Antidiarrheal activity of Bridelia ferruginea bark methanolic extract involves modulation ATPases in mice and inhibition of muscarinic acetylcholine receptor (M3) and prostaglandin E2 receptor 3 (EP3) in silico.

OBJECTIVES: Diarrhea, an abnormal state in which the individual has about three or more daily bowel movements, is now considered one of the most challenging global public health problems. Using plant products, such as Bridelia ferruginea is an alternative treatment option. The objective of this study was to investigate the antidiarrheal activity of B. ferruginea bark methanolic extract (BfME) and the mechanisms involved. METHODS: BfME antidiarrheal activity was evaluated in mice model of castor oil-induced diarrhea and enteropooling. To evaluate motility, gastrointestinal transit time was carried out using phenol red meal, while intestinal activities of selected ATPases were also evaluated. Furthermore, the active components in BfME were detected by GC-MS analysis, while molecular docking of the most abundant compounds with muscarinic acetylcholine receptor (M3) and prostaglandin E2 receptor 3 (EP3) were conducted. RESULTS: BfME at 400 and 800 mg/kg showed antidiarrheal activity by delaying onset of diarrhea, reduced gastrointestinal transit and increased intestinal activities of Na+ K+-ATPase, Ca2+ Mg2+-ATPase and Mg2+-ATPase. Molecular docking revealed that γ-sitosterol, α-amyrin, and stigmasterol have outstanding binding affinity for M3 and EP3. CONCLUSIONS: In view of these results, the observed antidiarrheal activity possibly occurs via the activation of ATPases activities and inhibition of M3 and EP3.

Computer-Aided Identification of Cholinergic and Monoaminergic Inhibitory Flavonoids from Hibiscus sabdariffa L.

BACKGROUND: The reduced levels of acetylcholine and dopamine lead to Alzheimer's disease (AD) and Parkinson's disease PD, respectively, due to the action of cholinesterase and monoamine oxidase B. METHODS: Therapeutic options for AD and PD involve respective cholinergic and monoaminergic inhibitors, and considering the adverse outcomes of cholinergic- and monoaminergic- inhibitory therapeutics, phytoconstituents may be promising alternatives. Reports have shown that different extracts of the calyx of Hibiscus sabdariffa exhibit anticholinesterase and monoamine oxidase B inhibitory properties with the potential to delay and prevent the development of AD and PD. However, there is limited knowledge on the multitarget cholinergic and monoaminergic inhibitory activities of individual compounds in this plant. Computational methods were used to identify the specific compounds responsible for the observed cholinergic and monoaminergic inhibitory activities of the H. sabdariffa calyx extracts. RESULTS: Results confirm that three flavonoids: delphinidin-3-sambubioside, kaempferol-3-O-rutinoside and quercetin-3-rutinoside showed strong binding affinity with acetylcholinesterase, butyrylcholinesterase and monoamine oxidase B while the observed stability of the ligands-enzymes complexes over the MD simulation time suggests their cholinergic and monoaminergic inhibitory properties. CONCLUSION: The three flavonoids may be responsible for the reported anticholinergic and monoaminergic inhibitory potentials of H. sabdariffa extracts and could be enlisted as multi-target inhibitory agents for cholinesterases and monoamine oxidase B.

A Computational Approach to Investigate the HDAC6 and HDAC10 Binding Propensity of Psidium guajava-derived Compounds as Potential Anticancer Agents.

BACKGROUND: Different parts of Psidium guajava are consumed as food and used for medicinal purposes around the world. Although studies have reported their antiproliferative effects via different biochemical mechanisms, their modulatory effects on epigenetic modification of DNA molecules via histone deacetylases (HDACs) are largely unknown. OBJECTIVE: This study was carried out to investigate the histone deacetylase 6 (HDAC6) and histone deacetylase 10 (HDAC10) binding propensity of guava-derived compounds, using in silico methods, in other to identify compounds with HDAC inhibitory potentials. METHODS: Fifty-nine guava-derived compounds and apicidin, a standard HDAC inhibitor, were docked with HDAC6 and HDAC10 using AutodockVina after modeling (SWISS-MODEL server) and validating (ERRAT and VERIFY-3D) the structure of HDAC10. Molecular interactions between the ligands and the HDACs were viewed with Discovery Studio Visualizer. Prediction of binding sites, surface structural pockets, active sites, area, shape and volume of every pocket and internal cavities of proteins was done using Computed Atlas of Surface Topography of proteins (CASTp) server, while absorption, distribution, metabolism, and excretion (ADME) study of notable compounds was done using Swiss online ADME web tool. RESULTS: 2α-hydroxyursolic acid, asiatic acid, betulinic acid, crategolic acid, guajadial A and B, guavacoumaric acid, guavanoic acid, ilelatifol D, isoneriucoumaric acid, jacoumaric acid, oleanolic acid, psiguadial A, B, and C demonstrated maximum interaction with the selected HDACs. ADME studies revealed that although isoneriucoumaric and jacoumaric acid ranked very high as HDAC inhibitors, they both violated the Lipinski's rule of 5. CONCLUSION: This study identified 13 drugable guava-derived compounds that can be enlisted for further studies as potential HDAC6 and HDAC10 inhibitors.

Nigerian antimalarial plants and their anticancer potential: A review.

Cancer is a leading cause of death globally, while malaria is the leading cause of death from parasitic diseases in Nigeria. Historically, plant remedies have been used to manage both cancer and malaria. Interestingly, the possibility of treating cancer with antimalarial remedies has long been reported, even though the two diseases appear to have little in common. However, a body of research has indicated the potential anticancer activity of both synthetic and nature-derived antimalarials. In Nigeria, over 100 plants are used for the management of malaria, but little is known for their potential role in combatting cancer. Therefore, this review is to highlight the documented anticancer activities of plants used to treat malaria in Nigeria, with the goal of supporting anticancer drug discovery. Scientific databases were used to search for antimalarial plants using selected keywords. Of over 100 plants used to treat malaria in Nigeria, 56 have documented anticancer properties, containing alkaloids, flavonoids, tannins, terpenes, terpenoids, quinones, anthraquinones, saponins, steroids, sterols, organosulfur compounds and other polyphenols as the major bioactive components. The major mechanisms of anticancer activity include induction of apoptosis and autophagy, arrest of cell growth, generation of reactive oxygen species and inhibition of angiogenesis. However, mechanistic and clinical investigations of the anticancer properties of most of these plants are still lacking. Notwithstanding, the huge anticancer potential uncovered by the in vitro or in vivo studies and a few clinical studies, Nigerian antimalarial plants may provide a valuable resource, ready to be harnessed for anticancer drug development.

Ameliorative effect of morin on dutasteride-tamsulosin-induced testicular oxidative stress in rat.

OBJECTIVES: Dutasteride-Tamsulosin (DUT-TAM), a drug of choice for the treatment of prostate enlargement (Benign Prostatic Hyperplasia, BPH) has been implicated in testicular toxicity. This study investigated the protective effect of morin, a plant-derived flavonoid on DUT-TAM-induced testicular toxicity in Wistar rat. METHODS: Twenty-four male Wistar rats (110-140 g) were randomly divided into four treatment groups (n=6). Group A animals served as the control and were administered olive oil, Group B animals were administered 5.4 mg/kg b.w. of dutasteride + 3.4 mg/kg b.w of tamsulosin., Group C animals were administered 100 mg/kg b.w. of morin, while Group D animals were administered DUT-TAM (5.4 mg/kg b.w. of dutasteride + 3.4 mg/kg b.w. of tamsulosin) and morin (100 mg/kg b.w.). The administration lasted for two weeks. RESULTS: DUT-TAM-induced abnormal sperm morphology (31.8%), significantly reduced (p<0.05) sperm count, sperm motility, live-dead sperm ratio, testicular superoxide dismutase (SOD), catalase, glutathione-S-transferase (GST) and acid phosphatase (ACP) activities, as well as the levels of ascorbic acid and reduced glutathione (GSH) which were ameliorated by co-treatment with morin. Also, DUT-TAM-induced increase in testicular malondialdehyde level and the activities of alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT) and lactate dehydrogenase (LDH) were significantly reversed (p<0.05) by co-treatment with morin. CONCLUSIONS: These results indicated the protective ability of morin against Dutasteride-Tamsulosin-induced testicular toxicity and oxidative stress.

Antimalarial plants with potential male-factor antifertility properties.

Malaria, caused mainly by Plasmodium falciparum among other Plasmodium species, is one of the main causes of death from parasitic diseases. Malaria is still a health problem mainly because of the cost of effective antimalarial drugs and the growing parasite resistance to conventional antimalarial drugs, making a great proportion of the people in malaria endemic countries dependent on plants for its treatment. Corollary, a large number of the rural populations consume antimalarial herbal preparations in large or excessive quantities despite the fact that it has been reported that some of them could cause male-factor infertility, a growing global health concern. Few studies have compiled information on the scientifically validated male-factor antifertility effects of these antimalarial plant remedies. The aim of this review therefore is to compile information on commonly used antimalarial plant remedies that have been experimentally validated as having male-factor antifertility effects. Thus, antimalarial plant remedies with experimentally confirmed male-factor antifertility potentials and compounds isolated from them are identified and discussed. The male-factor antifertility effects of these plants include reduction of sperm quality, regulation of reproductive hormone levels and induction of lipid peroxidation. Indiscriminate use of such antimalarial plants is discouraged when male contraception is not desired.

Phytosterols and triterpenes from Morinda lucida Benth. exhibit binding tendency against class I HDAC and HDAC7 isoforms.

The important role of histone deacetylases (HDACs) in the development of cancer has been demonstrated by various studies. Thus targeting HDACs with inhibitors is a major focus in anticancer drug research. Although few synthetic HDAC inhibitors (HDIs) have been approved for cancer treatment, they have significant undesirable side effects. Therefore emphases have been placed on natural HDIs as substitutes for the synthetic ones. In a bid to identify more HDIs, this study evaluated the binding tendency of compounds derived from Morinda lucida Benth. towards selected HDACs for the discovery of potent HDIs as potential candidates for anticancer therapeutics, based on the report of anticancer potentials of Morinda lucida-derived extracts and compounds. Givinostat and 49 Morinda-lucida derived compounds were docked against selected HDAC isoforms using AutodockVina, while binding interactions were viewed with Discovery Studio Visualizer, BIOVIA, 2016. Druglikeness and Absorption-Distribution-Metabolism-Excretion (ADME) parameters of the top 7 compounds were evaluated using the Swiss online ADME web tool. The results revealed that out of the 49 compounds, 3 phytosterols (campesterol, cycloartenol, and stigmasterol) and 2 triterpenes (oleanolic acid and ursolic acid) exhibited high HDAC inhibitory activity compared to givinostat. These 5 compounds also fulfill oral drugability of Lipinski rule of five. Morinda lucida-derived phytosterols and triterpenes show high binding tendency towards the selected HDACs and exhibited good drugability characteristics and are therefore good candidates for further studies in the search for therapies against abnormalities linked with over-activity of HDACs.