From the Bush to the Brain: Preclinical Stages of Ethnobotanical Anti-Inflammatory and Neuroprotective Drug Discovery—An Australian Example

Abstract

The Australian rainforest is a rich source of medicinal plants that have evolved in the face of dramatic environmental challenges over a million years due to its prolonged geographical isolation from other continents. The rainforest consists of an inherent richness of plant secondary metabolites that are the most intense in the rainforest. The search for more potent and more bioavailable compounds from other plant sources is ongoing, and our short review will outline the pathways from the discovery of bioactive plants to the structural identification of active compounds, testing for potency, and then neuroprotection in a triculture system, and finally, the validation in an appropriate neuro-inflammatory mouse model, using some examples from our current research. We will focus on neuroinflammation as a potential treatment target for neurodegenerative diseases including multiple sclerosis (MS), Parkinson’s (PD), and Alzheimer’s disease (AD) for these plant-derived, anti-inflammatory molecules and highlight cytokine suppressive anti-inflammatory drugs (CSAIDs) as a better alternative to conventional nonsteroidal anti-inflammatory drugs (NSAIDs) to treat neuroinflammatory disorders.

Approaches, Strategies and Procedures for Identifying Anti-Inflammatory Drug Lead Molecules from Natural Products

“…Other examples include apigenin (isolated from Mentha australis R.Br. ), salicin (from Salix alba L.) [ 46 , 47 ], and protopine and kaempferol (from Meconopsis species of Bhutan) [ 38 ].…”

Exploring the Anti‐Inflammatory Potential of Australian Native Plants Based on their Ethnopharmacological Knowledge

“…Ethnobotanical knowledge, which involves the study of how different cultures use plants for medicinal, ritual, or other purposes, can play a crucial role in drug discovery. [5] Here's how this process typically unfolds:…”

“…This traditional wisdom stands as a highly valuable resource, offering potential leads for new drugs that could combat a range of infectious and non-infectious diseases, including conditions linked to inflammation. [5,7] Due to this great biodiversity, and limited research on the biological screening and phytochemistry of Aboriginal and Torres Strait Islander medicinal plants open the opportunity to explore untapped natural resources for the discovery of new secondary metabolites that have the capacity to interfere with the inflammatory response. Evaluating the bioactive potential of these plants, which have rich historical usage, could contribute to their broader application.…”

Phytochemical analysis, GC–MS profile and determination of antibacterial, antifungal, anti-inflammatory, antioxidant activities of peel and seeds extracts (chloroform and ethyl acetate) of Tamarindus indica L

“…In recent times, antimicrobial, anti-inflammatory and anti-oxidative properties having biological molecules extracted from plant sources are gaining much attention ( Ain et al, 2023 , Bagewadi et al, 2019 , Brindhadevi et al, 2023 , Kumar et al, 2023 , Mitropoulou et al, 2023 , Shaukat et al, 2023 ). For example, anti-inflammatory agents are used to treat COVID-19 as well as neuroinflammation and also have anti-carcinogenic as well as diabetes-control properties ( Kumar et al, 2023 , Merecz-Sadowska et al, 2023 ; Perico et al, 2022 ).…”

“…In recent times, antimicrobial, anti-inflammatory and anti-oxidative properties having biological molecules extracted from plant sources are gaining much attention ( Ain et al, 2023 , Bagewadi et al, 2019 , Brindhadevi et al, 2023 , Kumar et al, 2023 , Mitropoulou et al, 2023 , Shaukat et al, 2023 ). For example, anti-inflammatory agents are used to treat COVID-19 as well as neuroinflammation and also have anti-carcinogenic as well as diabetes-control properties ( Kumar et al, 2023 , Merecz-Sadowska et al, 2023 ; Perico et al, 2022 ). Hence, various kinds of plant sources such as Aerva lanata flower, Ficus religiosa , Kaempferia rotunda Linn., Lavandula dentata L., Rosmarinus officinalis L., Rumex dentatus L., Teucrium multicaule , Tripleurospermum limosum etc., are used for different (medicinal/pharmaceutical) purposes like anti-inflammatory, antioxidant activity, antifertility, antifungal, in vitro biofilm inhibition of bacteria, antifungal, antidiarrheal, and so on ( Baliyan et al, 2022 , Brindhadevi et al, 2023 , Chen et al, 2022a , El Abdali et al, 2022 , Ersoy et al, 2023 , Ibrahim et al, 2022 , Khaliq et al, 2023 , Sahoo et al, 2023 ).…”