The effect of bitter honey against cerebral malaria-induced inflammasome cell death: network pharmacology-based in silico evaluation

Abstract

Cerebral malaria (CM) is a fatal complication of Plasmodium falciparum infection. The biological and physiological links between CM, inflammation, and inflammasome, point to the complexity of its pathology. Resistance to available and affordable drugs, worsening economic crisis, and urgent need for integration of orthodox with traditional/alternative medicine, actualized the search for sustainable pharmacotherapy. Previous works from our team on the medicinal properties of bitter honey have established botanical and bioactive markers, inhibitory effects on pancreatic alpha-amylase activity, and anti-dyslipidemia, cardio-protective, and ameliorative effects on hepatorenal damage in streptozotocin-induced diabetic rats. In this study, we have identified bitter honey (BH) derived phytochemicals using gas chromatography coupled with mass spectrometry (GC-MS), and 9 targets from genes associated with CM, inflammation, inflammasome, and BH phytochemicals. Network analysis revealed significant functional and physical interactions among these targets and NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3). Molecular docking of bitter honey-derived phytochemicals against these targets identified 3 most promising phytochemical candidates for further experimental validation. Based on these results, we predict that bitter honey may aid in the suppression of CM-mediated inflammasome cell death via its interactions with these targets.