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Targeting Inflammatory Pathways in Alzheimer’s Disease: A Focus on Natural Products and Phytomedicines

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Abstract

Studies of the brains of Alzheimer’s disease (AD) patients have revealed key neuropathological features, such as the deposition of aggregates of insoluble amyloid-β (Aβ) peptides and neurofibrillary tangles (NFTs). These pathological protein deposits, including Aβ peptides (which form senile plaques) and hyperphosphorylated tau (which aggregates into NFTs), have been assumed to be ‘the cause of AD’. Aβ has been extensively targeted to develop an effective disease-modifying therapy, but with limited clinical success. Emerging therapies are also now targeting further pathological processes in AD, including neuroinflammation. This review focuses on the inflammatory and oxidative stress-related changes that occur in AD, and discusses some emerging anti-inflammatory natural products and phytomedicines. Many of the promising compounds are cytokine-suppressive anti-inflammatory drugs (CSAIDs), which target the proinflammatory AP1 and nuclear factor-κB signalling pathways and inhibit the expression of many proinflammatory cytokines, such as interleukin (IL)-1, IL-6, tumour necrosis factor-α, or nitric oxide produced by inducible nitric oxide synthase. However, many of these phytomedicines have not been tested in rigorous clinical trials in AD patients. It is not yet clear if the active compounds reach an effective concentration in the brain (due to limited bioavailability) or if they can slow down AD progression in long-term trials. The authors suggest that it is crucial for both the pharmacological and complementary medicine industries to conduct and fund those studies to significantly advance the field.

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Acknowledgements

The authors thank Prof. Annemarie Hennessy for critical reading of this article.

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Authors and Affiliations

  1. School of Health Sciences, College of Health and Medicine, University of Tasmania, Locked Bag 1322, Launceston, TAS, 7250, Australia

    Matthew J. Sharman

  2. School of Pharmacy and Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Bentley, WA, 6102, Australia

    Giuseppe Verdile

  3. Department of Pharmacology, School of Medicine, Western Sydney University, Campbelltown, NSW, 2560, Australia

    Shanmugam Kirubakaran, Cristina Parenti, Ahilya Singh & Gerald Münch

  4. NICM Health Research Institute, Western Sydney University, Campbelltown, NSW, 2560, Australia

    Dennis Chang, Chun Guang Li & Gerald Münch

  5. Department of Behavioural Neuroscience, School of Medicine, Western Sydney University, Campbelltown, NSW, 2560, Australia

    Georgina Watt & Tim Karl

  6. School of Science and Health, Western Sydney University, Campbelltown, NSW, 2560, Australia

    Dennis Chang

  7. Pharmacology Unit, School of Medicine, Western Sydney University, Locked Bag 1797, Penrith, NSW, 2751, Australia

    Gerald Münch

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  1. Matthew J. Sharman
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Gerald Münch has received funding in this subject matter from the Australian Health and Medical Research Council, and also from Verdure Sciences, Indena and Nutrafur for research projects. Matthew J. Sharman, Giuseppe Verdile, Shanmugam Kirubakaran, Christina Parenti, Ahilya Singh, Georgina Watt, Chun Guang Li, Tim Karl and Dennis Chang have no conflicts of interest to declare that are directly relevant to the content of this manuscript.

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Sharman, M.J., Verdile, G., Kirubakaran, S. et al. Targeting Inflammatory Pathways in Alzheimer’s Disease: A Focus on Natural Products and Phytomedicines. CNS Drugs 33, 457–480 (2019). https://doi.org/10.1007/s40263-019-00619-1

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