Anti‐Inflammatory Effects of Traditional Chinese Medicines against Ischemic Injury in In Vivo Models of Cerebral Ischemia

Abstract

Inflammation plays a crucial role in the pathophysiology of acute ischemic stroke. In the ischemic cascade, resident microglia are rapidly activated in the brain parenchyma and subsequently trigger inflammatory mediator release, which facilitates leukocyte-endothelial cell interactions in inflammation. Activated leukocytes invade the endothelial cell junctions and destroy the blood-brain barrier integrity, leading to brain edema. Toll-like receptors (TLRs) stimulation in microglia/macrophages through the activation of intercellular signaling pathways secretes various proinflammatory cytokines and enzymes and then aggravates cerebral ischemic injury. The secreted cytokines activate the proinflammatory transcription factors, which subsequently regulate cytokine expression, leading to the amplification of the inflammatory response and exacerbation of the secondary brain injury. Traditional Chinese medicines (TCMs), including TCM-derived active compounds, Chinese herbs, and TCM formulations, exert neuroprotective effects against inflammatory responses by downregulating the following: ischemia-induced microglial activation, microglia/macrophage-mediated cytokine production, proinflammatory enzyme production, intercellular adhesion molecule-1, matrix metalloproteinases, TLR expression, and deleterious transcription factor activation. TCMs also aid in upregulating anti-inflammatory cytokine expression and neuroprotective transcription factor activation in the ischemic lesion in the inflammatory cascade during the acute phase of cerebral ischemia. Thus, TCMs exert potent anti-inflammatory properties in ischemic stroke and warrant further investigation.

Inflammatory Role of TLR-MyD88 Signaling in Multiple Sclerosis

“…The expression of these adhesion molecules can be regulated by the TLR-MyD88 pathway. TLR2 and TLR4 initiate the expression of ICAM-1 by activating the MyD88-dependent signaling pathway and promoting lymphocyte adhesion on the vessel wall (Cheng and Lee, 2016). The attenuated TLR signal pathway can reduce the expression of VCAM-1 and ICAM-1 on vascular endothelial cells (Bhaskar et al, 2016).…”

Curcumin exerts protective effects against hypoxia‑reoxygenation injury via the enhancement of apurinic/apyrimidinic endonuclease�1 in SH‑SY5Y cells: Involvement of the PI3K/AKT pathway

“…In recent years, the benefits of traditional Chinese medicine conferring neuroprotective effects have been increasingly investigated in cerebral I/R injury (8)(9)(10). curcumin, a natural antioxidant mainly extracted from the root of turmeric…”

CoQ10 Augments Rosuvastatin Neuroprotective Effect in a Model of Global Ischemia via Inhibition of NF-κB/JNK3/Bax and Activation of Akt/FOXO3A/Bim Cues

“…This transcription factor empowers the generation of proinflammatory enzymes and cytokines, including tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), and intracellular adhesion molecule-1 (ICAM-1) ( Zhang et al, 2016 ). These events amplify the inflammatory cascade and trigger the recruitment of neutrophils, thereby exacerbating the ischemic insult ( Cheng and Lee, 2016 ; Sapkota et al, 2017 ).…”