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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 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 (CCl{sub 4}) at day 6. Andrographolide pretreatment suppressed CCl{sub 4}-induced plasma aminotransferase activity and hepatic lipid peroxidation (p < 0.05). These results suggest that andrographolide is quickly absorbed in  More>>
Authors:
Chen, Haw-Wen; [1]  Huang, Chin-Shiu; [2]  Li, Chien-Chun; [3]  Department of Nutrition, Chung Shan Medical University Hospital, Taichung, Taiwan (China)]; Lin, Ai-Hsuan; Huang, Yu-Ju; [1]  Wang, Tsu-Shing; [4]  Yao, Hsien-Tsung; [1]  Lii, Chong-Kuei; [1]  Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan (China)]
  1. Department of Nutrition, China Medical University, Taichung, Taiwan (China)
  2. Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan (China)
  3. School of Nutrition, Chung Shan Medical University, Taichung, Taiwan (China)
  4. Department of Biomedical Science, Chung Shan Medical University, Taichung, Taiwan (China)
Publication Date:
Oct 01, 2014
Product Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 280; Journal Issue: 1; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Subject:
60 APPLIED LIFE SCIENCES; ANTIOXIDANTS; BIOLOGICAL AVAILABILITY; CARBON TETRACHLORIDE; CYSTEINE; DAMAGE; DNA; GENES; GLUTATHIONE; HEART; KIDNEYS; LIGASES; LIVER; MESSENGER-RNA; OXIDATION; RATS; SUPEROXIDE DISMUTASE; TRANSCRIPTION
OSTI ID:
22439846
Country of Origin:
United States
Language:
English
Other Identifying Numbers:
Journal ID: ISSN 0041-008X; CODEN: TXAPA9; Other: PII: S0041-008X(14)00290-7; TRN: US15R2977009380
Availability:
Available from http://dx.doi.org/10.1016/j.taap.2014.07.024
Submitting Site:
USN
Size:
page(s) 1-9
Announcement Date:
Mar 07, 2016

Citation Formats

Chen, Haw-Wen, Huang, Chin-Shiu, Li, Chien-Chun, Department of Nutrition, Chung Shan Medical University Hospital, Taichung, Taiwan (China)], Lin, Ai-Hsuan, Huang, Yu-Ju, Wang, Tsu-Shing, Yao, Hsien-Tsung, Lii, Chong-Kuei, and Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan (China)]. Bioavailability of andrographolide and protection against carbon tetrachloride-induced oxidative damage in rats. United States: N. p., 2014. Web. doi:10.1016/J.TAAP.2014.07.024.
Chen, Haw-Wen, Huang, Chin-Shiu, Li, Chien-Chun, Department of Nutrition, Chung Shan Medical University Hospital, Taichung, Taiwan (China)], Lin, Ai-Hsuan, Huang, Yu-Ju, Wang, Tsu-Shing, Yao, Hsien-Tsung, Lii, Chong-Kuei, &amp; Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan (China)]. Bioavailability of andrographolide and protection against carbon tetrachloride-induced oxidative damage in rats. United States. https://doi.org/10.1016/J.TAAP.2014.07.024
Chen, Haw-Wen, Huang, Chin-Shiu, Li, Chien-Chun, Department of Nutrition, Chung Shan Medical University Hospital, Taichung, Taiwan (China)], Lin, Ai-Hsuan, Huang, Yu-Ju, Wang, Tsu-Shing, Yao, Hsien-Tsung, Lii, Chong-Kuei, and Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan (China)]. 2014. "Bioavailability of andrographolide and protection against carbon tetrachloride-induced oxidative damage in rats." United States. https://doi.org/10.1016/J.TAAP.2014.07.024.
@misc{etde_22439846,
title = {Bioavailability of andrographolide and protection against carbon tetrachloride-induced oxidative damage in rats}
author = {Chen, Haw-Wen, Huang, Chin-Shiu, Li, Chien-Chun, Department of Nutrition, Chung Shan Medical University Hospital, Taichung, Taiwan (China)], Lin, Ai-Hsuan, Huang, Yu-Ju, Wang, Tsu-Shing, Yao, Hsien-Tsung, Lii, Chong-Kuei, and Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan (China)]}
abstractNote = {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 (CCl{sub 4}) at day 6. Andrographolide pretreatment suppressed CCl{sub 4}-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. - Highlights: • The bioavailability of andrographolide is 1.19% in rats. • Plasma concentration reaches 1 μM after giving 50 mg/kg andrographolide. • Andrographolide up-regulates Nrf2-dependent antioxidant genes. • Andrographolide increases antioxidant defense in various tissues. • Andrographolide ameliorates carbon tetrachloride-induced hepatotoxicity in rats.}
doi = {10.1016/J.TAAP.2014.07.024}
journal = []
issue = {1}
volume = {280}
journal type = {AC}
place = {United States}
year = {2014}
month = {Oct}
}