Homoyessotoxin alleviates inflammatory responses by regulating the TLR4/MyD88/NFκB and Nrf2/HO-1 pathways

Area of Science:

• Marine natural products
• Immunology
• Pharmacology

Background:

• Inflammation is a complex biological response implicated in numerous diseases.
• Marine polyether toxins, such as homoyessotoxin (hYTXs), are increasingly investigated for their therapeutic potential.
• Understanding the precise mechanisms of action for marine-derived compounds is crucial for drug development.

Purpose of the Study:

• To elucidate the anti-inflammatory mechanisms of homoyessotoxin (hYTXs).
• To investigate the effects of hYTXs on critical inflammatory signaling pathways.
• To validate the therapeutic potential of hYTXs in vitro and in vivo models of inflammation.

Main Methods:

• Network pharmacology and molecular simulations were used to predict hYTXs' targets.
• In vitro studies utilized LPS-stimulated macrophages to assess cytokine release, ROS production, and protein expression.
• In vivo efficacy was evaluated in mouse models of systemic inflammation and ear edema.

Main Results:

• hYTXs demonstrated strong binding to TLR4 and NFκB1, key inflammatory mediators.
• In vitro, hYTXs suppressed pro-inflammatory cytokines (IL-6, TNF-α) and suppressed iNOS/COX-2 expression.
• In vivo, hYTXs reduced systemic inflammation, lung edema, and ear swelling, while activating the Nrf2/HO-1 antioxidant pathway.

Conclusions:

• hYTXs exhibit significant anti-inflammatory properties by dual regulation of TLR4/NFκB and Nrf2/HO-1 pathways.
• This study highlights hYTXs as a promising marine-derived candidate for treating inflammatory conditions.
• Further research is needed to explore hYTXs' clinical applications in sepsis and sterile inflammation.