The Inhibition of NLRP3 Inflammasome and IL-6 Production by Hibiscus noldeae Baker f. Derived Constituents Provides a Link to Its Anti-Inflammatory Therapeutic Potentials.

Jean Claude Didelot Tomani,Luc Vanhamme,Alembert Tiabou Tchinda,Vedaste Kagisha,Jacob Souopgui,Raymond Muganga,Olivia Jansen,Allison Ledoux,Michel Frederich

doi:10.3390/molecules25204693

Abstract

The activation of NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome and/or its components is associated with the physio-pathogenesis of many respiratory diseases including asthma, COPD (chronic obstructive pulmonary disease), SARS Cov-2 (severe acute respiratory syndrome coronavirus 2), and in several autoimmune diseases. Hibiscus noldeae Baker f. has been widely reported to be traditionally used in the treatment of different ailments, some of which are of inflammatory background such as asthma, wounds, headache, etc. However, the claims have not been supported by evidence at the molecular and functional levels. Here, we report on the bio-guided fractionation of H. noldeae and assessment of the inhibitory properties of some fractions and purified compounds on NLRP3 inflammasome and Interleukin 6 (IL-6). The activation of the NLRP3 inflammasome was determined by detecting the activity of caspase-1 and the production of Interleukin 1β (IL-1β) in Lipopolysaccharide (LPS) and ATP-stimulated Tamm-Horsfall Protein 1 (THP-1) macrophages, while the production of IL-6 was studied in LPS-stimulated RAW264.7 mouse macrophages. It was observed that hexane and ethyl acetate fractions of the crude extract of the aerial parts of H. noldeae, as well as caffeic acid, isoquercetin, and ER2.4 and ER2.7 fractions revealed significant inhibitory effects on Caspase-1 activities, and on IL-1β and IL-6 production. The ER2.4 and ER2.7 fractions downregulated the production of IL-1β and IL-6, in a similar range as the caspase-1 inhibitor AC-YVAD-CHO and the drug Dexamethasone, both used as controls, respectively. Overall, our work does provide the very first scientific based evidence for Hibiscus noldeae anti-inflammatory effects and widespread use by traditional healers in Rwanda for a variety of ailments.

Highlights

Respiratory diseases, with asthma being the most important, are classified among the major categories of non-communicable diseases and their prevalence accounted for more than 1 billion patients worldwide in 2018 [1,2]
We report on the bio-guided fractionation of H. noldeae and assessment of the inhibitory properties of some fractions and purified compounds on NLRP3 inflammasome and Interleukin 6 (IL-6)
The activation of the NLRP3 inflammasome was determined by detecting the activity of caspase-1 and the production of Interleukin 1β (IL-1β) in Lipopolysaccharide (LPS)- and ATP-stimulated Tamm-Horsfall Protein 1 (THP-1) macrophages, while the production of IL-6 was studied in LPS-stimulated RAW264.7 mouse macrophages, a well-known standard method

Summary

Introduction

Respiratory diseases, with asthma being the most important, are classified among the major categories of non-communicable diseases and their prevalence accounted for more than 1 billion patients worldwide in 2018 [1,2]. Sometimes the delicate balance between immune-mediated clearance and noxious stimuli is troubled and this correlates with inadvertent self-harm from chronic inflammation. The immune system inappropriately leads to inflammation against its own cells, resulting in different chronic inflammatory diseases including respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD) [6]. Several studies have reported the role of different inflammatory cells and mediators in the pathogenesis of asthma where the volume and nature of involved inflammatory mediators determine the severity and exacerbations of the disease. Depending on those inflammatory patterns, there are two main subtypes of asthma, the eosinophilic

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Conclusion