Oxidative medicine and cellular longevity · 2026
New Mechanistic Insights Into Nobiletin's Protective Effects Against LPS-Induced Hyperinflammatory Acute Lung Injury in Rats: Targeting miR-200, AT1R/p38 MAPK, and HMGB1/NF-κB mTOR Pathways.
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El-Shaer Rehab Ahmed Ahmed, Ibrahim Sarah, AbuoHashish Norhan Ahmed, Eltokhy Amira K, Ghanem Heba Bassiony, Ibrahim Rowida Raafat, Hewady Passant Medhat, El-Deeb Omnia Safwat, Farghal Eman E, Eissa Radwa, Shalaby Marwa M, Awad Marwa Mahmoud
Аннотация
BACKGROUND: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are severe inflammatory lung disorders associated with high morbidity and mortality. Dysregulation of the renin-angiotensin system (RAS) and proinflammatory pathways play an indispensable role in ALI progression.
AIM: This study aimed to investigate the protective potential of nobiletin (NOB) in mitigating ALI and hyperinflammatory lung injury.
MATERIAL AND METHODS: The study enrolled 32 male albino rats allocated into four groups: (Control, NOB, lipopolysaccharide [LPS], and NOB + LPS groups). Rats received NOB 20 mg/kg by oral gavage for 1 week; on the seventh day, a single dose of 15 mg/kg LPS was given by intranasal instillation. After 24 h of LPS administration, plasma and lung tissue samples were analyzed for inflammatory cytokines, mitochondrial complex-I, oxidative stress markers, and molecular signaling pathways.
RESULTS: NOB administration significantly downregulated miR-200 expression, associated with ACE2 activation and attenuated AT1R-mediated inflammatory responses. It also decreased NF-κB and p38 MAPK signaling, reducing pulmonary and systemic levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), granulocyte monocyte-colony stimulating factor (GM-CSF), and interleukin-17A (IL-17A). Additionally, NOB improved the high mobility group box 1 (HMGB1)/NF-κB/mammalian target of rapamycin (mTOR) pathway, and increased mitochondrial complex-I may be consistent with improved tissue preservation.
CONCLUSION: NOB exerts protective effects against ALI by improving inflammatory cytokine, oxidative stress, miRNA-200, mitochondrial complex-I, and ACE2, highlighting its potential as a protective candidate for ALI and hyperinflammatory-associated lung injury.
AIM: This study aimed to investigate the protective potential of nobiletin (NOB) in mitigating ALI and hyperinflammatory lung injury.
MATERIAL AND METHODS: The study enrolled 32 male albino rats allocated into four groups: (Control, NOB, lipopolysaccharide [LPS], and NOB + LPS groups). Rats received NOB 20 mg/kg by oral gavage for 1 week; on the seventh day, a single dose of 15 mg/kg LPS was given by intranasal instillation. After 24 h of LPS administration, plasma and lung tissue samples were analyzed for inflammatory cytokines, mitochondrial complex-I, oxidative stress markers, and molecular signaling pathways.
RESULTS: NOB administration significantly downregulated miR-200 expression, associated with ACE2 activation and attenuated AT1R-mediated inflammatory responses. It also decreased NF-κB and p38 MAPK signaling, reducing pulmonary and systemic levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), granulocyte monocyte-colony stimulating factor (GM-CSF), and interleukin-17A (IL-17A). Additionally, NOB improved the high mobility group box 1 (HMGB1)/NF-κB/mammalian target of rapamycin (mTOR) pathway, and increased mitochondrial complex-I may be consistent with improved tissue preservation.
CONCLUSION: NOB exerts protective effects against ALI by improving inflammatory cytokine, oxidative stress, miRNA-200, mitochondrial complex-I, and ACE2, highlighting its potential as a protective candidate for ALI and hyperinflammatory-associated lung injury.