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

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.

In Vitro Antiplasmodial and Cytotoxic Activities of Compounds from the Roots of Eriosema montanum Baker f. (Fabaceae)

“…The roots of E. montanum were harvested from the Arboretum of Ruhande/Rwanda and were treated and extracted as previously described by Tomani and collaborators [ 10 ]. A total amount of 200 g of the powder was extracted with the mixture of methanol:dichloromethane (3:1) to give 27.75 g (13.9%) of crude extract.…”

“…The crude extract of E. montanum showed inhibition of P. falciparum parasites in vitro. It is well known that within a plant extract, there can be a myriad of compounds some of which are active individually or act synergistically to be effective in a given disease [ 10 ]. In most of the cases, major compounds are responsible for the activity of the extract though it is not always the case [ 10 ].…”

“…It is well known that within a plant extract, there can be a myriad of compounds some of which are active individually or act synergistically to be effective in a given disease [ 10 ]. In most of the cases, major compounds are responsible for the activity of the extract though it is not always the case [ 10 ]. Hence, major compounds of the crude extract, as identified by the HPLC-DAD analysis ( Figure S1 ), were isolated and tested against the 3D7 chloroquine-sensitive strains of P. falciparum .…”

“…Major compounds from the crude extract of E. montanum were isolated by preparative HPLC. To this end, an in-house HPLC method used to screen the major components of crude extracts was used as previously reported [ 10 ]. Briefly, analytical separation was carried out on a Hypersil ODS ® RP18 column (250 × 4.6 mm; particle size 5 µm).…”

Immunological Roles of NLR in Allergic Diseases and Its Underlying Mechanisms

“…Antitussive agent Suhuang can also improve the pulmonary function via suppressing NLRP3 inflammasome [102]. Medicinal plants such as Hibiscus noldeae, which has been traditionally used for treating asthma, were found to possess anti-inflammatory potential with NLRP3 inflammasome inhibition [125,126]. Traditional Chinese Medicine formula Yupingfeng San, identified by network pharmacology, was proven to attenuate airway inflammation via inhibiting NLRP3 inflammasome in asthmatic mice [127].…”