Differences in pharmacokinetics and ex vivo antioxidant activity following intravenous and oral administrations of emodin to rats.
Emodin, a natural anthraquinone polyphenol, has been reported to possess promising in vitro antioxidation, anticancer and anti-inflammatory activities. Whether the in vitro bioactivities can predict in vivo effects remained an unanswered question without understanding emodin pharmacokinetics in animals. To fill this blank, this study investigated the biological fate of emodin in rats. Emodin was intravenously (5.0 mg/kg) and orally (20.0 and 40.0 mg/kg) administered to rats. Blood samples were assayed by HPLC before and after hydrolysis with sulfatase and beta-glucuronidase. It is observed that after intravenous bolus of emodin, the parent form of emodin declined rapidly, and emodin glucuronides, omega-hydroxyemodin (omega-OHE) and omega-OHE sulfates/glucuronides all emerged instantaneously. In contrast, when emodin was given orally, emodin glucuronides were exclusively present in serum, whereas emodin, omega-OHE and omega-OHE sulfates/glucuronides were not detected. In order to evaluate the in vivo antioxidation activity, the serum metabolites of emodin following intravenous and oral administrations were prepared from rats and characterized, followed by investigating the effects on 2,2'-azobis(2-amidinopropane hydrochloride)-induced hemolysis. The results suggested that the serum metabolites of oral emodin exhibited more promising free radical scavenging activity than those of intravenous emodin and emodin parent form. We suggest biologists to redirect their targets to emodin glucuronide.
Shia
Chi-Sheng
CS
Institute of Pharmaceutical Chemistry, China Medical University, 40402 Taichung, Taiwan.
Hou
Yu-Chi
YC
Tsai
Shang-Yuan
SY
Huieh
Pei-Hsun
PH
Leu
Yann-Lii
YL
Chao
Pei-Dawn Lee
PD
D000284:Administration, Oral; D000578:Amidines / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics*; D004642:Emodin / Q000008:administration & dosage* / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D020719:Glucuronides / Q000097:blood / Q000378:metabolism; D006461:Hemolysis / Q000187:drug effects; D007275:Injections, Intravenous; D008297:Male; D016877:Oxidants / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000578:Amidines; D000975:Antioxidants; D020719:Glucuronides; D016877:Oxidants; C046728:2,2'-azobis(2-amidinopropane); D004642:Emodin