Computational Analysis to Investigate the Anti-inflammatory and Diuretic Potential of Natural Compounds to Treat High Altitude Pulmonary Oedema by Targeting Phosphodiesterase Type 5

Abstract

High altitude pulmonary edema (HAPE) is a syndrome of non-specific symptoms including dizziness, lack of energy, cough, cyanosis and nausea. HAPE is caused by fluid accumulation in lungs. Treatment of HAPE includes diuretics and pulmonary vasodilator medications. Bergenia stracheyi (Hook.f. & Thomson) Engl. and Anagallis arvensis L. can be potential antioxidant and anti-inflammatory components. Thus, active components of these plants could be used as ligands against targeted proteins to treat pulmonary oedema. ꞵ-eudesmol from B. strachyei  (Hook.f. & Thomson) Engl. was utilized as a ligand and phosphodiesterase-5 as the targeted protein for molecular docking. Targeted protein and selected ligand showed fulfilled ADMET properties as well as good binding energy with targeted protein. ꞵ-eudesmolshowed-5.6 binding affinity with targeted protein and appeared to have a good binding affinity. Molecular docking analysis used in this study for identification of novel compounds from therapeutic interest and ligand-target interactions at molecular level, utilized different online tools and softwares; (PubChem, ChemSketch, PyMOL, UniProt, Chimera, Depth residue, PyRx and Discovery Studio) in order to predict binding energies and appropriate drug targets. Thus, this complex is also suitable for MD simulation for novel drug discovery. MD simulation was performed by Desmond software, and it showed stability of complex. Thus, B. strachyei (Hook.f. & Thomson) Engl. showed great evidence of anti-inflammatory and diuretic activities and it can be further studied for in vitro trial experiments for their potential treatment of high-altitude pulmonary oedema as compared to A. arvensis L.