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Iranian Journal of Basic Medical Sciences، جلد ۲۹، شماره ۲، صفحات ۳۰۲-۳۱۲
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عنوان انگلیسی Syringic acid attenuates LPS-induced acute lung injury via modulation of the HMGB1/TLR4/NF-κB and Keap1/Nrf2/HO-1 pathways: Mechanistic insights from in vivo and in silico studies
چکیده انگلیسی مقاله Objective(s): Sepsis-induced acute lung injury (ALI), driven by uncontrolled inflammation and oxidative stress, remains a major cause of mortality in critically ill patients. This study aimed to investigate the protective and mechanistic effects of syringic acid (SA), a natural phenolic compound, against lipopolysaccharide (LPS)-induced ALI in rats.Materials and Methods: Male Sprague–Dawley rats were allocated into five groups: control, SA80, LPS, SA40+LPS, and SA80+LPS. SA was orally administered (40 or 80 mg/kg/day) for 14 days before a single intraperitoneal injection of LPS (10 mg/kg). Lung tissues were collected 12 hr post-LPS for histopathological, biochemical, and molecular evaluations. In silico docking using Schrödinger Maestro (2025/1) assessed SA interaction with the KEAP1 Kelch domain (PDB: 5FZN).Results: LPS challenge caused severe pulmonary edema, inflammatory infiltration, elevated proinflammatory cytokines, lipid peroxidation, and reduced antioxidant enzyme activities. SA pretreatment, particularly at 80 mg/kg, significantly (P<0.05) alleviated these alterations. Mechanistically, SA down-regulated the HMGB1/TLR4/NF-κB signaling cascade and activated the Keap1/Nrf2/HO-1 antioxidant pathway. Reduced 8-OHdG and caspase-3 expression indicated mitigation of oxidative DNA damage and apoptosis. Docking analysis revealed strong binding affinity and favorable MM-GBSA scores for SA within the KEAP1 active pocket, suggesting direct modulation of Nrf2 activation.Conclusion: SA confers potent protection against LPS-induced ALI through coordinated anti-inflammatory and antioxidant mechanisms involving HMGB1/TLR4/NF-κB inhibition and Keap1/Nrf2/HO-1 activation. These findings highlight SA as a promising therapeutic candidate for sepsis-associated pulmonary injury.
کلیدواژه‌های انگلیسی مقاله Acute lung injury, Inflammation, Lipopolysaccharide, NF-kappa B, Oxidative stress, Phenols
نویسندگان مقاله | Burak Lacin
Department of Physiology, Faculty of Veterinary Medicine, Ataturk University, Erzurum, Turkey


| Emin Şengul
Department of Physiology, Faculty of Veterinary Medicine, Ataturk University, Erzurum, Turkey|Department of Pharmacology, Faculty of Medicine, Atatürk University, Erzurum, Turkey


| Serkan Yildirim
Department of Pathology, Faculty of Veterinary Medicine, Ataturk University, Erzurum, Turkey|Department of Pathology, Faculty of Veterinary Medicine, Kyrgyzstan-Turkey Manas University, Bishkek, Kyrgyzstan


| Furkan Aykurt
Department of Physiology, Faculty of Veterinary Medicine, Ataturk University, Erzurum, Turkey


| Mohamad Warda
Department of Physiology, Faculty of Veterinary Medicine, Ataturk University, Erzurum, Turkey|Department of Biochemistry, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt


| Burak Cinar
Department of Pharmacology, Faculty of Medicine, Atatürk University, Erzurum, Turkey


| Ali Cinar
Department of Physiology, Faculty of Veterinary Medicine, Ataturk University, Erzurum, Turkey
نشانی اینترنتی https://ijbms.mums.ac.ir/article_27297.html
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