Molecular Docking–Guided Identification of Kaempferol, Glycitein, Corylin, and Cinnamic Acid as Multi-Target Anti-Psoriatic Agents and Evaluation of a Gel Formulation in Human Subjects
Jun 2026· International journal of current trends in pharmaceutical research· Vol 14, pp. 67-72· 0 citations· 26 references
TL;DR
The findings indicate that docking-guided phytochemical selection combined with topical delivery offers a promising, well-tolerated anti-psoriatic strategy warranting further large-scale investigation.
Abstract
Psoriasis is a chronic immune-mediated skin disorder associated with dysregulation of inflammatory pathways including STAT3, IL-12, IL-23, and TNF-α. In this study, a rational molecular-docking approach was employed to screen phytoconstituents traditionally used in psoriasis management. From an initial pool of over 250 compounds, kaempferol, glycitein, corylin, and cinnamic acid demonstrated strong binding affinity and favourable safety profiles against key inflammatory targets. These compounds were incorporated into a Carbopol-based topical gel and evaluated for safety and therapeutic benefit. Dermal irritation studies confirmed good tolerability. A clinical study in psoriatic patients showed progressive improvement in PASI scores from baseline (10.78) to during treatment (8.66) and post-treatment (6.45), with statistically significant improvement between weeks two and four (p = 0.0089). No major adverse effects were reported. The findings indicate that docking-guided phytochemical selection combined with topical delivery offers a promising, well-tolerated anti-psoriatic strategy warranting further large-scale investigation.
It is suggested that apigenin and luteolin may modulate inflammatory signaling pathways involved in OM and could serve as promising candidates for further in vitro and in vivo investigation.
Abu Bakar, Valendriyani Ningrum· European Journal of Dentistr...· 0 citations
Advanced technological approaches including in silico modelling, molecular docking, and computational target prediction have accelerated the identification of licorice-derived bio-actives and their therapeutic targets against SARS-CoV-2 and these findings advocate licorice as an adjunctive therapeutic candidate, pending optimised formulations.
Mohamed S. Sedeek, Nesma M. Ahmed, Salman Ahmed et al.· Science and Technology Nexus· 0 citations
Findings provide mechanistic insights into the potential modulation of S. cumini phytochemicals and BCL-2 inhibitors and support further experimental validation as apoptosis-inducing candidates against gastric cancer.
S. Pradhan, Ayushman Gadnayak, S. K. Pradhan et al.· In Silico Pharmacology· 0 citations
In vivo animal assays validated that eupatilin alleviated colonic injury and markedly reduced the levels of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 in mice with DSS-induced ulcerative colitis.
Inflammation is a key contributor to several chronic diseases, including rheumatoid arthritis, cardiovascular
disorders, and cancer. The endothelial protein C receptor (EPCR) plays a crucial role in regulating inflammation
and coagulation, making it a promising therapeutic target. In this study, a structure-based computational
approach was used to identify potential anti-inflammatory phytochemicals targeting EPCR. A large phytochemical
library from IMPPAT and COCONUT databases was screened, followed by ADMET filtering, resulting in 278
drug-like compounds for further analysis. Molecular docking identified four lead compounds (L10, L41, L111,
and L114) with stronger binding affinities than the reference drug diclofenac. These compounds formed stable
interactions with key EPCR residues through hydrogen bonding, hydrophobic contacts, and π–π stacking
interactions. Molecular dynamics simulations over 200 ns confirmed the structural stability of the ligand–EPCR
complexes, supported by favourable RMSD, RMSF, and free-energy profiles. MM-GBSA analysis further
demonstrated superior binding energies for L114 (-32.20 ± 0.02 kcal/mol), L41 (-30.15 ± 0.02 kcal/mol), and L111
(-28.19 ± 0.02 kcal/mol) compared to diclofenac (-25.18 ± 0.03 kcal/mol). Among the screened compounds, L114
emerged as the most promising EPCR inhibitor. These findings suggest that selected phytochemicals, particularly
L114, may serve as potential lead molecules for developing safer anti-inflammatory therapies targeting EPCR.
Aishwarya Jadhav, Elangbam Singh, Sagar S. Bhayye· International Journal of Dru...· 0 citations
Background Rosacea is a chronic inflammatory skin condition. Excessive LL-37 is produced when serine protease kallikrein-5 (KLK5) is hyperactivated, contributing to the inflammatory response in rosacea. Thus, inhibition of KLK5 has the potential to attenuate inflammation in this condition. Reports suggest that specnuezhenide (Spe), an isomer of oleanolic acid, is effective as an anti-inflammatory agent for the treatment of inflammatory diseases. However, little is known about the role of Spe and its mechanisms in alleviating rosacea. Methods Spe was identified as a potential KLK5 inhibitor through virtual screening and molecular docking, showing high-affinity binding via hydrophobic and hydrogen-bond interactions. Rosacea was induced in mice by intradermal LL-37 injection, followed by intraperitoneal administration of Spe. The severity of skin inflammation was assessed histologically. Serum cytokines, inflammatory gene expression, and protein levels of CD31, MMP-9, CD4, and KLK5 were analyzed by ELISA, RT-qPCR, and immunofluorescence, respectively. Inhibition of the TLR4/NF-κB pathway was examined by Western blot. Untargeted metabolomics was applied to characterize alterations in serum metabolites. Results Spe markedly reduced LL-37-induced skin inflammation, decreased inflammatory cell and mast cell infiltration, decreased MMP-9 expression, and reduced CD31 fluorescence intensity and CD4+ T cell recruitment. The study demonstrated that Spe inhibited the expression of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) in serum and suppressed activation of TLR2, MMP-9, KLK5, IL-1β, IL-6, and TNF-α genes. Moreover, Spe inhibited KLK5 expression and blocked activation of the TLR4/NF-κB pathway. Metabolomics identified 43 dysregulated metabolites in rosacea, 26 of which were normalized by Spe treatment. Pathway enrichment analysis suggested that regulation of unsaturated fatty acid biosynthesis is a key mechanism underlying the effects of Spe. Conclusions This study demonstrates for the first time that Spe, a novel KLK5 inhibitor, suppresses the inflammatory response mediated by the KLK5/TLR4/NF-κB pathway, accompanied by metabolic remodeling, particularly involving the biosynthesis of unsaturated fatty acids, thereby ameliorating rosacea-like dermatitis.
Jingang Xu, Xinyu Li, Manyu Chen et al.· Frontiers in Immunology· 0 citations
