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

Anti-inflammatory Potential of Apigenin and Luteolin in Oral Mucositis: An In Silico Docking Study Targeting IL-6, NF-κB, and COX-2

Abstract Objectives Oral mucositis (OM) is an oral mucosal inflammation induced by radiotherapy/chemotherapy, which is characterized by erythema, edema, and oral ulceration that significantly reduce patients' quality of life. Several pro-inflammatory cytokines such as interleukin-6 (IL-6), nuclear factor kappa B (NF-κB), and cyclooxygenase-2 (COX-2) are involved in the pathophysiological stage of OM. Natural flavonoids, for instance, apigenin and luteolin, have demonstrated anti-inflammatory and antioxidant properties. This study aimed to evaluate the anti-inflammatory potential of apigenin and luteolin through an in silico molecular docking approach targeting key inflammatory mediators, including IL-6, NF-κB, and COX-2. Materials and Methods Three-dimensional structures of the ligands and target proteins were obtained from public databases and prepared for docking simulations using validated computational tools. Binding affinity, interaction profiles, and stability of ligand–protein complexes were analyzed to determine inhibitory potential. Results The docking results demonstrated favorable binding energies of both apigenin and luteolin toward IL-6, NF-κB, and COX-2, with multiple hydrogen bonds and hydrophobic interactions stabilizing the complexes. Conclusion These findings suggest 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.

Therapeutic Potential of Glycyrrhiza glabra (Licorice) Against COVID-19: Mechanistic Insights and Technological Advances from In Silico, Preclinical and Clinical Evidence

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.

In silico evaluation of Syzygium cumini phytochemicals as BCL-2 inhibitors: molecular docking and molecular dynamics simulations for gastric cancer therapy

Anti-Inflammatory Components of Artemisia scoparia Alleviate Ulcerative Colitis: An Integrated Study Combining UPLC-Q-Exactive Orbitrap MS/MS, Network Pharmacology, Molecular Docking, and In Vivo/In Vitro Validation

Artemisia scoparia is a classic medicinal and edible plant with great exploitation potential in anti-inflammatory research. This study aimed to explore its anti-ulcerative colitis bioactive constituents and corresponding mechanisms of action. A total of 15 flavonoids and coumarins were identified by macroporous resin purification combined with ultra-performance liquid chromatography coupled to UPLC-Q-Exactive Orbitrap MS/MS. Seven key bioactive compounds (eupatilin, cirsimaritin, quercetin, scoparone, 7-hydroxycoumarin, scopoletin and esculetin) and six core targets (TNF, AKT1, SRC, EGFR, HSP90AA1 and ESR1) were further screened via network pharmacology. Subsequent molecular docking analysis verified that flavonoids exhibited markedly stronger binding affinity to target proteins than coumarins. In vitro cellular experiments revealed that eupatilin exhibited the strongest anti-inflammatory activity among all key components. In vivo animal assays further 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. This work provides vital experimental evidence for the development and utilization of anti-ulcerative colitis ingredients from A. scoparia, and validates its promising health-related application value in the food industry.

Identification of Potential Anti-Inflammatory Phytochemicals Targeting Endothelial Protein C Receptor (EPCR) Through Molecular Docking and Molecular Dynamics Simulations

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.

Virtual screening identifies specnuezhenide as a potential therapeutic agent for rosacea via KLK5/TLR4/NF-κB pathway inhibition and metabolic modulation

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.