Could medicinal plants be the key to reversing cognitive decline?

By Dr. Liji Thomas, MDReviewed by Benedette Cuffari, M.Sc.Sep 5 2023

Cognitive impairment is a major cause of disabling illness among older adults. A new paper published in the journal Brain Disorders explores available evidence that medicinal plants may help improve cognitive function by reducing brain inflammation.

Study: Reversing memory/cognitive impairment with medicinal plants targeting inflammation and its crosstalk with other pathologies. Image Credit: Antonova Ganna / Shutterstock.com

Introduction

Various neuroinflammatory conditions present with impaired memory and cognition, including Alzheimer's disease (AD), vascular dementia, Huntington's disease, multiple sclerosis (MS), as well as traumatic brain injury (TBI) and stroke. Pollution-induced brain injury, infectious meningitis, and brain damage due to infections like malaria or coronavirus disease 2019 (COVID-19) also have inflammation as their basis of toxicity.

There is some evidence that inflammation is responsible for most diseases involving cognitive impairment. In fact, for MS, all effective therapeutic interventions are anti-inflammatory in their mechanism of action.

Almost any neurological, neurodegenerative, traumatic damage or toxic insult to brain tissues involved in memory generation, may lead to memory deficits.”

Previous research has identified over 1,300 plants that contained potentially relevant bioactive compounds that could heal neurodegeneration. Many of these plants exhibited activity against 15 potential drivers of AD, including oxidative stress, mitochondrial dysfunction, hyperphosphorylated tau protein, and soluble amyloid, as well as gut dysbiosis, reduced estrogen levels, and impaired cholinergic neurotransmission.

What did the study show?

A total of 251 plant species with documented memory improvement effects were identified for the current analysis, 94% of which have anti-inflammatory activity. This observation supports the hypothesis that these types of protective plants act by combating both systemic and neuroinflammation, in addition to suggesting that inflammation underlies AD.

Some plants with reported memory improvement effects include neem, grapes, papaya, citrus plants, walnuts, mango, mint, onion species, including garlic, ginger, and cinnamon.

Moreover, over 120 of the species had specifically anti-neuroinflammatory activity, with over 100 showing both improvement of cognitive and memory function and inhibition of neuroinflammation. Most of the trials were preclinical, thus indicating the need for more human studies.

These plants produced their effects through the downregulation and inhibition of various signaling pathways mediated by pro-inflammatory chemicals such as nuclear factor κB (NF-κB), C/EBPβ, extracellular signal-regulated kinase (ERK)/c-Jun N-terminal kinases (JNK), p38 mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K)/ protein kinase B (Akt), Notch and Wnt, as well as the inflammatory molecules triggered by them.

Sustained hyperactivation of these pathways would produce persistent neuroinflammation, thereby activating the astrocytes and microglia. Subsequently, molecules like glutamate, reactive oxygen species (ROS), and reactive nitrogen species (RNS) can be released and ultimately contribute to neuronal death.

Activated microglia can also phagocytose live neurons due to the abnormal expression of cell surface molecules that induce this type of activity. Indirect neuronal death by microglia could also occur through apoptosis due to the release of proteolytic factors like cathepsins, as well as through tumor necrosis factor (TNF) activation of glial cells.

These processes can ultimately lead to memory loss and impaired cognition, both of which are due to the loss of neurons. Plants like those of the brassica family, including cabbage, broccoli, kale, brussels sprouts, and collard greens, as well as cashew plants, grapes rich in resveratrol, and pomegranates, have all been reported to inhibit the NF-κB pathway.

Each plant species was associated with the capacity to inhibit multiple pathways, including well-known plants like ginseng and less-known species such as sea ragweed.

Most of the identified plants also reduced the severity of other inflammatory disease processes and their interactions with each other. This led to reduced oxidative stress following treatment with plants like Brahmi (water hyssop) and the pigeon pea. Red sage and the oil palm also led to decreased levels of beta-amyloid and tau protein.

Toxic metal chelation was enhanced by silymarin and epigallocatechin gallate (EGCG). The anti-microbial activity was also associated with numerous plants such as coconut and fig plants, mango, onion, drumstick plants, and pomegranates, all of which also produced favorable changes in gut microbiota.

Many plants also led to autophagy, while mango and tamarind plants were reported to promote neurogenesis. Reduced acetylcholinesterase (AChE) activity was observed with vanillin from the vanilla plant, as well as the drumstick tree.

Microglial phagocytosis also improved, thereby allowing better clearance of cell debris like amyloid. Reduced astrogliosis, or reactive astrocyte activation, was also observed following treatment with these plants.

Taken together, these various compounds provide exciting prospects in the search for phytochemicals with enhanced therapeutic bioactivity.”

What are the implications?

The current study reports the wide-ranging effectiveness of many medicinal plants in inhibiting neuroinflammation and its accompanying pathologies. Moreover, these plants were found to improve memory and cognition, as well as exhibit antioxidant and anti-inflammatory activity.

Despite the promising benefits associated with these plants, clinical trials are needed to establish that these plants can target neurons in the human brain and identify the exact points of neuroinflammatory inhibition. Imaging, for example, could yield considerable data on how these types of plants affect inflammation and its associated pathologies over time and in different parts of the organism.  

Advanced technologies will also be needed for better neuroimaging and plasma testing to allow researchers to evaluate the effectiveness of plant chemicals on brain targets and in inhibiting inflammation and accompanying pathological processes. This type of research could also help understand how inflammation causes or contributes to memory and cognitive loss.

[This could eventually lead to] a much needed and crucial breakthrough of knowledge, to raise the prospect of reversing memory impairment and dramatically improve patient quality of life.”