Proaporphine alkaloids—cissamaline, cissamanine, and cissamdine—show promise against AD, with in silico studies highlighting their potential as new therapeutics.

Background: Silene undulata is historically used for inducing vivid and prophetic lucid dreams, but limited information exists on its phytochemical composition and potential pharmacological properties. Objective: This study aimed to investigate the phytochemical composition of S. undulata through LC-MS/MS analysis and explore its potential serotonergic activity, which could support and confirm the traditional use of S. undulata as a dream-inducing plant. Methods: LC-MS/MS analysis was conducted on S. undulata extract, identifying 51 phytochemicals, including norharman, harmalol, harmaline, harmine, and ibogaine alkaloids. ADMET and Molecular docking investigations were employed to assess the serotonergic potential of these compounds. Results: The analysis revealed the presence of β-carboline alkaloids, such as norharman, harmalol, harmaline, harmine, and ibogaine, within S. undulata extract. ADMET analysis showed that these compounds have a favourable pharmacokinetic properties. In addition, molecular docking investigations showed that harmaline (-8.90 Kcal/mol), harmalol (-8.56 Kcal/mol), and ibogaine (-8.75 Kcal/mol) exhibited binding affinities comparable to the control molecule, LSD (-9.14 Kcal/mol), indicating potential agonistic activity at serotonin 5-HT2A receptor. Conclusion: These findings provide insights into the potential therapeutic benefits of S. undulata, supporting its traditional use as a psychoactive plant. This study investigated the chemical constituents and potential serotonergic agonist activity of S. undulata for the first time. While promising, further research is necessary to uncover additional medicinal properties associated with the identified phytochemical components.

Breast cancer remains a significant challenge in oncology, highlighting the need for alternative therapeutic strategies that target necroptosis to overcome resistance to conventional therapies. Recent investigations into natural compounds have identified 8,12-dimethoxysanguinarine (SG-A) from Eomecon chionantha as a potential necroptosis inducer. This study presents the first computational exploration of SG-A interactions with key necroptotic proteins—RIPK1, RIPK3, and MLKL—through molecular docking, molecular dynamics (MD), density functional theory (DFT), and molecular electrostatic potential (MEP) analyses. Molecular docking revealed that SG-A exhibited a stronger affinity for MLKL (-9.40 kcal/mol) compared to the co-crystallized ligand (-6.29 kcal/mol), while its affinity for RIPK1 (-6.37 kcal/mol) and RIPK3 (-7.01 kcal/mol) was lower. MD simulations further demonstrated the stability of SG-A within the MLKL site, with RMSD values stabilizing between 1.4 and 3.3 Å over 300 ns, indicating a consistent interaction pattern. RMSF analysis indicated the preservation of protein backbone flexibility, with average fluctuations under 1.7 Å. The radius of gyration (Rg) results indicated a consistent value of ~15.3 Å across systems, confirming the role of SG-A in maintaining protein integrity. Notably, SG-A maintains two critical H-bonds within the active site of MLKL, reinforcing the stability of the interaction. Principal component analysis (PCA) indicated a significant reduction in MLKL’s conformational space upon SG-A binding, implying enhanced stabilization. Dynamic cross-correlation map (DCCM) analysis further revealed that SG-A induced highly correlated motions, reducing internal fluctuations within MLKL compared to the co-crystallized ligand. MM-PBSA revealed the enhanced binding efficacy of SG-A, with a significant binding free energy of -31.03 ± 0.16 kcal/mol against MLKL, surpassing that of the control (23.96 ± 0.11 kcal/mol). In addition, the individual residue contribution analysis highlighted key interactions, with ARG149 showing a significant contribution (-176.24 kcal/mol) in the MLKL-SG-A complex. DFT and MEP studies corroborated these findings, revealing that the electronic structure of SG-A is conducive to stable binding interactions, characterized by a narrow band gap (~0.16 units) and distinct electrostatic potential favourable for necroptosis induction. In conclusion, SG-A has emerged as a compelling inducer of necroptosis for breast cancer therapy, warranting further experimental validation to fully realize its therapeutic potential.

Background: Miswak, derived from Salvadora persica, has traditionally been used for oral hygiene. Although its antibacterial activity has been studied, multifaceted comparisons of its antioxidant potential, phenolic content, and bioavailability in various forms remain inadequate. Methods: This research assessed green and dry Miswak versus commercial toothpaste. Total phenolic amount and antioxidant activity were calculated utilising Folin-Ciocalteu and DPPH assays, respectively. A 60-minute dissolution study simulated phenolic release in artificial saliva. An in vivo study was performed on 60 volunteers separated into four groups (green Miswak, dry Miswak, toothpaste, and control) to evaluate antibacterial activity over 15 days via total plate count analysis. Results: Green Miswak shows the highest total phenolic content (9.59 mg GAE/g) and antioxidant activity (548.98% inhibition/100 mg), followed by dry Miswak and toothpaste. Toothpaste exhibited the fastest release of phenolic compounds, while Miswak exhibited more sustained profiles. Both green Miswak and toothpaste substantially reduced oral bacterial burdens, with toothpaste showing slightly steadier effects. Conclusion: Green Miswak shows strong antioxidant and antibacterial characteristics, comparable to commercial toothpaste. Its phytochemical richness supports its role as an effective planet based oral care agent, notably in populations preferring traditional ways or with limited access to commercial products. These results shed light on the integration of Miswak into modern dental hygiene practices.