Novel Natural Candidates for Replacing Synthetic Additives in Nutraceutical and Pharmaceutical Areas: Two <i>Senna</i> Species (<i>S. alata</i> (L.) Roxb. and <i>S. occidentalis</i> (L.) Link)

<i>Senna alata</i> (L.) Roxb. and <i>Senna occidentalis</i> (L.) Link (family Fabaceae) are commonly used in different systems of traditional medicine to treat ailments. The present study was designed to determine the phytoconstituents, antioxidant, enzyme inhibition, and antimicrobial activities of the methanolic extract from the leaves of these two <i>Senna</i> species. A total of 75 phenolic compounds belonging to dihydroxybenzoic acids, dihydroxycinnamic acids, flavonoid C-glycosides, flavonoid O-glycosides, flavonoid aglycones, anthraquinone glycosides, and anthraquinone aglycones were identified. Flavonoid C-glycosides were only found in <i>S. occidentalis</i> while sennosides A, B, and C were only detected in <i>S. alata</i>. In line with its higher total phenolic and flavonoids contents, <i>S. alata</i> exerted significantly (<i>p</i> < 0.05) higher antiradical (2,2-diphenyl-1-picrylhydrazy (DPPH) = 58.36 mg trolox equivalent (TE)/g; 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) = 118.86 mg TE/g), ions reducing (cupric reducing antioxidant capacity (CUPRAC) = 93.85 mg TE/g; ferric reducing antioxidant power (FRAP) = 50.42 mg TE/g), and total antioxidant (1.39 mmol TE/g) activities than <i>S. occidentalis</i>. <i>S. alata</i> revealed significantly (<i>p</i> < 0.05) higher inhibitory effect against butyrylcholinesterase (1.67 mg galantamine equivalent (GALAE)/g), tyrosinase (45.07 mg KAE/g) 45.07 mg kojic acid equivalent (KAE)/g), α-glucosidase (0.73 mmol acarbose equivalent (ACAE)/g), and α-amylase (2.95 mmol ACAE/g) enzymes. Both species showed high antibacterial and antifungal activities with remarkable antifungal activity exerted by <i>S. alata</i> against <i>Trichoderma viride</i> (minimum inhibition concentration (MIC) 1 mg/mL), similar to that of Ketoconazole. The study utilized molecular docking, molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) free energy calculations, and molecular dynamics simulations to evaluate the binding interactions between anthraquinone glycosides and various bacterial enzymes, including targets from <i>Escherichia coli</i> and <i>Staphylococcus aureus</i>. The findings suggest that compounds like sennoside A, sennoside B, and chrysophanol exhibit strong binding affinities, stable interactions, and potential as antimicrobial inhibitors, especially against vital bacterial proteins such as MurE and 30S ribosome S3. In conclusion, our findings underscore the biopharmaceutical potential of these two <i>Senna</i> species, suggesting their significance as sources of bioactive agents for health-related applications.