Older couple drinking tea.

Neuroprotective effects of apigenin against inflammation, neuronal excitability and apoptosis in an induced pluripotent stem cell model of Alzheimer’s disease

Written by: Mecene Research Team

|

Published

|

Time to read 7 min

Note From Dr. Pendleton


This article is my attempt at a simplified summary of a scientific paper I found interesting. I’m passionate about sharing scientific knowledge in a way that’s accessible to everyone. However, it's important to remember that many scientific studies, including this one, may not directly apply to you, let alone all people. For example, some studies are conducted on animals or involve small sample sizes, which limits the generalizability of the results. My goal is to present the information responsibly and in layman’s terms, so please keep in mind that the findings should be interpreted with care.


Medical Disclaimer: This article is for informational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay seeking it because of something you have read on this website. The information in this article is based on a scientific review and should not be used as the sole basis for treatment decisions. Always consult with a healthcare professional before starting any new treatment or therapy.

Overview

In the scientific paper Neuroprotective effects of apigenin against inflammation, neuronal excitability, and apoptosis in an induced pluripotent stem cell model of Alzheimer’s disease, Balez et al. investigate the potential of apigenin, a plant-derived polyphenol, to combat Alzheimer’s disease (AD). Alzheimer’s is characterized by the accumulation of amyloid-beta plaques and tau protein tangles, leading to inflammation, oxidative stress, and neuron death. Current treatments are limited, prompting the need for alternative approaches. Using a human induced pluripotent stem cell (iPSC) model, the authors tested how apigenin could reduce neuron damage, inflammation, and abnormal calcium signaling, which are key contributors to AD progression. This study highlights apigenin's promising neuroprotective properties in combating Alzheimer’s disease.

Understanding Alzheimer's Disease and Apigenin's Potential Benefits

Alzheimer's disease (AD) is a neurodegenerative condition that leads to the loss of memory, thinking abilities, and, eventually, the ability to carry out daily tasks. It is one of the leading causes of death among the elderly, affecting millions globally. AD comes in two main forms: familial AD (early-onset) and sporadic AD (late-onset). Both forms are characterized by abnormal changes in the brain, such as the buildup of amyloid-beta (Aβ) plaques and tau protein tangles, which disrupt the normal function of neurons. This leads to neuron death, inflammation, oxidative stress, and cognitive decline.


Unfortunately, current treatments for Alzheimer's are largely ineffective. However, there is growing interest in natural compounds like apigenin, a polyphenol found in foods such as celery, parsley, and chamomile. Apigenin is known for its anti-inflammatory and neuroprotective properties, which could make it a promising treatment for Alzheimer's. The aim of this study was to test how apigenin affects neurons in a model of Alzheimer's disease using human induced pluripotent stem cells (iPSCs). This model provides a unique way to study human brain cells and how they respond to potential treatments.


As described in the paper, "apigenin has potent anti-inflammatory properties with the ability to protect neurites and cell viability" in neurons affected by AD.

Illustration of Alzheimer

The research team explored how apigenin interacts with Alzheimer's disease neurons, focusing on reducing neuron damage, inflammation, and abnormal brain signaling.

Methodology

The research team used iPSC-derived neurons from both familial and sporadic AD patients and healthy individuals. These stem cells were reprogrammed to become neurons, making it possible to study the effects of Alzheimer's in human cells. Using this model, they tested how apigenin affected vital features of the disease, such as cell death and inflammation.


The neurons were exposed to oxidative stress and inflammatory conditions to mimic the environment found in Alzheimer's patients' brains. Key markers were measured to understand the effects of apigenin, including:


  1. Neuron viability – to determine whether apigenin can keep neurons alive under stress.
  2. Neurite length – the length of the neuron's extensions, which are essential for communication between brain cells. Shortened neurites are common in AD and signal damage.
  3. Calcium (Ca²⁺) signaling – critical for neuron function. This is often disrupted in Alzheimer's, leading to excessive neuronal excitability and damage.
  4. Apoptosis – the programmed death of cells, which occurs more frequently in Alzheimer 's-affected neurons.
  5. Nitrite levels – an indicator of nitric oxide (NO) production linked to brain inflammation.

As the paper highlights, "iPSC-derived AD neurons demonstrated a hyper-excitable calcium signaling phenotype," which means that these neurons were overly reactive. The researchers aimed to see if apigenin could help calm this abnormal activity and reduce damage.

Main Findings

The study found several essential ways in which apigenin helped protect neurons affected by Alzheimer's disease:

Reduced Inflammation

Apigenin significantly lowered the production of pro-inflammatory molecules, including nitric oxide (NO) and cytokines produced by immune cells in response to brain damage. The paper notes that apigenin "promotes a global down-regulation of cytokine and nitric oxide release," which means it reduces harmful inflammation. In Alzheimer's, inflammation plays a major role in further damaging neurons, so apigenin's ability to block these inflammatory processes is a key finding.

Improved Neurite Length and Neuron Survival

The study showed that neurons exposed to inflammatory conditions typically had shorter neurites, which impaired their communication ability. Apigenin prevented this shortening and promoted neuron survival. The paper states, "Treatment with apigenin protected neurons from neurite retraction and death," showing its role in maintaining healthy neuron structures. This is important because longer, healthy neurites mean better communication between brain cells, which is essential for memory and cognition.

Brain neurons glowing.

Lowered Abnormal Calcium Signaling

One hallmark of Alzheimer's is hyper-excitable calcium (Ca²⁺) signaling . This study found that apigenin reduced these abnormal calcium responses in neurons, which suggests that it can help stabilize neuron activity. The study describes how sporadic AD neurons showed multiple spontaneous calcium signals without any external stimulus, but with apigenin treatment, the "frequency of spontaneous Ca²⁺ signaling" was significantly reduced. This means apigenin could help calm overactive neurons that are prone to damage.

Reduced Apoptosis (Cell Death)

The paper shows that neurons affected by Alzheimer's often undergo apoptosis (programmed cell death) due to the stress of the disease. Apigenin reduced this type of cell death by lowering the activity of caspase-3/7, enzymes involved in the apoptotic process. According to the study, "apigenin is able to protect neurons from apoptosis" in both familial and sporadic AD models. However, the study noted that while apigenin helped prevent apoptosis, it did not significantly impact overall cytotoxicity, meaning it didn't stop all forms of cell damage.


These findings suggest that apigenin can protect neurons in multiple ways, making it a powerful tool against the progression of Alzheimer's disease.

How Apigenin Could Help Slow Alzheimer's Progression

Alzheimer's disease is driven by a combination of inflammation, neuron death, and abnormal calcium signaling. This study shows that apigenin targets several of these harmful processes at once, making it a strong candidate for treating Alzheimer's. Its anti-inflammatory and anti-apoptotic effects suggest that it could help protect brain cells before major damage occurs.


The ability to reduce inflammation and neuron death is particularly important because these are two of the earliest changes seen in AD. Since apigenin is a natural compound found in common foods like parsley, celery, and chamomile, it may offer a safe and accessible way to help slow the progression of Alzheimer's. The study authors suggest that "successful treatments need to be pre-emptive to prevent or delay disease onset" and that apigenin could play a preventive role in managing AD.


With further research, apigenin could be developed into a therapy that helps protect the brain from the early signs of Alzheimer's, potentially delaying memory loss and cognitive decline.

Apigenin source parsley.

Neuroprotective Effects of Apigenin in Alzheimer's Disease Study

This scientific study highlights the neuroprotective potential of apigenin in Alzheimer's disease. The natural compound, found in foods like parsley and chamomile, reduces inflammation, prevents neuron death, and lowers abnormal calcium signaling in neurons affected by Alzheimer's. Using a human cell model derived from induced pluripotent stem cells (iPSCs), the researchers could mimic the conditions of Alzheimer's disease and test apigenin's effects directly on human neurons.


Apigenin's ability to address multiple harmful pathways involved in Alzheimer's makes it a promising candidate for future treatments. As a naturally occurring compound, it also has the potential for long-term use as a preventive measure. This research supports the idea that apigenin could be used to slow the progression of Alzheimer's and protect the brain from early damage, offering new hope in the fight against this devastating disease.

Meet the Author

Dr. James Pendleton

Dr. James Pendleton is a primary care physician specializing in a naturopathic approach to family medicine. He has nurtured a family practice in Seattle, directed a VIP medical center in Abu Dhabi, published several books and scientific articles, and designed innovative nutritional supplements for manufacturers worldwide.

REFERENCES

  1. Balez, R., Steiner, N., Engel, M., Sanz Muñoz, S., Lum, J. S., Wu, Y., Wang, D., Vallotton, P., Sachdev, P., O’Connor, M., Sidhu, K., Münch, G., & Ooi, L. (2016). Neuroprotective effects of apigenin against inflammation, neuronal excitability, and apoptosis in an induced pluripotent stem cell model of Alzheimer’s disease. Scientific Reports, 6, 31450. https://doi.org/10.1038/srep31450
  2. Chen, P., Chen, F., Guo, Z., Lei, J., & Zhou, B. (2023). Recent advancement in bioeffect, metabolism, stability, and delivery systems of apigenin, a natural flavonoid compound: challenges and perspectives. Frontiers in nutrition, 10, 1221227. https://doi.org/10.3389/fnut.2023.1221227
  3. Lee, G. B., Mazli, W. N. A. B., & Hao, L. (2024). Multiomics Evaluation of Human iPSCs and iPSC-Derived Neurons. Journal of proteome research, 23(8), 3149–3160. https://doi.org/10.1021/acs.jproteome.3c00790
  4. Millán Solano, M. V., Salinas Lara, C., Sánchez-Garibay, C., Soto-Rojas, L. O., Escobedo-Ávila, I., Tena-Suck, M. L., Ortíz-Butrón, R., Choreño-Parra, J. A., Romero-López, J. P., & Meléndez Camargo, M. E. (2023). Effect of Systemic Inflammation in the CNS: A Silent History of Neuronal Damage. International journal of molecular sciences, 24(15), 11902. https://doi.org/10.3390/ijms241511902
  5. Shimohama S. (2000). Apoptosis in Alzheimer's disease--an update. Apoptosis : an international journal on programmed cell death, 5(1), 9–16. https://doi.org/10.1023/a:1009625323388
  6. Tong, B. C., Wu, A. J., Li, M., & Cheung, K. H. (2018). Calcium signaling in Alzheimer's disease & therapies. Biochimica et biophysica acta. Molecular cell research, 1865(11 Pt B), 1745–1760. https://doi.org/10.1016/j.bbamcr.2018.07.018