Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5846184 | Toxicology and Applied Pharmacology | 2014 | 9 Pages |
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 1 μM which peaked at 30 min. The bioavailability of andrographolide was 1.19%. In a hepatoprotection study, rats were intragastrically dosed with 30 or 50 mg/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.
Keywords
GCLCNrf2GCLMGSHGSTGSSGkeap1ROSElectrophoretic mobility shift assayAntioxidant enzymesAndrographolideHepatoprotectionSODEMSA یا electrophoretic mobility shift assay Superoxide dismutaseantioxidant response elementnuclear factor erythroid 2-related factor 2Bioavailabilitythiobarbituric acid-reactive substancesAREheme oxygenaseKelch-like ECH-associated protein 1Carbon tetrachlorideglutamate cysteine ligase modifier subunitGlutamate cysteine ligase catalytic subunitGlutathioneglutathione S-transferaseglutathione disulfideReactive oxygen species
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Authors
Haw-Wen Chen, Chin-Shiu Huang, Chien-Chun Li, Ai-Hsuan Lin, Yu-Ju Huang, Tsu-Shing Wang, Hsien-Tsung Yao, Chong-Kuei Lii,