Shizukaol D Isolated from Chloranthus japonicas Inhibits AMPK-Dependent Lipid Content in Hepatic Cells by Inducing Mitochondrial Dysfunction

Abstract

This study is the first to demonstrate that shizukaol D, a natural compound isolated from Chloranthus japonicus , can activate AMP- activated protein kinase (AMPK), a key sensor and regulator of intracellular energy metabolism, leading to a decrease in triglyceride and cholesterol levels in HepG2 cells. Furthermore, we found that shizukaol D induces mitochondrial dysfunction by depolarizing the mitochondrial membrane and suppressing energy production, which may result in AMPK activation. Our results provide a possible link between mitochondrial dysfunction and AMPK activation and suggest that shizukaol D might be used to treat metabolic syndrome.

Herbal Medicine in the Treatment of Non-Alcoholic Fatty Liver Diseases-Efficacy, Action Mechanism, and Clinical Application

“…Previous research has proved that herbal medicine such as cyclocarya paliurus, sida rhomboidea.roxb, punica granatum L., resveratrol, mangosteen pericarp, epigallocatechin gallate, and shexiang baoxin pill, were shown to be effective on mitochondrial dysfunction during treating the NAFLD . More detail, Shizukaol D (extracted from Chloranthus japonicas) improved mitochondrial dysfunction, leading to hepatic AMPK-dependent lipid content reduction (Hu et al, 2013). Polygonati Rhizoma and Polygonatum kingianum promote mitochondrial boxidation via increasing the CPT-1 activity to block long-chain fatty acid enter mitochondria, and improve mitochondrial function via inhibiting HFD-induced excessive production of ROS and malondialdehyde (MDA) .…”

Treatment implications of natural compounds targeting lipid metabolism in nonalcoholic fatty liver disease, obesity and cancer

“…Shizukaol D is a sesquiterpenoid isolated from chloranthus japonicas and was shown to activate AMPK and decrease triglyceride and cholesterol levels 42. AMPK activation results in both the phosphorylation and inactivation of ACC and also the phosphorylation of MCD, leading to reduced malonyl-CoA levels and FA synthesis.…”

Three Sesquiterpenoid Dimers from Chloranthus japonicus: Absolute Configuration of Chlorahololide A and Related Compounds

“…The previous phytochemical investigations on this plant have resulted in the isolation of a number of sesquiterpenoid dimers . Some of them were reported to show multibiological activities, such as antifungal, potent and selective tumor growth‐inhibitory, inhibition of cell adhesion molecule expression, and of tyrosinase …”

“…[6][7][8][9] Some of them were reported to show multibiological activities, such as antifungal, potent and selective tumor growth-inhibitory, inhibition of cell adhesion molecule expression, and of tyrosinase. [10][11][12] As part of our ongoing search for new bioactive natural products from the traditional Chinese herbal medicines in the Qinba Mountains, [13][14][15][16][17] a chemical study of the whole plant of C. japonicus was carried out, leading to the discovery of a new sesquiterpenoid dimer, named multistalide C (1), together with two known compounds, shizukaols C and D (2 and 3) (Chart 1). Herein, we describe the isolation, structural identification, including the absolute configuration, and brine shrimp larvae toxicity of the three compounds.…”