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.

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The Keap1-Nrf2 pathway plays a prominent role in activating cytoprotective genes, detoxification and antioxidative defense enzymes against oxidative stress and xenobiotics-induced damage. Oxidative stress is involved in the initiation and progression of numerous health complications. The present study investigated the antioxidant potential of aqueous methanolic extract of Hemidesmus indicus (L) R.Br., followed by a pharmacoinformatics-based screening of novel Keap1 protein inhibitors. Initially, the antioxidant potential of this target plant was assessed by antioxidant assays (DPPH, ABTS radical scavenging and FRAP). H. indicus (L) R.Br. extract (100 µg mL− 1) showed 85 ± 2.917%, 78.783 ± 0.24% of DPPH, ABTS radicals scavenging activity, and 161 ± 4 µg mol (Fe (II)) g− 1 ferric ion reducing power. Further, a total of sixty-nine phytocompounds were derived from this plant through the IMPPAT database, and their three-dimensional structures were obtained from the PubChem database. The chosen sixty-nine phytocompounds were docked against the Kelch-Neh2 complex protein (PDB entry ID: 2flu, resolution 1.50 Å) along with the standard drug (CPU192018). The top scored three hits were selected, namely Hemidescine (− 11.30 Kcal mol− 1), Beta-Amyrin (− 10.00 Kcal mol− 1), and Quercetin (− 9.80 Kcal mol− 1) based on their binding affinities. The selected three hits showed significant drug-likeness properties with the least toxicity profile. Molecular dynamics simulation studies showed that all the protein-ligand complexes (Keap1-HEM, Keap1-BET and Keap1-QUE) were highly stable during the entire simulation period, compared to standard CPUY192018-Keap1complex. Based on these findings, the top-scored three phytocompounds may be used as a significant and safe Keap1 inhibitor and could potentially use for oxidative stress-induced health complications.