New in vitro co-culture model study published with citrus flavonoid extract MicrobiomeX®

New in vitro co-culture model study published with citrus flavonoid extract MicrobiomeX®

Maastricht, Netherlands, April 21st, 2022

Press release
British Journal of Nutrition has recently published a new in vitro co-culture model study with a citrus flavonoid extract MicrobiomeX® and its metabolites, hesperetin and naringenin. The novel publication suggests that these citrus flavonoids, as well as their metabolites, may reduce intestinal inflammation.


New in vitro co-culture model study published with citrus flavonoid extract MicrobiomeX®

MicrobiomeX® is a first-in-class Flavobiotic® developed by BioActor, that combines active ingredients from Citrus sinensis and Citrus paradisi. MicrobiomeX® has already been studied and reported to have various beneficial effects on the gut and immunity. MicrobiomeX® consists of standardised citrus flavonoids, that form active metabolites, hesperetin and naringenin, in the gut after being deglycosylated by the gut microbiota.

In the recently published in-vitro study, a validated co-culture system of Caco-2/THP-1 cells as model for intestinal inflammation and cytokine-induced barrier disruption was used to determine the effects of citrus flavonoids and their metabolites on intestinal inflammation.

During the research, cells were treated with citrus flavonoids, their metabolites, or a vehicle control. Additionally, cells were incubated with lipopolysaccharide (LPS), which is known to induce inflammation and deterioration in epithelial integrity.

The conclusion highlights that hesperetin and naringenin significantly reduced NF-kB activity, leading to a reduction in intestinal inflammation. Pro-inflammatory cytokines IL-8, TNF-α and IL-6 were also significantly reduced after hesperetin and naringenin administration.

The mechanism behind this reduction in inflammation can be ascribed to partial inhibition of the NF-κB signalling pathway.

“We are very happy with the results of this study, as we were able to show that both the citrus flavonoids themselves and their metabolites are able to reduce inflammation in the intestine”, says Yala Stevens, CSO of BioActor. “These new scientific insights on MicrobiomeX® will allow us to consolidate its applications to products targeting gut health and immune function”.

About BioActor

BioActor, based at the Maastricht Health Campus, Netherlands, is a life science company that has developed a range of proprietary bioactive ingredients for the nutrition & consumer health industries. The company focuses on the development of plant-based health ingredients for active living and healthy ageing. The goal is to provide the nutrition & consumer health industries with clinically tested innovations that confer a real health benefit to the consumer.

Feel free to contact BioActor via for more information on the possibilities MicrobiomeX® has to offer.

Further information can be found on: and


What are the best substitutes for caffeine?

What are the best substitutes for caffeine?

April 21st, 2022

A wide variety of caffeine-containing products are available, ranging from coffee and tea to dietary supplements, sodas and energy drinks. However, consuming too much caffeine often leads to side effects such as stress, anxiety, and even sleeping problems. If you are looking for alternative products to boost energy levels and increase focus, Brainberry®, maca root, ginseng, Rhodiola, and Lion’s Mane are natural ingredients that can help you get through the day without side effects.


Why should you substitute caffeine with another ingredient?

Most people drink coffee regularly. It is consumed because people like the taste or because of the social aspects to drinking coffee. Even though there are many ways to improve your focus, coffee is often consumed because it makes people feel more awake, alert, and energetic.

Of course, coffee is a source of caffeine, which is the ingredient that gives coffee its effects. There are other drinks that contain caffeine, and some people even take dietary supplements containing caffeine to boost their energy levels during the day or for their workout. [1].

Besides positive effects, consumption of caffeine may also have some downsides. These include giving people feelings of stress and anxiety. Besides increasing these feelings, caffeine consumption could also lead to insomnia [2].

Caffeine is unique in its function, but these adverse effects are a reason for people to reduce the intake of caffeine and look for alternative ingredients. Here are some suggestions of natural substitutes that make you feel awake and help you focus, without leaving you feeling stressed.

The best substitutes for caffeine

1. Maca root

Maca is a plant that grows in Peru (also called Peruvian ginseng). It’s a plant that belongs to the brassica (mustard) family. It is traditionally used for nutritional and medicinal purposes. The plant is made into a powder that is often added to smoothies, juices, and shakes.

It has been used for centuries as a fertility enhancer in humans and animals, but now more benefits of consuming maca are being discovered. The benefits of maca root vary, and evidence shows it may help increase energy levels and improve mood.

Additionally, other findings show that maca can help against feelings of anxiety and stress. This makes Maca a good alternative to caffeine, which can have the opposite effect.


2. Ginseng

Like maca, ginseng is a herb made from the root of its plant. It has been one of the most important products for health care in Asia. There, it has been used to make traditional medicine for centuries.

There are different types of ginseng, which vary in the way they are grown and processed. White ginseng is dried naturally, while red ginseng is steamed before it is dried, which increases its efficacy. The most important compounds in ginseng are ginsenosides and gintonin [3].

Ginseng is one of the most popular caffeine substitutes. Various research demonstrated that this plant is able to improve brain functions, boost mood and memory, help against fatigue, and increase energy levels.


3. Brainberry® (Aronia berry extract)

Aronia berries are becoming increasingly popular among consumers because of their many demonstrated health benefits. Aronia plants are native to North America but are also commonly found in the Baltic region of Europe.

Brainberry® is an Aronia berry extract researched and developed by BioActor. It was demonstrated that the daily consumption of Brainberry® is able to boost mental energy and focus without side effects. An ideal alternative if you want to get rid of caffeine!

The main constituent of Brainberry is an anthocyanin called Cyanidin 3-O-galactoside, a powerful antioxidant that can improve brain health and support brain function.

If this sparked your interest, you can find out everything you need to know about Brainberry®, brain health and improving your focus here.


4. Rhodiola

Rhodiola is a plant that can be found in Europe and Asia. Like ginseng and maca its root is consumed for health benefits. Rosavin and salidroside are believed to be its most profitable compounds.

Rhodiola has been used for many years and has been mostly recommended to treat headaches, hernias and has also been used as an astringent. Nowadays, rhodiola is often consumed by people during stressful times.

If you’re looking for a natural alternative to caffeine that reduces fatigue, rhodiola is a good option because it has been shown to improve symptoms in participants that suffered from chronic fatigue. The stress-lowering and energizing effects of rhodiola make it a great natural replacement for coffee.


5. Lion’s Mane

Lion’s Mane is a mushroom that can grow long hair-like strings that resemble a lion’s mane. It is often found in North America, Europe, and Asia. It consists for roughly 20% out of protein.

Lion’s Mane is increasingly studied. It has properties that are believed to be neuroprotective. That is because two novel nerve growth factors have been discovered in this mushroom [4].

Lion’s Mane has thus been said to have positive effects on the brain. It can improve memory and helps to lower feelings of stress and anxiety. This makes it an ingredient that can help consumers cut down on their caffeine consumption.

The bottom line

We all love a good cup of coffee in the morning. However, there are several reasons to reduce caffeine intake and look for a substitute. The aforementioned ingredients are good natural alternatives to caffeine as they can boost energy levels and brain functions, without having any anxiety or stress inducing effects.

TIM-2 in-vitro-gastrointestinal-model

What is the TIM-2 system? An in-vitro model of the colon

What is the TIM-2 system? An in-vitro model of the colon

April 8th, 2022

The TIM-2 model is a dynamic gastrointestinal model, which is used for in-vitro research. The TIM-2 model can be used to study changes in the microbiota composition and the production of beneficial molecules in the gut. It resembles the human large intestine, including peristalsis, dialysis, and microorganisms. It is a good model that provides short experiment durations and the studies done with it are highly reproducible.

TIM-2 in-vitro-gastrointestinal-model

What is the TIM-2 model?

The TIM-2 (TNO in-vitro) model is a computer-controlled dynamic in-vitro gastrointestinal model of the colon used in research to study changes in the microbiota composition.

This model closely mimics part of the human large intestine, including its microorganisms, peristaltic movements, temperature (37ºC) and acidic pH (5.8).

What is the TIM-2 model used for in research?

The TIM-2 model has a wide range of applications in research. It can be used to study changes in the microbiota composition and production of beneficial molecules such as short-chain fatty acids associated with specific dietary patterns or ingredients and, consequently, to increase human health through the understanding of microbiota.

Due to the health benefits of short-chain fatty acids (SCFA), many studies have focused on carbohydrate fermentation and the subsequent production of SCFA.

However, it has also been used to study the effects of probiotics after antibiotic treatment, fermentation of prebiotic fibres, metabolization of molecules such as flavonoids and even to investigate the differences in microbiota from lean and obese individuals.

Watch the interview with prof. Koen Venema

Difference between TIM-2 model and other in-vitro models

Compared to other in-vitro models, TIM-2 holds some unique features, which allow predicting what would happen in an actual clinical trial.

The way the peristaltic movements are produced in the TIM-2 model gives a better mixing of the components than what would be accomplished by stirring or shaking. Thanks to this, in TIM-2 there is no phase-separation of solids and liquids, which is what occurs in other models.

On the other hand, in vivo microbial metabolites are normally taken up by the gut epithelium. This is, of course, not possible in an in-vitro model, but the TIM-2 model features a unique dialysis system that removes these metabolites produced by microorganisms.

The accumulation of these microbial metabolites would otherwise result in the inhibition or death of the microorganisms present in the model. Therefore, the dialysis system allows maintaining a highly active microbiota, with a similar density to that found in the human intestine.

In other systems, metabolites tend to accumulate. In fact, with the TIM-2 model, since all the microbial metabolites are collected, they can be measured, which is something not possible in a real-life setting.

What are the advantages and limitations of the TIM-2 model?

Advantages of the TIM-2 model include:

Short experiment duration. Compared to other models, experiments are quick, usually taking three test days or even less.

Presence of peristaltic movements and dialysis system. These two unique features allow predicting what would happen in an actual clinical trial.

Single parameter study. If a single parameter in the system is changed, the effect of that parameter on the microbiota can be studied.

Highly reproducible. Since the model is computer-controlled, it is highly reproducible.

Like other in-vitro models, the TIM-2 model has some limitations, which include:

Absence of gut epithelial cells, immune cells and neurons. However, samples can be taken and incubated with these kinds of cells to investigate interactions.

Based mostly on healthy individuals. The model has been developed based on data coming from mostly healthy individuals. For this reason, it is unclear exactly which parameters to adjust when simulating patient populations.

Absence of feedback mechanisms. Due to this, as with similar in-vitro models, the results will always be an indication of what may occur in real life and, therefore, they should be interpreted carefully.

BDNF: A key molecule for cognition and eye health

BDNF: A key molecule for cognition and eye health

April 1st, 2022

Brain-derived neurotrophic factor (BDNF) is a protein highly expressed in the central nervous system, especially in the brain. BDNF promotes the growth of dendrites and dendritic spines, contributing to synaptic strength and plasticity in the hippocampus, thus important for learning and long-term memory. Research shows that increased levels of BDNF in serum are correlated with improved cognitive functions while decrease in BDNF is associated with neurodegenerative and mental illnesses. Moreover, new scientific evidence suggests that BDNF is also an important factor in eye health.

What is BDNF and why is it so important?

BDNF belongs to the neurotrophin family of growth factors and plays an important role in brain development, mainly growth and maturation of neurons and synapses.

Highest levels of BDNF can be found in hippocampus, amygdala, cerebellum and cerebral cortex in both rodents and humans [1]. As well as in the brain, BDNF has been detected in other tissues such as the eye, lung, liver and skeletal muscle.

Today we know that BDNF is also crucial for the adult brain, where it regulates synaptic changes and efficacy.

BDNF is believed to be involved in the cellular mechanisms underlying memory formation and consolidation, learning and other complex behaviors by promoting long term potentiation in hippocampus [2].

BDNF in disease and the ageing brain

BDNF also seems to play a significant role in brain damage repair. Studies have shown that following traumatic brain injury, the mRNA expression level of BDNF is temporarily significantly upregulated in the injured cortex and in the hippocampus. These findings suggest that BDNF acts as an endogenous neuroprotective mechanism attenuating cell damage [3].

In addition, emerging scientific data suggest that BDNF could be involved in the pathophysiology of brain-associated diseases. Impaired BDNF signaling has been observed in several diseases, such as Huntington’s disease, Alzheimer’s disease, depression, schizophrenia, and bipolar and anxiety disorders.

Finally, part of the natural process of ageing is reduction of hippocampal volume and decrease in BDNF expression, which is associated with age-related cognitive decline [4].

What is the role of BDNF in eye health?

BDNF is produced by neurons and glial cells in the retina. Similarly to the brain, research indicates that BDNF could be involved in retinal development by modifying neuronal cell number or synapse formation [5].

Nowadays, our eyes are constantly being overworked as a consequence of increased usage of visual display terminal (VDT) devices, such as smartphones, computers or tablets. This can negatively affect blink frequency, which can induce dry eye and associated symptoms including pain, burning and visual disturbances.

Interestingly, BDNF knockdown mice showed decreased basal tear secretion, pointing at the role of BDNF in tear secretion and to the pathology of dry eye disease [6].

Moreover, recent studies show that BDNF plays a vital role in other eye diseases, such as age-related macular degeneration (AMD) or diabetic retinopathy (DR). In AMD patients, serum BDNF levels are decreased and the same trend is observed in DR patients.

These findings suggest that optimal BDNF levels may be necessary to exert protective effects on the eye and that decreased levels of BDNF signal eye disease [7, 8].

How can you increase BDNF naturally?

Control your stress levels
Acute stress down-regulates hippocampal BDNF mRNA expression and interestingly, antidepressants up-regulate BDNF expression [9]. Practicing yoga or other stress management techniques therefore seem to be an efficient way how to boost your BDNF [10].

Some studies have shown that exercise enhances the expression of BDNF. The reasoning is not fully understood but one possible explanation is that exercise leads to the release of the ketone body β-hydroxybutyrate, which in turn induces the activity of BDNF promoters [11].

Practice occasional fasting
Not every stress is bad for your brain: it appears that mild metabolic stress associated with dietary restriction leads to significantly enhanced expression of various neurotrophic factors, BDNF included. A study showed that following 48-hour fasting, BDNF was significantly upregulated in human skeletal muscle [12].

Eat anthocyanin rich foods
Apart from the above mentioned, dietary interventions have been also gaining on attention as a potential strategy to elevate BDNF levels. There is extensive scientific evidence that foods high in anthocyanins, such as edible berries, are good for your brain health [13]. A recent study showed that 6-week supplementation of pure anthocyanins increased BDNF expression and improved spatial and psychomotor performances in aged rats [14].

Aronia melanocarpa anthocyanins and BDNF

Aronia melanocarpa is a berry native to North America, which is higher in anthocyanins than any other berries. Aronia-specific anthocyanin, cyanidin-3-O-galactoside (Cy3Gal), crosses the blood brain barrier and interacts with BDNF sinaling pathway, thereby contributing to a better neuronal signalling.

In a double-blind placebo-controlled crossover study, we recently demonstrated that short-term supplementation of Brainberry®, aronia melanocarpa extract with a standardized content of Cy3Gal, significantly increased BDNF levels in healthy young adults.

Curious to know more about brain health and how Cy3Gal can increase BDNF? Find out more!

The bottom line

Given all the scientific evidence, BDNF plays a huge role in brain fitness, brain disease and eye health.

Manipulating BDNF levels through dietary factors might be a promising strategy to not only treat various neurological and psychiatric disorders, but also to naturally boost memory and learning.

To level-up BDNF is desirable for everyone: not only for the ageing population but also for young professionals seeking ways to enhance their cognition.