Neurodegenerative diseases (NDs), including Alzheimer's disease (AD) and Parkinson's disease (PD), are characterized by progressive neuronal loss. The aging population is experiencing an increasing prevalence of NDs. While current treatments primarily offer symptomatic relief, the search for disease-modifying therapies remains a significant challenge. Naturally occurring phytochemicals, known for their antioxidant and anti-inflammatory properties, represent a promising area of research due to their accessibility, affordability, and often lower risk of side effects compared to conventional medicines. The body's internal metabolism and environmental exposure generate reactive oxygen species (ROS) and reactive nitrogen species (RNS). While some ROS serve beneficial physiological roles, uncontrolled production can lead to cellular damage. The nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor vital in the antioxidant response element (ARE) pathway, which regulates the expression of phase II genes involved in cellular defense against oxidative damage. The efficiency of the Nrf2/ARE pathway declines with age, contributing to the increased susceptibility to age-related diseases. This decline, coupled with the overwhelming burden of AD and other dementias globally, necessitates exploring alternative therapeutic strategies.

The literature review utilized the PubMed database to identify relevant studies published since 1995. The search terms included: cardamonin, neurodegeneration, neuroprotection, neuroinflammation, cytokines, anti-inflammatory, antioxidant effects, AD, PD, Nrf2, microglia, MAPK and NF-kB signaling, autophagy, and micro-RNA. The review focused on existing research detailing the pharmacological properties of cardamonin and its mechanisms of action against neurodegeneration.

This narrative review synthesized existing literature on cardamonin's therapeutic role in neurodegeneration. The PubMed database was searched using keywords related to cardamonin's pharmacological properties and its effects on neurodegeneration, neuroinflammation, and oxidative stress. Studies investigating cardamonin's impact on various signaling pathways, including NF-kB, Nrf2, MAPK, autophagy, and microRNA, were included. The review was not limited to specific study designs or methodologies. The primary focus was on providing a comprehensive overview of existing knowledge of cardamonin's potential as a neuroprotective agent.

Cardamonin (CD) is a chalcone with various therapeutic properties including antioxidant, anti-inflammatory, and neuroprotective effects. CD's neuroprotective effects stem from its ability to modulate multiple signaling pathways implicated in Alzheimer's disease (AD) pathogenesis. CD has been shown to: 1) Modulate the expression of transcription factors such as NF-kB and STAT3; 2) Influence the levels of pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6; 3) Affect the activity of enzymes like COX-2 and MMP-9; 4) Regulate the expression of genes and proteins involved in cell survival, including Bcl-2 and XIAP. Moreover, CD's neuroprotective effects appear to be mediated by its ability to activate Nrf2, a key transcription factor in the antioxidant response, thereby upregulating the expression of antioxidant enzymes. CD also modulates microRNA levels, playing a role in gene regulation and cellular processes that influence neuroinflammation and neurodegeneration. Furthermore, CD's interaction with autophagy pathways suggests potential for removing misfolded proteins and damaged organelles, which is relevant to AD. In experimental models, CD demonstrated neuroprotection against oxidative damage and inflammation. Studies have shown its efficacy in reducing microglial activation and the production of pro-inflammatory cytokines. CD's impact on mTOR inhibition highlights its potential to modulate autophagy pathways which are intricately involved in AD pathogenesis.

This review highlights the multifaceted neuroprotective potential of cardamonin (CD) in Alzheimer's disease (AD). CD's ability to modulate multiple signaling pathways involved in neuroinflammation and oxidative stress positions it as a promising therapeutic agent. The findings support the growing interest in naturally occurring phytochemicals for preventing and managing neurodegenerative diseases. The activation of the Nrf2 pathway by CD is particularly significant, given Nrf2's role in maintaining cellular redox homeostasis and protecting against oxidative damage. CD's modulation of microRNA levels and autophagy pathways also underscore its complexity and potential as a multi-targeted therapy for AD. The observed effects of CD in preclinical studies warrant further investigation into its clinical efficacy and safety in AD patients.

Cardamonin (CD) demonstrates significant potential as a neuroprotective agent due to its antioxidant, anti-inflammatory, and autophagy-modulating properties. Its ability to activate the Nrf2 pathway and regulate various signaling molecules involved in AD pathogenesis warrants further research, including clinical trials to assess its efficacy and safety in humans. Future studies could investigate the optimal dosage and delivery methods for CD and explore potential synergistic effects when combined with existing AD therapies. Understanding CD's specific mechanisms and interactions with different cell types in the brain will also contribute to developing targeted and more effective AD treatments.

This review is limited by the scope of the available research on cardamonin's therapeutic effects. While several studies demonstrate promising results in preclinical models, more research, particularly clinical trials, is needed to validate the findings and establish the efficacy and safety of cardamonin in humans. Additionally, some studies included used varying methods and models. More standardized methods would facilitate better comparability and stronger conclusions.