Discovery of novel anti-inflammatory compounds from Australian native plants

Abstract

This PhD study describes the bioactivity-guided isolation and structural elucidation of anti- inflammatory compounds based on the ethnomedicinal knowledge of Dharawal Pharmacopeia curated by well-known botanist, Aboriginal (D’harawal) Elder and Traditional Knowledge Holder Dr. Frances Bodkin (Auntie Fran). Dharawal Pharmacopeia is a collection of medicinal properties of native plants in Dharawal Country. This ethnobotanical information has been employed as a guide for selecting plants for biological and chemical investigations. These native plants have a long history as medicinal plants for treating various ailments, including sores, wounds, coughs, colds, and skin infections. This traditional wisdom is a precious resource, offering potential leads for new drugs that could combat various infectious and non-infectious diseases, including conditions linked to inflammation. The overall aim of this project is to isolate and identify new anti-inflammatory compounds from Australian native plants. Chapter 1 of this thesis discusses the pathology of inflammation and major inflammatory signalling pathways of the pro-inflammatory response, which serve as targets for drug Discovery. Chapter 2 demonstrates the screening of eighty Australian native plants collected from the Royal Botanical Gardens, Mount Annan, for their anti-inflammatory activity (nitric oxide (NO) production inhibition) in lipopolysaccharide (LPS) and interferon (IFN)-γ activated RAW 264.7 macrophages. Chapter 3 describes the bioassay-guided isolation and structural elucidation of compounds 3.1- 3.4 from the crude ethanolic extract of Callitris rhomboidea (Cupressaceae) against inflammation. Chapter 4 describes the isolation and structural elucidation of two flavonoid glycosides, 4.1 and 4.2, from the sequential ethanolic extract of Persoonia pinifolia (Proteaceae) against inflammation. Chapter 5 describes the discovery of the novel anti-inflammatory compound tristaenone A (5.1) from leaves of Tristaniopsis laurina (Myrtaceae). Bioassay-guided fractionation of the most active fraction (dichloromethane (DCM) extract) from the sequential extracts led to the discovery of two known flavonoids (5.2 and 5.3) along with the new compound. Chapter 6 describes the anti-inflammatory investigation into the leaves of Backhousia mytifolia (Myrtaceae). Chapter 7 describes the isolation and structure elucidation of compounds (7.1-7.4) from the crude ethanolic extract of Kunzea ericoides (Myrtaceae). In summary, this thesis describes the screening of crude ethanolic extracts of 80 Australian native plant samples selected from Dharawal Pharmacopeia. Bioassay-guided fractionation of the most active five plant samples resulted in the identification of 22 compounds, including seven new compounds. This identification of anti-inflammatory constituents from medicinal plants not only supports the traditional medicinal uses of the D’harawal community but also contributes to expanding the knowledge and scientific evidence on these relatively untapped plants.

Date of Award	2023
Original language	English
Awarding Institution	Western Sydney University
Supervisor	Ritesh Raju (Supervisor), Gerald Muench (Supervisor) & Phoebe Zhou (Supervisor)