Computational investigation of Cissus quadrangularis phytoconstituents as aryl hydrocarbon receptor modulators for psoriasis therapy

Psoriasis is a chronic inflammatory skin disorder in which
dysregulation of the aryl hydrocarbon receptor (AhR) contributes
significantly to keratinocyte hyperproliferation and immune
imbalance. In this study, a comprehensive computational
investigation was conducted to evaluate the phytoconstituents of
Cissus quadrangularis as potential AhR modulators. Sixteen bioactive
compounds were screened through molecular docking against AhR
(PDB ID: 7ZUB) and the binding interactions were compared with
those of the native ligand. The docking analysis revealed that several
phytochemicals exhibited stronger affinities than the native ligand,
with quercetin-3-O-α-L-rhamnopyranoside (–10.4 kcal/mol), β
sitosterol acetate (–10.3 kcal/mol), cholesterin (–9.4 kcal/mol), and
β-amyrone (–9.0 kcal/mol) emerging as the most potent candidates.
These molecules demonstrated extensive hydrogen bonding, π
cation interactions, and hydrophobic stabilization, indicating their
high compatibility with the AhR-binding pocket. The top-performing
compounds were subsequently subjected to ADMET evaluation to
assess their pharmacokinetic behavior and safety. The predicted
physicochemical parameters indicated a broad logP range (1.31
8.34) and TPSA values spanning 17.07–190.28 Ų, reflecting diverse
permeability and solubility characteristics. Several candidates
demonstrated improved drug-likeness, favorable metabolic stability,
and reduced predicted carcinogenicity compared with the native
ligand. Notably, quercetin-3-O-α-L-rhamnopyranoside and diphenyl
sulfone exhibited balanced ADMET properties, whereas lipophilic
triterpenoids showed enhanced distribution potential. These results
support the therapeutic potential of Cissus quadrangularis
phytoconstituents and provide a strong foundation for future in vitro
and in vivo validation of psoriasis management.

KEYWORDS
Cissus quadrangularis; aryl hydrocarbon receptor; computational
investigation; psoriasis; phytoconstituents; drug discovery.