A Novel Bioactive Component, Efoba, From Aged Garlic Targets CTSC to Suppress NET-Driven Neuroinflammation and Ameliorate Secondary Brain Injury After Intracerebral Hemorrhage.
- 1Translational Pharmaceutical Laboratory, Jining NO.1 People's Hospital, Shandong First Medical University, Jining, China.
Abstract
Intracerebral hemorrhage (ICH) is a devastating neurological disorder with high mortality and disability, where neuroinflammation-driven secondary brain injury is a key pathological hallmark. Neutrophil extracellular traps (NETs) serve as critical pathogenic mediators that amplify neuroinflammation, disrupt blood-brain barrier integrity, and exacerbate brain damage after ICH. This study identifies Efoba, a novel bioactive monomer from aged garlic, and establishes a scalable total‑synthesis route for hundred‑gram‑scale high‑purity production, overcoming low‑yield and supply‑limiting bottlenecks for natural product research. In vivo and in vitro experiments show Efoba markedly ameliorates ICH‑induced neurological impairments and inhibits NET formation. Integrative analyses (Lip-MS, virtual screening, proteomics, transcriptomics) identified cathepsin C (CTSC) as the direct binding target of Efoba. Efoba stabilizes microglial lysosomal membranes, inhibits CTSC release, blocks NET generation, and exerts neuroprotection against NETs-driven neuroinflammation. CTSC knockout and CTSC overexpression assays further confirm the indispensable role of CTSC in mediating Efoba's neuroprotective and anti‑inflammatory activities. Collectively, this work demonstrates for the first time that Efoba targets CTSC to suppress NET-mediated neuroinflammation, highlighting its therapeutic potential and the translational value of natural active components.
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BibTeX
@article{meng2026novel,
title = {{A Novel Bioactive Component, Efoba, From Aged Garlic Targets CTSC to Suppress NET-Driven Neuroinflammation and Ameliorate Secondary Brain Injury After Intracerebral Hemorrhage.}},
author = {Junjun Meng and Jianhua Wang and Tao Zhang and Xiaofan Fan and Jinxiu Guo and Shiyuan Zhao and Wenxue Sun and Pei Jiang},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
year = {2026},
month = oct,
doi = {10.1002/advs.78538},
url = {https://europepmc.org/article/MED/42958721},
note = {CC BY},
}
RIS
TY - JOUR
TI - A Novel Bioactive Component, Efoba, From Aged Garlic Targets CTSC to Suppress NET-Driven Neuroinflammation and Ameliorate Secondary Brain Injury After Intracerebral Hemorrhage.
AU - Junjun Meng
AU - Jianhua Wang
AU - Tao Zhang
AU - Xiaofan Fan
AU - Jinxiu Guo
AU - Shiyuan Zhao
AU - Wenxue Sun
AU - Pei Jiang
PY - 2026
DA - 2026/10/29
JO - Advanced science (Weinheim, Baden-Wurttemberg, Germany)
DO - 10.1002/advs.78538
UR - https://europepmc.org/article/MED/42958721
AB - Intracerebral hemorrhage (ICH) is a devastating neurological disorder with high mortality and disability, where neuroinflammation-driven secondary brain injury is a key pathological hallmark. Neutrophil extracellular traps (NETs) serve as critical pathogenic mediators that amplify neuroinflammation, disrupt blood-brain barrier integrity, and exacerbate brain damage after ICH. This study identifies Efoba, a novel bioactive monomer from aged garlic, and establishes a scalable total‑synthesis route for hundred‑gram‑scale high‑purity production, overcoming low‑yield and supply‑limiting bottlenecks for natural product research. In vivo and in vitro experiments show Efoba markedly ameliorates ICH‑induced neurological impairments and inhibits NET formation. Integrative analyses (Lip-MS, virtual screening, proteomics, transcriptomics) identified cathepsin C (CTSC) as the direct binding target of Efoba. Efoba stabilizes microglial lysosomal membranes, inhibits CTSC release, blocks NET generation, and exerts neuroprotection against NETs-driven neuroinflammation. CTSC knockout and CTSC overexpression assays further confirm the indispensable role of CTSC in mediating Efoba's neuroprotective and anti‑inflammatory activities. Collectively, this work demonstrates for the first time that Efoba targets CTSC to suppress NET-mediated neuroinflammation, highlighting its therapeutic potential and the translational value of natural active components.
SN - 2198-3844
ER -