Exploring the medicinal potential of Senna siamea roots: an integrated study of antibacterial and antioxidant activities, phytochemical analysis, ADMET profiling, and molecular docking insights

Nowadays, infectious diseases pose an alarming global threat to human health. The genus Senna is among the most well-known taxonomic categories commonly used in folk medicine to confront these challenges. Motivated by its traditional uses, a comprehensive study was conducted on the roots extract of Senna siamea, aiming to address the in vitro antibacterial and antioxidant efficacy of phytochemicals from the dichloromethane: methanol (1:1) roots extract of the plant, along with in silico computational studies. The separation of compounds was achieved using silica gel column chromatography. Whereas, the antibacterial and antioxidant activities were examined using paper disc diffusion and 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assays, respectively. Silica gel column chromatography of the dichloromethane: methanol (1:1) roots extract afforded lupeol (1), beta-sitosterol (2a) and stigmasterol (2b), chrysophanol (3), betulinic acid (4), and glyceryl-1-hexacosanoate (5). Although these compounds have been previously reported from the plant, proof of their medicinal applications via in vitro and in silico studies is still lacking. Notably, our findings showed remarkable inhibition zones by the extract (18.00 +/- 0.00 mm and 17.17 +/- 0.24 mm) against E. coli and S. aureus, respectively, at 50 mg/mL compared to ciprofloxacin (23.33 +/- 0.47 mm and 22.00 +/- 0.00 mm, respectively), showcasing its potential antibacterial efficiency. Considerable inhibition zones were also recorded by chrysophanol (3) against E. coli (16.33 +/- 0.24 mm) and S. pyogenes (16.00 +/- 0.00 mm) at 2 mg/mL, compared to ciprofloxacin which showed 23.33 +/- 0.47 mm and 21.67 +/- 0.47 mm, respectively, signifying its potent antibacterial activities. In addition, the crude extract and chrysophanol (3) exhibited substantial IC50 values (1.24 and 1.71 mu g/mL, respectively), suggesting their significant antioxidant potential compared to that of ascorbic acid (IC50: 0.53 mu g/mL). Chrysophanol (3) fulfilled Lipinski's rule with no violation and lupeol (1), beta-sitosterol (2a), stigmasterol (2b), betulinic acid (4), and glyceryl-1-hexacosanoate (5) displayed one violation each which were in favor of the drug-likeness predictions. All the compounds exhibited no cytotoxicity and except betulinic acid (4), all the compounds also showed no carcinogenicity properties which were consistent with the prediction results of ciprofloxacin. The molecular docking computations revealed that all the compound isolates displayed strong and nearly strong binding affinities against all protein targets, ranging from - 6.6 kcal/mol to -9.2 kcal/mol (lupeol (1) against E. coli DNA gyrase B and topoisomerase II alpha, respectively). Thus, the present findings suggest the roots of Senna siamea for potential medicinal applications against multi-drug resistant pathogens hence validating its ethno-medicinal uses.