Xijiao Dihuang Decoction Alleviates Ischemic Brain Injury in MCAO Rats by Regulating Inflammation, Neurogenesis, and Angiogenesis

Abstract

Ischemic stroke is an increasingly important public health problem, and no effective treatments are approved. Xijiao Dihuang Decoction (XDD), a famous herbal formula for treating hemorrhagic fever syndromes, has been shown to exert powerful neuroprotective property. The aim of this study was to identify the chemical constituents in XDD, observe the neuroprotective effect of XDD against acute ischemic stroke, and explore the specific mechanisms by which these effects were mediated. With UHPLC-Q/TOF-MS, 47 components in XDD were detected and 25 of them were identified. In rats subjected to MCAO, XDD ameliorated neurological deficit, histopathology changes, and infarction volume. In addition, levels of TNF-ɑ, IL-6, and IL-1β in XDD-treated group were significantly lower compared to the model group. Mechanistic studies showed that XDD inhibited MCAO-induced NF-κB activation, presenting as downregulating the expression of phospho-NF-κB p65 and preventing IκBɑ degradation. Besides, BDNF, GDNF, VEGF, bFGF, and CD34 levels were significantly increased by XDD, suggesting that the protective effects of XDD may also be associated with the promotion of neurogenesis and angiogenesis. In conclusion, these findings provided a novel regulatory pathway of the neuroprotective effect of XDD that helped rehabilitate patients with stroke.

Small extracellular vesicles secreted by human iPSC-derived MSC enhance angiogenesis through inhibiting STAT3-dependent autophagy in ischemic stroke

“…Next, we examined if iMSC-sEV could promote angiogenesis after ischemic stroke in rats. Newly formed vessels and mature vessels in the infarct boundary zone were characterized by CD31/EdU, CD34 staining, and CD31 staining [38]. The vehicle group induced a significantly higher expression of CD31 + /EdU + (Fig.…”

PKM2 Aggravates Cerebral Ischemia Reperfusion-Induced Neuroinflammation via TLR4/MyD88/TRAF6 Signaling Pathway

“…Furthermore, since apoptosis [31] and oxidative stress (reactive oxygen species) [32] play important role in the progression of cerebral I/R injury, the effects of PKM2 on cell apoptosis and reactive oxygen species accumulation in OGD/R-stimulated HT-22 cells need further investigation. In addition to cell damages, inflammatory response also serves as dominating pathogenic factor for ischemic stroke [33], which is associated with all the phases of cerebral I/R injury [34]. Moreover, inflammation response induced by I/R injury could exacerbate the infarct region and tissue injury via release of inflammatory cytokines [35].…”

“…In addition to cell damages, inflammatory response also serves as dominating pathogenic factor for ischemic stroke [33], which is associated with all the phases of cerebral I/R injury [34]. Moreover, inflammation response induced by I/R injury could exacerbate the infarct region and tissue injury via release of inflammatory cytokines [35].…”

Pathophysiology of ischemic reperfusion injury and the molecular targets involved in amelioration of brain injury by herbal medicine

“…Pro-inflammatory cytokines, such as IL-1β and TNF-α, can stimulate the detrimental activity of Nuclear factor kappa B (NF-Κb) with nuclear translocation for upregulating the expression of phospho-NF-κB p65, promoting NF-κB inhibitory factor α (IκBα) degradation and heightening of the expression of Protein P53 (p53) [33,103]. These are well-known modulators of apoptosis (neuronal apoptosis) as well as structural brain injury (33,103). These pro-inflammatory cytokines have also been reported to facilitate the degradation of the microenvironment around the nascent neuron with associated injuries that cumulatively shorten the life span of the neuron [104].…”