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

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.