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

Chemical Profiling and Anti-Inflammatory Mechanisms of Heracleum millefolium Diels Revealed by Molecular Networking, Network Pharmacology, and Cellular Validation

Background/Objectives: Heracleum millefolium Diels (HMD) is a traditional Tibetan medicinal herb that has been reported to possess analgesic, anti-edematous, and anti-inflammatory activities. However, its chemical composition and anti-inflammatory mechanisms remain unclear. Methods: In this study, ultra-performance liquid chromatography coupled with high-resolution mass spectrometry (UPLC-HRMS), combined with database searching and “seed”-based molecular networking, was used to systematically characterize the chemical constituents of HMD. Furthermore, an integrated strategy combining network pharmacology, molecular docking, and cellular validation was applied to explore potential anti-inflammatory mechanisms associated with HMD. Results: A total of 472 compounds were identified or tentatively identified from HMD. Network pharmacology analysis predicted five key targets, namely TNF, IL-6, IL-1β, GAPDH, and AKT1, together with four potential bioactive constituents, including velutin, artemitin, kaempferol, and naringenin. Pathway enrichment analysis indicated that the potential anti-inflammatory effects of HMD were mainly associated with lipid and atherosclerosis and the AGE-RAGE signaling pathway. Molecular docking suggested potential favorable interactions between the selected constituents and key targets. Moreover, cellular experiments demonstrated that the four compounds significantly inhibited inflammatory responses in LPS-stimulated RAW264.7 macrophages. Conclusions: This study systematically characterized the chemical profile of HMD and preliminarily explored its potential anti-inflammatory mechanisms, providing a scientific basis for further investigation of its bioactive constituents and pharmacological properties.

Exploring the Therapeutic Effects of Artemisia rupestris L. Extract on Metabolic Dysfunction-Associated Fatty Liver Disease: Network Pharmacology and In Vitro Experiments

Background: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a prevalent chronic liver disorder with limited pharmacological therapies, highlighting the need for novel multi-target agents from traditional medicinal plants. Artemisia rupestris L. has hepatoprotective effects, but its active constituents and mechanisms against MAFLD remain unexplored. Methods: The chemical profile of an ultrasonically-assisted 70% ethanol extract of Artemisia rupestris L. (ARE) was determined using UPLC-Q-TOF-MS. Network pharmacology, molecular docking, 100-ns molecular dynamics (MD) simulations, and in vitro experiments in oleic acid-induced HepG2 cells were integrated to identify active compounds, core targets, and pathways, and to validate lipid-lowering and hepatoprotective effects. Results: Seventy-eight compounds were identified, mainly flavonoids, phenolic acids, and terpenoids. Network analysis highlighted AKR1B10 and MAPK14 as core targets and isorupestonic acid and rupestonic acid as key components. MD simulations supported the stable binding of isorupestonic acid to AKR1B10 (RMSD ~1.6–3.2 Å), driven by van der Waals and electrostatic interactions. In vitro, ARE dose-dependently reduced intracellular triglycerides, total cholesterol, and LDL-C, decreased lipid droplets, and lowered AST/ALT levels, with a high-dose efficacy comparable to atorvastatin. Conclusions: Through in vitro experiments and network pharmacology analyses, this study preliminarily elucidated the beneficial effects of ARE on lipid deposition in hepatocytes and its potential mechanism, thereby providing an experimental basis and potential avenues for subsequent in vivo studies on pharmacodynamics, pharmacokinetics, and toxicology.

In Silico Study of Bioactive Compounds from Moringa oleifera Extract as Anti-Inflammatory Candidates Targeting the Inflammatory Mediator PGD2

Conventional anti-inflammatory drugs may cause serious adverse effects, creating a need for safer plant-derived therapeutic candidates. Although Moringa oleifera has recognized biological potential, computational evidence regarding the anti-inflammatory activity of its phytoconstituents against prostaglandin D₂ 11-ketoreductase (AKR1C3; PDB ID: 1S2A) remains limited. This in silico study evaluated 12 bioactive compounds from an ethanolic extract of M. oleifera as potential inhibitors of this molecular target. Pharmacokinetic properties and oral bioavailability were predicted using SwissADME according to Lipinski’s rule of five. Molecular docking was subsequently performed using Molecular Operating Environment 2019 to evaluate ligand–receptor binding affinities based on Gibbs free energy (ΔG) and root-mean-square deviation (RMSD). The physicochemical assessment showed that 11 compounds had favorable predicted membrane permeability and systemic absorption, whereas rutin violated Lipinski’s criteria. Docking analysis identified quercetin, apigetrin, chlorogenic acid, ellagic acid, and naringenin as the most promising candidates. These compounds exhibited the lowest ΔG values and stable binding conformations, with RMSD values below 2.0 Å. The findings indicate that these five phytoconstituents have favorable predicted interactions with AKR1C3 and may possess potential anti-inflammatory activity associated with PGD₂ metabolism. Accordingly, they represent promising lead compounds for developing selective plant-derived anti-inflammatory agents. This study provides a computational foundation for future molecular dynamics simulations and clinical validation.

Phytochemical Profiling, In Vitro Bioactivity, and Network Pharmacology of Astragalus cruciatus Link Ethanolic Extract: Multitarget Mechanisms Underlying Potential Antidiabetic Effects

Astragalus species have long been recognized for their pharmacological relevance, yet the antidiabetic properties of Astragalus cruciatus Link (Ac) remain poorly explored. This study aimed to investigate the antidiabetic potential of A. cruciatus Link and to elucidate possible underlying mechanisms. The ethanolic extract of Ac (AcEE) was prepared and analyzed for phenolic and flavonoid content. Antioxidant activity was assessed through a series of in vitro assays. The in vitro inhibition of α-amylase and α-glucosidase was assessed, followed by molecular docking to probe ligand-enzyme interactions. LC-ESI-MS analysis revealed a polyphenol-rich profile, with rutin (953.54 µg/g extract) and quinic acid (797.18 µg/g of extract) identified as main compounds. The AcEE showed significant inhibitory activity against both α-amylase and α-glucosidase (IC50 = 239.30 ± 7.40 and 192.60 ± 15.51 μg/mL, respectively). Moreover, low cytotoxic effects were observed in hepatic cell lines. Computational analysis revealed stable interactions between rutin and both enzymes (−12.935 and −8.073 Kcal/mol, respectively). Network pharmacology revealed that AcEE may modulate key targets, including IL-6, TNF-α, IL-1β, Akt-1, STAT3, EGFR, and INSR as well as pathways related to insulin resistance, AGE-RAGE, and inflammation. These findings suggest that AcEE exerts significant antidiabetic effects through multitarget modulation, highlighting its potential as a natural therapeutic agent for T2DM.

Comprehensive Phytopharmacological Profiling of Polygonum aviculare L.: Antioxidant, Anti-Inflammatory, and α-Glucosidase Inhibitory Activities of Bioactive Constituents with Molecular Docking and In Silico Drug-Likeness Analysis

This study investigated the extracts and bioactive constituents of the aerial parts of Polygonum aviculare L., a well-known traditional medicine for inflammation and diuresis, through bioactivity-guided investigation and molecular docking analysis. Solvent extracts demonstrated significant antioxidant, anti-α-glucosidase, and anti-inflammatory activities, supporting their value for further pharmacological investigation. Among the isolated compounds, gallic acid (1), quercetin (3), myricetin (4), avicularin (6), and isorhamnetin (7) exhibited excellent antioxidant activity in the DPPH assay (SC50 ≤ 6.50 μM) and were stronger than the positive control BHT (SC50 = 36.99 μM). Kaempferol (9) (IC50 of 4.50 µM) demonstrated the highest α-glucosidase inhibition, surpassing that of the clinically used acarbose (IC50 = 519.7 µM). Additionally, gallic acid and quercetin demonstrated significantly stronger NO inhibition than apigenin, while kaempferol showed comparable activity (IC50 = 15.06 ± 1.50 μM vs. 16.08 ± 1.86 μM for apigenin). Molecular docking analyses supported favorable interactions between the active compounds and α-glucosidase and inducible nitric oxide synthase (iNOS). Kaempferol reduced the expression of iNOS and COX-2 in LPS-stimulated RAW 264.7 macrophages and was associated with increased KLF4 and Arg-1 expression and decreased phosphorylation of p38 MAPK and IκBα, suggesting a potential role in promoting an anti-inflammatory M2-like macrophage phenotype. Structure–activity relationship analysis indicated that flavonoid aglycones and specific hydroxylation patterns contribute to the observed biological activities. Collectively, these findings identify quercetin and kaempferol as highly active constituents of P. aviculare and support their potential for further pharmacological investigation.

Investigating the phytochemical composition of Curcuma longa, Azadirachta indica, and Asparagus racemosus using network pharmacology and molecular docking approaches for ovarian cancer therapy