Paeonol, an Ingredient of Kamishoyosan, Reduces Intracellular Lipid Accumulation by Inhibiting Glucocorticoid Receptor Activity in 3T3-L1 Cells

Abstract

Excessive triglyceride accumulation in lipid-metabolizing tissues is associated with an increased risk of a variety of metabolic diseases. Kamishoyosan (KSS) is a Kampo composed of 10 constituent herbs, and contains moutan cortex (MC) and paeonol (PN) as the major ingredient of MC. Here, we demonstrate the molecular mechanism underlying the effect of KSS on the differentiation of mouse preadipocytes (3T3-L1 cells). KSS inhibited the accumulation of triglycerides in a dose-dependent manner in 3T3-L1 cells that were induced to differentiate into adipocytes. We also found that MC and PN were responsible for the anti-adipogenetic effect of KSS and significantly suppressed the expression of CCAAT/enhancer-binding proteins-δ (C/EBP-δ) mRNA 3 days after the induction of differentiation. Thus, PN may contribute to the anti-adipogenetic property of MC in 3T3-L1 cells. In addition, PN inhibited dexamethasone (Dex)-induced glucocorticoid receptor (GR) promoter activity. Taken together, these results suggest that PN suppresses C/EBP-δ expression by inhibiting Dex-induced GR promoter activity at the early stage of differentiation and, consequently, delays differentiation into mature adipocytes. Our results suggest that the habitual intake of Kampo-containing PN contributes to the prevention of the onset of metabolic diseases by decreasing the excessive accumulation of triglycerides in lipid-metabolizing tissues.

Plant Extracts in Obesity: A Role of Gut Microbiota

“…In HFD-induced atherosclerotic rabbits, paeonol exerts anti-atherosclerosis effects by inhibition of lipid peroxidation and improvement of anti-inflammatory action ( 63 ). In accord with these findings in in vivo studies, several in vitro studies have reported that paeonol can markedly and dose-dependently reduce intracellular lipid accumulation in mouse preadipocytes and macrophages, and delay preadipocytes differentiation into mature adipocytes, thus protecting against metabolic diseases ( 64 , 65 ). Overall, overwhelming evidence suggests that paeonol treatment can combat obesity and its related metabolic diseases such as atherosclerosis and steatohepatitis.…”

Paeonol suppresses lipid formation and promotes lipid degradation in adipocytes

“…Paeonol, also known as peony, is derived from the dried bark of Paeonia suffruticosa , which belongs to Paeoniaceae (Ranunculaceae) or the dried root of Xu Chang qing (Asclepiadaceae) or the whole grass ( 4 ). The chemical name of paeonol is 2-hydroxy-4-methoxyacetophenone and it has a wide range of biological activities ( 5 ).…”