Discovery of novel anti-inflammatory compounds from Australian rainforest plants

Abstract

Inflammation is a complex pathophysiological process that occurs in response to infection or tissue injury and is essentially designed to eradicate microbes or irritants thus, initiating tissue repair. The inflammatory response involves immune cells, blood vessels, and a wide range of molecular mediators, which work to eliminate the initial cause of cell injury, clear out necrotic and damaged cells thus initiating tissue repair. Moreover, unregulated inflammatory responses are considered catastrophic as they lead to a state of chronic inflammation which signifies a long-term response to inflammatory stimuli resulting in tissue and organ damage. The overproduction of inflammatory mediators in chronic inflammation has been linked to the onset and progression of chronic degenerative diseases such as diabetes, rheumatoid arthritis, allergic asthma and Alzheimer’s disease. The currently available list of anti-inflammatory agents consists of steroidal, non-steroidal (NSAIDs) and cytokine suppressive anti-inflammatory drugs (CSAIDs). Despite being the gold standard in the treatment of anti-inflammatory diseases, these drugs are accompanied by specific limitations. Prolonged usage of steroids and NSAIDs have been linked to adverse side effects such as cardiovascular, gastrointestinal and renal complications, while CSAIDs are costly and have delivery limitations. Thus, there is a pressing need to discover and develop new drugs with strong anti-inflammatory efficacy, less toxic profiles and with the fewest possible side effects. This thesis describes the screening of crude EtOH extracts of 54 Australian rainforest plant samples from Northern Queensland region of Australia. It further reports the full phytochemical investigation of five highly active plants with potent anti-inflammatory activity. This study led to the isolation of 22 pure compounds, out of which 12 are reported for the first time. The anti-inflammatory activity of these compounds has been demonstrated as their potential to downregulate NO and TNF-α production in LPS and IFN-γ induced RAW 264.7 macrophage cell line. Further biological studies have been conducted for the most active compound [4.59] isolated in the study.

Date of Thesis submission	2026
Original language	English
Awarding Institution	Western Sydney University
Sponsors	Australian Government Research Training Program Scholarship
Supervisor	Ritesh Raju (Supervisor), Gerald Muench (Supervisor) & Phoebe Zhou (Supervisor)