Neuroinflammation is the process of inflammation in the nervous system, specifically in the brain and spinal cord. Inflammation is the body’s response to injury or infection, and it involves the activation of immune cells and the release of various chemicals to fight off the invading pathogens. However, in the case of CFS, this inflammatory response becomes chronic and widespread, leading to damage to the CNS.

Microglia, the immune cells of the CNS, play a crucial role in neuroinflammation. They are responsible for detecting and responding to any harmful stimuli in the brain or spinal cord. When activated, microglia release pro-inflammatory cytokines, which are signaling molecules that can damage neurons and lead to neuroinflammation.

The exact cause of neuroinflammation and microglial activation in CFS is still unknown. However, researchers have found evidence that suggests viral infections, oxidative stress, and mitochondrial dysfunction may all play a role in triggering this inflammatory response.

So, what does this mean for treating CFS? The focus now is to develop treatments that target neuroinflammation and microglial activation in the CNS.

The first line of treatment involves reducing inflammation in the body. This can be achieved through the use of non-steroidal anti-inflammatory drugs (NSAIDs) or corticosteroids. These medications work by suppressing the immune response, thereby reducing the release of pro-inflammatory cytokines.

Another approach is the use of anti-viral drugs. As viral infections have been linked to CFS, targeting the virus with antivirals can potentially reduce neuroinflammation and microglial activation. However, more research is needed in this area.

Suppressing the activation of microglia could be a promising way to treat neuroinflammation. Lately, there has been a lot of interest in natural products and their components as potential alternatives for therapy. They are known to be safe, affordable, and easily accessible. However, only a handful of substances have been thoroughly studied, and most of the research is still in its early stages. By further investigating how microglial activation works, how neuroinflammation is regulated, and the impact of natural products and their components, we could not only discover new neuroprotective agents for this condition but also for neurodegenerative diseases.

Ginsenosides from Panax Ginseng: Ginsenosides suppress inflammation by inhibiting NF-κB and MAP kinase activities. They also inhibit nitric oxide synthase (iNOS) and cytokine expressions.
Curcumin from Curcuma Longa: Curcumin decreases activated microglia and inhibits microglial expression. It also suppresses COX-2 and iNOS, important enzymes in inflammation.
Epigallocatechin-3-Gallate (EGCG) from Camellia Sinensis: EGCG inhibits the production of inflammatory mediators and crosses the blood brain barrier. It has antioxidant activity, reduces inflammation, and protects neural cells. It is more potent than vitamin C and E in scavenging free radicals.
Resveratrol: Resveratrol exhibits anti-carcinogenesis, cardiovascular protection, and anti-inflammatory effects. It attenuates immune cell activation and the release of pro-inflammatory mediators. It inhibits NF-κB and activator protein-1.
Gastrodin from Gastrodia Elata: Gastrodin has been used in traditional medicine for various conditions. It reduces oxygen free radicals, protects against neuronal damage, and exhibits anxiolytic-like effects. It inhibits NO production and expression of iNOS and COX-2.
Gingerol from Zingiber officinale: Ginger inhibits pro-inflammatory cytokines and decreases synthesis of pro-inflammatory prostaglandins and leukotrienes. It inhibits COX-2 and 5-LOX enzymes.
Obovatol from Magnolia Obovata has been found to inhibit inflammatory activation of microglia and neuroinflammation, providing protective effects against microglia-mediated neurotoxicity. However, its ability to cross the blood-brain barrier has not been confirmed.
Inflexin from Isodon Excisus has shown potential in inhibiting NF-κB activation and reducing the release of nitric oxide (NO) and expression of pro-inflammatory cytokines. It also inhibits COX-2 expression.
Piper Kadsura, a medicinal plant, exhibits strong anti-neuroinflammatory activity by reducing nitric oxide (NO) production in microglial cells.
Ganoderma Lucidum extracts prevent the production of pro-inflammatory and cytotoxic factors from microglia and down-regulate gene expressions of TNF-α and IL-1β.
Berberine, found in Rhizoma coptidis, suppresses neuroinflammatory responses through AMP-activated protein kinase activation in microglial cells. It is commonly sourced from goldenseal, barberry, and Coptis chinensis.
Icariin from Epimedium Brevicornum inhibits the inflammatory response by decreasing the production of TNF-α, IL-6, NO, and adhesion molecules. It has a neuroprotective effect.
Isodojaponin from Isodon Japonicus inhibits microglial activation and decreases the production of COX-2, iNOS, and pro-inflammatory cytokines through signaling pathways.
Tetrandrine and fangchinoline from Stephania Tetrandra decrease the production of IL-1β, IL-6, IL-8, TNF-α, leukotrienes, and prostaglandins. They also inhibit the production of TNF-α and IL-6, which can damage nerve cells.
Stinging nettle, also known as Urtica dioica, reduces the production of IL-1β, IL-2, IFN-, and TNF-α. Supplementation of stinging nettle has shown significant reductions in TNF-α and IL-1β.
Fisetin is flavonoid found in various fruits (strawberries, apples, mangoes, persimmons, kiwis, and grapes), vegetables (tomatoes, onions, and cucumbers), nuts, and wine. It exhibits anti-inflammatory effects in peripheral mast cells and brain microglia. It inhibits the production of inflammatory mediators and suppresses NF-κB and p38 MAPK activation. It also has a neuroprotective effect.

– Various flavonoids derived from plants, such as wogonin, tectorigenin, tectoridin, apigenin, and luteolin, modulate microglial activation and possess anti-neuroinflammatory properties.

In addition to these treatments, lifestyle changes, such as a healthy diet and regular exercise, can also help reduce neuroinflammation and improve symptoms of CFS. A healthy lifestyle can reduce oxidative stress and improve mitochondrial function, both of which play a role in neuroinflammation and microglial activation.

In conclusion, the understanding of neuroinflammation and microglial activation in CFS has opened up new avenues for the treatment of this complex illness. By targeting these mechanisms, researchers hope to develop more effective and targeted treatments that can alleviate symptoms and improve the quality of life for those living with CFS. With continued research and development, there is hope that one day we will have a cure. 

Neuroinflammation Treatments Summary

Neuroinflammation Symptoms:

  • Fatigue
  • Cognitive impairment
  • Sleep problems
  • PEM (Post-exertional malaise)
  • Pain

Natural Support:

  • Fisetine
  • Vitamin D
  • Resveratrol
  • Ginesoide
  • Green tea
  • Ganoderma
  • Berberine
  • Luteoline