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

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.

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

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.

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

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.

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.

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.

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.

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.

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.