Protective Mechanisms of Acacetin against d-Galactosamine and Lipopolysaccharide-Induced Fulminant Hepatic Failure in Mice

Abstract

This study examined the hepatoprotective effects of acacetin (1), a flavonoid isolated from Agastache rugosa, against d-galactosamine (GalN) and lipopolysaccharide (LPS)-induced fulminant hepatic failure. Mice were given an intraperitoneal injection of 1 (25, 50, and 100 mg/kg), or the vehicle alone (5% dimethyl sulfoxide-saline), 1 h before GalN (800 mg/kg)/LPS (40 μg/kg) treatment and sacrificed at 6 h after GalN/LPS injection. GalN/LPS markedly increased mortality and serum aminotransferase activity, and these increases were attenuated by 1. GalN/LPS increased serum tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels, while 1 attenuated TNF-α levels and further increased IL-6 levels. GalN/LPS increased protein expression of toll-like receptor 4, phosphorylation of extracellular signal-related kinase, and p38 and c-Jun N-terminal kinase and increased nuclear protein expression of nuclear factor κB; these increases were attenuated by 1. GalN/LPS increased Atg5 and Atg7 protein expressions, and these increases were augmented by 1. GalN/LPS activated autophagic flux as indicated by decreased microtubule-associated protein 1 light chain 3-II and sequestosome1/p62 protein expression. This activation was enhanced by 1. These findings suggest that 1 protects against GalN/LPS-induced liver injury by suppressing TLR4 signaling and enhancing autophagic flux.

Chemical constituents and coagulation activity of Agastache rugosa

“…The techniques for isolation and separation of both compounds are simple and easy to operate. The acute toxicity experiment of acacetin showed that it was a safe clinical medication (LD 50 = 933 mg/kg) [ 26 ]. The acute toxicity test of tilianin had not been done yet and there was no report about its toxicity.…”

Natural Compounds from the Marine Brown Alga Caulocystis cephalornithos with Potent In Vitro-Activity against the Parasitic Nematode Haemonchus contortus

“…(mustard sponge), 6-undecylsalicyclic acid ( 3 ) and 6-tridecylsalicylic acid ( 4 ) from Caulocystis cephalornithos (marine brown alga), 6-hydroxy-2,5-dimethoxy-9-phenylphenalen-1-one ( 5 ) from Haemodorum spicatum (bloodroot), fuliginosin A ( 6 ) and anigopreissin A ( 7 ) from Macropidia fuliginosa (black kangaroo paw), and acacetin ( 8 ) from Agastache rugosa (Korean mint). These compounds have been shown to possess anti-inflammatory, anti-cancer and/or antimicrobial properties [ 29 , 33 , 34 , 35 , 36 , 37 ]; the latter properties suggest that some of these compounds might also have activities against pathogens such as parasites. In the present study, we explored the activity of select secondary metabolites against H. contortus using established in vitro methods, with the aim of identifying candidate compounds to optimise and develop as anthelmintic drugs.…”

Shikonin protects against D-Galactosamine and lipopolysaccharide-induced acute hepatic injury by inhibiting TLR4 signaling pathway

“…LPS/GalN-induced mice liver injury model has been widely used to evaluate the biological activities of hepatoprotective agents [ 21 ]. In this study, we evaluated the protective effects of shikonin on liver injury using this model.…”