Exploring global natural product databases for NLRP3 inhibition: Unveiling novel combinatorial therapeutic strategy for hidradenitis suppurativa

Suleman M 1 , Murshed A 2 , Sayaf AM 3 , Khan A 4 , Khan SA 5 , Tricarico PM 6 Show all authors , Moltrasio C 7 , Agouni A 8 , Yeoh KK 9 , Marzano AV 10 , Crovella S 11

Affiliations 

  • 1 Laboratory of Animal Research Center (LARC), Qatar University, Doha, Qatar; Center for Biotechnology and Microbiology, University of Swat, Swat, Pakistan. Electronic address: suleman@uswat.edu.pk
  • 2 Department of Intensive Care Unit, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524000, China. Electronic address: alkubati99@yahoo.com
  • 3 School of Chemical Sciences, Universiti Sains Malaysia, Gelugor, Penang, Malaysia. Electronic address: amsayaf@gmail.com
  • 4 Department of Pharmaceutical Sciences, College of Pharmacy, QU Health, Qatar University, P.O. Box 2713, Doha, Qatar. Electronic address: abbas.khan@qu.edu.qa
  • 5 Tunneling Group, Biotechnology Centre, Doctoral School, Silesian University of Technology, Akademicka 2, Gliwice 44-100, Poland. Electronic address: salman.ali@polsl.pl
  • 6 Pediatric Department, Institute for Maternal and Child Health-IRCCS Burlo Garofolo, Trieste 34137, Italy. Electronic address: paolamaura.tricarico@burlo.trieste.it
  • 7 Dermatology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan 20122, Italy. Electronic address: chiara.moltrasio@policlinico.mi.it
  • 8 Department of Pharmaceutical Sciences, College of Pharmacy, QU Health, Qatar University, P.O. Box 2713, Doha, Qatar. Electronic address: aagouni@qu.edu.qa
  • 9 School of Chemical Sciences, Universiti Sains Malaysia, Gelugor, Penang, Malaysia. Electronic address: kkyeoh@usm.my
  • 10 Dermatology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan 20122, Italy; Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy. Electronic address: angelo.marzano@unimi.it
  • 11 Laboratory of Animal Research Center (LARC), Qatar University, Doha, Qatar. Electronic address: sgrovella@qu.edu.qa
J Infect Public Health, 2025 Feb 13;18(4):102697.
PMID: 39970853 DOI: 10.1016/j.jiph.2025.102697

Abstract

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition of the terminal hair follicle, which can present in sporadic, familial, or syndromic forms. The exact pathogenesis of HS remains elusive, posing a challenge for the development of effective treatments. Among the various immunological mechanisms, the NLRP3 inflammasome is thought to contribute to the pathogenesis of HS, releasing cytokines such as IL-1β and IL-18 which initiates and exacerbates inflammation. Consequently, targeting NLRP3 offers a potential strategy for mitigating inflammation in HS-affected skin.

METHODS: In this study we used the docking, molecular dynamics simulation and binding free energy approaches to identify the potent inhibitor of NLRP3 by screening the African phytocompounds and traditional Chinese medicine databases.

RESULTS: Our virtual drug screening analysis identified two lead compounds from each database, characterized by high docking scores such as SA-21676268 (-8.135 kcal/mol), SA-167673 (-10.251 kcal/mol), EA-45360194 (-10.376 kcal/mol), EA-46881231 (-10.011 kcal/mol), NEA-44258150 (-9.856 kcal/mol), NEA-135926572 (-7.662 kcal/mol), NA-163089376 (-9.237 kcal/mol), NA-440735 (-8.826 kcal/mol), TCM-392442 (-10.438 kcal/mol), and TCM-10043097 (-9.046 kcal/mol) which highlighted the strong binding affinity as compared to the control NP3-146 drug (-5.09 kcal/mol). Moreover, the values of dissociation constant further validated the strong binding affinity between the identified lead compounds and NLRP3. The dynamic stability and strong bonding energies of the lead compounds-NLRP3 complexes were confirmed by the molecular dynamic simulation and binding free energy calculation. The analysis of ADMET properties for all compounds indicated high intestinal absorption, water solubility, absence of hepatotoxicity, and skin sensitivity.

CONCLUSION: In conclusion, our molecular simulations and binding free energy calculations confirmed the strong affinity of these lead compounds for NLRP3 as compared to the control drug, highlighting their potential as part of a combinatorial therapeutic strategy for HS to effectively reduce disease-related inflammation.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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