When we think of inflammation, we tend to think of swollen joints or maybe red skin and fever. The fact is that inflammation is anytime the immune system is having a response. Usually this is short-lived as the body is fighting a virus or bacteria. But chronic inflammation can cause serious damage to healthy cells and organs. This can even happen in the brain.
Neuroinflammation is the body’s natural immune response to injury, infection, or disease in the brain. However, prolonged inflammation in the brain can cause damage to healthy tissue. This is well documented in the following conditions:
- Brain injuries like head trauma (https://pubmed.ncbi.nlm.nih.gov/35461293/)
- Infections leading to encephalitis (https://pubmed.ncbi.nlm.nih.gov/34792015/)
- Neurodegenerative diseases including Alzheimer’s (https://pubmed.ncbi.nlm.nih.gov/27179961/), Parkinsons’s (https://pubmed.ncbi.nlm.nih.gov/27179961/), and multiple sclerosis (https://pubmed.ncbi.nlm.nih.gov/38513664/)
There are many other examples where neuroinflammation plays a key role in the progression of a significant brain disorder. Interestingly, even common conditions such as brain fog and mental fatigue have a neuroinflammatory component (https://pubmed.ncbi.nlm.nih.gov/36846556/). Microglia are the in-house immune cell of the brain that play vital roles in brain development, immune defense, and maintaining the neural environment, but are also key drivers of neuroinflammation. While they are normally meant to protect the brain from viruses or other infections, they can sometimes cause damage given the right conditions. Microglia exist in two main states:
- M2 state is considered ani-inflammatory and neuroprotective
- M1 state is classically perceived as inflammatory and neurotoxic (https://pubmed.ncbi.nlm.nih.gov/19269040/; https://pubmed.ncbi.nlm.nih.gov/25598354/)
When microglia are stuck in the M1 state, they secrete pro-inflammatory cytokines that damage neurons and disrupt the blood brain barrier allowing neutrophils, our immune first responders, to enter the brain and further amplify damage (see figure). Neutrophils produce that familiar puss in fresh wounds and can do worse in our brains. Chronic neuroinflammation characterized by overreactive M1 microglial cells means bad news for our neurons and overall brain health. Neurodegeneration, driven by this mechanism, is a major public health concern in an aging population (https://pubmed.ncbi.nlm.nih.gov/25598354/).
Diet plays a critical role in M1 microglial differentiation and neuroinflammation. For example, excess high-fructose corn syrup impaired learning and promoted neuroinflammation as measured by increases in the inflammatory cytokine IL-6 in the brains of adolescent rats (https://pubmed.ncbi.nlm.nih.gov/25242636/). This was not observed with sucrose, which is found in raw cane sugar like that used in Brain Wave gummies. Other drivers of dietary induced-neuroinflammation include saturated fats (https://pubmed.ncbi.nlm.nih.gov/39842474/), ultra-processed foods (https://pubmed.ncbi.nlm.nih.gov/31837645/), and excessive salt intake (https://pubmed.ncbi.nlm.nih.gov/39045090/).
Can mushrooms help this phenomenon? Research suggests yes.
Cordyceps mushrooms produce a protein called cordycepin, which exhibits diverse bioactivity, including anti-inflammatory, antioxidant, and hypoglycemic effects. A recent study showed that cordycepin decreased neuroinflammation by attenuating the secretion of inflammatory cytokines (IL-6, IL-1β, and TNFα) by M1 microglia (https://www.dl.begellhouse.com/journals/708ae68d64b17c52,forthcoming,63597.html). It was also shown that cordycepin suppressed the expression of TLR4, a receptor on microglia associated with inflammation. Essentially, cordycepin turns microglia from enemies into helpers.
After brain injury, neuroinflammation can hinder recovery. In this setting, cordycepin reduced neuroinflammation and prevented neutrophil infiltration, promoting long-term neuroprotection following brain trauma (https://pubmed.ncbi.nlm.nih.gov/34130727/).
In a reference to one my previous blogs (https://www.brainwaveusa.com/blogs/dr-andys-answers-medicinal-mushroom-questions/is-it-ok-to-take-lions-mane-and-other-medicinal-mushrooms-while-pregnant-or-nursing), cordycepin also helped mice with memory after sepsis (https://link.springer.com/article/10.1007/s12035-025-05399-y). The study showed that cordycepin protected neurons and astrocytes, and reduced swelling and inflammation during a sepsis reaction. It did this by calming down the microglia mentioned above that were overreacting and causing damage, switching them from the neuroinflammatory M1 state to an anti-inflammatory/neuroprotective M2 state. Taken together, these results highlight the therapeutic potential of cordyceps in neuroinflammatory conditions.
The medicinal mushroom lion’s mane (Hericium erinaceus) has been shown to have therapeutic potential for brain disorders due to its neuroprotective effects. The mycelia of lion’s mane contain erinacines. Erinacine A was shown to uniquely induce the accumulation of the transcription factor Nrf2, a key regulator of the antioxidant response. This helps neurons survive. Erinacine A was also anti-inflammatory, enhanced new neuron growth and survival, and improved cognitive and behavioral outcomes in vivo (https://pmc.ncbi.nlm.nih.gov/articles/PMC12230622/).
Reishi has been widely used in traditional Chinese medicine to promote health and longevity. Bioactive compounds from reishi also interact with microglia
(https://pubmed.ncbi.nlm.nih.gov/28340576/). The study noted a reduction of induced neuroinflammation and provided evidence that the neuroprotective function of reishi might be achieved through modulation of M1 microglial inflammatory responses.
Maitke mushroom is believed to be a potent choice as a therapeutic agent for neurodegenerative diseases due to its antioxidative properties and its ability to reduce neuroinflammation. It even has anti-beta amyloid properties that can help with Alzheimer’s disease. The neuroprotective properties of maitake have been well documented (https://pubmed.ncbi.nlm.nih.gov/36749053/).
Chaga mushroom is well known for its high antioxidant content, which protects cells from free radical damage and oxidative stress, and is used to reduce chronic inflammation. More recently, inotodiol, a bioactive compound from chaga, was found to reduce neuroinflammation as shown by a reduction in inflammatory cytokine release by mouse M1 microglia (https://pubmed.ncbi.nlm.nih.gov/40429872/). Furthermore, inotodial mitigated Alzheimer’s- progression by reducing amyloid plaques and neuroinflammation, ultimately leading to cognitive enhancement.
In conclusion, mushrooms have been shown to help reduce inflammation in our brains. Cordyceps, lion’s mane, reishi, maitake, and chaga in Brain Wave’s blend all help tip the scale towards neuroprotective M2 microglia and a healthy brain.
Let’s keep our microglia happy. Til next time, cheers,
Dr. Andy