Modulation of alveolar macrophage and mitochondrial fitness by medicinal plant-derived nanovesicles to mitigate acute lung injury and viral pneumonia

• DOI: 10.1186/s12951-024-02473-w
• Publication Date: 2024-04-18T05:01:57Z
• Authors: Lusha Ye; Yanan Gao; Simon Wing Fai Mok; Wucan Liao; Yazhou Wang; Changjiang Chen; Lijun Yang; Junfeng Zhang; Liyun Shi
• Keywords: Alveolar macrophage

Acute lung injury (ALI) is generally caused by severe respiratory infection and characterized overexuberant inflammatory responses inefficient pathogens-containing, the two major processes wherein alveolar macrophages (AMs) play a central role. Dysfunctional mitochondria have been linked with distorted hence disorders, but few treatments are currently available to correct these defects. Plant-derive nanovesicles gained significant attention because of their therapeutic potential, targeting cells underlying mechanism remain elusive. We herein prepared from Artemisia annua, well-known medicinal plant multiple attributes involving anti-inflammatory, anti-infection, metabolism-regulating properties. By applying three mice models acute bacterial endotoxin, influenza A virus (IAV) SARS-CoV-2 pseudovirus respectively, we showed that Artemisia-derived (ADNVs) substantially alleviated immunopathology raised survival rate challenged mice. Macrophage depletion adoptive transfer studies confirmed requirement AMs for ADNVs effects. identified gamma-aminobutyric acid (GABA) enclosed in vesicles molecular effector mediating regulatory roles ADNVs. Specifically, GABA acts on through receptors, promoting mitochondrial gene programming bioenergy generation, reducing oxidative stress signals, thereby enhancing adaptability inflammation resolution. Collectively, this study identifies promising nanotherapeutics alleviating pathology, elucidates whereby canonical neurotransmitter modifies resume tissue homeostasis, which may broader implications treating critical pulmonary diseases such as COVID-19.