The plant Zanthoxylum zanthoxyloides (Lam.) Zepern. & Timler is one of the most important medicinal species of the genus Zanthoxylum on the African continent. It is used in the treatment and management of parasitic diseases in sub-Saharan Africa. These properties have inspired scientists to investigate species within the genus for bioactive compounds. However, a study, which details a spectroscopic, spectrometric and bioactivity guided extraction and isolation of antiparasitic compounds from the genus Zanthoxylum is currently non-existent. Tortozanthoxylamide (1), which is a derivative of the known compound armatamide was isolated from Z. zanthoxyloides and the full structure determined using UV, IR, 1D/2D-NMR and high-resolution liquid chromatography tandem mass spectrometry (HRESI-LC-MS) data. When tested against Trypanosoma brucei subsp. brucei, the parasite responsible for animal African trypanosomiasis in sub-Saharan Africa, 1 (IC50 7.78 µM) was just four times less active than the commercially available drug diminazene aceturate (IC50 1.88 µM). Diminazene aceturate is a potent drug for the treatment of animal African trypanosomiasis. Tortozanthoxylamide (1) exhibits a significant antitrypanosomal activity through remarkable alteration of the cell cycle in T. brucei subsp. brucei, but it is selectively non-toxic to mouse macrophages RAW 264.7 cell lines. This suggests that 1 may be considered as a scaffold for the further development of natural antitrypanosomal compounds.

African trypanosomiasis is a disease caused by the parasitic protozoa of the Trypanosoma genus. Despite several efforts at chemotherapeutic interventions, the disease poses serious health and economic concerns to humans and livestock of many sub-Saharan African countries. Zanthoxylum zanthoxyloides (Lam.) Zepern. & Timler (Z. zanthoxyloides LZT) is a plant species of important phytochemical and pharmacological relevance in the subtropical zones of the African continent. However, the mechanisms of its antitrypanosomal effects in African trypanosomes remain to be elucidated. The aim of the study was to determine the in vitro effects and mechanisms of action of Z. zanthoxyloides LZT (root) fractions against Trypanosoma brucei. T. brucei (GUTat 3.1 strain), L. donovani (D10 strain), P. falciparum (3D 7 strain), Jurkat cells, and Chang liver cells were cultivated in vitro to the log phase in their respective media at 37°C. Crude extracts and fractions were prepared from air-dried pulverized plant material of Z. zanthoxyloides LZT (root) using the modified Kupchan method of solvent partitioning. Half-maximal inhibitory concentrations (IC50) were determined through the alamar blue cell viability assay. Effects of fractions on cell death and cell cycle of T. brucei were determined using flow cytometry. Fluorescence microscopy was used to investigate the effects of fractions on the morphology and distribution of T. brucei. Antitrypanosomal compounds of fractions were characterized using high-performance liquid chromatography (HPLC) and attenuated total reflectance infrared (ATR-IR) spectroscopy. Methanol, butanol, and dichloromethane fractions were selectively active against T. brucei with respective IC50 values of 3.89, 4.02, and 5.70 μg/ml. Moreover, methanol, butanol, and dichloromethane fractions significantly induced apoptosis-like cell death with remarkable alteration in the cell cycle of T. brucei. Furthermore, dichloromethane and methanol fractions altered the morphology, induced aggregation, and altered the ratio of nuclei to kinetoplasts in the parasite. The HPLC chromatograms and ATR-IR spectra of the active fractions suggested the presence of aromatic hydrocarbons with hydroxyl, carbonyl, amine, or amide functional groups. The results suggest that Z. zanthoxyloides LZT have potential chemotherapeutic effects on African trypanosomes with implications for novel therapeutic interventions in African trypanosomiasis.

In the absence of vaccines, there is a need for alternative sources of effective chemotherapy for African trypanosomiasis (AT). The increasing rate of resistance and toxicity of commercially available antitrypanosomal drugs also necessitates an investigation into the mode of action of new antitrypanosomals for AT. In this study, furoquinoline 4, 7, 8-trimethoxyfuro (2, 3-b) quinoline (compound 1) and oxylipin 9-oxo-10, 12-octadecadienoic acid (compound 2) were isolated from the plant species Zanthoxylum zanthoxyloides (Lam) Zepern and Timler (root), and their in vitro efficacy and mechanisms of action investigated in Trypanosoma brucei (T. brucei), the species responsible for AT. Both compounds resulted in a selectively significant growth inhibition of T. brucei (compound 1, half-maximal effective concentration EC50 = 1.7 μM, selectivity indices SI = 74.9; compound 2, EC50 = 1.2 μM, SI = 107.3). With regards to effect on the cell cycle phases of T. brucei, only compound 1 significantly arrested the second growth-mitotic (G2-M) phase progression even though G2-M and DNA replication (S) phase arrest resulted in the overall reduction of T. brucei cells in G0-G1 for both compounds. Moreover, both compounds resulted in the aggregation and distortion of the elongated slender morphology of T. brucei. Analysis of antioxidant potential revealed that at their minimum and maximum concentrations, the compounds exhibited significant oxidative activities in T. brucei (compound 1, 22.7 μM Trolox equivalent (TE), 221.2 μM TE; compound 2, 15.0 μM TE, 297.7 μM TE). Analysis of growth kinetics also showed that compound 1 exhibited a relatively consistent growth inhibition of T. brucei at different concentrations as compared to compound 2. The results suggest that compounds 1 and 2 are promising antitrypanosomals with the potential for further development into novel AT chemotherapy.

The Ghanaian Paenibacillus sp. DE2SH (GenBank Accession Number: MH091697) is a prolific producer of potent antiparasitic alkaloids. Further detailed study of the culture broth of this strain produced the compound Paenidigyamycin G (1), which is a derivative of the known antiparasitic compound Paenidigyamycin A (2). Compound (1) was isolated on HPLC at tR ≈ 37.5 min and its structure determined by IR, UV, MS, 1D, and 2D-NMR data. Compound 1 produced weak to moderate antileishmanial and antitrypanosomal activity when tested against Leishmania donovani (Laveran and Mesnil) Ross (D10) and Trypanosoma brucei subsp. brucei strain GUTat 3.1 with IC50 = 115.41 and 28.75 μM, respectively. This result is interesting since the parent compound 2 is known to possess consistent and potent antiparasitic activity. However, 1 displayed a promising selectivity profile towards T. brucei subsp. brucei due to its relatively low toxicity against normal mouse macrophages RAW 264.7 cells (SI = 8.70). Given that compound 1 is also the main metabolite found in the hexane fraction of all extracts produced by Paenibacillus sp. DE2SH when it is co-cultured with other bacteria strains, it must possess some unique biological functions which should make it an excellent candidate for further biological activity screening in other bioassays.

Digyaindoleacid A (1) is one of the novel alkaloids produced by the Ghanaian Paenibacillus sp. DE2SH (GenBank Accession Number: MH091697) isolated from the mangrove rhizosphere soils of the Pterocarpus santalinoides tree growing in the wetlands of the Digya National Park, Brong Ahafo Region, Ghana. This compound was isolated on HPLC at tR ≈ 60 min and its structure determined by MS, 1D, and 2D-NMR data. When tested against Trypanosoma brucei subsp. brucei strain GUTat 3.1, 1 produced a half-maximal inhibitory concentration (IC50) 5.21 μM compared to the standard diminazene aceturate (IC50 = 1.86 μM). In the presence of normal mouse macrophages RAW 264.7, 1 displayed a higher selectivity towards T. brucei subsp. brucei (selectivity indices (SI) = 30.2) with low toxicity. This result is interesting given that the drug diminazene aceturate is considerably toxic and 1 is a natural product isolate. The structure of 1 incorporates the backbone of the amino acid tryptophan which is crucial in the metabolism of Trypanosoma brucei subsp. brucei strain GUTat 3.1. It is possible that 1, could interfere with the normal uptake and metabolism of tryptophan in the parasite. However, 1 (IC50 = 135.41 μM) produced weak antileishmanial activity when tested against Leishmania donovani (Laveran and Mesnil) Ross (D10).

The search for novel antitrypanosomals and the investigation into their mode of action remain crucial due to the toxicity and resistance of commercially available antitrypanosomal drugs. In this study, two novel antitrypanosomals, tortodofuordioxamide (compound 2) and tortodofuorpyramide (compound 3), were chemically derived from the natural N-alkylamide tortozanthoxylamide (compound 1) through structural modification. The chemical structures of these compounds were confirmed through spectrometric and spectroscopic analysis, and their in vitro efficacy and possible mechanisms of action were, subsequently, investigated in Trypanosoma brucei (T. brucei), one of the causative species of African trypanosomiasis (AT). The novel compounds 2 and 3 displayed significant antitrypanosomal potencies in terms of half-maximal effective concentrations (EC50) and selectivity indices (SI) (compound 1, EC50 = 7.3 μM, SI = 29.5; compound 2, EC50 = 3.2 μM, SI = 91.3; compound 3, EC50 = 4.5 μM, SI = 69.9). Microscopic analysis indicated that at the EC50 values, the compounds resulted in the coiling and clumping of parasite subpopulations without significantly affecting the normal ratio of nuclei to kinetoplasts. In contrast to the animal antitrypanosomal drug diminazene, compounds 1, 2 and 3 exhibited antioxidant absorbance properties comparable to the standard antioxidant Trolox (Trolox, 0.11 A; diminazene, 0.50 A; compound 1, 0.10 A; compound 2, 0.09 A; compound 3, 0.11 A). The analysis of growth kinetics suggested that the compounds exhibited a relatively gradual but consistent growth inhibition of T. brucei at different concentrations. The results suggest that further pharmacological optimization of compounds 2 and 3 may facilitate their development into novel AT chemotherapy.

Insects are a significant source of food for millions of people worldwide. Since ancient times, insects in medicine have been contributing to the treatment of diseases in humans and animals. Compared to conventional animal farming, the production of insects for food and feed generates significantly less greenhouse gas emissions and uses considerably less land. Edible insects provide many ecosystem services, including pollination, environmental health monitoring, and the decomposition of organic waste materials. Some wild edible insects are pests of cash crops. Thus, harvesting and consuming edible insect pests as food and utilizing them for therapeutic purposes could be a significant progress in the biological control of insect pests. Our review discusses the contribution of edible insects to food and nutritional security. It highlights therapeutic uses of insects and recommends ways to ensure a sustainable insect diet. We stress that the design and implementation of guidelines for producing, harvesting, processing, and consuming edible insects must be prioritized to ensure safe and sustainable use.

Malaria and trypanosomiasis are protozoan diseases which pose a devastating challenge to human health and productivity especially, in Africa where their respective vectors (female Anopheles mosquito and tsetse fly) abound. Various medicinal plants are used to treat these parasitic diseases. However, the scientific basis of their use and toxicological profiles have not been assessed. We have, therefore, evaluated the antiplasmodial, antitrypanosomal, and cytotoxic activities of four African medicinal plant extracts namely, Anthonotha macrophylla leaf (AML), Annickia polycarpa leaf (APLE), Tieghemella heckelii stem bark (THBE), and Antrocaryon micraster stem bark (AMSBE) extracts in vitro against P. falciparum (W2mef laboratory strain), T. brucei (GUTat 3.1 strain), and mammalian RAW 264.7 macrophage cell line, respectively. The most active antiplasmodial extract was AML (IC50 = 5.0 ± 0.08 μg/mL with SI of 21.9). THBE also, produced the most effective antitrypanosomal activity (IC50 = 11.0 ± 0.09 μg/mL and SI of 10.2) among the extracts. In addition, none of the extracts produced toxic effect in the RAW 264.7 macrophage cell line except APLE which was moderately cytotoxic and also produced the least SI in both antitrypanosomal and antiplasmodial assays. These results suggest that AML and THBE could offer safe and alternative therapy for malaria and trypanosomiasis. This is the first study to report the antitrypanosomal and in vitro antiplasmodial activities of these four plants/plant parts. The cytotoxicity of the plant parts used is also being reported for the first time except for the T. heckelii stem bark.