Abstract
Chronic inflammation is increasingly recognized as a key contributor to numerous diseases, particularly inflammatory bowel disease (IBD), which presents a growing global health challenge due to its persistent nature and lack of a definitive cure. Emerging evidence supports the use of plant-derived compounds to modulate immune responses and mitigate inflammation. In this context, Trochocarpa bellendenkerensis, an endemic montane shrub of the Australian Ericaceae family, was investigated for its phytochemical composition and biological activity using an ecologically guided approach. This study examined polar (methanol) and non-polar (chloroform) extracts derived from the leaves and stems of both wild high-altitude and cultivated specimens. Phytochemical analysis revealed that methanol leaf extracts had the highest concentrations of total phenolics and flavonoids, which correlated with strong antioxidant activity. In lipopolysaccharide (LPS)-stimulated THP-1 macrophages, the methanol leaf extract from cultivated plants significantly suppressed the secretion of major inflammatory cytokines, including IL-6, IL-23, and IFN-γ, at non-cytotoxic concentrations. Bioassay-guided fractionation of the most active methanol extract yielded 12 compounds. Structural elucidation using NMR spectroscopy identified eight known compounds and four novel molecules. Subsequent testing of the isolated compounds at 12.25 μM (a concentration deemed non-toxic by MTT assay) demonstrated potent immunomodulatory effects. The test compounds notably inhibited key pro-inflammatory cytokines, including IL-1β, IL-6, TNF-α, IL-8, and MCP-1, relative to LPS-only controls.
These findings underscore the potent anti-inflammatory potential of T. bellendenkerensis, positioning it as a promising candidate for the development of novel therapeutic agents targeting immune-mediated disorders. The discovery of bioactive compounds, including several previously unreported molecules, not only expands the chemical space of natural immunomodulators but also emphasizes the value of integrating ecological insights into bioprospecting strategies. Collectively, this work reinforces the critical role of biodiversity in drug discovery and advocates for the sustainable utilization and conservation of species with pharmacological relevance.