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Bixin attenuates carbon tetrachloride induced oxidative stress, inflammation and fibrosis in kidney by regulating the Nrf2/TLR4/MyD88 and PPAR-γ/TGF-β1/Smad3 pathway.

Abstract
Bixin, an natural carotenoid extracted from the seeds of the Bixa orellana has been shown to possess numerous important pharmacological activities. The present study was aimed to investigate the mechanisms of Bixin on carbon tetrachloride (CCl4)-induced kidney inflammation, fibrosis and oxidative stress in mice. Our results showed that Bixin improved renal damage by decreasing the serum levels of creatinine, urea, uric acid and alleviating kidney fibrosis. Bixin ameliorated CCl4-induced inflammation in kidneys by reducing the levels of TNF-α and IL-1β. Bixin suppressed oxidative stress by decreasing the MDA level and increasing the activation of SOD, CAT and GPx. Furthermore, Bixin increased the levels of PPAR-γ, NQO1, HO-1 and the nuclear translocation of Nrf2 in the kidneys of mice. Bixin supplementation inhibited the activation of TLR4, MyD88, NF-κB, TGF-β and Smad3. Thus, this study demonstrated that Bixin possesses anti-oxidant, anti-inflammatory and anti-fibrosis properties through regulating the Nrf2/TLR4/MyD88 and PPAR-γ/TGF-β1/Smad3 pathways.
AuthorsJie-Qiong Ma, Yu-Jia Zhang, Zhi-Kai Tian, Chan-Min Liu
JournalInternational immunopharmacology (Int Immunopharmacol) Vol. 90 Pg. 107117 (Jan 2021) ISSN: 1878-1705 [Electronic] Netherlands
PMID33162346 (Publication Type: Journal Article)
CopyrightCopyright © 2020 Elsevier B.V. All rights reserved.
Chemical References
  • Anti-Inflammatory Agents
  • Antioxidants
  • Inflammation Mediators
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, mouse
  • PPAR gamma
  • Pparg protein, mouse
  • Smad3 Protein
  • Smad3 protein, mouse
  • Tgfb1 protein, mouse
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • Transforming Growth Factor beta1
  • Carotenoids
  • bixin
  • Carbon Tetrachloride
Topics
  • Animals
  • Anti-Inflammatory Agents (pharmacology)
  • Antioxidants (pharmacology)
  • Carbon Tetrachloride
  • Carotenoids (pharmacology)
  • Disease Models, Animal
  • Fibrosis
  • Inflammation Mediators (metabolism)
  • Kidney (drug effects, metabolism, pathology)
  • Kidney Diseases (chemically induced, metabolism, pathology, prevention & control)
  • Male
  • Mice, Inbred ICR
  • Myeloid Differentiation Factor 88 (metabolism)
  • NF-E2-Related Factor 2 (metabolism)
  • Oxidative Stress (drug effects)
  • PPAR gamma (metabolism)
  • Signal Transduction
  • Smad3 Protein (metabolism)
  • Toll-Like Receptor 4 (metabolism)
  • Transforming Growth Factor beta1 (metabolism)

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