Showing posts with label Bacopa monnieri. Show all posts
Showing posts with label Bacopa monnieri. Show all posts

Monday, 4 September 2023

The therapeutic effects of apigenin are pleiotropic. Is its effect on sound sensitivity mediated via potassium channels?

Chamomile, a good source of Apigenin


Today we return to flavonoids, those healthy chemicals found in fruits, vegetables, flowers etc.

In particular, the focus is on apigenin, found in things like chamomile, parsley, oregano and in medicinal herbs like Bacopa monnieri.


Why the interest in Apigenin?

I did discover a while back that sound sensitivity in some autism responds almost immediately to low dose Ponstan (Mefenamic acid), which is a widely used as a pain reliever.

I was recently informed by a reader who responds well to Ponstan (250mg once a day) that he gets exactly the same relief from sound sensitivity from taking the flavonoid Apigenin (500mg a day). 

Both Ponstan and Apigenin are OTC in many countries. In countries like Greece Ponstan is extremely cheap.  In the US Ponstan is very expensive and supplements tend to be cheap. 

For adults with sound sensitivity drinking chamomile tea might be a good source of 50 mg of Apigenin (you would need about 20g of chamomile flowers). Using the dried flowers likely gives better results than ready-made tea bags.


Pleiotropic effects

Both Ponstan and apigenin have numerous beneficial effects.  I noted in my earlier posts on Ponstan that it seems to offer protection from Alzheimer’s. Perhaps surprisingly, people who take Ponstan are much less likely to develop Alzheimer’s. Nobody has studied apigenin in human Alzheimer’s, but in animal studies, apigenin has been shown to improve cognitive function, reduce amyloid plaques, and protect neurons from damage.


Other Flavonoids used in Autism

Dr Theoharides wrote a lot about flavonoids to treat autism and mast cell disorders.  His product Neuroprotek is a combination of three flavonoids: luteolin, quercetin, and rutin, which are found in plants such as celery, onions, and citrus fruits.

Epigallocatechin gallate (EGCG) is a flavonoid found in green tea. The Spanish like doing research on EGCG and they believe it has promise as an autism therapy. One of the effects is to modify the gut microbiome. EGCG has also been shown to accumulates in mitochondria making it an interesting therapeutic candidate for neurodegenerative diseases involving neuronal apoptosis triggered by mitochondrial oxidative stress. It has been studied in Down syndrome, Rett syndrome and some other models of autism.


A very detailed overview is available in the paper below:-

The Emerging Role of Flavonoids in Autism Spectrum Disorder: A Systematic Review

Although autism spectrum disorder (ASD) is a multifaceted neurodevelopmental syndrome, accumulating evidence indicates that oxidative stress and inflammation are common features of ASD. Flavonoids, one of the largest and best-investigated classes of plant-derived compounds, are known to exert antioxidant, anti-inflammatory, and neuroprotective effects. This review used a systematic search process to assess the available evidence on the effect of flavonoids on ASD. A comprehensive literature search was carried out in PubMed, Scopus, and Web of Science databases following the PRISMA guidelines. A total of 17 preclinical studies and 4 clinical investigations met our inclusion criteria and were included in the final review. Most findings from animal studies suggest that treatment with flavonoids improves oxidative stress parameters, reduces inflammatory mediators, and promotes pro-neurogenic effects. These studies also showed that flavonoids ameliorate the core symptoms of ASD, such as social deficits, repetitive behavior, learning and memory impairments, and motor coordination. However, there are no randomized placebo-controlled trials that support the clinical efficacy of flavonoids in ASD. We only found open-label studies and case reports/series, using only two flavonoids such as luteolin and quercetin. These preliminary clinical studies indicate that flavonoid administration may improve specific behavioral symptoms of ASD. Overall, this review is the first one to systematically report evidence for the putative beneficial effects of flavonoids on features of ASD. These promising preliminary results may provide the rationale for future randomized controlled trials aimed at confirming these outcomes.


It seems that the many flavonoids have numerous beneficial effects - this is why it is important to include them in your diet.



Years ago, I wrote about Sytrinol, a dietary supplement that is made from citrus peel extract. It contains polymethoxylated flavones (PMFs), which are a type of flavonoid. It mainly contains nobiletin and tangeritin, flavones that are found in citrus fruits, such as lemons, oranges, and grapefruits. They have been shown to have a number of health benefits, including lowering cholesterol, reducing inflammation, and protecting cells from damage.

The idea was of interest because these flavones are known to activate PPAR-gamma, which seemed potentially beneficial in autism.  Readers did confirm Sytrinol provided a cognitive benefit, but it only lasts a few days and is then lost.


Sources of Apigenin

Apigenin is sold as a supplement.

Chamomile is one of the oldest, most widely used and well documented medicinal plants in the world and has been recommended for a variety of healing applications for centuries. Apigenin is thought to be one of the most potent substances found within it.

Bacopa monnieri is another rich source of flavonoids being a good source of luteolin and apigenin. An extract of Bacopa monnieri, a nootropic herb, has been used to evaluate its neuroprotective effect in a valproic acid (VPA) model of ASD. The results showed that B. monnieri extract may attenuate VPA-induced damage by restoring antioxidant enzymes and reducing inflammatory cytokines in the hippocampus and prefrontal cortex.


The biological effects of Apigenin

 What does the Google AI (artificial intelligence) program Bard have to say:-


Apigenin is a flavonoid that is found in a variety of plants, including chamomile, parsley, celery, and citrus fruits. It has several potential health benefits, including:

Antioxidant. Apigenin is an antioxidant, which means it can help protect cells from damage caused by free radicals. Free radicals are unstable molecules that can damage DNA, proteins, and other cellular structures.

Anti-inflammatory. Apigenin has anti-inflammatory properties, which can help reduce inflammation in the body. Inflammation is a contributing factor to many diseases, including heart disease, cancer, and arthritis.

Cancer prevention. Apigenin has been shown to have cancer-fighting properties in both animal and human studies. It may help prevent cancer by blocking the growth and spread of cancer cells.

Brain health. Apigenin may be beneficial for brain health. It has been shown to improve cognitive function in animal studies, and it may also help protect against Alzheimer's disease and other neurodegenerative diseases.

Heart health. Apigenin may help improve heart health. It has been shown to lower blood pressure and cholesterol levels, and it may also help protect against heart arrhythmias.

Hormone modulation. Apigenin may modulate the production of hormones, such as estrogen and testosterone. This could have benefits for women's health, such as reducing the risk of breast cancer and improving menopausal symptoms.

Immune health. Apigenin may boost the immune system. It has been shown to increase the production of white blood cells, which help fight infection.

Other benefits. Apigenin may also have other health benefits, such as relieving anxiety, promoting sleep, and strengthening bones.

When you push Bard a little bit you get more:

Apigenin and ion channels, Bard?

Apigenin is a flavonoid that has been shown to interact with a variety of ion channels in the body. These include:

Voltage-gated calcium channels. Apigenin has been shown to inhibit the activity of voltage-gated calcium channels, which are involved in the regulation of many cellular processes, including muscle contraction, cell growth, and cell death.

Transient receptor potential vanilloid 4 (TRPV4) channels. TRPV4 channels are activated by heat and inflammation, and they play a role in pain perception, thermoregulation, and inflammation. Apigenin has been shown to activate TRPV4 channels, which could have potential implications for the treatment of pain and inflammation.

Nicotinic acetylcholine receptors (nAChRs). nAChRs are ligand-gated ion channels that are activated by acetylcholine. They are involved in a variety of functions, including learning, memory, and muscle contraction. Apigenin has been shown to potentiate the activity of nAChRs, which could have potential implications for the treatment of Alzheimer's disease and other neurodegenerative diseases.

Potassium channels: Potassium channels are responsible for the efflux of potassium ions from cells. Apigenin has been shown to activate some types of potassium channels, which can have cardioprotective effects.

Gamma-aminobutyric acid (GABA)A receptors. GABAA receptors are ligand-gated ion channels that are activated by GABA. They are involved in the regulation of anxiety, sleep, and epilepsy. Apigenin has been shown to modulate the activity of GABAA receptors, which could have potential implications for the treatment of anxiety and epilepsy.


Which potassium channels, Bard? 

Apigenin has been shown to activate some types of potassium channels, including:

Small conductance calcium-activated potassium channels (SK channels): SK channels are activated by calcium ions and play a role in regulating cell excitability. Apigenin has been shown to activate SK channels in a number of cell types, including neurons, smooth muscle cells, and cardiac cells.

Large conductance calcium-activated potassium channels (BK channels): BK channels are also activated by calcium ions and play a role in regulating cell excitability and blood pressure. Apigenin has been shown to activate BK channels in some cell types, but the effects are less well-studied than the effects on SK channels.

Transient receptor potential vanilloid 4 (TRPV4) channels: TRPV4 channels are activated by a variety of stimuli, including heat, inflammation, and mechanical stress. Apigenin has been shown to activate TRPV4 channels in some cell types, but the effects are less well-studied than the effects on SK and BK channels.


The effect of mefenamic acid on potassium channels, Bard? 

Mefenamic acid has been shown to have effects on a variety of ion channels, including potassium channels.

In vitro studies have shown that mefenamic acid can activate certain types of potassium channels, such as small conductance calcium-activated potassium channels (SK channels) and large conductance calcium-activated potassium channels (BK channels). This activation of potassium channels can lead to a decrease in the excitability of cells, which can be beneficial in conditions where excessive cell excitability is a problem, such as epilepsy and arrhythmias.

 However, mefenamic acid can also inhibit certain types of potassium channels, such as ATP-sensitive potassium channels (KATP channels). This inhibition of KATP channels can lead to an increase in the excitability of cells, which can be harmful in conditions where excessive cell excitability is a problem, such as heart arrhythmias.

The effects of mefenamic acid on potassium channels are complex and depend on the type of channel, the concentration of mefenamic acid, and the cell type. More research is needed to fully understand the mechanisms by which mefenamic acid interacts with potassium channels and the implications for its potential therapeutic applications.


Apigenin in Down syndrome


Plant Compound Apigenin Reduces Cognitive Deficits in Mouse Model of Down Syndrome

Mice treated with apigenin had better memory and developmental milestone scores.

The plant compound apigenin improved the cognitive and memory deficits usually seen in a mouse model of Down syndrome, according to a study by researchers at the National Institutes of Health and other institutions.

Apigenin is found in chamomile flowers, parsley, celery, peppermint, and citrus fruits. The researchers fed the compound to pregnant mice carrying fetuses with Down syndrome characteristics and then to the animals after they were born and as they matured.

The findings raise the possibility that a treatment to lessen the cognitive deficits seen in Down syndrome could one day be offered to pregnant women whose fetuses have been diagnosed with Down syndrome through prenatal testing. The study appears in the American Journal of Human Genetics.

Down syndrome is a set of symptoms resulting from an extra copy or piece of chromosome 21. The intellectual and developmental disabilities accompanying the condition are believed to result from decreased brain growth caused by increased inflammation in the fetal brain.

Apigenin is not known to have any toxic effects, and previous studies have indicated that it is an antioxidant that reduces inflammation. Unlike many compounds, it is absorbed through the placenta and the blood brain barrier, the cellular layer that prevents potentially harmful substances from entering the brain.

Compared to mice with Down symptoms whose mothers were not fed apigenin, those exposed to the compound showed improvements in tests of developmental milestones and had improvements in spatial and olfactory memory. Tests of gene activity and protein levels showed the apigenin-treated mice had less inflammation and increased blood vessel and nervous system growth.


Apigenin as a Candidate Prenatal Treatment for Trisomy 21: Effects in Human Amniocytes and the Ts1Cje Mouse Model

Human fetuses with trisomy 21 (T21) have atypical brain development that is apparent sonographically in the second trimester. We hypothesize that by analyzing and integrating dysregulated gene expression and pathways common to humans with Down syndrome (DS) and mouse models we can discover novel targets for prenatal therapy. Here, we tested the safety and efficacy of apigenin, identified with this approach, in both human amniocytes from fetuses with T21 and in the Ts1Cje mouse model. In vitro, T21 cells cultured with apigenin had significantly reduced oxidative stress and improved antioxidant defense response. In vivo, apigenin treatment mixed with chow was administered prenatally to the dams and fed to the pups over their lifetimes. There was no significant increase in birth defects or pup deaths resulting from prenatal apigenin treatment. Apigenin significantly improved several developmental milestones and spatial olfactory memory in Ts1Cje neonates. In addition, we noted sex-specific effects on exploratory behavior and long-term hippocampal memory in adult mice, and males showed significantly more improvement than females. We demonstrated that the therapeutic effects of apigenin are pleiotropic, resulting in decreased oxidative stress, activation of pro-proliferative and pro-neurogenic genes (KI67, Nestin, Sox2, and PAX6), reduction of the pro-inflammatory cytokines INFG, IL1A, and IL12P70 through the inhibition of NFκB signaling, increase of the anti-inflammatory cytokines IL10 and IL12P40, and increased expression of the angiogenic and neurotrophic factors VEGFA and IL7. These studies provide proof of principle that apigenin has multiple therapeutic targets in preclinical models of DS.



I am still delighted to have found a treatment for my son’s sound sensitivity, which got much more extreme almost overnight a couple of years ago.

I had already established long ago that he got short term sound sensitivity relief from taking a potassium supplement.  Some readers found a potassium supplement provided long term relief.

I thought that Ponstan might provide a good longer term solution and indeed it worked from the first pill.  This low dose therapy also works for other people with sound sensitivity, even one adult who has no autism.  The effective adult dose is 250 mg once a day.

Unlike other fenamate class drugs, like Diclofenac, Ponstan seems to be free from GI side effects at this low dose in most people.

Apigenin is an interesting alternative for those who do not tolerate Ponstan well, or who cannot access it.

A common link between what seems to improve sound sensitivity:

                    Oral potassium

                    Ponstan (Mefenamic acid)


is potassium ion channels. 

If you ask Google’s AI program Bard, he will tell you:

“It is possible that all 3 substances could affect the same potassium ion channel in some cell types, but this has not been definitively shown. More research is needed to fully understand the effects of these substances on potassium ion channels.”

Technically Bard is genderless, but he is a reflection of the programmers behind the software. In our house he is called Bart anyway.

Bart does make mistakes, contradicts himself in the same answer and he gives you different answers if you ask the same question more than once. He is also prone to mixing things up, just like humans do.