Anti-Shigella and antioxidant-based screening of some Cameroonian medicinal plants, UHPLC-LIT-MS/MS fingerprints, and prediction of pharmacokinetic and drug-likeness properties of identified chemicals.

ETHNOPHARMACOLOGICAL RELEVANCE: Shigella 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 STUDY: This 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 METHODS: Briefly, 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. RESULTS: Thirty-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. CONCLUSION: The findings from this investigation demonstrated that Cameroonian medicinal plants are suitable reservoirs of anti-Shigella and antioxidant agents with good drug candidate properties.

In Vivo Antiplasmodial Activity of Terminalia mantaly Stem Bark Aqueous Extract in Mice Infected by Plasmodium berghei.

BACKGROUND: Terminalia mantaly is used in Cameroon traditional medicine to treat malaria and related symptoms. However, its antiplasmodial efficacy is still to be established. OBJECTIVES: The present study is aimed at evaluating the in vitro and in vivo antiplasmodial activity and the oral acute toxicity of the Terminalia mantaly extracts. MATERIALS AND METHODS: Extracts were prepared from leaves and stem bark of T. mantaly, by maceration in distilled water, methanol, ethanol, dichloromethane (DCM), and hexane. All extracts were initially screened in vitro against the chloroquine-resistant strain W2 of P. falciparum to confirm its in vitro activity, and the most potent one was assessed in malaria mouse model at three concentrations (100, 200, and 400 mg/kg/bw). Biochemical, hematological, and histological parameters were also determined. RESULTS: Overall, 7 extracts showed in vitro antiplasmodial activity with IC50 ranging from 0.809 µg/mL to 5.886 µg/mL. The aqueous extract from the stem bark of T. mantaly (Tmsbw) was the most potent (IC50 = 0.809 µg/mL) and was further assessed for acute toxicity and efficacy in Plasmodium berghei-infected mice. Tmsbw was safe in mice with a median lethal dose (LD50) higher than 2000 mg/kg of body weight. It also exerted a good antimalarial efficacy in vivo with ED50 of 69.50 mg/kg and had no significant effect on biochemical, hematological, and histological parameters. CONCLUSION: The results suggest that the stem bark extract of T. mantaly possesses antimalarial activity.