Related Experiment Video
Updated: Apr 12, 2026
Synthesis and Characterization of an Aspirin-fumarate Prodrug that Inhibits NFκB Activity and Breast Cancer Stem Cells
Published on: January 18, 2017
Understanding the mode of action of a pterostilbene derivative as anti-inflammatory agent
Kumar Nikhil1, Shruti Sharan1, Srinivasa Rao Palla2
1Molecular Endocrinology Laboratory, Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee 247 667, Uttarakhand, India.
Abstract:
Inflammatory response plays an important role not only in the normal physiology, but also in the pathology of certain diseases such as cancers. In our previous study, we found a novel derivative of pterostilbene (PTER), to be an effective inducer of apoptosis in human breast and prostate cancer cells affecting various cellular targets. Herein, we further attempted to investigate its anti-inflammatory potential followed by its probable mode of action. The newly developed compound was tested for its anti-inflammatory actions in lipopolysaccharide (LPS) stimulated RAW264.7 macrophages and carrageenan induced rat paw edema models. Our data showed that the derivative inhibited the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) as well as the downstream products like nitric oxide (NO) and PGE2, at much lower doses as compared to PTER. This effect was found to be associated with the inhibition of phosphorylation/degradation of IκB-α and nuclear translocation of the p-NFκB p65. Moreover, inhibition of mitogen-activated protein kinases (MAPKs) and activator protein-1 (AP-1) was also observed. In addition, the newly developed compound also reduced the paw edema, the tissue content of NO, PGE2 and expression of iNOS and COX-2 proteins within the tissues after λ-carrageenan stimulation. Taken together, our findings provide the possibility that the PTER derivative might have enhanced cancer chemopreventive potential based on its stronger anti-NFκB and anti-inflammatory activities as compared to its natural counterpart, i.e., PTER. Thus, this compound can be used towards the development of an effective anti-inflammatory agent.
Insights
A novel pterostilbene derivative shows potent anti-inflammatory effects by inhibiting key inflammatory pathways. This compound demonstrates enhanced potential for cancer chemoprevention compared to pterostilbene.
Area of Science:
- Pharmacology
- Immunology
- Oncology
Background:
- Inflammatory responses are crucial in both normal physiology and diseases like cancer.
- A previous study identified a novel pterostilbene (PTER) derivative as an effective apoptosis inducer in cancer cells.
Purpose of the Study:
- To investigate the anti-inflammatory potential of a novel pterostilbene derivative.
- To elucidate the probable mechanism of its anti-inflammatory action.
Main Methods:
- Tested anti-inflammatory actions in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and carrageenan-induced rat paw edema models.
- Assessed inhibition of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nitric oxide (NO), and prostaglandin E2 (PGE2).
- Evaluated effects on IκB-α, nuclear factor-kappa B (NF-κB), mitogen-activated protein kinases (MAPKs), and activator protein-1 (AP-1) signaling pathways.
Main Results:
- The PTER derivative significantly inhibited iNOS and COX-2 expression and their downstream products (NO, PGE2) at lower doses than PTER.
- Inhibition was linked to suppressed IκB-α degradation and p-NF-κB p65 nuclear translocation.
- The compound also reduced MAPK and AP-1 activation, decreased paw edema, and lowered inflammatory markers in tissue.
Conclusions:
- The novel PTER derivative exhibits stronger anti-inflammatory and anti-NF-κB activities than PTER.
- This enhanced activity suggests potential for improved cancer chemoprevention.
- The compound holds promise for developing effective anti-inflammatory agents.
Related Concept Videos
01:19Antiasthma Drugs: Leukotriene Modifiers
Leukotriene modifiers work through two distinct mechanisms:
01:24Antiasthma Drugs: Methylxanthines
Theophylline is thought to inhibit phosphodiesterase enzymes, increasing intracellular levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). This rise in cAMP and cGMP concentrations stimulates cardiac function,...
01:23Treatment for Pulmonary Arterial Hypertension: Prostacyclin Receptor Agonists
These agonists bind to the IPR receptor situated on the plasma membrane of the pulmonary artery smooth muscle cells. This binding triggers a cascade of reactions known as the GS-AC-cAMP-PKA pathway. This pathway results in the relaxation of smooth muscle...
01:25Antiasthma Drugs: Mast Cell Stabilizers and Anti-IgE Drugs
Mast cell stabilizers, such as cromolyn (also known as sodium cromoglycate) and nedocromil (Tilade), are effective drugs in asthma management. These stabilizers hinder histamine release by skillfully obstructing the activation of mast cells and other cellular entities. Notably, they navigate this task without...
01:25Antiasthma Drugs: Inhaled Corticosteroids and Glucocorticoids
ICS work through a multifaceted mechanism of action. They suppress the inflammatory response caused by the proliferation of TH cells. They also reduce the transcription of the IL-2 gene, which is involved in the...
01:20Antiasthma Drugs: Muscarinic Receptor Antagonists
Antimuscarinic agents compete with ACh for the same binding site on the muscarinic receptors. By binding to these receptors, they inhibit the downstream effects of ACh and block the parasympathetic...