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Nrf2 knockout attenuates the anti-inflammatory effects of phenethyl isothiocyanate and curcumin

Sarandeep S S Boyanapalli1, Ximena Paredes-Gonzalez, Francisco Fuentes

  • 1Center for Cancer Prevention Research, Department of Pharmaceutics, Ernest-Mario School of Pharmacy, Rutgers, The State University of New Jersey , 160 Frelinghuysen Road, Piscataway, New Jersey 08854, United States.

Chemical Research in Toxicology
|November 12, 2014
PubMed

Insights

Phytochemicals like phenethyl isothiocyanate (PEITC) and curcumin (CUR) show anti-inflammatory and antioxidative effects, but these depend on the Nrf2 (nuclear factor erythroid 2-related factor 2) pathway. Nrf2 activation is crucial for these compounds to reduce inflammation and oxidative stress.

Area of Science:

  • Phytochemistry and Molecular Biology
  • Immunology and Inflammation Research
  • Pharmacology and Drug Discovery

Background:

  • Phytochemicals are increasingly studied for their medicinal properties.
  • Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a key role in cellular defense mechanisms.
  • Understanding Nrf2's role is vital for harnessing phytochemicals therapeutically.

Purpose of the Study:

  • To investigate the role of Nrf2 in mediating the anti-inflammatory and antioxidative effects of phenethyl isothiocyanate (PEITC) and curcumin (CUR).
  • To compare the efficacy of PEITC and CUR in modulating inflammatory and oxidative stress markers in macrophages with and without Nrf2.
  • To elucidate the molecular mechanisms underlying the action of PEITC and CUR in relation to Nrf2 activation.

Main Methods:

  • Ex vivo treatment of peritoneal macrophages from Nrf2(+/+) and Nrf2(-/-) mice with PEITC and CUR.
  • Stimulation of macrophages with lipopolysaccharides (LPS) to induce inflammation.
  • Assessment of gene expression (qPCR) for inflammatory markers (COX-2, iNOS, IL-6, TNF-α) and antioxidative markers (HO-1).
  • Evaluation of protein expression (Western blot, ELISA) for key inflammatory and antioxidative proteins.

Main Results:

  • LPS increased inflammatory markers in both Nrf2(+/+) and Nrf2(-/-) macrophages.
  • PEITC and CUR significantly reduced inflammatory gene expression and increased HO-1 in Nrf2(+/+) macrophages.
  • These anti-inflammatory and antioxidative effects were significantly diminished in Nrf2(-/-) macrophages.
  • PEITC showed greater efficacy than CUR in reducing COX-2 and increasing HO-1 protein expression in Nrf2(+/+) macrophages.

Conclusions:

  • Nrf2 is essential for the anti-inflammatory and antioxidative activities of PEITC and CUR.
  • The study highlights the therapeutic potential of Nrf2-activating phytochemicals in managing inflammatory and oxidative stress-related conditions.
  • PEITC demonstrates potent Nrf2-dependent anti-inflammatory effects in macrophages.

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