Lipid-lowering agents in the management of nonalcoholic fatty liver disease

Τζιόμαλος, Κωνσταντίνος

doi:10.4254/wjh.v6.i10.738

Cited by 16 publications

(13 citation statements)

References 59 publications

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“…2 ), colesevelam and colestilan 26 . BASs can bind to BAs in the intestine and act as cholesterol-lowering polymer drugs 27 . BASs are barely absorbed owing to their high molecular weight and positive charge 28 .…”

mentioning

confidence: 99%

Intestinally-targeted TGR5 agonists equipped with quaternary ammonium have an improved hypoglycemic effect and reduced gallbladder filling effect

Cao

Chen

Wang

et al. 2016

Sci Rep

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TGR5 activation of enteroendocrine cells increases glucagon-like peptide 1 (GLP-1) release, which maintains glycemic homeostasis. However, TGR5 activation in the gallbladder and heart is associated with severe side effects. Therefore, intestinally-targeted TGR5 agonists were suggested as potential hypoglycemic agents with minimal side effects. However, until now no such compounds with robust glucose-lowering effects were reported, especially in diabetic animal models. Herein, we identify a TGR5 agonist, 26a, which was proven to be intestinally-targeted through pharmacokinetic studies. 26a was used as a tool drug to verify the intestinally-targeted strategy. 26a displayed a robust and long-lasting hypoglycemic effect in ob/ob mice (once a day dosing (QD) and 18-day treatment) owing to sustained stimulation of GLP-1 secretion, which suggested that robust hypoglycemic effect could be achieved with activation of TGR5 in intestine alone. However, the gallbladder filling effect of 26a was rather complicated. Although the gallbladder filling effect of 26a was decreased in mice after once a day dosing, this side effect was still not eliminated. To solve the problem above, several research strategies were raised for further optimization.

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mentioning

confidence: 99%

Intestinally-targeted TGR5 agonists equipped with quaternary ammonium have an improved hypoglycemic effect and reduced gallbladder filling effect

Cao

Chen

Wang

et al. 2016

Sci Rep

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“…Given the involvement of oxidative stress, subclinical inflammation and increased apoptosis in the pathogenesis of NAFLD, statins might improve liver histology in these patients through their pleiotropic effects [68][69][70][71]. …”

Section: Effects Of Statins On Liver Histology In Patients With Nafldmentioning

confidence: 99%

Nonalcoholic fatty liver disease and statins

et al. 2015

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“…Additionally, metformin, statins, and fibrates, are currently being tested as NAFLD treatments in clinical trials. However, these drugs have significant adverse side effects, including enhanced risk of infection and osteoporosis (55)(56). Hence, novel treatment candidates with high efficacy and minimal side effects are urgently demanded for the treatment of NAFLD (57).…”

Section: Treatmentmentioning

confidence: 99%

Toward Nonalcoholic Fatty Liver Treatment; A Review on Herbal Medicine Treatment

2020

jcr

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This study, review the nonalcoholic fatty liver treatment with emphasis on herbal medicine treatment. The accumulation of the mass of triglycerides by 5% in the liver cells of those who are not alcoholic leads to a situation called nonalcoholic fatty liver disease (NAFLD). Nonalcoholic fatty liver is known as the most common liver disorder in the world, such that its prevalence varies from 3% to 25% in different populations of the world per race, age, sex, place of residence and lifestyle. Numerous studies have been carried out on the NAFLD and its pathological mechanism and are still ongoing. In classification of the causes of fatty liver, two general groups can be noted: (i) an effective group with indirect effects such as hypothyroidism, pituitary hypoplasia, polycystic ovarian syndrome, and sleep apnea; (ii) The other group is directly involved in the development of this disease in individuals such as abdominal obesity, metabolic syndrome and type 2 diabetes. Most patients are asymptomatic and are diagnosed by disturbed liver tests. This disease is the most common cause of liver enzymes disorder after hepatitis and chronic liver disease. In more than three-fourths of patients during a clinical examination, the increased size of liver is visible, and the most common symptom is excessive fatigue, lethargy, and pain in the upper right abdomen. The patients may complain of persistent itching, jaundice or complications caused by the increased portal pressure. If the disease leads to liver cirrhosis, hepatomegaly is seen in most cases. In most cases, the patient only finds out about the fatty liver when a regular blood test (generally liver function tests) shows a problem. "Alanine aminotransferase" and "Aspartate aminotransferase" are the most important liver enzymes, and their increase of 1.5-2 times in the tests shows the involvement of liver with this disease. Due to the key role of lipid accumulation in NAFLD progression, inhibition of lipid accumulation is a major focus of anti-NAFLD drug development. A variety of anti-NAFLD agents are currently in preclinical development. Additionally, metformin, statins, and fibrates, are currently being tested as NAFLD treatments in clinical trials. This study aims to review medicinal herbs used to treat NAFLD around the world. The obtained results of the present review investigation demonstrated that 27 medicinal herbs were found that traditionally used to treat NAFLD around the world. The most parts of these plants are leaves, root, and flowers, respectively; whereas these medicinal herbs are most commonly used in countries of Asian and African such as Iran, Pakistan, India and South Africa, etc. The results demonstrated that medicinal herbs have universally used to treat NAFLD. Thus, we can consider them as alternative agents for treatment of NAFLD; nevertheless, more investigations are mandatory to elucidate the precise mechanisms and also toxicity of these plants in human subjects.

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Lipid-lowering agents in the management of nonalcoholic fatty liver disease

Cited by 16 publications

References 59 publications

Intestinally-targeted TGR5 agonists equipped with quaternary ammonium have an improved hypoglycemic effect and reduced gallbladder filling effect

Intestinally-targeted TGR5 agonists equipped with quaternary ammonium have an improved hypoglycemic effect and reduced gallbladder filling effect

Nonalcoholic fatty liver disease and statins

Toward Nonalcoholic Fatty Liver Treatment; A Review on Herbal Medicine Treatment

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