In-vitro Anti-cercarial activity of extracts and steroidal alkaloids from the stem bark of Holarrhena floribunda (G. Don) Dur. & Schinz

Context: Schistosomiasis continues to be the leading cause of morbidity and mortality among the neglected tropical diseases. Apart from the high cost of chemotherapy, concerns over drug resistance and tolerance have been raised in the past decade. Objective: The aim of the study was to evaluate the anticercarial activity of extracts and compounds from the stem bark of Holarrhena floribunda on cercaria of Schistosoma haematobium. Methods: Hydroethanolic and alkaloidal extracts from the stem bark of H. floribunda were tested on cercaria at concentrations between 500.00 and 15.625 μg/mL for 180 minutes and assessing the percentage viability at time intervals of 0, 15, 30, 60, 120 and 180 minutes. Praziquantel, used as reference drug, and the isolated compounds were tested at similar concentrations. The cercaria mortalities and IC50 of extracts and compounds were estimated after 30 minutes of incubation. Results: The 70 %v/v ethanol extract showed the highest activity (IC50=20.09±1.11 μg/mL) with praziquantel giving IC50 of 695.50±1.12. The alkaloids holonamine, holadienine and conessine, isolated from the stem bark, showed considerable cercaricidal activity with the latter recording an IC50 of 33.28±1.04. Conclusion: The study gives first-hand knowledge of the anti-cercarial activity of H. floribunda and its steroidal alkaloids. This gives credence to the traditional uses of the plant as an anti-parasitic agent

Applications of molecular docking in natural products-based drug discovery

Natural products have a long history of use in the treatment of various diseases particularly in developing countries. The use of compounds of natural origin as lead compounds for the development of conventional drugs is widely recognised. Natural product-based drug discovery efforts in developing countries mostly involve the use of crude extracts in in-vitro and/or in-vivo assays. There are limited efforts at isolating active principles for structure elucidation studies. Studies that isolate pure secondary metabolites and characterize their structures have limited bioactivity evaluations. In conventional drug discovery programs, molecular docking serves as a useful tool for predicting interactions of small molecules with drug target(s) to guide synthesis decisions. Medicinal chemists use this tool to predict and synthesize compounds likely to have pharmacological activity and thus save time and cost for drug discovery. Efforts have been made to incorporate molecular docking techniques into natural products-based drug discovery. The objective of this review is to discuss molecular docking in natural product drug discovery programs with the goal of providing easy-to-understand information to help beginners interested in incorporating molecular docking in their research. This is expected to enhance natural product screening programs by predicting which phytochemicals are likely to show success, especially in new disease situations such as COVID-19. Applications in the repositioning of plants for emerging conditions are also discussed

Indigenous Medicinal Plants as Biofilm Inhibitors for the Mitigation of Antimicrobial Resistance

The majority of indigenes in the rural areas of Ghana use herbal medicines for their primary health care. In this study, an ethnobotanical survey was undertaken to document medicinal plants used by traditional healers in the Ejisu-Juaben district in the Ashanti region of Ghana to treat infections and to further investigate the antibiofilm formation properties of selected plants in resisting pathogenic bacteria. Seventy medicinal plants used by traditional practitioners for the treatment of skin infections and wounds were documented from the ethnobotanical survey. Forty out of the seventy plants were collected and their methanol extracts evaluated for antimicrobial activity by the agar diffusion assay. Extracts that showed antibacterial activity were tested for biofilm inhibitory activity, and the most active plant was subsequently purified to obtain the active constituents. Biofilm formation was significantly mitigated by petroleum ether, ethyl acetate, and methanol extracts of Holarrhena floribunda stem bark. Bioassay-guided fractionation of an alkaloidal extract prepared from the methanol fraction led to the isolation of three steroidal alkaloids, namely, holonamine, holadienine, and conessine. The isolated compounds demonstrated varying degrees of biofilm formation inhibitory properties. The current study reveals that screening of indigenous medicinal plants could unravel potential leads to salvage the declining efficacy of conventional antibiotics. Holarrhena floribunda stem bark extract has strong biofilm formation inhibition properties, which could be attributed to the presence of steroidal alkaloids

Effect of pre-existing Schistosoma haematobium infection on Plasmodium berghei multiplications in imprinting control region mice

Objective: To investigate the effect of pre-existing Schistosoma haematobium (S. haematobium) infection on malaria disease severity. Methods: The study involved the use of twenty-five imprinting control region mice, fifteen of which were initially infected with S. haematobium. Five of the remaining ten schisto-uninfected mice together with five schisto-infected mice were infected with Plasmodium berghei (P. berghei) after four weeks (acute stage) of schistosoma infection. The remaining five schisto-uninfected mice together with five schisto-infected mice were also infected with P. berghei after seven weeks (chronic stage) of schistosoma infection. The last five schisto-infected mice were used as control group. They were then monitored for changes in P. berghei parasitaemia on Days 3, 5, 7, 9 and 11 post-infection. Records on their survivability were also taken. Results: The co-infected mice had significantly higher malaria parasitaemia, compared with the mono-infected mice during acute S. haematobium infection. In contrast, the co-infected mice had significantly lower malaria parasitaemia during chronic S. haematobium infection and a higher survival rate. Conclusions: Co-infection of mice with P. berghei during acute S. haematobium infection resulted in rapid P. berghei development and increased malaria parasitaemia. However, the co-infection resulted in slower P. berghei development and decreased malaria parasitaemia with enhanced survivability of the mice during chronic S. haematobium infection. Therefore, pre-existing chronic S. haematobium infection may provide some protection to the host by reducing parasitaemia

Ethnobotanical Survey and Cercaricidal Activity Screening of Medicinal Plants Used for Schistosomiasis Treatment in Atwima-Nwabiagya District, Ashanti Region, Ghana

This study focused on documenting and evaluating the cercaricidal activity of medicinal plants used for schistosomiasis treatment in an endemic area in Ghana. Through semistructured questionnaires, personal interviews with herbalists in communities surrounding the Barekese dam in the Atwima-Nwabiagya district, where the disease is endemic, were carried out. Thirty medicinal plants distributed in 19 families were reported to be used for schistosomiasis treatment in the survey. Information on the plants, including scientific names, common names, families, and the used plant part were recorded. The families Apocynaceae and Euphorbiaceae recorded the highest number of plants (14% each), followed by Asteraceae (10%), Loranthaceae (7%), and Rubiaceae (7%). In vitro cercaricidal activity of methanol extracts of nine out of the thirty plants was performed by exposing human Schistosoma mansoni cercariae obtained from Biomphalaria pfeifferi to various concentrations of extracts over a duration of 240 minutes. All the plants tested demonstrated time- and concentration-dependent cercaricidal activity. With lethality being set at  Balanites aegyptiaca (LC50 = 7.1) > Xylia evansii (LC50 = 11.14) > Jathropha multifida (LC50 = 12.9) > Justicia flava (LC50 = 22.9) > Anopyxis klaineana (LC50 = 182.81) > Ximenia americana (LC50 = 194.98) > Loranthus lecardii (LC50 = 223.87) > Bridelia tenufolia (LC50 = 309.03) > Zanthoxylium zanthoxyloides (LC50 = 851.94). Phytochemicals, including alkaloids, tannins, triterpenes, saponins, phytosterols, and flavonoids were identified in the plants. The result of this study gives scientific credence to the traditional use of these plants in the treatment of schistosomiasis and proves that the rich botanical knowledge of medicinal plants provides an incredible starting point for the discovery of new anti-schistosomal drugs for the local population

Allanblackia floribunda Seed Extract Attenuates the Ethanol-Induced Gastric Ulcer in Rats via the Inhibition of TNF-α and INF-γ Levels and Modulation in the Expression of Ki67 Protein

Allanblackia floribunda has been used to treat an upset stomach in African traditional medicine, but its efficacy and safety have not been scientifically studied. The present research is aimed at assessing the antiulcer property of the seed extract of the plant to validate its traditional claim. Rats were pretreated with three doses of aqueous extract of A. floribunda (AFE) at 30, 100, and 300 mg/kg or omeprazole 10 mg/kg for 1 hr before the acute gastric ulcer was induced by oral administration of 5 mL/kg of 98% ethanol. The animals were sacrificed under anesthesia, and the stomach and blood were collected. The gross histology of the stomach, percentage protection conferred by the treatment, gastric pH, and serum TNF-α and INF-γ were assessed as well as the expression of Ki67 antigens. The antioxidant properties as well as the acute toxicity profile of the plant extract were also assessed. The results show that A. floribunda conferred significant protection on the rats against gastric ulceration with % protection of 46.15, 57.69, and 65.38 for AFE 30, 100, and 300 mg/kg, respectively, as well as 69.23% for omeprazole 10 mg/kg. The plant extract caused marked reductions in gastric pH, TNF-α, and INF-γ with statistical significance (p<0.001) for AFE 300 mg/kg and omeprazole 10 mg/kg. Also, the plant showed good antioxidant activity comparable to gallic acid. Furthermore, the plant extract modulated the expression of Ki67 antigens. All animals survived the 14-day delayed toxicity test with no significant differences in physical, hematological, and biochemical parameters between rats orally administered with supratherapeutic doses of AFE (5000 mg/kg) or normal saline. The study established that the gastroprotective effect of the seed extract of A. floribunda is attributable to its antisecretory, antioxidant, and anti-inflammatory properties. Additionally, the plant was found to promote ulcer healing via the modulation of the expression Ki67 and was safe at supratherapeutic doses