Cholinesterase inhibitory activity and structure elucidation of a new phytol derivative and a new cinnamic acid ester from Pycnanthus angolensis

AbstractThe leaves of Pycnanthus angolensis (Welw.) Warb., Myristicaceae, are used as memory enhancer and anti-ageing in Nigerian ethnomedicine. This study aimed at evaluating the cholinesterase inhibitory property as well as isolates the bioactive compounds from the plant. The acetylcholinesterase and butyrylcholinesterase inhibitory potentials of extracts, fractions, and isolated compounds were evaluated by colorimetric and TLC bioautographic assay techniques. The extract inhibited both enzymes with activity increasing with purification, ethyl acetate fraction being most active fraction at 65.66±1.06% and 49.38±1.66% against acetylcholinesterase and butyrylcholinesterase, respectively while the supernatant had 77.44±1.18 inhibition against acetylcholinesterase. Two new bioactive compounds, (2E, 18E)-3,7,11,15,18-pentamethylhenicosa-2,18-dien-1-ol (named eluptol) and [12-(4-hydroxy-3-methyl-oxo-cyclopenta-1,3-dien-1yl)-11-methyl-dodecyl](E)-3-(3,4-dimethylphenyl)prop-2-enoate (named omifoate A) were isolated from the plant with IC50 of 22.26μg/ml (AChE), 34.61μg/ml (BuChE) and 6.51μg/ml (AChE), 9.07μg/ml (BuChE) respectively. The results showed that the plant has cholinesterase inhibitory activity which might be responsible for its memory enhancing action, thus justifying its inclusion in traditional memory enhancing preparation

Computational screening of phytochemicals from three medicinal plants as inhibitors of transmembrane protease serine 2 implicated in SARS-CoV-2 infection

Background: SARS-CoV-2 infection or COVID-19 is a major global public health issue that requires urgent attention in terms of drug development. Transmembrane Protease Serine 2 (TMPRSS2) is a good drug target against SARS-CoV-2 because of the role it plays during the viral entry into the cell. Virtual screening of phytochemicals as potential inhibitors of TMPRSS2 can lead to the discovery of drug candidates for the treatment of COVID-19. Purpose: The study was designed to screen 132 phytochemicals from three medicinal plants traditionally used as antivirals; Zingiber officinalis Roscoe (Zingiberaceae), Artemisia annua L. (Asteraceae), and Moringa oleifera Lam. (Moringaceae), as potential inhibitors of TMPRSS2 for the purpose of finding therapeutic options to treat COVID19. Methods: Homology model of TMPRSS2 was built using the ProMod3 3.1.1 program of the SWISS-MODEL. Binding affinities and interaction between compounds and TMPRSS2 model was examined using molecular docking and molecular dynamics simulation. The drug-likeness and ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties of potential inhibitors of TMPRSS2 were also assessed using admetSAR web tool. Results: Three compounds, namely, niazirin, quercetin, and moringyne from M. oleifera demonstrated better molecular interactions with binding affinities ranging from -7.1 to -8.0 kcal/mol compared to -7.0 kcal/mol obtained for camostat mesylate (a known TMPRSS2 inhibitor), which served as a control. All the three compounds exhibited good drug-like properties by not violating the Lipinski rule of 5. Niazirin and moringyne possessed good ADMET properties and were stable in their interactions with the TMPRSS2 based on the molecular dynamics simulation. However, the ADMET tool predicted the potential hepatotoxic and mutagenic effects of quercetin. Conclusion: This study demonstrated the potentials of niazirin, quercetin, and moringyne from M. oleifera, to inhibit the activities of human TMPRSS2, thus probably being good candidates for further development as new drugs for the treatment or management of COVID-19

Plausible causes of low incidence of COVID 19 in Tropical Africa: A review

No Abstract

Trypanocidal properties of Terminalia ivorensis A. Chev. (Combretaceae)

Human African Trypanosomiasis (sleeping sickness) cause considerable mortality and morbidity throughout the world with Trypansoma brucei, T. gambiense and T. brucei rhodesiense as the major causative agents. The Terminalia ivorensis gradient extracts were tested against T. brucei rhodesiense parasites and the E.D50 values of 11.11 and 12.32 μg/mL were obtained for the ethyl acetate and ethanolic gradient extracts respectively. The column fractions of the ethyl acetate fraction gave E.D50 value between 1.98 and 5.46 μg/mL for the very active fractions indicating prospect for the development of potential trypanocidal agent from the plant. Keywords: Terminalis ivorensis, Trypanosoma brucei rhodesiensis, trypanocidal African Journal of Traditional, Complementary and Alternative Medicines Vol. 3(2) 2006: 51-5

Studies on the effect of a nutritious vegetable, Telfairia occidentalis, on HbSS blood

Medicinal plants have been used traditionally in Africa, especially Nigeria, in the management of sickle cell disorder (SCD) whose treatment has been mainly palliative. The antisickling properties of ethanol extract of Telfairia occidentalis Hook, F. (TO) (Family Cucurbitaceae) leaf was tested in vitro at concentrations 1, 2, 4, 8 and 16 mg/mL using inhibitory and reversal models. Nitrogen gas was used to induce hypoxia for 1 h. The effect of TO on red cell density and cell membrane were also determined. The methanol sub fraction of TO extract was subjected to GC/MS to identify some of the active compounds. The TO gave antisickling activities of 78.84 ± 1.34% inhibition and 95.4 ± 0.81% reversal, which are significantly (p < 0.05) higher than that of Ciklavit®. The TO extract gave a change in density of 17.83 ± 0.77% and a dose dependent activity on RBC membrane. Methyl 9-cis 11- trans-octadecadienoate; 1, 4- benzenedicarboxylic acid; 9, 12-octadecadienoic acid (Linoleic acid); and hexadecanoic acid methyl ester (palmitic acid); were identified from TO ethanol leaf extract for the first time using GC/MS. This study authenticated the ethnomedicinal claims of the use of T. occidentalis in the management of sickle cell disorder. Keywords: Sickle cell disorder, Ethnomedicine, Membrane stability, Red cell densit

Chemotherapeutic Interaction Between Khaya Grandifoliola (Welw) Cdc Stem Bark Extract And Two Anti-Malarial Drugs In Mice

In malarial endemic countries especially in the tropics, conventional antimalarial drugs are used with herbal remedies either concurrently or successively. Khaya grandifoliola is one of such popular herbs used in the treatment of malaria. Various doses of ethanol extract of K. grandifoliola stem bark (50-400 mg/kg/day) were administered orally to Swiss albino mice infected with Plasmodium yoelii nigerense. A dose of 100 mg/kg/day of the extract was also combined with 2.5 mg/kg/day of chloroquine or 6.25 mg/kg/day of halofantrine in both early and established malaria infection test models. The results showed that in the early malaria infection test, K. grandifoliola in combination with chloroquine or halofantrine elicited enhanced antiplasmodial effect in the established infection, there was significantly greater parasite clearance following administration of the combination when compared to the effects of K. grandifoliola or the conventional drugs alone. The mean survival period of parasitized animals was also enhanced by the extract/halofantrine combination. Lower therapeutic doses of halofantrine may be required to potentiate parasite clearance when used in combination with K. grandifoliola. This may constitute great advantage to halofantrine which is associated with cardiotoxicity at high doses