A Comprehensive Systematic Review of the Effects of Naringenin, a Citrus-Derived Flavonoid, on Risk Factors for Nonalcoholic Fatty Liver Disease

Abstract

Nonalcoholic fatty liver disease (NAFLD) has become the most common cause of liver dysfunction worldwide. Recently, some natural compounds have attracted growing interest in the treatment of NAFLD. In this context, most attention has been paid to natural products derived from fruits, vegetables, and medicinal herbs. Naringenin, a natural flavanone, has been revealed to have pharmacological effects in the treatment of obesity and associated metabolic disorders such as NAFLD. The aim of this study was to examine the therapeutic effects of naringenin and its possible mechanisms of action in the management of NAFLD and related risk factors. The current systematic review was performed according to the guidelines of the 2015 PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) statements. We searched PubMed/Medline, Science Direct, Scopus, ProQuest, and Google Scholar databases up until February 2020. Of 1217 full-text articles assessed, 36 studies met the inclusion criteria. The evidence reviewed in the present study indicates that naringenin modulates several biological processes related to NAFLD including energy balance, lipid and glucose metabolism, inflammation, and oxidative stress by different mechanisms. Overall, the favorable effects of naringenin along with its more potency and efficacy, compared with other antioxidants, indicate that naringenin may be a promising therapeutic approach for the management of NAFLD and associated complications. However, due to the lack of clinical trials, future robust human randomized clinical trials that address the effects of naringenin on NAFLD and other liver-related diseases are crucial. Further careful human pharmacokinetic studies are also needed to establish dosage ranges, as well as addressing preliminary safety and tolerability of naringenin, before proceeding to larger-scale endpoint trials.

Naringenin Attenuates Non-Alcoholic Fatty Liver Disease by Enhancing Energy Expenditure and Regulating Autophagy via AMPK

“…Thus, the relative bioavailability of NAR was higher than quercetin and hesperetin. Most studies of NAR’s effects for NAFLD on animal models were conducted in large doses (50–100 mg/kg) and (or) in a long time (4–12 weeks) ( Naeini et al, 2020 ). Wang et al reported that NAR attenuated hepatic lipid accumulation and inflammation in methionine and choline deficient diet-induced NAFLD mice at 100 mg/kg for 7 days ( Wang Q. et al, 2020 ).…”

“…NAR is abundant in a lot of fruits, vegetables, and nuts, such as lemon, grapefruit, oranges, and tomatoes. NAR has been reported to modulate several biological processes related to NAFLD including energy balance, lipid and glucose metabolism, inflammation, and oxidative stress ( Naeini et al, 2020 ). However, whether or not NAR attenuates NAFLD by activating adenosine 5′-monophosphate (AMP)-activated protein (AMPK), the key regulator in energy balance, is unclear.…”

Naringenin Improves Ovalbumin-Induced Allergic Asthma in Rats through Antioxidant and Anti-Inflammatory Effects

“…Naringenin (4, 5, 7-trihydroxyflavanone) is a flavonoid derived from grapes and citrus, which has recently shown positive effects on the respiratory system [ 15 ]. This flavonoid has also been proven to possess various pharmacological properties such as anticancer, antimutation, and antiatherogenic [ 16 , 17 ].…”

Effects of naringenin supplementation on cardiovascular risk factors in overweight/obese patients with nonalcoholic fatty liver disease: a pilot double-blind, placebo-controlled, randomized clinical trial

“…Initial clinical studies have demonstrated that naringenin possesses preventive effects against NAFLD and its related complications by ameliorating obesity, insulin resistance, hepatic steatosis, and liver fibrosis through attenuation of oxidative stress, inflammation, and profibrogenic pathways, as well as regulation of energy homeostasis and lipid metabolism [21]. Additionally, a large number of experimental models found a meaningful decline in the serum levels of bilirubin and hepatic enzymes including aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and lactate dehydrogenase by naringenin treatment [23][24][25][26].…”