(-)-Epicatechin gallate prevents inflammatory response in hypoxia-activated microglia and cerebral edema by inhibiting NF-κB signaling

  • Arch Biochem Biophys. 2022 Oct 30;729:109393. doi: 10.1016/j.abb.2022.109393.
Guijuan Chen  1 ,  Kang Cheng  1 ,  Yun Niu  1 ,  Li Zhu  2 ,  Xueting Wang  3
Affiliations
  • 1. Institute of Special Environmental Medicine, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, China.
  • 2. Institute of Special Environmental Medicine, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, China. Electronic address: [email protected].
  • 3. Institute of Special Environmental Medicine, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, China. Electronic address: [email protected].
PMID: 36084697 DOI: 10.1016/j.abb.2022.109393
Abstract

High-altitude cerebral edema (HACE), a potentially lethal disease, is associated with a time-dependent exposure to altitude-related hypobaric hypoxia (HH) and has reportedly been associated with microglia hyperactivation. Catechins are substances with good antioxidant properties, among which (-)-epigallocatechin gallate (EGCG) may play a neuroprotective role through the inhibition of microglia overactivation; however, the function of its analog- (-)-epicatechin gallate (ECG)-requires further elucidation. The aim of the present study was to investigate whether ECG prevented HACE by inhibiting HH-activated microglia. Primary microglia exposed to lipopolysaccharide (LPS)/ATP were co-treated with EGCG, ECG, and (-)-epigallocatechin, and ECG and EGCG exerted significant anti-inflammatory and neuroprotective effects. ECG inhibited the NF-κB pathway to prevent the activation of microglia induced by 1% O2. In addition, ECG ameliorated the increase in brain water content and Aquaporin 4 expression induced by HH in mice. ECG also reduced the number of Iba1+ microglia in the brain, the release of proinflammatory factors, and the recruitment of microglia to blood vessels in HH-exposed mice. The outcomes of the present study revealed that ECG alleviated hypoxic hyperactivated microglia, reduced the neuroinflammation and blood-brain barrier permeability, and prevented HACE by inhibiting NF-κB signaling.

Keywords
(−)-Epicatechin gallate; High-altitude cerebral edema; Hypobaric hypoxia; Inflammation; Microglia; NF-κB signaling.
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