Liquiritigenin, an aglycone of liquiritin in Glycyrrhizae radix, prevents acute liver injuries in rats induced by acetaminophen with or without buthionine sulfoximine.
Glycyrrhizae radix has been used as one of the oldest and most frequently employed botanicals in both western and oriental countries. Previously, we showed that liquiritigenin (LQ), an aglycone of liquiritin in G. radix, exerts cytoprotective effects against heavy metal-induced toxicity in vitro. This study investigated in vivo protective effects of LQ against acute liver injuries induced by acetaminophen (APAP) or APAP plus buthionine sulfoximine (BSO). Liver injuries were assessed by blood biochemistry and histopathology in rats administered with LQ purified from the acid hydrolyates of liquiritin singly (p.o. or i.v., 2-4 days) or in combination with dimethyl-4,4'-dimethoxy-5,6,5',6'-dimethylenedioxybiphenyl-2,2'-dicarboxylate (DDB), a synthetic derivative of Schisandrin C in Fructus shizandrae, and exposed to APAP or APAP + BSO. LQ treatments (oral) effectively decreased liver injuries induced by a single dose of APAP, as evidenced by decreases in hepatic necrosis and inflammation as well as plasma alanine aminotransferase and lactate dehydrogenase activities. LQ, when intravenously applied, enhanced hepatoprotective effect with a greater potency. APAP + BSO led to severe liver injuries, resulting in lethality. LQ pretreatments significantly reduced the potentiated liver necrosis, decreasing mortality. In spite of the improvement in blood biochemistry, DDB failed to protect the liver from injuries induced by APAP or APAP + BSO. Combined treatments of rats with LQ and DDB showed some additive protective effect. The present study demonstrates that LQ efficaciously protects the liver from acute injuries induced by APAP or from APAP-induced severe injuries during GSH deficiency, indicating that LQ is one of the principal cytoprotective components comprised in G. radix.
Kim
Young Woo
YW
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Republic of Korea.
Ki
Sung Hwan
SH
Lee
Jong Rok
JR
Lee
Song Jin
SJ
Kim
Choon Won
CW
Kim
Sang Chan
SC
Kim
Sang Geon
SG
D000082:Acetaminophen / Q000633:toxicity*; D000208:Acute Disease; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D019328:Buthionine Sulfoximine / Q000633:toxicity*; D002851:Chromatography, High Pressure Liquid; D007887:Fabaceae / Q000737:chemistry*; D044950:Flavanones / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D005960:Glucosides / Q000737:chemistry*; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism / Q000473:pathology*; D015394:Molecular Structure; D051381:Rats; D017207:Rats, Sprague-Dawley
D044950:Flavanones; D005960:Glucosides; D000082:Acetaminophen; D019328:Buthionine Sulfoximine; D007770:L-Lactate Dehydrogenase; D000410:Alanine Transaminase; C512196:liquiritin; C083152:liquiritigenin