Plants and their derived molecules have been traditionally used to manage numerous pathological complications, including male erectile dysfunction (ED). Mimosa pudica Linn. commonly referred to as the touch-me-not plant, and its extract are important sources of new lead molecules in drug discovery research. The main goal of this study was to predict highly effective molecules from M. pudica Linn. for reaching and maintaining penile erection before and during sexual intercourse through in silico molecular docking and dynamics simulation tools. A total of 28 bioactive molecules were identified from this target plant through public repositories, and their chemical structures were drawn using Chemsketch software. Graph theoretical network principles were applied to identify the ideal target (phosphodiesterase type 5) and rebuild the network to visualize the responsible signaling genes, proteins, and enzymes. The 28 identified bioactive molecules were docked against the phosphodiesterase type 5 (PDE5) enzyme and compared with the standard PDE5 inhibitor (sildenafil). Pharmacokinetics (ADME), toxicity, and several physicochemical properties of bioactive molecules were assessed to confirm their drug-likeness property. Molecular dynamics (MD) simulation modeling was performed to investigate the stability of PDE5–ligand complexes. Four bioactive molecules (Bufadienolide (−12.30 kcal mol⁻¹), Stigmasterol (−11.40 kcal mol⁻¹), Isovitexin (−11.20 kcal mol⁻¹), and Apigetrin (−11.20 kcal mol⁻¹)) showed the top binding affinities with the PDE5 enzyme, much more powerful than the standard PDE5 inhibitor (−9.80 kcal mol⁻¹). The four top binding bioactive molecules were further validated for a stable binding affinity with the PDE5 enzyme and conformation during the MD simulation period as compared to the apoprotein and standard PDE5 inhibitor complexes. Further, the four top binding bioactive molecules demonstrated significant drug-likeness characteristics with lower toxicity profiles. According to the findings, the four top binding molecules may be used as potent and safe PDE5 inhibitors and could potentially be used in the treatment of ED.

Parkinson’s disease (PD) is an advanced neurodegenerative condition distinguished by the rapid decline of dopamine neurons in the midbrain, leading to an imbalance in dopamine and acetylcholine levels, precipitating associated symptoms. The main objective of this work was to fabricate solid lipid nanoparticles (SLNs) loaded with S-carboxymethyl-L-cystine (SC) for enhanced delivery to the brain. This study examines the impact of these SLNs on rotenone (RT) caused Parkinson’s disease (PD) in both rat and zebrafish models. The process of loading SC into SLNs was achieved through the solvent evaporation-emulsification method. The SC-encapsulated solid lipid nanoparticles (SCSLNs) were subjected to physicochemical evaluation, and their properties were verified. For 28 days, the rats received subcutaneous injections of RT at a dosage of 2 mg × kg⁻¹ body weight. Additionally, the rats in the experimental group received SCSLNs from the 14th to the 28th days of the trial. Interestingly, the locomotor activity, grip strength, and exploratory behaviour of the rats with SCSLNs significantly improved. Furthermore, it was observed that the quantities of acetylcholinesterase (AchE) inside the brain tissue had increased, and oxidative biomarkers had decreased. In addition, there was a discernible decrease in Lewy body development and cellular damage compared to the positive control group. Zebrafish were dosed with SCSLNs simultaneously as they were subjected to a 5 µg × L⁻¹ RT concentration for 28 days during the experiment. AchE levels in the fish brain increased, resulting in improved locomotor activity in the SCSLN group of zebrafish. The findings of this investigation imply that using SCSLNs may reduce Parkinson’s disease symptoms via enhanced delivery of SC into the brain.

Introduction: Parkinson's disease (PD) is a chronic, devastating neurodegenerative disorder marked by the death of dopaminergic neurons in the midbrain's substantia nigra pars compacta (Snpc). In alpha-synuclein (α-Syn) self-aggregation, the existence of intracytoplasmic inclusion bodies called Lewy bodies (LBs) and Lewy neurites (LNs) causes PD, which is a cause of neuronal death. Methods: The present study is aimed at finding potential bioactive compounds from Cynodon dectylon that can degrade α-Syn aggregation in the brain, through in silico molecular docking investigations. Graph theoretical network analysis was used to identify the bioactive compounds that target α-Syn and decipher their network as a graph. From the data repository, twenty-nine bioactive chemicals from C. dactylon were chosen and their structures were retrieved from Pubchem. On the basis of their docking scores and binding energies, significant compounds were chosen for future investigation. The in silico prediction of chosen compounds, and their pharmacokinetic and physicochemical parameters were utilized to confirm their drug-likeness profile. Results: During molecular docking investigation the bioactive compounds vitexin (-7.3 kcal.mol-1) and homoorientin (-7.1 kcal.mol-1) showed significant binding energy against the α-Syn target protein. A computer investigation of molecular dynamics simulation study verifies the stability of the α-Syn-ligand complex. The intermolecular interactions assessed by the dynamic conditions indicate that the bioactive compound vitexin has the potency to prevent α-Syn aggregation. Conclusion: Interestingly, the observed results indicate that vitexin is a potential lead compound against α-Syn aggregation, and in vitro and in vivo studies are warranted to confirm the promising therapeutic capability.