Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a multifactorial disorder driven by tightly interconnected metabolic, inflammatory, and lipid dysregulation pathways. Glycyrrhetinic acid, a pentacyclic triterpenoid derived from Glycyrrhiza species, has demonstrated anti-inflammatory and hepatoprotective activities in previous experimental studies. Objectives: This study aimed to systematically investigate the potential molecular targets and signaling pathways of glycyrrhetinic acid in MASLD using an integrated network pharmacology and molecular docking strategy. Methods: Predicted protein targets of glycyrrhetinic acid and MASLD-associated genes were collected from public databases. A protein–protein interaction (PPI) network was constructed, and hub genes were identified using the maximal clique centrality algorithm in Cytoscape. Functional annotation was performed through Gene Ontology and KEGG pathway enrichment analyses. Molecular docking simulations were subsequently conducted to assess the binding affinity of glycyrrhetinic acid with biologically prioritized targets derived from the network analysis. Results: Intersection analysis identified 26 shared targets between glycyrrhetinic acid and MASLD. PPI network analysis highlighted IL6, TNFα, AKT1, and PPARγ as central hub genes. Functional enrichment indicated that these targets were mainly involved in NF-κB, TNFα, and PI3K–Akt signaling pathways. Molecular docking results revealed favorable predicted binding affinities, with glycyrrhetinic acid exhibiting the strongest binding toward PPARγ among the evaluated targets. Conclusions: This integrative in silico analysis suggests that glycyrrhetinic acid may interact with multiple MASLD-related targets involved in inflammatory and metabolic regulation. These findings provide a computational framework for target prioritization and support further experimental investigations to elucidate the pharmacological relevance of glycyrrhetinic acid in MASLD.

Background: Safer analgesic strategies are needed to reduce the adverse effects associated with prolonged use of nonsteroidal anti-inflammatory drugs. The dry juice extract of Agave tequilana (ESPA), a chemically complex matrix with anti-inflammatory potential, may represent a promising adjuvant for modulating inflammatory pain. Objective: This study evaluated the antinociceptive activity of ESPA and its pharmacological interaction with diclofenac in the formalin test. Methods: BALB/c mice received ESPA or diclofenac orally 30 min before pain induction, and nociceptive behavior was quantified by counting paw flinches during the neurogenic and inflammatory phases. The GC–MS-detectable fraction of ESPA was chemically characterized, while the pharmacokinetic and bioactivity profiles of selected compounds were explored in silico using SwissADME and PASSonline. Molecular docking with COX-1 and COX-2 was performed using AutoDock Vina. Acute toxicity was evaluated according to OECD Guideline 423, and the ESPA–diclofenac interaction was examined using isobolographic analysis. Results: ESPA produced significant antinociceptive effects during the inflammatory phase. Although diclofenac exhibited greater potency, ESPA showed consistent efficacy in reducing inflammatory nociceptive behavior. GC–MS analysis identified several compounds within the detectable volatile/lipophilic fraction, including n-hexadecanoic, octadecanoic, and oleic acids. In silico evaluations suggested favorable predicted oral absorption and potential bioactivities related to inflammatory mediator regulation. Docking studies showed moderate predicted affinities for COX-1 and COX-2, lower than those observed for diclofenac. Isobolographic analysis demonstrated a synergistic interaction between ESPA and diclofenac, allowing dose reduction while maintaining antinociceptive efficacy. Acute toxicity testing indicated no signs of toxicity at the evaluated dose. Conclusions: These findings suggest that ESPA may act as a potential adjuvant in diclofenac-based analgesic strategies for inflammatory pain; however, further studies are required to clarify the active constituents and underlying mechanisms.

Background/Objectives: Estrogen deficiency is associated with metabolic disturbances and impaired glucose homeostasis. Morin, a natural flavonol, has shown promising hypoglycemic and antioxidant properties, but its effects under hypoestrogenic diabetic conditions remain poorly understood. The aim of this study was to evaluate the effects of morin on body weight, fasting blood glucose, glucose tolerance, and selected serum biochemical markers in an experimental model of diabetes under estrogen-deficient conditions (ovariectomized diabetic female mice). Methods: Female CD1 mice underwent sham surgery or ovariectomy (OVX), and each surgical condition was further divided into non-diabetic and diabetic subgroups treated with vehicle, glibenclamide (10 mg/kg), or morin (30 mg/kg). Body weight and fasting blood glucose were monitored over a 15-day treatment period. Oral glucose tolerance was assessed on day 15, and serum biochemical markers, including glucose, cholesterol, triglycerides, uric acid, blood urea nitrogen, creatinine, ALT, and AST, were measured thereafter. Results: Ovariectomy aggravated diabetes-associated hyperglycemia, impaired glucose tolerance, and triglyceride elevation. Morin treatment reduced fasting blood glucose and improved glucose tolerance in diabetic mice, including ovariectomized animals. Morin also attenuated the increase in serum triglycerides and blood urea nitrogen in ovariectomized diabetic mice, although it did not significantly improve cholesterol, uric acid, creatinine, ALT, or AST levels. Compared with glibenclamide, morin showed relevant glucose-lowering activity but had a more limited effect on the overall biochemical profile. Conclusions: These findings suggest that morin may partially improve glycemic control and selected metabolic alterations in experimental diabetes associated with estrogen deficiency. Further studies are required to clarify its mechanisms of action, long-term efficacy, and translational relevance.

Pain is a widespread global issue and one of the most common disabling conditions in daily life. A wide range of medications are available to reduce or eliminate pain, with nonsteroidal anti-inflammatory drugs (NSAIDs) being among those most commonly used. Additionally, new analgesic approaches, such as antioxidants (Ascorbic Acid), have been explored for their potential to relieve acute pain after surgery, cancer-related pain, and chronic pain not related to cancer with fewer adverse effects. Furthermore, the use of pharmacological combinations is an alternative treatment strategy to obtain a higher efficacy using lower drug concentrations, at which side effects are minimal. Background/Objectives: The aim of this study was to evaluate the pharmacological synergism of ketorolac and ascorbic acid in an inflammatory pain model. Methods: The individual and combined effects of ketorolac and ascorbic acid were evaluated in a formalin-induced pain model in mice. Four experimental groups were established: control (vehicle), ketorolac (KET), ascorbic acid (AA), and combination (KET/AA). Results: The combination of ketorolac and ascorbic acid produced a greater antinociceptive effect compared to the vehicle and individual treatments in the formalin model. Notably, even the lowest dose of the combination (KET 6.26/AA 3.21 µg/paw) exhibited a stronger effect than the maximum doses of each individual treatment KET (100 µg/paw) and AA (100 µg/paw). The effective concentration that produced 30% of antinociception (EC₃₀) for the tested treatments were determined, and an isobologram analysis confirmed the presence of a synergistic interaction in these combinations. Conclusions: These findings suggest that the combination of ketorolac and ascorbic acid produces a synergistic antinociceptive effect in the formalin-induced pain model. The enhanced efficacy of the combination indicates a potential therapeutic advantage in pain management by reducing the required dosage of each compound while maintaining or improving analgesic effects.