Polyherbal and Multimodal Treatments: Kaempferol- and Quercetin-Rich Herbs Alleviate Symptoms of Alzheimer's Disease

Abstract

Alzheimer's Disease (AD) is a progressive neurodegenerative disorder impairing cognition and memory in the elderly. This disorder has a complex etiology, including senile plaque and neurofibrillary tangle formation, neuroinflammation, oxidative stress, and damaged neuroplasticity. Current treatment options are limited, so alternative treatments such as herbal medicine could suppress symptoms while slowing cognitive decline. We followed PRISMA guidelines to identify potential herbal treatments, their associated medicinal phytochemicals, and the potential mechanisms of these treatments. Common herbs, including Ginkgo biloba, Camellia sinensis, Glycyrrhiza uralensis, Cyperus rotundus, and Buplerum falcatum, produced promising pre-clinical results. These herbs are rich in kaempferol and quercetin, flavonoids with a polyphenolic structure that facilitate multiple mechanisms of action. These mechanisms include the inhibition of Aβ plaque formation, a reduction in tau hyperphosphorylation, the suppression of oxidative stress, and the modulation of BDNF and PI3K/AKT pathways. Using pre-clinical findings from quercetin research and the comparatively limited data on kaempferol, we proposed that kaempferol ameliorates the neuroinflammatory state, maintains proper cellular function, and restores pro-neuroplastic signaling. In this review, we discuss the anti-AD mechanisms of quercetin and kaempferol and their limitations, and we suggest a potential alternative treatment for AD. Our findings lead us to conclude that a polyherbal kaempferol- and quercetin-rich cocktail could treat AD-related brain damage.

Keywords: Alzheimer’s disease (AD); dementia; flavonoids; kaempferol; quercetin; traditional Chinese medicine.

Figure 2

The chemical structure of quercetin, deduced from PubChem [164].

Figure 3

The chemical structure of kaempferol, deduced from PubChem [202].

Figure 4

(A) Neuroplasticity deficits accelerate AD progression and must be treated. Impaired PI3K-AKT signaling facilitates GSK3β-mediated phosphorylation of tau. Aβ may potentiate tau hyperphosphorylation via GSK3β. (B) Kaempferol and quercetin (K/Q) invoke the PI3K/AKT pathway to antagonize Aβ and reduce tau hyperphosphorylation in neurons. As a result, neuroplasticity is increased in the AD brain [283].

Figure 1

Flowchart depicting the article screening and selection process according to PRISMA guidelines.

Figure 5

A graphical summary of the underlying mechanisms behind AD progression (pathogenesis), the proposed mechanisms of kaempferol and quercetin (K/Q), where K/Q represents kaempferol and quercetin, and the impact of these molecular changes on behavior and disease progression (outcomes). Each category is presented in a top-to-bottom chronological order.