title: Bioavailability of andrographolide and protection against carbon tetrachloride-induced oxidative damage in rats.
abstract: Andrographolide, a bioactive diterpenoid, is identified in Andrographis paniculata. In this study, we investigated the pharmacokinetics and bioavailability of andrographolide in rats and studied whether andrographolide enhances antioxidant defense in a variety of tissues and protects against carbon tetrachloride-induced oxidative damage. After a single 50-mg/kg administration, the maximum plasma concentration of andrographolide was 1μM which peaked at 30min. The bioavailability of andrographolide was 1.19%. In a hepatoprotection study, rats were intragastrically dosed with 30 or 50mg/kg andrographolide for 5 consecutive days. The results showed that andrographolide up-regulated glutamate cysteine ligase (GCL) catalytic and modifier subunits, superoxide dismutase (SOD)-1, heme oxygenase (HO)-1, and glutathione (GSH) S-transferase (GST) Ya/Yb protein and mRNA expression in the liver, heart, and kidneys. The activity of SOD, GST, and GSH reductase was also increased in rats dosed with andrographolide (p<0.05). Immunoblot analysis and EMSA revealed that andrographolide increased nuclear Nrf2 contents and Nrf2 binding to DNA, respectively. After the 5-day andrographolide treatment, one group of animals was intraperitoneally injected with carbon tetrachloride (CCl4) at day 6. Andrographolide pretreatment suppressed CCl4-induced plasma aminotransferase activity and hepatic lipid peroxidation (p<0.05). These results suggest that andrographolide is quickly absorbed in the intestinal tract in rats with a bioavailability of 1.19%. Andrographolide protects against chemical-induced oxidative damage by up-regulating the gene transcription and activity of antioxidant enzymes in various tissues.
authors.affiliation: Department of Nutrition, China Medical University, Taichung, Taiwan.
authors.forename: Haw-Wen
authors.initials: HW
authors.lastname: Chen
authors.affiliation: Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan.
authors.forename: Chin-Shiu
authors.initials: CS
authors.lastname: Huang
authors.affiliation: School of Nutrition, Chung Shan Medical University, Taichung, Taiwan; Department of Nutrition, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Chien-Chun
authors.initials: CC
authors.lastname: Li
authors.affiliation: Department of Nutrition, China Medical University, Taichung, Taiwan.
authors.forename: Ai-Hsuan
authors.initials: AH
authors.lastname: Lin
authors.affiliation: Department of Nutrition, China Medical University, Taichung, Taiwan.
authors.forename: Yu-Ju
authors.initials: YJ
authors.lastname: Huang
authors.affiliation: Department of Biomedical Science, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Tsu-Shing
authors.initials: TS
authors.lastname: Wang
authors.affiliation: Department of Nutrition, China Medical University, Taichung, Taiwan. Electronic address: htyao@mail.cmu.edu.tw.
authors.forename: Hsien-Tsung
authors.initials: HT
authors.lastname: Yao
authors.affiliation: Department of Nutrition, China Medical University, Taichung, Taiwan; Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan. Electronic address: cklii@mail.cmu.edu.tw.
authors.forename: Chong-Kuei
authors.initials: CK
authors.lastname: Lii
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000493:pharmacokinetics*; D001682:Biological Availability; D002251:Carbon Tetrachloride / Q000633:toxicity*; D004224:Diterpenes / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000975:Antioxidants; D004224:Diterpenes; C030419:andrographolide; D002251:Carbon Tetrachloride
keywords: Andrographolide; Antioxidant enzymes; Bioavailability; Carbon tetrachloride; Hepatoprotection; Nrf2