Pycnogenol, sıçanlarda Nrf2/HO-1 aktivasyonu ve NF-κB kısıtlaması yoluyla obeziteye bağlı karaciğer hasarını hafifletiyor

Öz

Obezite, insülin direnci, dislipidemi ve düşük düzeyli kronik inflamasyon ile karakterize metabolik disfonksiyonun başlıca belirleyicilerinden biridir ve en yaygın olarak steatotik karaciğer hastalığı şeklinde ortaya çıkar. Bu çalışma, Pycnogenol® (Pinus pinaster kabuk ekstresi)’nin obeziteye bağlı karaciğer hasarı üzerindeki etkilerini histolojik ve moleküler düzeyde araştırmıştır. Toplam 28 erkek Sprague Dawley sıçanı, standart diyet veya yüksek yağlı diyetle (30 gün) beslenmiş ve kontrol, Pycnogenol, obezite ve obezite + Pycnogenol gruplarına ayrılmıştır. Pycnogenol, 15 gün boyunca oral yoldan 30 mg/kg dozunda uygulanmıştır. Deney sonunda karaciğer dokuları histopatolojik değerlendirme ve Western blot analizi için toplanmıştır. Obezite grubunda belirgin makroveziküler steatoz, lobüler inflamasyon ve hepatoselüler balonlaşma gözlenmiş ve Nonalkolik Yağlı Karaciğer Hastalığı Aktivite Skoru (NAS) anlamlı biçimde artmıştır. Pycnogenol uygulaması, NAS skorlarını anlamlı derecede azaltmış ve karaciğer mimarisini kısmen geri kazandırmıştır. Moleküler düzeyde, obezite grubunda artmış Caspase-3 ve nükleer faktör kappa B (NF-κB) ekspresyonları Pycnogenol tarafından belirgin şekilde baskılanırken, azalmış Bcl-2, Nuclear factor–erythroid 2–related factor 2 (Nrf2) ve Heme oxygenase-1 (HO-1) düzeyleri kontrol değerlerine doğru yeniden düzenlenmiştir. Pycnogenol tek başına uygulandığında kontrol grubuna kıyasla anlamlı bir değişiklik oluşturmamıştır. Sonuç olarak, Pycnogenol obeziteye bağlı karaciğer hasarını histopatolojik şiddeti azaltarak, inflamatuvar/apoptotik sinyallemeyi baskılayarak ve antioksidan savunma mekanizmalarını yeniden aktive ederek hafifletmiştir. Bu bulgular, Pycnogenol’ün obeziteyle ilişkili karaciğer hastalıklarında tamamlayıcı bir tedavi stratejisi olarak potansiyel taşıdığını göstermektedir.

Anahtar Kelimeler

• Karaciğer hasarı
• NF-κB
• Nrf2/HO-1
• Obesite
• Pycnogenol

Pycnogenol mitigates obesity-associated liver injury via Nrf2/HO-1 activation and NF-κB restraint in rats

Abstract

Obesity is a major determinant of metabolic dysfunction, characterized by insulin resistance, dyslipidemia, and low-grade chronic inflammation, and most commonly manifests as steatotic liver disease. This study investigated the effects of Pycnogenol® (Pinus pinaster bark extract) on obesity-induced hepatic injury at histological and molecular levels. A total of 28 male Sprague Dawley rats were fed either a standard diet or a high-fat diet (30 days) and allocated into control, Pycnogenol, obesity, and obesity + Pycnogenol groups. Pycnogenol was administered orally at 30 mg/kg for 15 days. At the end of the experiment, liver tissues were collected for histopathological evaluation and Western blot analysis. In the obesity group, marked macrovesicular steatosis, lobular inflammation, and hepatocellular ballooning were observed, with significantly increased Nonalcoholic Fatty Liver Disease Activity Score (NAS) scores. Pycnogenol administration significantly reduced NAS scores and partially restored hepatic architecture. At the molecular level, elevated Caspase-3 and nuclear factor kappa B (NF-κB) expression in the obesity group were significantly suppressed by Pycnogenol, while decreased Bcl-2, Nuclear factor–erythroid 2–related factor 2 (Nrf2), and (Heme oxygenase-1) HO-1 levels were restored toward control values. Pycnogenol alone did not produce significant alterations compared with the control group. In conclusion, Pycnogenol attenuated obesity-induced liver injury by reduced histopathological severity, suppressing inflammatory/apoptotic signaling, and reactivating antioxidant defenses. These findings suggest that Pycnogenol may serve as a potential complementary strategy for obesity-associated liver diseases.

Keywords

• Liver injury
• NF-κB
• Nrf2/HO-1
• Pycnogenol
• Obesity

Kaynakça

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