wallig MA2, Jeffery EH. (PubMed)
(129) Healthy #Foods - Nuts & Seeds - Walnuts (Juglans) by Kyle J. Norton
(130) Preventive effects of dietary walnuts on high-fat-induced hepatic fat accumulation, oxidative stress, and apoptosis in mice by Choi Y1, Abdelmegeed MA1, Song BJ. (PubMed)
(131) Dietary walnut reduces hepatic triglyceride content in high-fat-fed mice via modulation of hepatic fatty acid metabolism and adipose tissue inflammation by Choi Y1, Abdelmegeed MA1, Akbar M1, Song BJ. (PubMed)
(132) Healthy #Foods - Fruits - Avocado by Kyle J. Norton
(133) Effect of virgin avocado oil on diet-induced hypercholesterolemia in rats via 1 H NMR-based metabolomics approach by Tan CX1, Chong GH2, Hamzah H3, Ghazali HM. (PubMed)
(134) Protective effects of dietary avocado oil on impaired electron transport chain function and exacerbated oxidative stress in liver mitochondria from diabetic rats by Ortiz-Avila O1, Gallegos-Corona MA, Sánchez-Briones LA, Calderón-Cortés E, Montoya-Pérez R, Rodriguez-Orozco AR, Campos-García J, Saavedra-Molina A, Mejía-Zepeda R, Cortés-Rojo C. (PubMed)

Sunday, May 12, 2019

Whole Food Tomato and Its Bioactive Compound Lycopene Protect the Obese Patients Against Complications

Obesity is a progressive chronic disease, associated with abnormal or excessive fat accumulation in the body.

People who have a BMI of over 30 is considered to be obese.

According to the statistics provided by Obesity Cabada, the rate of obesity has increased at an alarming rate in Canada over the past few decades.

Approximately over 30% of Canadian adults are considered obese that may require medical support to manage their disease.


Epidemiologically, type 2 diabetes, high blood pressure, heart disease, stroke, arthritis, cancer and other major health problems have been found in most obese patients, causing concern to the scientist community in the health care system.

Believe it or not, obesity has been found contributing to one 10 premature deaths among Canadian adults age 20 to 64. As of today, the health care system in Canada has spent between $5 billion and $7 billion for the treatment of obese related complications.


Furthermore, obesity is associated with increased mortality and a number of complications including diabetes, heart disease, dementia, and cancer.

And, the commitment of reduced weight through a healthy diet accompanied by moderate exercise has been proposed to target the complications.

Out of many risk factors associated with the onset of obesity, the social economy may have some implication involved in the onset of the disease.

Dr. BRIAN HOULE, wrote in the article "How Obesity Relates to Socioeconomic Status" "...obesity rose with a nation’s economic development, but also that socioeconomic status as it related to obesity changed. In lower-income countries, people with higher SES were more likely to be obese. Conversely, in high-income countries, those with higher SES were less likely to be obese".


And, "Why the reversal? It may be that in lower-income countries, higher SES leads to consuming high-calorie food and avoiding physically tough tasks. But in higher-income countries, individuals with higher SES may respond with healthy eating and regular exercise".

Tomato is red, edible fruit, genus Solanum, belongs to family Solanaceae, native to South America. Because of its health benefits, the tomato is grown worldwide for the commercial purpose
and often in the greenhouse.

On finding a natural and potential compound for the treatment of obesity, researchers review the link of high intake of lycopene or tomatoes products in the risk for metabolic diseases by comparing the effect of lycopene and tomato powder on obesity-associated disorders.

The study included selected Male C57BL/J6 mice randomly assigned into four groups to receive: control diet (Chigh-fat fat diet (HFD), high fat diet supplemented with lycopene or with tomato powder (TP) for 12 weeks.

In mice treated with HFD, lycopene and TP supplementation significantly improve the obese complications caused by adiposity index, organ, and relative organ weights, serum triglycerides, free fatty acids.


Furthermore, lycopene and TP supplementation also 8-iso-prostaglandin GF2α associated with an increased risk of heart disease and improved glucose homeostasis, against the onset of abnormal blood glucose.

Furthermore, Lycopene and TP supplementation prevented HFD-induced hepatosteatosis and hypertrophy of adipocytes associated with patients of obesity.

Moreover, lycopene and TP also decreased HFD-induced the production of proinflammatory cytokines in the liver and in the epididymal adipose tissue found in obese subjects.

According to the tested assay, lycopene and TP anti-inflammatory effects were attributed to the inhibition of the protein involved promotion of the expression of inflammation in adipose tissue.


Based on the findings, lycopene, and TP protected significantly obese subjects against the onset of obesity complications.

Dr. Fenni S after taking other factors into account wrote, "These results suggest that lycopene or TP supplementation display similar beneficial health effects that could be particularly relevant in the context of nutritional approaches to fight obesity-associated pathologies".


Taken altogether, tomatoes processed a high amount of lycopene may be considered whole food for the prevention and treatment of diseases associated with obesity, pending to the confirmation of the larger sample size and multicenter human study.

Intake of lycopene in the form of supplement should be taken with extreme care to prevent overdose acute liver toxicity.

Natural Medicine for Fatty Liver And Obesity Reversal - The Revolutionary Findings To Achieve Optimal Health And Lose Weight

How To Get Rid Of Eye Floaters
Contrary To Professionals Prediction, Floaters Can Be Cured Naturally

Ovarian Cysts And PCOS Elimination
Holistic System In Existence That Will Show You How To
Permanently Eliminate All Types of Ovarian Cysts Within 2 Months

Back to Kyle J. Norton Homepage http://kylejnorton.blogspot.ca


Author Biography
Kyle J. Norton (Scholar, Master of Nutrition, All right reserved)

Health article writer and researcher; Over 10.000 articles and research papers have been written and published online, including worldwide health, ezine articles, article base, health blogs, self-growth, best before it's news, the karate GB daily, etc.,.
Named TOP 50 MEDICAL ESSAYS FOR ARTISTS & AUTHORS TO READ by Disilgold.com Named 50 of the best health Tweeters Canada - Huffington Post
Nominated for shorty award over last 4 years
Some articles have been used as references in medical research, such as international journal Pharma and Bioscience, ISSN 0975-6299.

Sources
(1) Lycopene and tomato powder supplementation similarly inhibit high-fat diet induced obesity, inflammatory response, and associated metabolic disorders by Fenni S1,2, Hammou H2, Astier J1, Bonnet L1, Karkeni E1, Couturier C1, Tourniaire F1, Landrier JF. (PubMed)

Cucumbers (Cucumis sativus), the Potential Anti-Pancreatic Cancer Functional Food

Primary pancreatic cancer is a medical condition originated from the pancreas as a result of the alternation of cells DNA in the pancreas tissue.

Most cases of pancreatic cancer at the early stage begin in the cell on the surface of the inner lining of the pancreas before growing in the size that affects the function of the organ.

At the very early stage of the pancreas, most patients are asymptomatic. However, at the advanced stage, patients may experience the symptoms shared by all cancers such as unintended weight loss, loss of appetite, persistent fatigue and gastrointestinal discomforts accompanied by jaundice, belly and back pain, enlarged liver and gallbladder and blood clot.

According to the statistics provided by the American Cancer Society, in the US this year, approximately 56,770 people (29,940 men and 26,830 women) will be diagnosed with pancreatic cancer. The disease also will cause the death of 45,750 people (23,800 men and 21,950 women) in the US.


The 5 years survival rate of localized pancreatic cancer is only 34%. The rate is relatively low compared to other types of cancer in the localized stage such as 100% in breast cancer.

The causes of pancreatic cancer are unknown. Epidemiological studies suggested that aging, gender, ethnicity, family history, smoking, people with certain medical con conditions as diabetes, are the most prevalent risk found in patients with pancreatic cancer.

Dr. Michaud DS in the examination of the rate of pancreatic cancer risk arisen in patients with obesity compared to overweight and healthy subjects over past few decades wrote, "Obesity has surfaced as an important risk factor for pancreatic cancer as epidemiological studies with strong methodological designs have removed important biases and solidified the obesity associations".


And, "Moreover, studies indicate that obesity early in adulthood is strongly associated with future risk of pancreatic cancer and that abdominal obesity is an independent risk factor".
Cucumber plant is a species of Cucumis Sativus, belongs to the family Cucurbitaceae and native to Western Asia. It is a creeping vine with roots in the ground and grows up with the support of frames.

In the urgency to find a potential compound for the treatment of pancreatic cancer, researchers examined the Cucurbitacin B (CuB), a natural tetracyclic triterpene product found abundantly in cucumber antitumor activity.

According to the tested assays, CuB arrested pancreatic cancer (PC) cells in the G2/M cell cycle phase by suppressing the expression of AFAP1-AS1, an RNA gene associated with poor prognosis in cancer patients.


Elevated AFAP1-AS1 expression is found in patients' TSCC tumor tissues and tested cell lines.


Additional differentiation of the CuB effects, researchers found that Cub suppression the tumor proliferation by enhancing high miR-146b-5p expression in pancreatic cancer (PC) cells, an indication of cancer cells suppression.


Based on the findings, researchers said, "CuB suppresses the proliferation, in vitro and in vivo, of PC cells through the... effect of AFAP1-AS1 on miR-146b-5p".

Additionally, according to the results from the Shengjing Hospital of China Medical University,* CuB inhibited of the expression of epidermal growth factor receptor (EGFR) in the promotion of solid tumor growth.


* CuB blocked the activation of signaling pathways (PI3K/Akt/mTOR and STAT3.) associated with the cell proliferative stimulation.
* CuB also exhibited cytotoxicity by enhancing t

The protein (ERK-activating AMPK signaling) associated with cellular metabolism and tumor suppression


Taken altogether, cucumber processed abundantly bioactive compound CuB may be considered a functional food for the prevention and treatment of pancreatic cancer, pending to the confirmation of the larger sample size and multicenter human study.

Intake of CuB in the form of supplement should be taken with extreme care to prevent overdose acute liver toxicity.

Natural Medicine for Fatty Liver And Obesity Reversal - The Revolutionary Findings To Achieve Optimal Health And Lose Weight

How To Get Rid Of Eye Floaters
Contrary To Professionals Prediction, Floaters Can Be Cured Naturally

Ovarian Cysts And PCOS Elimination
Holistic System In Existence That Will Show You How To
Permanently Eliminate All Types of Ovarian Cysts Within 2 Months

Back to Kyle J. Norton Homepage http://kylejnorton.blogspot.ca


Author Biography
Kyle J. Norton (Scholar, Master of Nutrition, All right reserved)
Health article writer and researcher; Over 10.000 articles and research papers have been written and published online, including worldwide health, ezine articles, article base, health blogs, self-growth, best before it's news, the karate GB daily, etc.,.
Named TOP 50 MEDICAL ESSAYS FOR ARTISTS & AUTHORS TO READ by Disilgold.com Named 50 of the best health Tweeters Canada - Huffington Post
Nominated for shorty award over last 4 years
Some articles have been used as references in medical research, such as international journal Pharma and Bioscience, ISSN 0975-6299.



Sources
(1) Cucurbitacin B suppresses proliferation of pancreatic cancer cells by ceRNA: Effect of miR-146b-5p and lncRNA-AFAP1-AS by Zhou J1, Liu M2, Chen Y1, Xu S1, Guo Y3, Zhao L. (PubMed)
(2) Cucurbitacin B and SCH772984 exhibit synergistic anti-pancreatic canceractivities by suppressing EGFR, PI3K/Akt/mTOR, STAT3 and ERK signaling by Zhou J1, Zhao T2, Ma L2, Liang M2, Guo YJ2, Zhao LM. (PubMed)
(3) Obesity and Pancreatic Cancer by Michaud DS. (PubMed)

Saturday, May 11, 2019

The Natural Herbal Remedies for the Treatment of Non Alcoholic Liver Fatty Disease, Scientists Say

Nonalcoholic fatty liver disease (NAFLD) is a chronic condition caused by fat accumulated in the liver over time, in the absence of excessive alcohol use. The disease can be classified into the types of non-inflammatory fatty liver (NAFl) and inflammatory nonalcoholic steatohepatitis (NASH)(1).

Nonalcoholic fatty liver disease (NAFLD) is one of the major causes of cirrhosis and liver cancer.

According to world statistics, nonalcoholic fatty liver disease (NAFLD) is normally known as a disease of the Western world(2). However, due to the economic prosperity of Southeast Asian(3), the disease also was found in a large number of population in the cities, causing concerns of many scientists in the region(4)(6).

According to the joint assessment of the prevalence of non-alcoholic fatty liver disease and risk factors for advanced fibrosis and mortality in the US, led by the Stanford University School of Medicine, "The prevalence of NAFLD in the United States (U.S.) has risen from 18% in 1988–1991 to 31% in 2011–2012. Estimates of NAFLD prevalence for adults in Western countries is 20–30%, with much higher prevalence in adults with obesity (80–90%), diabetes (30–50%), and hyperlipidemia (90%)"(5).

Among the more affluent regions of China, the prevalence rate of non-alcoholic fatty liver disease (NAFLD) is approximately 15%(6). The number may decrease substantially if the poor rural populations where obesity is non-existence are also taking into account(7).

The exact causes of NAFLD aren't well understood. Some researchers suggested that certain risk factors such as long-term use of certain medications(8), genetic preposition(8), insulin resistance(8), high cholesterol(8) and triglycerides(8) in the blood, polycystic ovary syndrome(8), metabolic syndrome(8), obesity(8), and type 2 diabetes(8) are associated with the onset of the disease.

Recent studies also found that people with obstructive sleep apnea(11), underactive thyroid (hypothyroidism(10) and underactive pituitary gland (hypopituitarism) (9) also at an increased risk of the NALFD.

Some researchers suggested that unhealthy diet such as high-fat diet may also have a strong implication on NAFLD(12)(13).


Dr. Jensen VS, the lead scientist in the study high-fat diet-induced non-alcoholic fatty liver disease, wrote, "In humans and animal models, excessive intake of dietary fat, fructose, and cholesterol has been linked to the development of non-alcoholic fatty liver disease (NAFLD)"(13).

And, " Only HFr-fed rats developed dyslipidemia as characterized by higher levels of plasma triglycerides compared to all other groups (p < 0.0001). Hepatic dysfunction and inflammation was confirmed in HFD-fed rats by elevated levels of hepatic MCP-1 (p < 0.0001), TNF-alpha (p < 0.001) and plasma β-hydroxybutyrate (p < 0.0001), and in NASH-fed rats by elevated levels of hepatic MCP-1 (p < 0.01), increased hepatic macrophage infiltration (p < 0.001), and higher plasma levels of alanine aminotransferase (p < 0.0001) aspartate aminotransferase (p < 0.05), haptoglobin (p < 0.001) and TIMP-1 (p < 0.01) compared to Control"(13).

According to the statistics, in the US, over 100 million people have non-alcoholic fatty liver disease and the condition is more double over the past 20 years(14). The disease also is the most prevalent liver disease in children(14).

The prevalence rate of NAFLD is varied among different ethnic groups in the US. Dr. Rich NE, the lead scientist in the investigation of the ethnicity and NAFLD, wrote, "NAFLD prevalence was highest in Hispanics, intermediate in Whites, and lowest in Blacks, although differences between groups were smaller in high-risk cohorts (range 47.6%-55.5%) than population-based cohorts (range, 13.0%-22.9%)(15)".

And, "Among patients with NAFLD, the risk of NASH was higher in Hispanics (relative risk, 1.09; 95% CI, 0.98-1.21) and lower in Blacks (relative risk, 0.72; 95% CI, 0.60-0.87) than Whites"(15).

The progression of NAFLD and NASH led to cirrhosis, the late stage of liver scarring are well defined, as the liver tries to heal itself by halting inflammation(16), leading to symptoms of ascites(16)(18), swell esophageal varices(16)(19), hepatic encephalopathy(16)(17) and complications of liver cancer(16)(17) and liver failure(16)(17).

Most people at the early stage NAFLD are asymptomatic, however, as the disease progression into the later stage, most patients experience symptoms of right upper abdominal discomfort(20), fatigue(20), and/or malaise(20), and jaundice(20) with yellowing of the skin and eyes(20).

Most patients with NAFLD have elevated levels of liver enzymes gamma-glutamyl transferase (GGT)(21) and/or Aspartate Aminotransferase (AST)(21) to platelet ratio index (APRI) score(21), and/or Alanine Aminotransferase (ALT) (21) which are the markers used to predict the severity of liver disease including the fatty liver. A blood test is required if you suspected to have developing nonfatty liver disease.

Conventionally, as of today, there is no effective treatment of NAFLD(22)(23). Weight loss for overweight and obese patients(22) has been recommended through our the industry accompanied by the change of lifestyles(22) such as moderate exercise and reduced intake of alcohol, depending on individuals.

Patients who are hepatitis virus B and C carriers are also recommended to be vaccinated(22).

Given the nature of the nonalcoholic fatty liver disease, the search for effective treatment for NAFLD from the natural sources used over thousands of years in traditional medicine for the treatment of liver disease has been intensified(23). Many secondary metabolites, whole foods, and herbal medicine have been found to be effective in vivo, vitro and small human trials(24). However, most of them were stopped due to a simple reason. Who will spend billions to prove the thing which has no commercial values? Secondary metabolites, whole foods, and herbal medicine cannot be patented.

B. Herbal medicines
Herbal medicines have been used as medicines over thousands of year in human history.
1. Herbal Anise
Herbal anise is a flowering plant of the species of Pimpinella anisum, genus Pimpinella, belongings to the family Apiaceae native to Egypt and the Mediterranean region, used in traditional herbal medicine as a fragrance in soaps, oils, and mouth fresheners and stomachic, antiseptic, anti-spasmodic (61).

On animal with NAFLD induced by choline-deficient diet for 90 days, 30 days treatment with hydroethanolic extract (AE) at 25, 50, 100, and 200 mg/kg/day and essential oil (AO) at 0.125, 0.25, and 0.5 mg/kg/day, reversed plasma levels of total cholesterol(62), low-density lipoprotein(62), and triacylglycerol(62) and decreased in high-density lipoprotein level(62) caused by choline-deficient diet in dose-dependent manner.

AE and AO also reduced the elevated levels of enzymes aspartate transaminase (AST)(62) and alanine transaminase (ALT)(62) which are considered as an indication of either liver injury or damage caused by the acute inflammation.

Additionally, anise AE and AO demonstrated a strong effect in ameliorated lipid peroxidation induced by oxidative stress(62) indicated by elevation of plasma level of 8-isoprostane(62) which is correlated to the prevalence of non-alcoholic fatty liver disease (NAFLD).

2. Hawthorn Fruit
Hawthorn is shrubs and trees of the genus Crataegus, belonging to the family Rosaceae, native to temperate regions of the Northern Hemisphere in Europe, Asia and North America(63) used in traditional medicine to treat heart disease and symptoms of heart diseases(63) such as irregular heartbeat(63), high blood pressure(63), chest pain(63), hardening of the arteries(63), circulatory disorders and respiratory illnesses(63).

Researchers at The First Affiliated Hospital of Wenzhou Medical College, in the concerns that nonalcoholic fatty liver disease (NAFLD) is emerging as a widespread condition worldwide, and reaffirmation of the natural treatments of nonalcoholic fatty liver disease (NAFLD) in the traditional Chinese medicine (TCM), launched an investigation to find natural medicines for the treatment of NAFLD, suggested that hawthorn fruit was one the favorite herb used in TCM for the treatment of NAFLD compared to other herbs(64).


Furthermore, the search of the database of PubMed and China National Knowledge Infrastructure from January 1995 to June 2010 for RCTs by comparing either traditional Chinese medicine (TCM) formulations alone or in combination with placebo for the treatment of NAFLD, a formula containing hawthorn normalized alanine aminotransferase(65) and disappearance of radiological steatosis(65) in patients with NAFLD, without inducing any side effects(65).



3. Sida rhomboidea Roxb
Sida rhomboidea Roxb is a shrubby weed found growing throughout India belonging to the Malvaceae family, used in North-East India for the treatment of hypolipidemia and diabetes properties(66).

On a high-fat diet (HFD) induced insulin resistance in C57BL/6J mice, Sida rhomboidea ROXB. (S. rhomboidea ROXB., SR) compared to mice fed with rosiglitazone (ROS) lowered the plasma(67) and hepatic TC(67), TG(67) and FFA(67) in HFD+SR groups.

According to the efficient clearance of glucose in intraperitoneal glucose tolerance test (IPGTT), Sida rhomboidea ROXB also lowered the plasma insulin(67) and fasting insulin resistance(67) levels in HFD+SR groups.

Furthermore, in vivo, sida rhomboidea. Roxb leaf extract (SRLE) supplementation with SRLE significantly prevented HFD induced increment in body weight(68), plasma lipids(68) and leptin(68), visceral adiposity(68)and adipocyte hypertrophy(68) by modulation of related genes expression(68).

In vitro, Roxb leaf extract (SRLE) decreased triglyceride accumulation(68), leptin release(68) and glyceraldehyde-3-Phosphate dehydrogenase activity(68) along with higher glycerol release(68) without significant alteration of the viability of 3T3L1 pre-adipocytes(68).

4. Teucrium polium (Golden Germander)
Teucrium polium, known popularly as felty germander, is a sub-shrub and herb, belonging to the Lamiaceae family, native to the western Mediterranean, found abundantly in South-Western Asia, Europe, and North Africa. and used in traditional medicine for the treatment of abdominal pain, indigestion, common cold, and type 2 diabetes(69).


In nonalcoholic steatohepatitis induced in male N‐Mary rats by a methionine/choline‐deficient (MCD) diet, ethyl acetate (EtOAc) extract of Teucrium polium, inhibited inflammation(70) and ballooning degeneration by 80%(70) of the rats treated by MCD diet.


Furthermore, EtOAc extract also lowered the lipoprotein profiles(70) and levels of liver oxidative stress(70) markers such as alkaline phosphatase(70), aspartate aminotransferase(70), and alanine aminotransferase(70) by improving the liver superoxide dismutase(70), glutathione peroxidase(70), and glutathione reductase enzymes(70).

Moreover, in N-Mary rats induced NASH by methionine and choline-deficient (MCD) diet for 8 weeks, injection of ethyl acetate fraction of T. polium orally for 3 weeks, lowered the elevated levels of proteins(71) associated with inflammation and malondialdehyde (MDA)(71) in the liver.

The extract increased the levels of antioxidants enzymes activities such as superoxide dismutase (SOD)(71), glutathione peroxidase (GPx)(71) and hepatic glutathione (GSH)(71).

In other words, the ethyl acetate fraction of T. poium effectively protected the liver by reversing NASH(71), through its strong antioxidant(71) and anti-inflammatory properties(71).

5. Grape seed extract
Grape Seed Extract is the commercial extracts from whole grape seeds that contains many concentrations, including vitamin E, flavonoids, linoleic acid, oligomeric proanthocyanidins(OPCs), and used in traditional medicine as antioxidant, anti-inflammatory agents and to treat skin wounds with less scarring, allergies, macular degeneration, arthritis, enhance circulation of blood vessels, lower cholesterol(72)


In rats fed a high-fat diet to induce non-alcoholic fatty liver disease(NAFLD), resveratrol (RSV) administration reversed the abdominal obesity(73), NAFLD(73), and insulin resistance (IR)(73) by 10 weeks.

In vitro, RSV treatment inhibited the triacylglycerol (TG) accumulation(73) in HepG2 cells incubated with a high concentration of glucose(73), and insulin(73).


In other words, resveratrol (RSV) improved NAFLD(73) and IR(73) by suppressing the 2 lipogenesis genes(73) associated with the elevation of NAFLD(73) and IR expression (73).

Additionally, injection of resveratrol (RSV) also found to induced production of hepatic low-density lipoprotein(74) which has been found to process similarly activity as high-density lipoprotein which returns cholesterol to the liver.

6. Milk thistles
Milk Thistle is a flowering plant, in the genus Silybum Adans, belonging to the family Asteraceae, native to the Mediterranean, used in traditional medicine for the treatment of liver, kidney, and gall bladder problems(75).

According to the study lead by First Hospital of Jilin University in the review of eight RCTs involving 587 patients with NAFLD, Silymarin (SIL), an active extraction of milk thistle, significantly reduced liver oxidative stress(76) associated with the AST(76) and ALT levels(76).

In other words, SIL improved the liver parameters(76) by reducing transaminases levels(76) in NAFLD patients.

Furthermore, on hepatic steatosis and oxidative stress during the development of nonalcoholic fatty liver disease (NAFLD), administration of SMO decreased the histological injury of the liver(77) and the levels of hepatic triglyceride(77), cholesterol(77) and free fatty acid(77) in HFD-fed mice.

Moreover, SMO administration elevated the activities of superoxide dismutase (SOD)(77) and catalase (CAT)(77) and reduced the level of malondialdehyde (MDA)(77) and lowered the levels of proteins(77) involved in the production of pro-inflammatory cytokines(77) in the liver, thus preventing the onset of NAFLD.


7. Acanthopanax senticosus (Siberian Ginseng)
Acanthopanax senticosus or Siberian Ginseng is an oriental herb belonging to the Araliaceae family commonly distributed throughout the North Eastern parts of Asia, used in traditional Chinese medicine for the treatment of arthritis, hypertension, heart disease, gastric ulcers, and tumors(78).

On 10 obesity C57BL/6J mice fed either a normal diet (10 kcal fat%) or high-fat diet (60 kcal fat%) with or without oral administration of A. senticosus extract (ASE; 0.5 g/kg of body weight) for 12 weeks, ASE inhibited the significantly higher low-density lipoprotein (LDL)-cholesterol in serum(79) and higher triglyceride accumulation in liver(79), of mice high-fat diet without altering the levels of carnitine status(79).

Collectively, oral administration of ASE lowered the weight gain(79), serum LDL-cholesterol concentration(79), and liver triglycerides accumulation(79) in mice with obesity induced by high-fat diets.

In insulin-resistant ob/ob mice with fatty livers, 50% ethanol extract ofAcanthopanax senticosus stem bark (ASSB) reversed the hepatomegaly(80), by reducing the % liver weight/body weight ratio(80) in 8 weeks.

The ASSB ethanol extract also specifically lowered circulating glucose(80) and lipids(80) and enhanced insulin(80) action in the liver and triglyceride synthesis(80) in non-adipose tissues including liver and skeletal muscle(80).

Genes expression of glucose 6-phosphatase and lipogenic enzymes associated with the development of hepatic steatosis(80) also were reduced by the injection of ASSB ethanol extract.

8. Alisma Orientalis (Alismatis rhizome) or Ze Xie in traditional Chinese Medicine
Ze Xie is also known as Alisma, used in TCM as anti-pyretic, as anti-bacterial, hypoglycemic, hypotensive, antitumor, and anti-allergic medicine(81).

On rats fed with high‐fat diet for six weeks induced nonalcoholic fatty liver disease (NAFLD), followed by AOME for another six weeks, administration of AOME (150,300 and 600 mg kg−1) markedly decreased the serum and liver lipids(82), fasting serum glucose(82) and improved insulin resistance(82).

AOME lessened the lipid peroxidation(82) and activated antioxidant enzymes(82) through inhibiting the oxidative stress in the liver(82).


Furthermore, according to the tested assays, AOME also protected the liver against injury(82) by reducing the aminotransferase abnormalities(82) and hepatomegaly(82).


9. Cissus quadrangularis (Asthisamharaka)
Cissus quadrangularis is a perennial plant, belonging to the grape family, native to India, Srilanka, Malaysia, Thailand, and Africa used in the traditional medicine for the treatment of obesity, diabetes, and metabolic syndrome(83)

On oxidant-antioxidant balance and insulin resistance (IR) in rats fed high fat–high fructose diet (HFFD) and free-radical scavenging property in vitro, CQEt addition for 45 days restored insulin sensitivity (84), liver damage(84), and oxidative changes(84), on (HFFD) rats by and bring back the antioxidants and lipids towards normal(84).

Furthermore, CQEt protected the liver by improving the histopathology(84)of the liver.

In vivo, CQEtin also exerted liver protective effect(84) comparable with that of standard drug, metformin.

In vitro, CQEt exhibited radical scavenging ability(84) in a dose-dependent manner.

In other words, dietary supplementation of CQ extract (10%) for 45 days significantly improved insulin sensitivity(84), reduced liver damage(84), prevented oxidative changes(84).

10. Clerodendron glandulosum
Clerodendron glandulosum is comprised of small trees, shrub sand herbs belonging to the Verbenaceae family, native the tropical and sub-tropical regions of the world used in the traditional medicine for the treatment of hypertension, fever, diabetes, and abdominal pain(85).

On hyperlipidemic chronically rat fed by a high-fat diet (HL), administration of aqueous extract of Clerodendron glandulosum. Caleb (CG) (400 mg/kg/day) for 90 days, showed to reduce the levels of LDL-C (81.36%) (86)and VLDL-C (43%)(86) along with an increase in HDL-C (52.84%)(86).

On alteration in lipid and cholesterol metabolism in high-fat diet fed hyperlipidemic rats, compared to hypolipidemic drug Lovastatin (LVS), injection of ECG exerted a strong effect in experimental hyperlipidemia(86) by a significant alteration in plasma and tissue lipid profiles(86).

Further differentiation of the efficacy of ECG, researchers found that ECG reduced absorption(86), improved elimination(86) and augmented catabolism(86) of lipids and cholesterol.

11. Curcuma longa (Turmeric)
Turmeric, principal curcuminoid of the popular Indian spice, a rhizomatous herbaceous perennial plant of the ginger family, Zingiberaceae, native to tropical South Asia used in traditional medicine for the treatment of varies illness, including metabolic syndrome and inflammatory conditions(87).


On C57BL/6 mice fed an HFD for 16 weeks, daily oral administration (os) of the NDS inhibited steatosis (88), aortic lesions(88) or carotid artery thickening(88) induced by the HFD.

Furthermore, NDS inhibited dyslipidemia(88) compared to untreated animals.


In other words, NDS prevented the onset of NAFLD and atherogenesis(88) by modulating the expression of different genes(88) involved in NAFLD.


According to the double-blind randomized controlled clinical trial conducted on 46 patients with NAFLD (21males and 25 females) aged 20-60 years old and body mass index (BMI) between 24.9 and 40 kg/m2, turmeric group (n = 23) given six turmeric capsules daily for 12 weeks with each capsule contained 500 mg turmeric powder (6×500 mg) showed the decreased serum levels of glucose(89), insulin(89), HOMA-IR(89), and leptin(89) compared to the placebo group without affecting the weight, BMI and liver enzymes.

Collectively, turmeric supplementation inhibited NAFLD complications by improving glucose indexes(89) and serum leptin levels(89).

12. Ginkgo biloba (Maidenhair Tree)
Ginkgo biloba is the oldest living tree species, genus Ginkgo, belonging to the family Ginkgoaceae, native to China, from the temperate zone to subtropical zone and some parts of North America, used in traditional herbal medicine in treating impotence, memory loss, respiratory diseases, circulatory disorders, and deafness as well as preventing drunkenness, and bedwetting(90).


In vivo, on Male Wistar rats divided into 4 groups (the control group, GBE group, high-fat diet [HFD] group, and HFD + GBE group) researchers examined the effect of Ginkgo biloba extract (GBE) on nonalcoholic fatty liver disease (NAFLD).

According to the experimental results, GBE reduced the elevations of hepatic triglyceride contents(91) and the increased hepatic fatty acids(91) in rat livers caused by HFD.

Furthermore, GBE also enhanced the expression palmitoyltransferase I (CPT I) and total activity of the fatty acid β-oxidation rate-limiting enzyme, in the regulation of whole-body metabolism, inflammatory vigor, and pathogenesis of nonalcoholic fatty liver disease(91).

The effects of GBE was attributed to its chemical compounds and ingredients, quercetin, kaempferol, and isorhamnetin which work synergistically to decrease the cellular triglyceride content(91) and promote the expression and total activity of CPT1A(91) in converting fat to energy.


Based on the finding, researchers wrote, "The triglyceride-lowering effect of GBE on the HFD rat liver is closely associated with the increased expression and activity of CPT1A, and the flavonoid ingredients are the major contributors of GBE".


13. Linum usitatissimum (Linseed/Flaxseed)
Flaxseed is native to the region of the eastern Mediterranean to India and also known as common flax or linseed. Flax is an erect annual plant, it can grow to 1.2 m tall. The leaves are 20–40 mm long and 3 mm broad, used in traditional medicine for the treatment of constipation(92).


A double-blinded, randomized, and placebo-controlled study in moderately hypercholesterolemic men suggested that oral administration of SDG (20 or 100 mg) decreases the level of blood cholesterol(93) and liver disease risk factors(93) induced by hypercholesterolemia in humans.


In a study of 30 men with total cholesterol levels of 4.65 to 6.21 mmol/L (180-240 mg/dL), SDG exhibited a significant reduction in the ratio of low-density lipoprotein/high-density lipoprotein cholesterol(93) compared to baseline at week 12.


Furthermore, injection of SDG also showed a significant percentage decrease in the levels of glutamic pyruvic transaminase(93) and γ-glutamyl transpeptidase(93) associated with liver injury markers related to the levels at the baseline.

In other words, daily administration of 100 mg SDG may be effective in reducing the levels of blood cholesterol(93) and hepatic diseases risk(93) in moderately hypercholesterolemic men.


In the testing of 7-d diets including a low-fiber control diet (Control), a diet with flaxseed fiber drink (3/day) (Flax drink), and a diet with flaxseed fiber bread (3/day) (Flax bread), researchers found that compared to control, Flax drink lowered fasting total-cholesterol and LDL-cholesterol by 12 and 15%(94), respectively.

Fecal fat and energy excretion increased by 50 and 23% with Flax drink consumption compared to control(94).

In other words, Flax drink decreased plasma total and LDL-cholesterol(94) and increased fat excretion(94).


14. Nelumbo nucifera (Lotus)
Nelumbo nucifera (Lotus) is a perennial plant belonging to the Nymphaeaceae family produced individual leaves and flowers directly from the root system and used in traditional medicine for the treatment of respiratory, hepatic, digestive, and reproductive diseases(95).


On 3T3-L1 preadipocytes and high-fat diet (HFD)-induced obese SD rats, injection of N. nucifera leaves extract, N. nucifera alkaloid (NNA) decreased cell population growth of 3T3-L1(a cell line derived from (mouse) 3T3 cells used in biological research on adipose tissue) preadipocytes(96) and increased the apoptotic cells(96) in a time- and dose-dependent manner and reduced the body weight(96), the lee's index(96), adipose tissue weight(96), and plasma lipid levels((96) in HFD-induced obese rats.


In vivo, C57BL/6 mice induced obesity by a high-fat diet (HFD), oral administration of NLFE reduced the body weight(97), body lipid accumulation(97), and activities of fatty acid synthase (FAS)(97), glutamic oxaloacetic transaminase(97), and glutamic pyruvic transaminase(97) associated with the risk of NAFLD.

Additionally, NLFE efficacy in the attenuation of body lipid accumulation(97) and prevention of obesity(97) was associated with the inhibition of lipid-regulated enzymes involved in synthesizing lipids right in the cell(97).

D. Summary
Taken altogether, phytochemicals, herbal medicines, healthy foods found in the research paper may be considered remedies for the prevention and treatment of non-alcoholic fatty liver disease, pending to large sample size and multicenter human study.


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Author Biography
Kyle J. Norton (Scholar, Master of Nutrition, All right reserved)

Health article writer and researcher; Over 10.000 articles and research papers have been written and published online, including worldwide health, ezine articles, article base, health blogs, self-growth, best before it's news, the karate GB daily, etc.,.
Named TOP 50 MEDICAL ESSAYS FOR ARTISTS & AUTHORS TO READ by Disilgold.com Named 50 of the best health Tweeters Canada - Huffington Post
Nominated for shorty award over last 4 years
Some articles have been used as references in medical research, such as international journal Pharma and Bioscience, ISSN 0975-6299.

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(61) Popular #Herbs - Anise Kyle J. Norton
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(75) Popular #Herbs - Milk Thistle by Kyle J. Norton
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(78) Popular #Herbs - #Ginseng, Asian (Panax ginseng) and Ginseng, North America by Kyle J. Norton
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