Abstract
The resurgence of Antimicrobial Resistance (AMR) is a worldwide challenge to people’s well-being. This occurs when drugs become inefficient due to some mutations developed by the bacteria to avoid death. In 2019, around 5 million deaths were reported, which are associated with AMR fatality. Africa bears the highest incidence, with 27.3 deaths registered out of 100,000 inhabitants, just in Western Sub-Saharan Africa. Six bacteria strains were responsible for most of the resistance observed; these include (in order of priority) Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa. They were responsible for 3.57 million deaths in 2019. If nothing is done, 10 million people are estimated to succumb to AMR yearly by 2050. A clear link was established between prostate cancer and some of the bacteria from the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) group, being the second most prevalent cancer among men after lung cancer. On the other hand. To curb the rising lethality orchestrated by bacteria and prostate cancer, Hypodaphnis zenkeri Engl. Stapf. (Lauraceae). and Staudtia kamerunensis Warb. (Myristicaceae) were both selected in this study for their use in traditional medicine in that region and because they are used as spices for traditional recipes. Their traditional uses suggested that these plants can be promising in isolating antibacterial and antineoplastic agents. The plant materials were extracted using methanol and a mixture of dichloromethane: methanol (1:1, v/v) respectively. They were screened for their antibacterial potency against 4 of the leading resistant pathogens: Staphylococcus aureus (SA), Escherichia coli (EC), Klebsiella pneumoniae (KP), Pseudomonas aeruginosa (PA), along with other Gram-positive and Gram-negative bacterial strains including Bacillus subtilis (BS), Staphylococcus epidermidis (SE), Enterococcus faecalis (EF), Mycobacterium smegmatis (MS), Enterobacter cloacae (ECL), Klebsiella oxytoca (KO), Proteus vulgaris (PV) and Proteus mirabilis (PM) utilising microdilution methods.
Six compounds were isolated from the stem bark and sap of S. kamerunensis; these include biochanin A [4.1], formononetin [4.2], odorantine [4.3], (-) epicatechin [4.4], (2α,3β) oleanan-12-ene-2,3-diol [4.5], (2α,3β) dihydroxylup-20-ene [4.6], and staudtienic acid [7.1]. Compounds [4.1] – [4.6] were isolated from the species for the first time, though present in the family. Six compounds were isolated from the leaves: eicosane [5.1], nonacos-1-ene [5.2], palmitic acid [5.3], and stigmasterol glucoside [5.4] and butane-1,2,3,4-tetraol [5.5] and asperphenamate [8.1]. Two compounds were isolated from the fruits: stigmasterol [5.6] and palmitic acid [5.3]. Except for stigmasterol [5.6], these compounds were reported for the first time from the genus. Asperphenamate [8.1]. The GC/MS analysis of the leaves and seeds of
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H. zenkeri revealed the presence of 50 phytoconstituents in each extract. Fatty esters were prevalent in the leaf extract at approximately 36.1%, whereas the seed extract was rich in hydrocarbons (37.8%). The chemical profiling of the stem bark of S. kamerunensis through GC/MS revealed the presence of 20 compounds with fatty esters representing more than 50% of the overall composition.
The activity of the compounds was assessed against the four resistant strains identified and the remaining eight. The compounds displayed significant activity with the lowest MIC = 15.63 μg/mL- against the studied panel of bacteria. Synergistic activity was also observed between compounds [4.5] and [4.6], where the activity of 4.5 was doubled against E. coli and K. pneumoniae and increased 16 times against P. aerogenes. Compound [4.5] and the mixture of [4.5] and [4.6] were tested for their ability to inhibit the growth of DU145, PC3, and LNCaP. Compound [4.5] showed a significant (p < 0.001) and concentration-dependent inhibition of DU145, PC3 and LNCaP cell growth, with optimal effect at 20 μg/mL, but when mixed with [4.6], activity was lost. These results suggest that this traditional spice possesses potential anticancer and antibacterial ingredients.
The leaf extract of H. zenkeri showed better and broader activity on the studied cells than the other extract, with a CC50 of 180 μg/mL in DU145, 184 μg/mL in PC3, and 198 μg/mL in LNCaP cells and was the object of a bio-guided fractionation to isolate the active principle. The compounds isolated displayed weak cytotoxic effects against the considered prostate cancer cell lines.