Neochlorogenic Acid Attenuates Hepatic Lipid Accumulation and Inflammation via Regulating miR-34a In Vitro

Abstract

Neochlorogenic acid (5-Caffeoylquinic acid; 5-CQA), a major phenolic compound isolated from mulberry leaves, possesses anti-oxidative and anti-inflammatory effects. Although it modulates lipid metabolism, the molecular mechanism is unknown. Using an in-vitro model of nonalcoholic fatty liver disease (NAFLD) in which oleic acid (OA) induced lipid accumulation in HepG2 cells, we evaluated the alleviation effect of 5-CQA. We observed that 5-CQA improved OA-induced intracellular lipid accumulation by downregulating sterol regulatory element-binding protein 1 (SREBP1) and fatty acid synthase (FASN) expression, which regulates the fatty acid synthesis, as well as SREBP2 and HMG-CoA reductases (HMG-CoR) expressions, which regulate cholesterol synthesis. Treatment with 5-CQA also increased the expression of fatty acid β-oxidation enzymes. Remarkably, 5-CQA attenuated OA-induced miR-34a expression. A transfection assay with an miR-34a mimic or miR-34a inhibitor revealed that miR-34a suppressed Moreover, Sirtuin 1 (SIRT1) expression and inactivated 5’ adenosine monophosphate-activated protein kinase (AMPK). Our results suggest that 5-CQA alleviates lipid accumulation by downregulating miR-34a, leading to activation of the SIRT1/AMPK pathway.

Nutraceutical activation of Sirt1: a review

“…38 39 Urolithin A, carnosic acid and neochlorogenic acid appear to exert their upregulatory impacts on Sirt1 synthesis by suppressing expression of miR-34a, which binds to the 3'UTR of Sirt1 mRNA and promotes its degradation. [40][41][42][43][44][45][46][47] Agents of this type may be of particular interest in cardiovascular medicine, inasmuch as upregulation of miR-34a, in addition to its suppressive effect on Sirt1 expression, works in additional ways to compromise vascular health. 48 Astaxanthin is reported to increase protein expression of Sirt1 in a range of rodent tissues; the mechanism responsible remains unclear.…”

The Potential of Plum Seed Residue: Unraveling the Effect of Processing on Phytochemical Composition and Bioactive Properties

“…According to the functionalities, the main phenolic compounds determined in the seeds studied were neochlorogenic, chlorogenic, and protocatechuate acids, which are known to be phenolic compounds with neuroprotective, antibacterial, anti-inflammatory, anti-cancer, anti-diabetic, and hypoallergenic activities [ 65 , 66 , 67 , 68 ]. 2,3-dihydroxybenzoic acid is attributed to present antibacterial properties against the growth of pathogens such as Escherichia coli , Listeria motocytogenes , or Staphylococcus aureus among others; thus, it is widely used against antibiotic resistance [ 69 ].…”

The anti-obesity effect of mulberry leaf (Mori Folium) extracts was increased by bioconversion with Pectinex

“…However, it is expected that the reason why Pectinex only increased the content of 5-CQA and 4-CQA like this can be elucidated through future research. Several studies reported that 5-CQA had an anti-inflammatory effect in brain disease by inhibiting proinflammatory cytokines 56 , high potential for the development of human immunodeficiency virus-1 drug by inhibiting its reverse transcriptase activity 57 , and improved hepatic lipid accumulation and inflammation by regulating miR-34a 58 . In addition, 4-CQA was reported to have antioxidant activity 59 .…”