| Summary: | Inflammation has a key role in driving memory/cognitive impairment in conditions ranging from Alzheimer's disease, vascular dementia, Parkinson's disease, traumatic brain injury, stroke and cerebral malaria. The current study analyses evidence for a therapeutic role of medicinal plants in targeting this inflammation. Plant species with therapeutic effects of memory improvement were identified from ethnomedical surveys worldwide. The findings reveal that an increasing number of such plants can target crucial regulators of inflammation, via inhibiting multiple signalling pathways including NF-κB, C/EBPβ, ERK/JNK, p38 MAPK, PI3K/Akt, Notch and Wnt, and their downstream pro-inflammatory mediators. The plants reduced other pathologies impacted by inflammation and the crosstalk between them, including lowered amyloid β, tau and oxidative stress, AChE inhibition, inducing autophagy and neurogenesis, anti-microbial activity, toxic metal chelation and gut microbiota modulation. Of 251 plant species with reports of memory improvement, up to 94% demonstrated anti-inflammatory activity. In particular, the therapeutic effects reinforce evidence that inflammation drives Alzheimer's progression. Phytochemicals for which anti-inflammatory activity could be experimentally demonstrated were discovered for 110 plant species. These phytochemicals exhibited diverse molecular structures, including novel ones. Future directions describe technological developments to assess clinical effectiveness of phytochemicals to reach their intended CNS targets, and discern their ability to target the critical players in inflammation and its crosstalk with inflammation-related pathologies. Since the causes of some of these medical conditions, such as Alzheimer's, are still unclear, these new research strategies raise expectations for a much needed breakthrough of knowledge into underlying causal mechanisms of inflammation in memory/cognitive loss.
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