Alantolactone reduced neuron injury via activating PI3K/Akt signaling pathway after subarachnoid hemorrhage in rats

Abstract

Subarachnoid hemorrhage (SAH) is a common disease with high morbidity and mortality, which can cause pathological, physiological, and biological reactions. SAH causes a series of responses such as neuronal and cerebral cortex damage, which in turn leads to inflammation and apoptosis. Traditional Chinese medicine has a strong anti-inflammatory effect, such as Alantolactone (ATL). However, studies on ATL therapy for SAH have not been reported. We observed the neurological scores, brain water content, Evans blue (EB) extravasation, neuroinflammation, and apoptosis via performing an enzyme-linked immunosorbent assay (ELISA), western blotting, immunofluorescence staining, and other methods after SAH. In this study, we found that ATL treatment attenuated the neurologic deficits, inhibited neuronal apoptosis and inflammatory reaction, promoted polarization of microglia toward the M2 phenotype, and activated the PI3K/Akt signaling pathway. ATL can reduce the neurons and cerebral cortex damage of SAH rats through activating PI3K/Akt signaling pathway.

Eriocitrin Alleviates Inflammation and Oxidative Stress in Subarachnoid Hemorrhage by Regulating DUSP14

“…Moreover, MLB dose-dependently suppressed microglial activation and neuronal apoptosis and decreased TNF-α and cleaved caspase-3 [20]. Alantolactone (ATL) can alleviate injury to neurons and the cerebral cortex in SAH rats, reduce neurological impairment, inhibit neuronal apoptosis and inflammation, facilitate microglial polarization toward the M2 phenotype, and activate the PI3K/Akt signaling pathway [21]. In addition, the protective effect of other Chinese herbal extracts in SAH has also been reported [22].…”

Discovery of alantolactone as a naturally occurring NLRP3 inhibitor to alleviate NLRP3‐driven inflammatory diseases in mice

“…Alantolactone, a sesquiterpene lactone found in many kinds of Chinese herbal plants, has shown anti-inflammatory, antibacterial and antitumour activities (Liu et al, 2021). Recently, alantolactone exhibited anti-inflammatory activity in a range of inflammatory animal models, including colitis (Ren et al, 2019), streptozocin-induced diabetes (Zhu et al, 2020), brain injury (Zhou et al, 2022) and arthritis (H. L. Chen et al, 2021). Alantolactone inhibited the activation of NF-κB and MAPK signalling, reducing the production of proinflammatory IL-1β, IL-6 and TNF-α (Chun et al, 2012) and, more recently, this compound also suppressed muscle inflammation through inhibiting the STAT3 pathway (Pei et al, 2021).…”

CNS-peripheral immune interactions in hemorrhagic stroke

“…123,124 Moreover, modulating microglia polarization could attenuate brain injuries after SAH, such as LRP1 activation, TSPO ligand Ro5-4864, Alantolactone (ATL), and sirt1. [125][126][127][128] Astrocytes is also an important member of the CNS immune system. There are several strategies targeting astrocytes.…”

“…123,124 Moreover, modulating microglia polarization could attenuate brain injuries after SAH, such as LRP1 activation, TSPO ligand Ro5-4864, Alantolactone (ATL), and sirt1. 125–128…”

“…139 In addition, propranolol (b-adrenergic receptor blocker) and RU486 (glucocorticoid receptor (GCR) blocker) could partially inhibit spleen shrinkage induced by ICH and improve the outcome of ICH. 106 For the cholinergic anti-inflammatory pathway (CHAIP) is a physiological mechanism for the central nervous system regulating immune response, and targeting the 125 Alantolactone (ATL) 126 and so on cholinergic anti-inflammatory pathway is a promising way for immunomodulation. 100 It has been reported that muscarine improved neurologic outcomes in ICH rats, showing that reduction of brain water content and levels of inflammatory mediators decrease in both brain and spleen.…”