Related Experiment Video
Updated: Jul 16, 2026
Visualization of Vascular Ca2+ Signaling Triggered by Paracrine Derived ROS
Published on: December 21, 2011
Sesamol protects against LPS-induced inflammation in rat peritoneal macrophages by promoting SIRT1-induced repression
Aparna Nandakumaran Sakunthala1, Aswani Sukumaran Sreedevi1, Mithra Sudha Mohan1
11Department of Biochemistry, University of Kerala, Thiruvananthapuram, Kerala 695581, India.
Objectives:
Sesamol, a polyphenolic compound isolated from roasted sesame seeds exhibits significant anti-inflammatory effect, but the molecular mechanism is poorly understood. Peritoneal macrophages play a pivotal role in the control of infections and inflammatory pathologies and are also found in injured tissues along with resident macrophages. The present study aimed to examine the anti-inflammatory effect of sesamol and the molecular mechanisms involved, particularly the role of sesamol in modulating SIRT1- and SIRT1-mediated deacetylation of NF-κB p65 using in vivo activated peritoneal macrophages.
Materials:
Sprague Dawley rats were injected with LPS to induce inflammation and sesamol was intraperitoneally administered to study its anti-inflammatory effect. ELISA and real time PCR were used to study the expression of proinflammatory cytokines. Effects of sesamol on iNOS and COX-2 were studied with activity assays and ELISA. ICAM-1, MMP-9 and TIMP-1 expressions were analysed by ELISA, RT PCR and zymography. Western blot analysis was performed to determine p65 acetylation. Nuclear translocation of p65 was evaluated by ELISA. The gene and protein expression of SIRT1 was analysed with ELISA and real time PCR.
Results:
Sesamol downregulated the expression of proinflammatory markers TNF-α, IL-6, iNOS, COX-2, TLR-4, ICAM-1 and MMP-9 in rat peritoneal macrophages. Additionally, sesamol upregulated SIRT1expression and attenuated the nuclear translocation of NF-κB p65 by promoting its deacetylation. Inhibition of SIRT1 by its specific inhibitor EX527 diminished the inhibitory effect of sesamol on TNF-α and IL-6. Moreover, EX527 reduced the suppressive impact of sesamol on p65 acetylation and subsequent nuclear translocation.
Conclusion:
Our findings suggest that the anti-inflammatory effect of sesamol involves upregulation of SIRT-1, leading to the downregulation of the nuclear translocation of NF-κB p65 through its deacetylation. Therefore, the dietary bioactive compound sesamol shows potential as a promising strategy for preventing inflammatory diseases by modulating SIRT1 expression.
Insights
Sesamol, a compound from sesame seeds, reduces inflammation by increasing SIRT1. This process inhibits NF-κB p65 nuclear translocation, offering potential for inflammatory disease prevention.
Area of Science:
- Biochemistry
- Immunology
- Pharmacology
Background:
- Sesamol, a natural polyphenol from sesame seeds, possesses anti-inflammatory properties.
- The precise molecular mechanisms underlying sesamol's anti-inflammatory effects remain largely unelucidated.
- Peritoneal macrophages are critical immune cells involved in inflammatory responses and tissue injury.
Purpose of the Study:
- To investigate the anti-inflammatory effects of sesamol on activated peritoneal macrophages.
- To elucidate the molecular mechanisms, focusing on the role of SIRT1 and NF-κB p65.
- To assess sesamol's impact on key inflammatory markers and signaling pathways.
Main Methods:
- Induction of inflammation in Sprague Dawley rats using LPS.
- Intraperitoneal administration of sesamol and assessment of its effects on inflammatory markers.
- Utilized techniques including ELISA, real-time PCR, Western blot, and zymography.
- Investigated the modulation of SIRT1 expression and NF-κB p65 acetylation and nuclear translocation.
Main Results:
- Sesamol significantly downregulated pro-inflammatory cytokines (TNF-α, IL-6) and markers (iNOS, COX-2, TLR-4, ICAM-1, MMP-9).
- Sesamol upregulated SIRT1 expression and inhibited NF-κB p65 nuclear translocation via deacetylation.
- Inhibition of SIRT1 with EX527 reversed the anti-inflammatory effects of sesamol.
Conclusions:
- Sesamol exerts anti-inflammatory effects by upregulating SIRT1, which deacetylates and inhibits NF-κB p65 nuclear translocation.
- Sesamol demonstrates potential as a dietary strategy for managing inflammatory diseases through SIRT1 modulation.
