Simulation Study of Interactions Between Two Bioactive Components from Zingiber cassumunar and 5-Lipoxygenase

Abstract

Introduction-Compound D and DMPBD are compounds extracted from Plai or Zingiber cassumunar Roxb., which have antiasthmatic properties. Thai herbal pharmacopoeia have indicated that approximate 50% of Thai prescriptions for asthma contain Plai. However, the inhibition mechanisms of these compounds are not clearly known. Methods-In this study, molecular docking and molecular dynamics (MD) simulations have been used to simulate complex systems and analyze molecular interactions between these compounds and protein target, 5-lipoxygenase (5-LO) enzyme, which is an enzyme involved with asthma symptoms. Results-From our MD simulations, Compound D and DMPBD molecules bind at the same binding site of its natural substrate (arachidonic acid) on 5-LO enzyme, which is similar to the binding of commercial asthma drug (Zileuton). Molecular mechanics generalized born surface area binding energy calculations of the 5-LO complex with Compound D and DMPBD are À26.83 and À29.15 kcal/mol, respectively. Conclusions-This work indicated that Compound D and DMPBD are competitive inhibitors, which are able to bind at the same 5-LO substrate binding site. This reveals opportunities for using Compound D and DMPBD as novel antiasthmatic drugs.

Phytochemicals and Bioactivities of Zingiber cassumunar Roxb

“…( E )-1-(3′,4′-Dimethoxyphenyl)buta-1,3-diene ( 1 ) and ( E )-4-(3′,4′-dimethoxyphenyl)but-3-en-1-ol ( 2 ) bound at the same catalytic site of its natural substrate (AA) on the 5-LO enzyme. The binding energy calculations of the 5-LO complex with 1 , 2 , and zileuton (anti-asthma agent) were −29.15, −26.83, and −29.40 kcal/mol, respectively, which supports the competition between the 1 and 2 substrate inhibitors, which was the same as zileuton [ 53 ]. Overall, these accumulated results indicated that the extracts and components of the Z. cassumunar possess potential value in the prevention and treatment of various diseases related to inflammation.…”

“…The extracts (100 mg/mL) and compound D (50 and 100 mg/mL) attenuated the PMA-induced MMP-9 gene and expression in NCI-H292 cells. Recently, the analysis of molecular interactions between two constituents of Z. cassumunar and a protein target, the 5-lipoxygenase (5-LO) enzyme, involved with asthma symptoms, were studied using molecular docking and molecular dynamics simulations [ 53 ]. ( E )-1-(3′,4′-Dimethoxyphenyl)buta-1,3-diene ( 1 ) and ( E )-4-(3′,4′-dimethoxyphenyl)but-3-en-1-ol ( 2 ) bound at the same catalytic site of its natural substrate (AA) on the 5-LO enzyme.…”

“…Carrageenin-induced hind-paw edema test in rats; acetic acid-induced vascular permeability and writhing test in mice [46] TPA-induced ear edema in rats [ Chondroprotective effect Cytokine-induced cartilage degradation in explant culture [50] Cytokine-induced up-regulation of catabolic genes involved in joint erosion in SW982 cells [51] Anti-asthma Pro-MMP-9 by house dust mite allergens; MMP-9 expression in PMA-stimulated NCI-H292cells [52] Molecular docking and molecular dynamics simulations with 5-LO enzyme [53] Melanogenic effect…”

Potential bangle (Zingiber montanum J.König) rhizome extract as a supplement to prevent and reduce symptoms of Covid-19

“…According to Jitapunkul et al (2018) , herbal pharmacopoeia of Thailand showed that about 50% of Thai recipes for asthma disease contain bangle rhizome extract. ( Jitapunkul et al, 2018 ), likewise in Indonesia and Malaysia, a lot of people use it to treat asthma ( Iswantini et al, 2011 , Jantan et al, 2008 , Kaewchoothong, 2009 , Lim, 2016 ).…”

“…Still related to asthma, Jitapunkul et al (2018) conducted a study of compound D and DMPBD (( E )-1-(3,4-dimethoxyphenyl) butadiene), extracted from the rhizome bangle, by molecular docking and molecular dynamics (MD) simulations with simulate complex systems and analyze molecular interactions between these compounds and protein target, 5-lipoxygenase (5-LO) enzyme. The results of this study showed that Compound D and DMPBD molecules bind at the same binding site of its natural substrate (arachidonic acid) on 5-LO enzyme, which is similar to the binding of commercial asthma drug (Zileuton) ( Jitapunkul et al, 2018 ).…”