Figure 8
Inflammatory response in the brain after TBI and the pathomechanism of the anti-inflammatory effect of XFZY.
Following TBI, the mechanical injury-stimulated cell membrane releases arachidonic acid (AA), which is metabolized into prostaglandin E2 (PGE2) and prostacyclin (PGI2) by cyclooxygenase-2 (COX-2) and into leukotrienes (LTB4) by 5-lipoxygenase (5-LO). The three inflammatory mediators initiate acute inflammation, including changes in blood flow, increased capillary permeability and inflammatory cell recruitment in the brain injury ambitus zone, including polymorphonuclear leukocytes (i.e., neutrophils) and monocytes. Excess prostaglandins and leukotrienes contribute to chronic inflammation. The neutrophils are activated to further release chemotactic factors, devour necrotic tissue and sterilize bacteria. The influx of monocytes and resident microglial cells develop into macrophages, which secrete pro-inflammatory factors (e.g., TNF-α and IL-1β) and consume foreign bodies, necrotic tissue or apoptotic cells (e.g., efferocytosis). XFZY significantly suppressed the increased levels of blood AA, TNF-α and IL-1β in brain tissue, indicating that XFZY possesses anti-inflammatory effects. To target the PI3K-AKT-mTOR signaling pathway, XFZY significantly reversed the elevated phosphorylation of AKT/mTOR in brain tissue post-TBI, as well as the downstream p70S6K, resulting in a reduced translation ratio of inflammatory factors and exerting anti-inflammatory effects.
