Ethnopharmacological relevanceShigella infection is a public health problem responsible for approximately 700,000 deaths annually. The management of this disease is impaired by the emergence of multidrug-resistant Shigella species, highlighting the urgent need to search for alternative treatment options. In this regard, investigating medicinal plants traditionally used for the treatment of dysentery, diarrheal infections, and/or associated symptoms in endemic regions might provide an opportunity to identify phytochemicals that could be further used as a basis for the development of future anti-shigella drug candidates. Aim of the studyThis study was designed to investigate the anti-shigella and antioxidant-based ethnopharmacological potency of some Cameroonian medicinal plants with an emphasis on pharmacokinetic properties of the identified chemical pharmacophore. Materials and methodsBriefly, plant species were selected and collected based on their ethnopharmacological uses and information reported in the literature. Crude aqueous, ethanolic, methanolic, and hydroethanolic (30:70, v/v) extracts from these plants were prepared and then screened for their anti-Shigella activity against four Shigella strains and cytotoxicity against Vero and Raw cell lines using microdilution and resazurin-based methods, respectively. The antioxidant activities of potent extracts were evaluated using DPPH, ABTS, NO, and FRAP scavenging assays. The chemical profile of potent extracts was performed using the UHPLC-LIT-MS/MS and the pharmacokinetic properties, druglikeness, and likely molecular targets of the chemical scaffolds identified were predicted using SwissADME and SwissTargetPredictor. ResultsThirty-nine (39) plants belonging to 26 plant families were harvested. Out of the 228 extracts tested, 18 extracts originating from 6 plants (15.38 %) were active (MICs 250–1000 μg/mL) and nontoxic toward Vero (CC50 129.25–684.55 μg/mL) and Raw cell lines (CC50 336.20 to >1000 μg/mL). Six potent extracts from the two plants exhibited moderate to potent DPPH (SC50 8.870–54.410 μg/mL), ABTS (SC50 12.020–27.36 μg/mL), and NO (SC50 0.02–195.85 μg/mL) scavenging activities. Later, these extracts showed interesting ferric iron-reducing power (1.28–12.14 μg equivalent NH2OH/g of extract). The shortest onset of action time (4 and 6 h) observed following inhibition kinetics studies was observed with extracts BFSHE, PMSE, and PMSM. The UHPLC-LIT-MS/MS and some databases (Mass Spectral Library (NIST 14), Human Metabolome Database (HMD), MassBank, SuperNatural 3.0, The Food Database (FooDB), and Chemical Entities of Biological Interest (ChEBI)) allowed the annotation of 18 and 17 metabolites in the extracts from stem bark of P. macrophylla and B. ferruginea respectively. Pharmacokinetic prediction of these chemicals showed that compound 6 (4,6a-bis(Hydroxymethyl)-9a-methyl-3-oxo-1a,1b,3,5,6,6a,7a,9a-octahydrobis (oxireno)[2′,3':5,6; 2″,3'':9,10]cyclodeca[1,2-b]furan-5-yl methacrylate), compound 8 (Corynoxeine), and compounds 35 (Stachybotrydial acetate) demonstrated acceptable druglike and pharmacokinetic properties and might act through inhibition of kinase, transferase, protease, oxidoreductase, and family AG protein-linked receptors. ConclusionThe findings from this investigation demonstrated that Cameroonian medicinal plants are suitable reservoirs of anti-Shigella and antioxidant agents with good drug candidate properties.
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Open Access
Mar 6, 2024
Mohd Rahaizuddin Rani + 5
