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Abstract #105856 Published in IGR 23-3
Magnolol limits NFκB-dependent inflammation by targeting PPARγ relieving retinal ischemia/reperfusion injury
Wang N; Yang Y; Liu Y; Huang L; Gu M; Wu Y; Xu L; Sun H; Guo WInternational immunopharmacology 2022; 112: 109242
BACKGROUND: Glaucoma is the leading cause of irreversible blindness in the world. Elevated intraocular pressure (IOP) is recognized as one of the most critical factors, but the loss of retinal ganglia cells (RGCs) often persists when IOP is controlled. Recently, a large number of studies focus on the inflammatory and immune responses in the occurrence and development of glaucoma. Magnolol (MAG), the principal ingredient of magnoliae officinalis cortex, has anti-inflammatory effects, but its role and mechanism in retinal protection need to be further studied. METHODS: The neurodegeneration of retina in mice model following ischemia/reperfusion (IR) injury was evaluated by immunohistochemistry, hematoxylin and eosin (H&E) staining and electroretinography (ERG). The inflammation-regulatory effect of MAG was detected by quantitative RT-PCR, western blot, and immunohistochemistry. Peroxisome proliferator-activated receptor-γ (PPARγ) inhibitor assays by H&E staining and western blot were used to test the target and mechanism pathway of MAG. RESULTS: We found MAG relieved IR-induced retinal damages and inflammation. Further studies revealed MAG alleviated nuclear factor kappa B (NFκB)-dependent inflammatory process by preserving the expression of NFκB inhibitor alpha (IκBα), and it modulated microglia polarization after IR injury. PPARγ was a primary target of MAG, and treatment with PPARγ inhibitor GW9662 attenuated the neuroprotective and anti-inflammatory effects of MAG. CONCLUSIONS: Our findings revealed that MAG inhibits NFκB-dependent inflammatory processes by elevating PPARγ in mice retinas to achieve its neuroprotective role following IR, which suggesting that MAG could be developed to a novel anti-inflammatory therapeutic agent for relieving the progression of glaucoma.
Department of Ophthalmology, Shanghai 9th People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200011, China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China.
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