Spearmint, the "natural enemy" of the microglia of restless cleaners

microglia are the resident immune cells of central nervous system. They play an important role in maintaining tissue homeostasis. Their normal physiological function is to maintain the homeostasis of the tissue by monitoring the brain microenvironment , Promote neuron development, adult neurogenesis and synapse plasticity. Under normal circumstances, it has an important contribution to brain development.

However, when neuronal damage or other damage occurs, microglia will be activated, and the activated microglia will be polarized to the M1 phenotype or M2 phenotype. The former secretes a variety of inflammatory cytokines, chemokines and neurotoxic factors, while the latter produces a series of anti-inflammatory factors, neuroprotective factors and wound healing factors. However, excessive activation of microglia will damage the surrounding healthy nerve tissue, and the factors secreted by dead or dying neurons will in turn aggravate the chronic activation of microglia, leading to the progressive loss of neurons.

Note: The process of M1 microglia polarization and polarization to the M2 phenotype

In the development of many brain diseases, such as , ischemic stroke, multiple sclerosis In neurodegenerative diseases, microglia are activated for a long time, thereby amplifying the death of neurons. Therefore, inhibiting microglia-mediated neuroinflammation is a potential therapeutic strategy for the treatment of these brain diseases.

Researchers found that spearmint can inhibit the polarization of M1 microglia and promote the polarization of microglia to the M2 phenotype under neuroinflammatory conditions in vitro and in vivo in mice. Then they found that the PDPK1/Akt/mTOR pathway promotes the polarization of microglia to the M2 phenotype through the degradation of hypoxia-inducible factor induced by spearmint. Increased mitochondrial respiration is a feature and requirement of the anti-inflammatory response of M2 macrophages. To determine the role of mitochondrial respiration in spearmint-mediated polarization of microglia to the M2 phenotype, they measured cells treated with spearmint Production of mitochondria in ATP.It was found that the promotion of spearmint-mediated microglia polarization to the M2 phenotype requires an increase in mitochondrial respiration and metabolic reprogramming. Surprisingly, hypoxia-inducible factors are also involved in spearmint-regulated mitochondrial respiration and metabolic reprogramming. Programming to promote the polarization of microglia to the M2 phenotype.

research shows that hypoxia-inducible factors are the key effector molecules responsible for coordinating the metabolism and functional reprogramming of M1/M2 microglia polarization. Under neuroinflammatory conditions, these factors can be regulated by the PDPK1/Akt/mTOR pathway. Therefore, the inhibition of PDPK1/Akt/mTOR by spearmint may be a potential therapeutic method to inhibit neuroinflammation by regulating the polarization of microglia M1/M2.

【References】

1. Subhramanyam CS, Wang C, Hu Q, Dheen ST. Microglia-mediated neuroinflammation in neurodegenerative diseases. Semin Cell Dev Biol. 2019 Oct;94:112-120. doi: 10.1016/j.semcdb .2019.05.004. Epub 2019 May 11. PMID: 31077796.
2. Wei Y, Chen J, Cai GE, Lu W, Xu W, Wang R, Lin Y, Yang C. Rosmarinic Acid Regulates Microglial M1/M2 Polarization via the PDPK1/Akt/HIF Pathway Under Conditions of Neuroinflammation. Inflammation. 2021 Feb;44(1):129-147. doi: 10.1007/s10753-020-01314-w. PMID: 32940818.