Background/Objectives: Anxiety and depression are leading causes of disability worldwide. Although current pharmaceuticals are effective, adverse effects reduce adherence, driving the search for alternatives in traditional plant-based medicine. This article analyzes ancient Mesoamerican codices and documents to identify candidate plants, establishing a baseline for pharmacological validation and potential treatment development. Methods: This narrative review analyzes and synthesizes data from specialized databases and physical libraries in Spanish and English. Results: Plants described in Mesoamerican codices demonstrate anxiolytic- and antidepressant-like effects in preclinical models, linked to phytochemicals such as sterols, flavonoids, alkaloids, and terpenes. Mechanisms appear to involve oxytocinergic cells; the GABAergic, serotonergic, noradrenergic, and dopaminergic systems; BDNF activation; and monoamine oxidase regulation. Although translation is complicated by uncertainties in historical interpretation, botanical identification, and reproducibility, these studies remain essential for identifying natural products to inform future drug discovery. Conclusions: Analyzing ancient Mesoamerican medical records helps identify plants with anxiolytic and antidepressant potential. However, characterizing their pharmacokinetic, toxicological, and neurochemical profiles is required before proposing clinical trials to ensure patient safety.
Background/Objectives: This study characterized an ethanol-eluted, semi-purified fraction (F4) from Myrtus communis L. leaves and compared its anti-inflammatory activity in free and nanoemulsified forms. Methods: F4 was obtained by C8 fractionation, examined by colorimetric assays, targeted LC–MS (SIM) and COX-2 docking, and incorporated into an oil-in-water nanoemulsion. Oral activity at 200 and 400 mg/kg was assessed in male Wistar rats with carrageenan-induced paw edema (seven groups; n = 6/group). The primary endpoint was the individual area under the curve (AUC) of edema over 1–5 h. Results: Targeted LC–MS tentatively annotated ten compounds. The total phenolic content of F4 was 186.75 ± 0.43 mg GAE/g, and apigenin had the most favorable predicted COX-2 docking score (−8.1 kcal/mol). The nanoemulsion measured 119.07 ± 16.28 nm on day 0 and showed no phase separation under stress tests. Free F4 and F4 nanoemulsion (F4 NE) reduced AUC versus the inflamed control, and F4 NE reduced AUC versus the blank nanoemulsion (Holm-adjusted p < 0.0001). Compared with free F4, nanoemulsification decreased mean AUC by 37.7% and 42.9% at 200 and 400 mg/kg (Holm-adjusted p = 0.0362 for both comparisons). After baseline adjustment, the difference persisted at 400 mg/kg (−2.94 mL·h; 95% CI −5.16 to −0.72; Holm-adjusted p = 0.0304) but not at 200 mg/kg (−1.61 mL·h; 95% CI −4.27 to 1.06; Holm-adjusted p = 0.2053). Conclusions: Orally administered F4 had anti-inflammatory activity, and nanoemulsification produced improved anti-inflammatory efficacy under the tested conditions, as shown by the lower cumulative edema. Bioavailability was not assessed; pharmacokinetic studies are needed to determine whether it underlies this effect.
The journal retracts the article titled “Design and Synthesis of New Hydantoin Acetanilide Derivatives as Anti-NSCLC Targeting EGFRL858R/T790M Mutations” [...]
Background/Objectives: Methionine adenosyltransferase 2A (MAT2A) has emerged as a promising therapeutic target in cancers harboring methylthioadenosine phosphorylase (MTAP) deletion. However, the development of potent, drug-like MAT2A inhibitors with favorable pharmacokinetic profiles remains challenging. This study aimed to design, synthesize, and evaluate a library of benzofuran-based oxadiazole derivatives as novel MAT2A inhibitors and to elucidate their molecular basis of action through integrated computational studies. Methods: A series of benzofuran-based oxadiazole derivatives (10a–10j and 16–19) was designed, synthesized, and characterized by 1H NMR, 13C NMR, and high-resolution mass spectrometry (HRMS). All compounds were evaluated for MAT2A inhibitory activity, with AZ-28 used as the reference inhibitor. The most active compounds were subjected to molecular docking, 200 ns molecular dynamics (MD) simulations, density functional theory (DFT) calculations, and in silico ADME/toxicity prediction. No preregistration was applicable, and no animals were used in this study. Results: The synthesized compounds exhibited a broad range of MAT2A inhibition, with IC50 values from 0.0116 ± 0.0020 to 28.77 ± 1.79 μM, benchmarked against AZ-28 (IC50 = 0.0419 ± 0.0032 μM). Compounds 10g (IC50 = 0.0116 ± 0.0020 μM), 10a (IC50 = 0.0883 ± 0.0060 μM), and 19 (IC50 = 0.158 ± 0.015 μM) were the most potent. Docking revealed favorable binding orientations within the MAT2A active site, supported by hydrogen-bonding and hydrophobic interactions. MD simulations showed stable protein–ligand complexes with favorable RMSD profiles, and binding free-energy calculations supported complex stability. DFT analyses (HOMO–LUMO and MEP) provided insight into electronic properties and reactive sites. Furthermore, in silico ADME and toxicity assessments provided preliminary insights into the drug-likeness and pharmacokinetic properties of the studied compounds. Nevertheless, these computational predictions remain preliminary and require experimental validation. Conclusions: Compounds 10g, 10a, and 19 are promising MAT2A inhibitors, with 10g identified as the most favorable lead. These computational predictions remain preliminary and require experimental validation. Further pharmacokinetic, toxicological, and in vivo studies of 10g are warranted.
Cancer remains one of the main causes of death worldwide. The development of drug resistance, systemic toxicity, and poor therapeutic selectivity continues to limit the efficacy of conventional treatments. Multi-target therapeutic agents that can modulate complex oncogenic networks are gaining increasing interest among natural products. Alpinia galanga (L.) Willd. is a medicinal plant that is a promising source of bioactive compounds with high anticancer potential. This review summarizes the current evidence on the anticancer activities of A. galanga extracts and its major phytochemicals, including 1′-acetoxychavicol acetate (ACA), 1′-acetoxyeugenol acetate (AEA), galangin, chrysin, pinocembrin, and related flavonoids. Mechanistically, these compounds modulate various hallmarks of cancer by modulating oxidative stress, apoptosis, autophagy, cell-cycle arrest, mitochondrial dysfunction, inflammatory signaling, and metastatic pathways, particularly NF-κB, PI3K/Akt, MAPK, and p53-associated networks. Recent findings have shed light on the emerging roles of A. galanga compounds in overcoming resistance to targeted therapy, suppressing immune evasion through efferocytosis, remodeling the tumor microenvironment, and augmenting chemosensitivity and immunotherapeutic responses. Importantly, advances in nanotechnology-based formulations, such as lipid nanocarriers, exosome-mediated delivery systems, and biomimetic nanovaccines, have greatly improved the translational potential of galangin and other phytochemicals by improving their bioavailability, tumor targeting, and immune activation. This review also provides a critical discussion of the current pharmacokinetic limitations, translational challenges, and future opportunities for integrating A. galanga-derived compounds in precision oncology and combination-based cancer therapies. Collectively, the available evidence suggests that A. galanga is a platform with mechanistic versatility and clinical promise for next-generation anticancer therapeutics.
