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

Int J Mol Sci. 2023 Jul 4;24(13):11086. doi: 10.3390/ijms241311086.

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.

Keywords: Alzheimer’s disease; anti-inflammatory drugs; drug discovery; metabolites; neuroinflammation; pre-clinical drug discovery.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Australia
  • Brain
  • Mice
  • Neurodegenerative Diseases* / drug therapy
  • Neuroprotective Agents* / chemistry
  • Neuroprotective Agents* / pharmacology
  • Neuroprotective Agents* / therapeutic use

Substances

  • Neuroprotective Agents
  • Anti-Inflammatory Agents, Non-Steroidal

Grants and funding

This research was funded by NICM and Western Sydney University through Ph.D. scholarships for Paayal Kumar and Shintu Mathew. Ilaria Rossetti and Ingrid Wagnon are funded by the Ainsworth Medical Research Fund. Xian Zhou is supported by the VC’s Research Support Program Fellowship.