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.
A. Phytochemicals
Phytochemicals, the natural chemical constituents, protect the plants against diseases and form their outer's color.
Phytochemicals may be the next potential sources of a new medicine for treatment of diseases with little or no side effects(32), including
* Secondary metabolites
Secondary metabolites produced by plants have been used as medicines, flavorings, pigments, and recreational drugs over thousands of year in human history(24).
* Bioactive compounds isolated from plant include vegetables, fruits, and nut.
1. Triterpenoid
Triterpenoid is a various unsaturated hydrocarbon, found in essential oils and oleoresins of plants, including Ilex, hainanensis Merr(25).
In the study to test the effect of Triterpenoid-rich fraction (TP) from Ilex hainanensis Merr. on NAFLD with Male Sprague-Dawley (SD) fed with a normal diet (control) or high fat diet (NAFLD model), after 4 weeks, then orally administrated TF (250 mg/kg) for another two weeks(26), researchers showed that TP not only improves the symptoms of the subjects but also decreases the levels of triglyceride(26), total cholesterol(26), low-density lipoprotein cholesterol(26), abnormality of lipid accumulation(26), levels of inflammation(26) and infection(26) and apoptosis response(26) in the liver.
Of these results, TF is effective in protecting the liver against NAFLD by regulating lipids metabolism(26) and alleviating insulin resistance(26), inflammation(26) and oxidative stress(26).
2. Curcumin
Turmeric is a perennial plant in the genus Curcuma, belonging to the family Zingiberaceae, native to tropical South Asia(27)., used in traditional medicine as anti-oxidant, hypoglycemic, colorant, antiseptic, wound healing agent, and to treat flatulence, bloating, and appetite loss, ulcers, eczema, inflammations, etc(27)(28). Curcumin is one of the natural phenols in the plant(28).
Curcumin, as an antihyperlipidemic agent, has been found to lower the “bad cholesterol” low-density lipoprotein (LDL) and increase high-density lipoprotein (HDL)(29), thus reducing the risk of fat accumulated in the tissues in the liver(29).
In the support of the above, the water-soluble curcumin derivative was tested for its efficacy against steatohepatitis which is an inflammation of the liver(30)(31) with concurrent fat accumulation in the liver(30)(31), researchers found that the derivative not only significantly alleviates fibrosis(30)(31) but also decreases the grade of liver steatosis(30)(31).
3. Piperine
Piperine is a phytochemical alkaloid in the class of organosulfur compound, found abundantly in white and black pepper, long pepper, etc.
Administration of piperine appeared to reverse hepatic steatosis (33) and insulin resistance(33) in mice fed with high fat, probably inactivation of adiponectin-AMPK signaling(33) associated with stimulated fatty acid oxidation and enhance insulin sensitivity.
In other words, piperine not only inhibited hepatic steatosis and insulin resistance by reducing the expressions of lipogenic target genes(33) associated with insulin resistance (33) but also increased the expression of carnitine palmitoyltransferase 1 (CPT1) gene(33) involved in fatty acid oxidation.
4. Resveratrol
Resveratrol, a phytochemical in the class of Stilbenoids found abundantly in many vegetables and fruits as well as herbs and herbal formulas(34) including found abundantly in skins and seed of grape wine, nuts, peanuts, etc.
According to studies, the formulas of berberine and resveratrol not only improved a biochemical and histological change in nonalcoholic fatty liver disease(35)(36), but also inhibited lipid accumulation(36) by up-regulating low-density lipoprotein receptor (LDLR) expression(36), alleviating lipid peroxidation(36), and reducing the production of inflammatory cytokines(36).
5. Carotenoids
Carotenoids are class of phytochemicals that give yellow, orange, or red fat-soluble pigments, including lycopene and carotene, found in ripe tomatoes and autumn leaves(38).
According to studies, in the examination of a total of 2687 in middle-aged and elderly Chinese adults. who completed both NAFLD tests were classified into stable, improved and progressed groups, serum carotenoids(37) are inversely associated with non-alcoholic fatty liver disease (NAFLD)(37) by reducing serum RBP4 and HOMA-IR(37), associated with insulin resistance(37), triglycerides(37), and body max index (BMI)(37).
More precisely, higher levels of α-carotene, β-carotene, lutein + zeaxanthin(39), and total carotenoids(39) have a strong impact on a significant decrease in the severity of NAFLD(39).
6. Quercetin
Quercetin is a type of flavonoid antioxidant found in leafy greens, tomatoes, berries, and broccoli(40). Recent studies have shown that the beneficial effects of quercetin include the activation of mitochondrial biogenesis(41).
In Male Sprague-Dawley rats fed high-fat diet (HFD) induced alcoholic fatty liver disease (NAFLD), quercetin intake decreased hepatic TG content by 39%,(42) with a 1.5-fold increase in very low-density lipoproteins (VLDL)(42) which transport hepatic lipids to peripheral tissue acquired apoC-II and apoE from high-density lipoprotein (HDL) and exhibited the function of a protein involved in stress response(42) compared with the HFD group.
Injection of quercetin also is found to increase the protein complex expression of lipid transfer with a function to promote the very low-density lipoproteins (VLDL)(42) secreted by the liver.
In other words, these findings suggested that quercetin inhibits the expression NAFLD by increasing hepatic VLDL assembly and autophagy in hepatic lipid metabolism(42).
Additonally, quercetin exhibited hepatoprotective activity in 30-day HFD-induced NAFLD rats by regulating fatty acid related metabolites(43) (adrenic acid, etc.) including the inflammation-related metabolites (arachidonic acid, etc.), oxidative stress-related metabolites(43) (2-hydroxybutyric acid) and other differential metabolites(43) (citric acid, etc.).
8. Anthocyanin
Anthocyanins are water-soluble pigments of colored berries, fruits, and vegetables (44). They can protect hepatocytes against injury caused by high glucose-induced oxidative damage(45), by improving the antioxidant status and inhibiting the mitochondria pathways of apoptosis(45).
In male C57BL/6 J mice fed with a high fat high cholesterol (HFC) diet with or without 200 mg/kg B.W Cy-3-G for 8 weeks, injection of cyanidin-3-O-β-glucoside (Cy-3-G) regulated the activation of brown adipose tissue (BAT)(46) and the expression of adipokines in BAT disrupted by HFC diet associated with the induction of fatty liver(46).
In other words, Cy-3-G exerted the liver protective effect of on hepatic lipid accumulation(46) via regulating the secretion of adipokines from BAT(46).
9. Epigallocatechin gallate
Epigallocatechin gallate is the ester of epigallocatechin and gallic acid, belonging to the chemical class of flavan-3-ols (catechins) found most abundant in green tea (Camellia sinensis L.), accounting for about 50% of its total polyphenols(47).
In the examination of gene expression profiles with non-alcoholic fatty liver disease (NAFLD) and associated advanced liver diseases(48), application of Epigallocatechin-3-gallate (EGCG) inhibited the fibrosis-related genes (48)Col1a1, Col1a2, Col3a1, and Col6a3) that have a strong impact on the onset of NAFLD found in an independent mouse dataset (48).
In other words, EGCG protects the liver against genes related to liver fibrosis(48).
Furthermore, EGCG also exhibits multi-pronged preventive and therapeutic activities(49), including promoted lipid(49) and glucose metabolism(49), anti-lipid peroxidation(49) and anti-inflammation activities(49), anti-fibrosis(49), and anti-NAFLD related tumor(49), thus contributing to the mitigation of NAFLD occurrence and progression(49).
10. Astaxanthin
Astaxanthin is a phytochemical in the class of Xanthophylls, belonging to the group of Carotenoids (tetraterpenoids), found abundantly in yeast, krill, shrimp, salmon, lobsters, and green microalga(50). Astaxanthin showed to exhibit antifibrotic effects in the liver(51).
On the steatotic liver model by giving mice a methionine and choline-deficient high fat (MCDHF) diet, pretreatment of astaxanthin reduced levels of lipid peroxidation(52) and reduced number of liver cells apoptosis(52) by inhibiting the expression of inflammatory cytokines(52) and gene(52) involved oxidative stress in the liver(52)
11. Fucoxanthin
Fucoxanthin is one of the most abundant marine carotenoids, accounting for more than 10% of the estimated total carotenoids in nature(53).
Fucoxanthin protected the liver induced by obesity(54) by improving insulin resistance(54) and decreasing blood glucose levels (54) through the regulation of cytokine secretions(54).
On body weight, body fat, liver lipids, and blood biochemistry in obese, non-diabetic female volunteers with non-alcoholic fatty liver disease (NAFLD) and normal liver fat (NLF) content, Xanthigen (brown marine algae fucoxanthin + pomegranate seed oil (PSO)) promoted weight loss(55), reduced body(55) and liver fat content)(55), and improved liver function tests in obese non-diabetic women(55).
Xanthigen may be considered a promising food supplement in the management of obesity(55).
12. Glucoraphanin (4-methyl sulfinyl butyl glucosinolate)
Glucoraphanin (4-methyl sulfinyl butyl glucosinolate), the major glucosinolate is the precursor of sulforaphane found abundantly in broccoli Brussels sprouts and cabbages(56).
Obesity-induced insulin resistance and nonalcoholic fatty liver disease (NAFLD), glucoraphanin, a precursor of the Nrf2 activator sulforaphane, ameliorated obesity by enhancing energy expenditure(57) and browning of white adipose tissue(57), and attenuated obesity-related inflammation(57) and insulin resistance(57) and reduced metabolic endotoxemia(57).
Where nuclear factor erythroid 2-related factor 2 (Nrf2) is a key regulator of antioxidant signaling that serves as a primary cellular defense against the cytotoxic effects.
In chronic inflammation, insulin resistance, and NAFLD in high-fat diet (HFD)-fed mice, Glucoraphanin supplementation attenuated weight gain(58), decreased hepatic steatosis(58), and improved glucose tolerance(58) and insulin sensitivity(58).
Furthermore, glucoraphanin attenuated hepatic lipogenic gene expression(58), lipid peroxidation(58), classically activated M1-like macrophage accumulation(58), and inflammatory signaling pathways(58).
In other words, by promoting fat browning, limiting metabolic endotoxemia-related chronic inflammation, and modulating redox stress, glucoraphanin may have a therapeutic effect for the treatment of obesity(58), insulin resistance(58), and NAFLD(58).
13. Sinigrin
Sinigrin is a major component of commonly consumed cruciferous vegetables, such as horseradish and wasabi(59).
Sinigrin found in glucosinolates, a class of antioxidants has been found to reverse of fatty liver (60) probably through indirect interaction with mitochondrial metabolism(60) which encompasses a range of conditions caused by lipid deposition within liver cells.
In other words, by targeting the mitochondrial metabolism, sinigrin modulates antioxidant molecules for a potential treatment for hepatic steatosis(60).
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.
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).
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).
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)
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).
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).
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).
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).
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).
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).
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).
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).
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).
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.
C. Healthy foods
Eating a healthy diet with high 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 fruit 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 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, on 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 aqueous-ethanolic (50%, v/v)extracts of pomegranate led to significant lowering the blood glucose(102)with a maximum dose up to 400 mg/kg, b.w.
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 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).
On 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 to involved with hepatic lipogenesis(108) and triglycerides outflux(108) from the liver.
SlimTrym®, a formulated product composed of citrus polymethoxyflavones (PMFs), green tea extract, and lychee extract, 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 SlimTrym® exerts 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).
On 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, 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) associated with 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 for the treatment of 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, inhibited 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, with 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).
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).
On 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 to involved with hepatic lipogenesis(108) and triglycerides outflux(108) from the liver.
SlimTrym®, a formulated product composed of citrus polymethoxyflavones (PMFs), green tea extract, and lychee extract, 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 SlimTrym® exerts 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).
On 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, 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) associated with 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 for the treatment of 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, inhibited 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, with 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 the 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".
On 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 comparing 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 with WFX and defatted flaxseed meal (DFM).
Compared to other group fed with flax 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 have been suggested to mitigate several cardiometabolic risk factors(123).
On 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 protected the liver against 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) compared 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).
Furthermore, the serum AST(121) associated with liver injury or damage(121) also was reduced in hens provided with WFX and defatted flaxseed meal (DFM).
Compared to other group fed with flax 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 have been suggested to mitigate several cardiometabolic risk factors(123).
On 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 protected the liver against 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) compared 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".
On mice exposed to the hepatocarcinogen diethylnitrosamine (DEN), sulforaphane from broccoli exerted significant liver protection against NAFLD and liver cancer.
On male 15-day-old C57BL/6J mice 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 that elevate 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
Avocado is a commercially valuable fruit cultivated in tropical climates throughout the world. The fruit 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).
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
Avocado is a commercially valuable fruit cultivated in tropical climates throughout the world. The fruit 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 recovered 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).
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 by 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".
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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(90) Popular Herbs - Ginkgo biloba by Kyle J. Norton
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(92) Superfoods - Flaxseed oil by Kyle J. Norton
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(97) Improvement in High-Fat Diet-Induced Obesity and Body Fat Accumulation by a Nelumbo nucifera Leaf Flavonoid-Rich Extract in Mice by Cheng-Hsun Wu, Mon-Yuan Yang, Kuei-Chuan Chan, and Pei-Jun Chung. (Research Gate)
(61) Popular #Herbs - Anise Kyle J. Norton
(62) Pimpinella anisum L. fruit: Chemical composition and effect on a rat model of nonalcoholic fatty liver disease by Asadollahpoor A1, Abdollahi M2, Rahimi R3,(PubMed)
(63) Popular Herbs - Hawthorn (Crataegus)
(64) Traditional Chinese medicines benefit to nonalcoholic fatty liver disease: a systematic review and meta-analysis by Shi KQ, Fan YC, Liu WY, Li LF, Chen YP, Zheng MH. (PubMed)
(65) The relationship between obesity and the severity of non-alcoholic fatty liver disease: systematic review and meta-analysis by Lu FB1, Hu ED1, Xu LM1, Chen L1, Wu JL1, Li H1, Chen DZ2, Chen YP. (PubMed)
(66) Sida rhomboidea. Roxb Leaf Extract Down-Regulates Expression of PPARγ2 and Leptin Genes in High Fat Diet-Fed C57BL/6J Mice and Retards in Vitro 3T3L1 Pre-Adipocyte Differentiation by Menaka C. Thounaojam,1 Ravirajsinh N. Jadeja,1 Umed V. Ramani,2 Ranjitsinh V. Devkar,1,*and A. V. Ramachandran. (PMC)
(67) Prevention of High Fat Diet-Induced Insulin Resistance in C57BL/6J Mice by Sida rhomboidea ROXB. Extract by Menaka Chanu Thounaojam, Ravirajsinh Navalsinh Jadeja, Ansarullah, Ranjitsinh Vijaysinh Devkar, A. V. Ramachandran. (Journal of Health Science)
(68) Sida rhomboidea. Roxb Leaf Extract Down-Regulates Expression of PPARγ2 and Leptin Genes in High Fat Diet-Fed C57BL/6J Mice and Retards inVitro 3T3L1 Pre-Adipocyte Differentiation
Menaka C. Thounaojam 1, Ravirajsinh N. Jadeja 1, Umed V. Ramani 2, Ranjitsinh V. Devkar 1,* and. V. Ramachandran. ( International Journal of Molecular Science)
(69) Phytochemistry and medicinal properties of Teucrium polium L. (Lamiaceae) by Bahramikia S1, Yazdanparast R. (PubMed)
(70) Teucrium polium in the prevention of steatohepatitis in rats by Rahim Amini, Narges Nosrati, Razieh Yazdanparast, Mahsa Molaei. ( Liver International)
(71) Teucrium polium reversed the MCD diet-induced liver injury in rats by Rahim Amini, Razieh Yazdanparast and Safiyeh Aghazadeh. (Sage Journal)
(72) Popular Herbs - Grapefruit Seed Extract by Kyle J. Norton
(73) Resveratrol improves non-alcoholic fatty liver disease by activating AMP-activated protein kinase by Shang J1, Chen LL, Xiao FX, Sun H, Ding HC, Xiao H. (PubMed)
(74) SIRT1 as a potential therapeutic target for the treatment of nonalcoholic fatty liver disease by Colak Y1, Ozturk O, Senates E, Tuncer I, Yorulmaz E, Adali G, Doganay L, Enc FY. (PubMed)
(75) Popular #Herbs - Milk Thistle by Kyle J. Norton
(76) The therapeutic effect of silymarin in the treatment of nonalcoholic fatty disease: A meta-analysis (PRISMA) of randomized control trials by Zhong S1, Fan Y, Yan Q, Fan X, Wu B, Han Y, Zhang Y, Chen Y, Zhang H, Niu J. (PubMed)
(77) Silybum marianum oil attenuates hepatic steatosis and oxidative stress in high fat diet-fed mice by Zhu SY1, Jiang N2, Yang J3, Tu J4, Zhou Y3, Xiao X3, Dong Y. (PubMed)
(78) Popular #Herbs - #Ginseng, Asian (Panax ginseng) and Ginseng, North America by Kyle J. Norton
(79) Acanthopanax senticosus Extract Prepared from Cultured Cells Decreases Adiposity and Obesity Indices in C57BL/6J Mice Fed a High Fat Diet by Youn-Soo Cha, Soon-Jae Rhee, and Young-Ran Heo. (Journal of Medicinal Food)
(80) Acanthopanax senticosus reverses fatty liver disease and hyperglycemia in ob/ob mice by Sang, Hyun Park, Sang Gil Lee, Sung Keel Kang, and Sung Hyun Chung. (Springer Link)
(81) Chinese Herbs – Ze Xie by Kyle J. Norton
(82) Protective effects of the Alisma Orientalis extract on the experimental nonalcoholic fatty liver disease byXuezhi Hong, Huiqing Tang, Limao Wu, and Lianda Li. (Wiley Online Library)
(83) Cissus quadrangularis by Wikipedia
(84) Cissus quadrangularis stem alleviates insulin resistance, oxidative injury and fatty liver disease by Chidambaram, Jaya, Carani Venkatraman, and Anuradha. (Science Direct)
(85) Cissus quadrangularis - Wikipedia
(86) Clerodendron glandulosum Coleb., Verbenaceae, ameliorates high fat diet-induced alteration in lipid and cholesterol metabolism in rats by Jadeja RN; Thounaojam MC; Ansarullah; Devkar RV*; Ramachandran AV. (Scielo)
(87) Popular #Herbs - Turmeric (Curcuma longa) by Kyle J. Norton
(88) NAFLD and Atherosclerosis Are Prevented by a Natural Dietary Supplement Containing Curcumin, Silymarin, Guggul, Chlorogenic Acid and Inulin in Mice Fed a High-Fat Diet by Amato A1, Caldara GF2, Nuzzo D3, Baldassano S4, Picone P5, Rizzo M6, Mulè F7, Di Carlo M. (PubMed)
(89) Turmeric Supplementation Improves Serum Glucose Indices and Leptin Levels in Patients with Nonalcoholic Fatty Liver Diseases by Navekar R1, Rafraf M1, Ghaffari A1, Asghari-Jafarabadi M2, Khoshbaten M. (PubMed)
(90) Popular Herbs - Ginkgo biloba by Kyle J. Norton
(91) Inhibitory effect of Ginkgo biloba extract on fatty liver: Regulation of carnitine palmitoyltransferase 1a and fatty acid metabolism by Shi Dong Wang, Zuoquan Xie, Jia Chen, and Ke Wang. (Research Gate)
(92) Superfoods - Flaxseed oil by Kyle J. Norton
(93) Flaxseed lignan lowers blood cholesterol and decreases liver disease risk factors in moderately hypercholesterolemic men by Fukumitsu S1, Aida K, Shimizu H, Toyoda K. (PubMed)
(94) Flaxseed dietary fibers lower cholesterol and increase fecal fat excretion, but the magnitude of the effect depends on food type by Kristensen M1, Jensen MG, Aarestrup J, Petersen KE, Søndergaard L, Mikkelsen MS, Astrup A. (PubMed)
(95) A comprehensive review on Nymphaea stellata: A traditionally used bitter by M. K. Mohan Maruga Raja, Neeraj Kumar Sethiya, and S. H. Mishra. (PMC)
(96) Nelumbo nucifera alkaloid inhibits 3T3-L1 preadipocyte differentiation and improves high-fat-diet-induced obesity and body fat accumulation in rats by Xie Bin, Wan Jin, Wang Wenqing, and Shi Chunyang. (Research Gate)
(97) Improvement in High-Fat Diet-Induced Obesity and Body Fat Accumulation by a Nelumbo nucifera Leaf Flavonoid-Rich Extract in Mice by Cheng-Hsun Wu, Mon-Yuan Yang, Kuei-Chuan Chan, and Pei-Jun Chung. (Research Gate)
(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
(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)
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