Leonurine suppresses neuroinflammation through promoting oligodendrocyte maturation

Abstract

Focal inflammation and remyelination failure are major hallmarks of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). In this study, we found that leonurine, a bioactive alkaloid, alleviated EAE disease severity along with reduced central nervous system inflammation and myelin damage. During the pathogenesis of EAE, leonurine dramatically suppressed the recruitment of encephalitogenic T cells into the central nervous system, whereas did not impair periphery immune responses and microglia activation. Mechanistically, leonurine protected mice against demyelination along with enhanced remyelination through promoting the maturation of oligodendrocytes in both EAE and cuprizone‐induced demyelination mouse models. Moreover, we identified that the expression of demethylase jumonji domain‐containing protein D3 was significantly enhanced upon treatment of leonurine, which suppressed the trimethylation of histone H3 lysine‐27 and enhanced oligodendrocyte maturation accordingly. Collectively, our study identified the therapeutic effect of leonurine on EAE model, which potentially represents a promising therapeutic strategy for multiple sclerosis, even other demyelination disorders.

Supplementation of Plants with Immunomodulatory Properties during Pregnancy and Lactation—Maternal and Offspring Health Effects

“…Nowadays, there are more than 300 plants which exhibit beneficial properties for humans. Plant-derived compounds which affect the immune system belong to chemical groups of compounds such as: alkaloids (i.e., leonurine [4], piperine [5], and sophocarpine [6]), terpenoids (i.e., ginsan [7] or oleanolic acid [8]), polysaccharides (from licorice Glycyrrhiza uralensis Fisch [9], or from Lentinus edodes [10]), lactones (from Datura quercifolia [11] or sesquiterpene lactones from Loranthus parasiticus ), and essential oils (Z-ligustilide [12] or Tetramethylpyra-zine [13]). However, the most well-known and numerous group of immune-affecting compounds belongs to flavonoids, which are divided into flavones, flavanones, flavanols, flavonols, catechins, isoflavones, and anthocyanins [14].…”

Activation of GPR40 attenuates neuroinflammation and improves neurological function via PAK4/CREB/KDM6B pathway in an experimental GMH rat model

“…Suppression of KDM6B in microglia resulted in the decrease of M2 populations and was met with an exponential increase in M1 microglial populations, thereby increasing the inflammatory response which led to an extensive neuronal death [ 28 ]. An increase of microglial KDM6B expression was shown to attenuate inflammation and promoted anti-inflammatory effects of M2 after hemoglobin exposure, thereby suppressing inflammation in CNS injury models [ 27 , 50 ]. In this present study, we are the first to demonstrate that GMH decreased the expression of endogenous KDM6B level in the brain.…”

Protein kinase C is involved in the neuroprotective effect of berberine against intrastriatal injection of quinolinic acid‐induced biochemical alteration in mice

“…Furthermore, the proinflammatory cytokines cause neuronal death, synaptic damage and glutamate release. Inhibiting progressive neuroinflammation is an important mechanism for protecting neuronal cells . Decreasing proinflammatory cytokines may be a therapeutic target in HD treatment.…”