Diterpenoids and Triterpenoids From Frankincense Are Excellent Anti-psoriatic Agents: An in silico Approach

Abstract

Psoriasis is a chronic autoimmune disease that affects 2–3% of the global population and requires an effective treatment. Frankincense has been long known for its potent anti-inflammatory activities. In this study, a structural bioinformatics approach was used to evaluate the efficacy of individual active components of frankincense, macrocyclic diterpenoid derivatives ( 1 - 27 ), and boswellic acids ( 28 - 46 ) in the treatment of psoriasis. Initially, major druggable targets of psoriasis were identified. Subsequently, structure-based screening was employed by using three different docking algorithms and scoring functions (MOE, AutoDock Vina, and MVD) for the target fishing of compounds against 18 possible targets of psoriasis. Janus Kinase 1, 2, 3 (JAK 1/2/3), eNOS, iNOS, interleukin-17 (IL-17), and Tumor necrosis factor-α (TNF-α) were identified as the preferred molecular targets for these compounds. This computational analysis reflects that frankincense diterpenoids and triterpenoids can serve as excellent anti-psoriatic agents by targeting major cytokines (TNF-α, IL-17, IL-13, IL-23, and IL-36γ,) exacerbated in psoriasis, and inflammatory pathways particularly JAK1/2/3, eNOS, iNOS, MAPK2, and IFNγ. The results were compared with the reported experimental findings which correlates well with our in-silico verdicts.

The Healing Power of Clean Rivers: In Silico Evaluation of the Antipsoriatic Potential of Apiin and Hyperoside Plant Metabolites Contained in River Waters

“…Psoriasis is a chronic autoimmune skin disease affecting more than 2% of the population around the globe, characterized by keratinocyte hyperplasia, with inflammatory cell infiltration into the dermis and neovascularization [ 28 ]. The main psoriasis protein targets in the antipsoriatic drug discovery are NF-κB, IL-17, and IL-36 which can be subjected to molecular docking investigations for screening potential drug candidates [ 26 ]. Antipsoriatic treatments are typically searched in several classes of compounds including plant-derived products such as diterpenoids, triterpenoids [ 26 ], and hydroxycinnamic acids [ 29 ].…”

“…More details on HDOCK docking server and on the procedures for docking experiments can be found at (accessed on 9 November 2021). The docking method was validated using as reference compounds the known inhibitors [ 26 ]: (6aS,10aS)-9-(hydroxymethyl)-6,6-dimethyl-3-(2-methyloctan-2-yl)-6a,7,10,10a-tetrahydrobenzo[c]chromen-1-ol (dexanabinol, NF-kB); (4S,20R)-7-chloro-N-methyl-4-{[(1-methyl-1H-pyrazol-5-yl)carbonyl]amino}-3,18-dioxo-2,19-diazatetracyclo[20.2.2.1_6,10_.1_11,15_]octacosa-1(24),6(28),7,9,11(27),12,14,22,25-nonaene-20-carboxamide (IL-17); (2S)-2-{[4-(3-amino-4-methylphenyl)-6-methylpyrimidin2-yl]oxy}-3-methoxy-3,3-diphenylpropanoic acid (IL-36). …”

“…In our blind docking, the reference compounds bound the respective protein targets involving amino acid residues ( Table 1 , Table 2 and Table 3 ) that were reported in the literature as binding residues for the given complexes [ 26 ]; moreover, we analyzed the top-ranked poses (Top-1) and the top 10 ranked poses for the complexes predicted by HDOCK according to the energy scores provided by the program as explained in the Results and Discussion section. Ligand/Protein complexes were visualized in the structure viewer of the HDOCK server.…”

“…Herein, we aim at discussing the potential benefits provided by clean rivers on human health from a therapeutic perspective using in silico techniques to show that some secondary plant metabolites which are relatively abundant in river waters could provide benefits in the treatment of psoriasis. To this aim, conscious of the role of molecular docking (MD) in the exploration of biomedically-relevant molecular interactions, we conducted an MD study with the program HDOCK [ 20 , 21 , 22 , 23 , 24 , 25 ] using the 3D structures of NF-kB, IL-17 and IL-36, that are the protein targets involved in psoriasis [ 26 ] and those from three plant metabolites found in rivers. HDOCK is used for both macromolecule-macromolecule [ 20 , 21 , 22 , 23 ] and small molecule-macromolecule [ 24 ] dockings, with types of macromolecules including proteins.…”

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“…The diterpenoid and triterpenoid obtained from frankincense have been evaluated as a good anti-psoriatic agent by some diverged mechanisms. These compounds act on some possible targets such as TNF-α, IL17, IL13, IL23, IL36-γ, and some inflammatory pathways such as MAPK-2, JAK-1/2/3 and INF-γ, which proves its anti-psoriatic potential 91 . Frankincense has been found to decrease the irritation and redness in the skin to restore the skin tone, and it has also been investigated to treat skin bruises and sores in the dermal layer of skin.…”