Reactive oxygen and nitrogen species (RONS) are key signaling molecules that play an important role in the progression of inflammatory diseases. Although various antioxidants have RONS scavenging properties, they are difficult to be used to cope with acute inflammation which requires inflammatory site-targeting, effective anti-inflammatory activity, and low toxicity. In this work, we developed a safe and effective nano-antioxidant ZMF formed by simply self-assembly of natural plant protein zein and natural drug mangiferin for the synergistic treatment of inflammation-related acute liver injury. ZMF could eliminate RONS, inhibit the activation of macrophages, and modulate the level of inflammatory cytokines through the synergistic effects of mangiferin and zein. In addition, in the mouse models of inflammation-related acute liver injury, ZMF showed superior efficacy in reducing inflammatory reactions. Importantly, the preliminary in vitro and in vivo experiments proved the good safety of ZMF. This study proved the remarkable anti-inflammatory activities of nanomedicine self-assembled by RONS-eliminating natural products, which could provide a reference for the green development of efficient nano-antioxidant from natural products for the treatment of inflammation-related diseases.
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