ACTIVE COMPOUNDS FROM MEDICINAL PLANTS AS NOVEL APPROACHES FOR ASTHMA THERAPY: IN SILICO DOCKING ANALYSIS

Öz

Objective: Pharmaceutical molecules have historically drawn inspiration from natural substances. Nowadays, research on natural compounds is escalating, particularly on phytochemicals. In this context, asthma, characterized by airway constriction and inflammation, occupies a significant place in the search for effective herbal treatments. Nonetheless, the bronchodilatory efficacy of the bioactive phytochemicals remains ambiguous. This study explores plant-derived compounds proposed for asthma treatment, focusing on their bronchodilator effects mediated through β2-adrenergic and M3-muscarinic receptors. These receptors facilitate muscle relaxation respectively by increasing intracellular cAMP levels and reducing intracellular calcium release from the endoplasmic reticulum. Material and Method: A comprehensive literature search was performed on phytochemicals tested on asthmatic animal models. A total of 898 articles were assessed in this manner. Following the elimination of duplicates, 100 bioactive plant compounds in 3D format, demonstrating potential bronchodilator effects, were assessed in silico for their impact on β2 and M3 receptors. The receptors were obtained from the Protein Data Bank. Compounds and references were docked to specific proteins by the PyRx program to facilitate the docking, and high-scored molecules were visualized by the DSV program. Besides, in silico pharmacokinetic parameters were evaluated via SwissADME tool and toxicity parameters were determined using ADMETLab 3.0 platform. Result and Discussion: In the docking experiments, 34 out of the 100 compounds were demonstrated to have a potentially high affinity to β2 and/or M3 receptors. Several molecules like cryptotanshinone, paeoniflorin and rottlerin were found to have high binding affinities for the β2 receptor. On the other hand, it has been demonstrated that tetrandrine, fisetin, and cryptotanshinone have strong affinities for the M3 receptor. Considering the findings, these bioactive substances could benefit bronchodilation, particularly through the β2 and M3 receptor pathways. This in silico study highlighted the potential of plant compounds for bronchodilation in respiratory diseases and suggested avenues for future research and experimental validation in asthma therapy.

Anahtar Kelimeler

• Asthma
• β2 adrenergic receptor
• M3 muscarinic receptor
• molecular docking
• phytochemical

ASTIM TEDAVİSİNDE YENİ YAKLAŞIMLAR İÇİN TIBBİ BİTKİLERDEN ELDE EDİLEN AKTİF BİLEŞİKLERİN İN SİLİKO DOCKING ANALİZİ

Öz

Amaç: İlaç molekülleri tarihsel olarak doğal maddelerden ilham alagelmektedir. Günümüzde doğal bileşikler ve özellikle fitokimyasallar üzerinde yapılan araştırmalar giderek artmaktadır. Bu bağlamda, solunum yolu daralması ve enflamasyonu ile karakterize astım hastalığı, etkili bitkisel tedavilere yönelik araştırmalarda önemli bir yer tutmaktadır. Bununla birlikte, biyoaktif fitokimyasalların bronkodilatör etkinliği belirsizliğini korumaktadır. Bu çalışmada astım tedavisi için önerilen bitkisel kaynaklı bileşiklerin, β2-adrenerjik ve M3-muskarinik reseptör aracılı bronkodilatör etkilerine odaklanılmıştır. Bu reseptörler, sırasıyla hücre içi cAMP seviyelerini artırarak ve endoplazmik retikulumdan hücre içi kalsiyum salınımını azaltarak kas gevşemesini sağlar. Gereç ve Yöntem: Astımlı hayvan modelleri üzerinde çalışılmış bitkisel bileşikler hakkında kapsamlı bir literatür araştırması yapılmıştır. Toplamda 898 makale bu şekilde değerlendirmeye alınmıştır. Tekrar eden literatürlerin çıkarılmasının ardından, potansiyel bronkodilatör etkinlik gösteren üç boyutlu yapıdaki 100 farklı bitkisel bileşik, β2 ve M3 reseptörleri üzerindeki etkileri açısından in silico olarak değerlendirilmiştir. Reseptörler Protein Data Bank'tan elde edilmiştir. Bileşikler ve referanslar, kenetlenmeyi kolaylaştırmak için PyRx programı tarafından belirli proteinlere kenetlenmiş ve yüksek puanlı moleküller DSV programı tarafından görselleştirilmiştir. Ayrıca, in silico farmakokinetik parametreleri SwissADME aracılığıyla değerlendirilmiş ve toksisite parametreleri ADMETLab 3.0 platformu kullanılarak belirlenmiştir. Sonuç ve Tartışma: Docking deneylerinde, 100 bileşikten 34'ünün β2 ve/veya M3 reseptörlerine potansiyel olarak yüksek afiniteye sahip olduğu gösterilmiştir. Kriptotanşinon, paeoniflorin ve rottlerin gibi birkaç molekülün β2 reseptörü için yüksek bağlanma afinitesine sahip olduğu bulunmuştur. Diğer taraftan, tetrandrin, fisetin ve kriptotanşinonun M3 reseptörü için güçlü afinitelere sahip olduğu gösterilmiştir. Bulgular göz önünde bulundurulduğunda, bu biyoaktif maddeler özellikle β2 ve M3 reseptör yolları aracılığıyla bronkodilatasyona fayda sağlayabilir. Bu in silico çalışma, solunum yolu hastalıklarında bronkodilatasyon için bitki bileşiklerinin potansiyelini göstermiştir. Astım tedavisinin gelecekteki araştırmaları ve deneysel çalışmaları için yollar göstermiştir.

Anahtar Kelimeler

• Astım
• β2 adrenerjik reseptör
• bitkisel bileşik
• M3 muskarinik reseptör
• moleküler yerleştirme

Kaynakça

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