Magnolia officinalis reverses alcoholic fatty liver by inhibiting the maturation of sterol regulatory element-binding protein-1c.
The generally accepted hypothesis for the pathogenesis of alcoholic liver disease (ALD) is the two-hit model, which proposes that fat accumulation in the liver increases the sensitivity of the liver to a second hit that leads to inflammatory liver cell damage. In this study we evaluated the effects of Magnolia officinalis (MO), which contains honokiol and magnolol as the primary pharmacological components, to eradicate fatty liver in rats fed an ethanol diet. In vitro studies showed that MO was able to protect RAW 264.7 cells from ethanol-induced production of tumor necrosis factor-alpha, reactive oxygen species, and superoxide anion radicals; the activation of NADPH oxidase; and subsequent cell death. We also investigated the therapeutic effects of MO on alcoholic fatty liver in Lieber-DeCarli ethanol diet-fed rats. MO treatment of the rats for the last 2 weeks of ethanol feeding completely reversed all the serum, hepatic parameters, and fatty liver changes. The increased maturation of sterol regulatory element-binding protein-1c in the liver by ethanol treatment was completely inhibited by treatment with MO. Therefore, MO may be a promising candidate for development as a therapeutic agent for ALD.
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Korea.
Hu-Quan
HQ
Yin
Young-Tae
YT
Je
Young-Chul
YC
Kim
Young-Kee
YK
Shin
Sanghyun
S
Sung
Kiyong
K
Lee
Gil-Saeng
GS
Jeong
Youn-Chul
YC
Kim
Byung-Hoon
BH
Lee
D000818:Animals; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000633:toxicity; D016207:Cytokines / Q000096:biosynthesis; D000431:Ethanol / Q000633:toxicity; D005235:Fatty Liver, Alcoholic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005978:Glutathione / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D031566:Magnolia / Q000737:chemistry*; D008297:Male; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D024301:Plant Bark / Q000737:chemistry; D010936:Plant Extracts / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012436:S-Adenosylmethionine / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D013481:Superoxides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D002492:Central Nervous System Depressants; D016207:Cytokines; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D051780:Sterol Regulatory Element Binding Protein 1; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D000431:Ethanol; D012436:S-Adenosylmethionine; D019255:NADPH Oxidases; D005978:Glutathione