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Z-Guggulsterone Attenuates Astrocytes-Mediated Neuroinflammation After Ischemia by Inhibiting Toll-Like Receptor 4 Pathway

Z-Guggulsterone Attenuates Astrocytes-Mediated Neuroinflammation After Ischemia by Inhibiting Toll-Like Receptor 4 Pathway

Tianlong Liu, Minna Liu, Tiejun Zhang, Wenxing Liu, Hang Xu, Fei Mu, Danjun Ren, Na Jia, Zhengjun Li, Yi Ding, Aidong Wen, Yuwen Li

J Neurochem. 2018 Dec;147(6):803-815.

PMID: 30168601

Abstract:

Inflammatory damage plays a pivotal role in ischemic stroke pathogenesis and may represent one of the therapeutic targets. Z-Guggulsterone (Z-GS), an active component derived from myrrh, has been used to treat various diseases. The traditional uses suggest that myrrh is a good candidate for anti-inflammatory damage. This study was to investigate the anti-inflammatory and neuroprotective effects of Z-GS following cerebral ischemic injury, as well as the exact mechanisms behind them. Rat middle cerebral artery occlusion (MCAO) model and in vitro astrocytes oxygen-glucose deprivation (OGD) model were adopted to simulate ischemic stroke. Z-GS (30 or 60 mg/kg) was administered intraperitoneally immediately after reperfusion, while astrocytes were maintained in 30 or 60 μM Z-GS before OGD treatment. The results indicated that Z-GS significantly alleviated neurological deficits, infarct volume and histopathological damage in vivo, and increased the astrocytes viability in vitro. Moreover, the treatment of Z-GS inhibited the astrocytes activation and down-regulated the mRNA levels of pro-inflammatory cytokines. Furthermore, the activated TLR4-NF-κB signaling pathways induced by MCAO or OGD were significantly suppressed by Z-GS treatment, which was achieved via inhibiting the phosphorylation of JNK. Our results demonstrated that Z-GS exerted neuroprotective and anti-inflammatory properties through preventing activation of TLR4-mediated pathway in the activated astrocytes after ischemia injury. Therefore, Z-GS could be considered as a promising candidate for the treatment of ischemic stroke.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP39025235	(Z)-Guggulsterone		39025-23-5	Price
AP39025235-A	Guggulsterone Z		39025-23-5	Price

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