Eupatilin alleviates inflammatory response after subarachnoid hemorrhage by inhibition of TLR4/MyD88/NF‐κB axis

Abstract

Early brain injury (EBI) is associated with the adverse prognosis of subarachnoid hemorrhage (SAH) patients. The key bioactive component of the Chinese herbal medicine Artemisia asiatica Nakai (Asteraceae) is eupatilin. Recent research reports that eupatilin suppresses inflammatory responses induced by intracranial hemorrhage. This work is performed to validate whether eupatilin can attenuate EBI and deciphers its mechanism. A SAH rat model was established by intravascular perforation in vivo. At 6 h after SAH in rats, 10 mg/kg eupatilin was injected into the rats via the caudal vein. A Sham group was set as the control. In vitro, BV2 microglia was treated with 10 μM Oxyhemoglobin (OxyHb) for 24 h, followed by 50 μM eupatilin treatment for 24 h. The SAH grade, brain water content, neurological score, and blood-brain barrier (BBB) permeability of the rats were measured 24 h later. The content of proinflammatory factors was detected via enzyme-linked immunosorbent assay. Western blot analysis was conducted to analyze the expression levels of TLR4/MyD88/NF-κB pathway-associated proteins. In vivo, eupatilin administration alleviated neurological injury, and decreased brain edema and BBB injury after SAH in rats. Eupatilin markedly reduced the levels of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α), and suppressed the expression levels of MyD88, TLR4, and p-NF-κB p65 in the SAH rats' cerebral tissues. Eupatilin treatment also reduced the levels of IL-1β, IL-6, and TNF-α, and repressed the expression levels of MyD88, TLR4, and p-NF-κB p65 in OxyHb-induced BV2 microglia. Additionally, pyrrolidine dithiocarbamate or resatorvid enhanced the suppressive effects of eupatilin on OxyHb-induced inflammatory responses in BV2 microglia. Eupatilin ameliorates SAH-induced EBI via modulating the TLR4/MyD88/NF-κB pathway in rat model.

Eupatilin Ameliorates Lipopolysaccharide-Induced Acute Kidney Injury by Inhibiting Inflammation, Oxidative Stress, and Apoptosis in Mice

“…However, since complex mechanisms such as inflammation, oxidative stress, and apoptosis are involved in the pathogenesis of sepsis, there are currently no effective drugs that can delay or reverse the development of organ dysfunction. EUP is a flavone found in a variety of medicinal plants, particularly in the genus Artemisia and has multiple biological functions including anti-inflammatory, antioxidant, and anti-apoptotic properties [ 13 , 14 , 15 ]. Therefore, we investigated whether EUP has a favorable effect on septic AKI using a murine model of LPS-evoked AKI.…”

“…Eupatilin (EUP) is a bioactive flavone found in a variety of medicinal plants, particularly in the genus Artemisia [ 12 ]. Previous studies have shown that EUP exerts multiple biological activities including anti-inflammatory, antioxidant, and anti-apoptotic effects [ 13 , 14 , 15 ]. Accumulating evidence suggests that EUP inhibits excessive production of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) in animal models of gastric mucosal injury [ 16 ], inflammatory skin diseases [ 17 , 18 ], asthma [ 19 ], anaphylactic shock [ 20 ], and colitis [ 21 ].…”

Eupatilin ameliorates postmenopausal osteoporosis via elevating microRNA‐211‐5p and repressing JAK2/STAT3 pathway

“…16 Besides, Eupatilin represses inflammatory response in subarachnoid hemorrhage-induced early brain injury. 17 In the meantime, a recent report has confirmed the protective effects of Eupatilin on collagen-induced arthritis models. 18 Although several flavonoids have been testified to manifest osteogenic abilities, the latent molecular mechanisms of Eupatin in PMOP have not been completely explored.…”

“…Similarly, Eupatilin inhibits proliferation and promotes apoptosis of cervical cancer cells 16 . Besides, Eupatilin represses inflammatory response in subarachnoid hemorrhage‐induced early brain injury 17 . In the meantime, a recent report has confirmed the protective effects of Eupatilin on collagen‐induced arthritis models 18 .…”

Ferroptosis in early brain injury after subarachnoid hemorrhage: review of literature

“…The main active ingredient of traditional Chinese medicine Asteraceae is eupatilin, which can significantly reduce IL-1β, IL-6, and TNFα, and the inhibit TLR4/MyD88/NF-κB signaling pathway reduces blood-brain barrier damage and brain edema and improves EBI [ 79 ]. Alpha asarone (ASA), extracted from the Chinese medical herb Acorus tatarinowii Schott, can promote NR2B/CaMKII interactions, further activate the CREB/BDNF/TrkB signaling pathway, and improve neural function in rats [ 80 ].…”