Exploring The Medicinal Potential Of Selected Medicinal Plants Of Ethiopia: An Integrated Study Of Phytochemical Analysis, Biological Activities, And Computational Insights

Abstract

Medicinal plants including herbs and spices are among the most popular sources of bioactive compounds that possess tremendous biological effects. Plant secondary metabolites such as flavonoids, quinones, alkaloids, tannins, saponins, and terpenoids have been reported as remarkable classes of natural products used in drug development. This research aimed to study the medicinal properties of extracts and compounds isolated from roots of selected medicinal plants of the Ethiopian flora, namely Cyphostemma adenocaule, Delonix regia, Senna siamea, and Ziziphus spina-christi along with their Computational Chemistry profiles. Documented protocols were used to screen the selected plants for their chemical composition, biological activities, and in silico molecular docking, drug-likeness, and ADMET profiles of the isolated compounds. A maceration technique was utilized to prepare the extracts of each plant material. The compounds were isolated using silica gel column chromatography and the structural information of the isolated compounds were established using IR and NMR spectroscopic techniques. Essential oils were extracted from the leaves and roots of the plants using Clevenger’s apparatus and their compositions were analyzed using GC-MS. The antibacterial activities of the extracts and isolated compounds were screened using paper disc diffusion assay against four bacterial strains, including two Gram-negative (Escherichia coli and Pseudomonas aeruginosa) and two Gram-positive (Staphylococcus aureus and Streptococcus pyogenes) bacteria. In addition, the antioxidant activities were tested via the 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging assay. The anti-acanthamoeba and antiviral properties of the extracts were studied using the dilution method in a 96-well polystyrene microtiter plate and micro tetrazolium (MTT) assays, respectively. In silico molecular docking screening, pharmacokinetics, and toxicity protocols of the isolated compounds were performed to offer the potential applications of the compounds in developing novel medications. An AutoDock Vina software in combination with the BIOVIA Discovery Studio Visualizer 2021, SwissADME, and ProTox-II prediction web tools were applied to generate the molecular docking, pharmacokinetics, and toxicity profiles, respectively. Notably, the chromatographic separation of the plant extracts afforded twenty four known compounds including, ten compounds namely; β-sitosterol (19), parthenocissin A (23), ε-viniferin (25), 3-hydroxy isoagatholactone (28), tricuspidatol A (29), myricetin (66), hexadec-1-ene (82), palmitic acid (83), β-sitosteryl palmitate (84), and diethyl phthalate (85) from Cyphostemma adenocaule, seven compounds namely; quercetin-3-O-rutinoside (37), stigmasterol (40), quercetin (42), diethyl phthalate (85), a mixture of β-sitosterol (19) and stigmasterol (40), β- sitosteryl-3β-glucopyranoside-6'-O-palmitate (86), and apigenin (87) from Delonix regia, seven compounds namely; lupeol (39), chrysophanol (53), betulinic acid (63), a mixture of β-sitosterol (19) and stigmasterol (40), glyceryl-1-hexacosanoate (88), and 4-(2'-hydroxymethyl-4'- hydroxyphenyl)-chrysophanol (89) from Senna siamea, and five compounds namely; stigmasterol (40), β-sitosteryl-3β-glucopyranoside-6'-O-palmitate (86), trimethyl trilinolein (90), stearic acid (91), and 13-hydroxyoctadeca-9, 11-dienoic acid (92) from Ziziphus spina-christi. The GC-MS analysis revealed perillyl alcohol (93, 13.08%) and nootkatone (106, 30.12% in leaves and 26.52% in roots) as the major components in the essential oils of Cyphostemma adenocaule and Ziziphus spina-christi, respectively. Heneicosane (102) was identified as the principal compound in the essential oils of Delonix regia (49.26%) and Senna siamea (53.17%). The antibacterial activity tests of the extracts and isolated compounds showed potential effects against the bacterial strains of the study. At the lowest concentrations (extracts; 6.25 mg/mL and compounds; 0.25 mg/mL), the highest inhibitory activities were observed by the Senna siamea extract (SSE, 12.00 xxii± 0.41 mm) and chrysophanol (53, 11.17 ± 0.24 mm), respectively, against E. coli compared to ciprofloxacin (23.33 ± 0.47 mm). The 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity assay showed auspicious IC50 values for parthenocissin A (23, 0.98 µg/mL), ε-viniferin (25, 0.32 µg/mL), tricuspidatol A (29, 0.67 µg/mL), and quercetin-3-O-rutinoside (37, 0.81 µg/mL) compared to ascorbic acid standard (0.08 µg/mL) showcasing their potent antioxidant effects. The micro tetrazolium (MTT) assay of the CH2Cl2: CH3OH (1:1) extract of Senna siamea (SI: 13.32) and methanol extract of Z. spina-christi (SI: 28.03) showed significant selectivity index (SI) values signifying their cytotoxicity against influenza types A and B viruses. The molecular docking computations showed the highest binding affinity for ε-viniferin (-9.9 kcal/mol) against topoisomerase IIα, and the drug-likeness predictions showed that only quercetin-3-O-rutinoside (37), β-sitosteryl palmitate (84), and β-sitosteryl-3β-glucopyranoside-6'-O-palmitate (86) failed to fulfill Lipinski’s rule, though the others do with zero/one violations. All the screened compounds showed no hepatotoxicity and cytotoxicity in accordance with the prediction results of ciprofloxacin. Thus, the findings of this study support the ethno medicinal uses of the plants and further works are needed to transform the traditional uses of the plants into modern and scientific usage.