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Purpose and methods In this study, the analgesic activity of the crude alcohol (acetone-methanol) and aqueous (in PBS, pH 7.2) extracts of the marine molluscs, Pachymelania aurita and Tympanotonus fuscatus, has been evaluated using the formalin test (for chronic antinociceptive) and the tail-flick (acute antinociceptive) pain models in male swiss albino mice. Results The results show that the extracts of P. aurita and T. fuscatus demonstrated high safety margins as single doses of up to 2000 mg/kg bwt proved to be well tolerated and non-lethal, although the alcohol extract of P. aurita caused necrosis in the liver and kidney when administered at a dose level of 2000 mg/kg bwt. In the formalin test, treatment with the aqueous extracts of P. aurita and T. fuscatus as well as the alcohol extract of T. fuscatus 30 min before the subcutaneous injection of 5% formalin to the paw of the mice resulted in a significant time- and dose-dependent reduction in total and phase 2a pain-related behavior and thus nociception. The extracts had no analgesic effect in tail-flick test up to the highest dose tested. Conclusion Hence, the results from both models indicate that the site of their analgesic action is probably peripheral.

Aim: To determine the phytochemicals in Ocimum gratissimum leaves, their phenolic content, antioxidant potential and antiproliferative activity against human prostate (DU145), colon (CT26) and cervical (HeLa 229) cancer cells. Place and Duration of the Study: Leaves of O. gratissimum were collected from cultivated plants in Wakiso district of Uganda. The samples were analyzed at Directorate of Government Analytical Laboratory, Kampala (Uganda) and Kenya Medical Research Institute, Centre for Traditional Medicine and Drug Research, Nairobi (Kenya) between August 2019 and January 2020. Methodology: The leaves were separately extracted by maceration using hexane, dichloromethane, ethyl acetate and methanol. The methanolic extract was further fractionated and subjected to solid phase extraction. Antiproliferative assay was done using dimethylthiazol-2,5-diphenyl-tetrazolium bromide assay while total phenolic content and antioxidant activity were determined by Folin-Ciocalteu method and 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay respectively. Compounds were identified by Fourier transform infrared spectroscopy and liquid chromatography-tandem mass spectrometry. Results: A total of 34 compounds were identified in the fractions. The highest mean total phenolic content was 401.07 ± 6.47 µg/ml for the methanolic extract which also had the highest antioxidant activity with minimum inhibitory concentration of 5.79 ± 0.13 mg/ml. There was a positive correlation between the antioxidant activity of the extracts and antiproliferative activity of the extracts on prostate and cervical cancer cell lines. The extracts exhibited the highest toxicity against prostate cancer cells and the least against cervical cancer cells. Conclusion: The results of this study support the traditional use of this plant in cancer therapy in Uganda. Further research should isolate pure anticancer compounds from this plant which could act as lead candidates in the development of anticancer drugs.

Despite past decades of steady advances in the fight against Malaria, statistics show that the disease is still a threat to human health. Previous successes in the development of antimalarial drugs from medicinal plants have fuelled research in this area. However, antimalarial studies on fractionated extracts from such plants have progressed slowly. This study reports the antimalarial potential of fractions from Lippia kituiensis Vatke, for the first time. Column chromatography was used during fractionation. Antiplasmodial assay against chloroquine-sensitive (D6) and resistant (W2) plasmodium strains were done using hypoxanthine incorporation assay. MTT assay was used to assess the cytotoxicity of fractions against the Vero cell line. Fractions obtained exhibited varied inhibitory concentrations (IC50); with the most efficacious being, Lk-5 (19.45 ± 6.20 μg/ml), Lk-3 (30.43 ± 0.68 μg/ml), Lk-4 (30.82 ± 18.01 μg/ml), and Lk-6 (36.53 ± 14.42 μg/ml) against D6. Generally, lower activity against W2 was obtained with the most active being LK-4 (24.18±2.50 μg/ml), and Lk-5 (24.42±5.95 μg/ml), while chloroquine (positive control) exerted IC50 of 77.86±4.09 ng/ml (W2) and 15.71±6.49 ng/ml (D6). LK-4 was the most cytotoxic showing cytotoxic concentration (CC50), 46.26 μg/ml. When tested in mice, fractions suppressed Plasmodium berghei significantly compared to the negative control with Lk-3 being most efficacious (80.01±1). Due to substantive efficacy, GC-MS done on Lk-3 revealed 8 compounds where three have previously been ascribed to antimalarial activity and other pharmacological effects. This study adds to present knowledge of antimalarial efficacy of L. kituiensis and provides the basis for further work to be done on the isolation of compounds from its extracts. Key words: Malaria, chromatography, alkaloids, cytotoxicity, phytochemistry.

Phytochemicals in Rosmarinus officinalis leaves, their total phenolic content, antioxidant potential and antiproliferative activity against human prostate (DU145), colon (CT26) and cervical (HeLa 229) cancer cells were investigated. Extraction was done separately using hexane, dichloromethane, ethyl acetate and methanol. A total of 32 compounds were identified, eight of which were reported for the first time. The highest phenolic content was 476.80 ± 0.69 µg/ml for the methanolic extract which also had the highest antioxidant activity with a minimum inhibitory concentration of 5.39 ± 0.09 mg/ml. Extracts exhibited the highest toxicity against prostate cancer cells and the least against cervical cancer cells.

Marine organisms make up approximately half of the total global biodiversity, with the Mollusca containing the second largest number of species, including snails and bivalves. The marine environment is highly competitive, hostile and aggressive, which has led to the production of specific and potent bioactive compounds by the mollusca and their associated microorganisms, in a bid to protect themselves and ensure their survival. A diverse array of bioactive compounds can be isolated from the extracts of marine molluscs of which linear, cyclic, and conjugated peptides and depsipeptides form some of the most important bioactive compounds that have been well characterized and some of have already reached clinical trials or been approved for use as therapeutic agents and supplements. This review highlights some of the bioactive peptides that have been obtained from marine molluscs as well the challenges facing bioprospecting of valuable peptides from marine mollusc sources.

A thesis submitted in partial fulfillment for the degree of Master of Science in Molecular Medicine in the Jomo Kenyatta University of Agriculture and Technology 2015

The anti-fungal activity of schefflone, a mixture of dimmer, 3,5 dimethoxy carvacrol and annonaceous acetogenin, extracted from stem-bark and root of Uvaria scheffleri and Artabotrys bruchypetalus against Fusarium solani, Botryodiplodia theobromae, Asperillus niger and Aspergillus flavus was determined. An in-vitro bioassay showed that the minimum inhibitory effect of the compounds to the fungal pathogens occurred at 200 ppm in both radial growth and mycelia dry weight measurements. Acetogenin from A brachypetalus had a very strong anti-fungal effect on all the test fungi. The effects of the compounds were more pronounced on F solani than on the other. The bioassay methods also play a significant role in the sensitivity of the samples on the pathogens. .

Field observations have demonstrated that gravid Anopheles gambiae Giles s.s. (Diptera: Culicidae) are selective in their choice of oviposition sites. For example, immature stages of An. gambiae s.s. are rarely found in water that contains Culex quinquefasciatus Say immatures. The possibility that this may, in part at least, reflect a response by ovipositing An. gambiae s.s. females to volatile signals associated with Culex juveniles was evaluated by testing the response of An. gambiae s.s. females to varying densities of Cx. quinquefasciatus egg rafts and/or larvae in oviposition choice assays. For comparison, the oviposition choices of Cx. quinquefasciatus to conspecific egg rafts and/or larvae were similarly assayed. At a low density of Cx. quinquefasciatus egg rafts (1-15 egg rafts/100 mL water), An. gambiae s.s. females laid more eggs in the treatment water than in the control, with a maximum of twice as many in the treatment water at 5 egg rafts/100 mL water. At higher egg raft densities and in all treatments that included Cx. quinquefasciatus larvae, oviposition decreased significantly in the treatment dishes in a density-dependent manner. As previous studies have indicated, ovipositing Cx. quinquefasciatus females were attracted to and laid egg rafts in dishes containing conspecific egg rafts and, interestingly, also in dishes containing larvae.

The trimeric monoterpene and mildly mosquito larvicidal agent, (±)-schefflone, that is an apparent derivative of the antiparasitic aromatic monoterpene espintanol, was isolated from the antimalarial extracts of the root bark of Uvaria scheffleri, together with espintanol. Structural determination of (±)-schefflone was achieved from spectroscopic data and confirmed by single-crystal X-ray diffraction analysis. (±)-Schefflone can be considered a product of a non-enzymatic Diels–Alder-type cycloaddition reaction of the quinonemethide derivative of espintanol as the diene and dienophile.

Background The African malaria vector, Anopheles gambiae s.s., is known to feed selectively on certain plants for sugar sources. However, the adaptive significance of this behaviour especially on how the extracts of such plants impact on the fitness of this vector has not been explored. This study determined the toxicity and larvicidal activity on this vector of extracts from six selected plants found in Kenya and two compounds identified from Ricinus communis: 3-carbonitrile-4-methoxy-N-methyl-2-pyridone (ricinine), and its carboxylic acid derivative 3-carboxy-4-methoxy-N-methyl-2-pyridone, the latter compound being reported for the first time from this plant. Methods Feeding assays tested for toxic effects of extracts from the plants Artemisia afra Jacq. ex Willd, Bidens pilosa L., Parthenium hysterophorus L., Ricinus coummunis L., Senna didymobotrya Fresen. and Tithonia diversifolia Hemsl. on adult females and larvicidal activity was tested against third-instar larvae of Anopheles gambiae s.s. Mortality of larvae and adult females was monitored for three and eight days, respectively; Probit analysis was used to calculate LC50. Survival was analysed with Kaplan-Meier Model. LC-MS was used to identify the pure compounds. Results Of the six plants screened, extracts from T. diversifolia and R. communis were the most toxic against adult female mosquitoes after 7 days of feeding, with LC50 of 1.52 and 2.56 mg/mL respectively. Larvicidal activity of all the extracts increased with the exposure time with the highest mortality recorded for the extract from R. communis after 72 h of exposure (LC50 0.18 mg/mL). Mosquitoes fed on solutions of the pure compounds, 3-carboxy-4-methoxy-N-methyl-2-pyridone and ricinine survived almost as long as those fed on the R. communis extract with mean survival of 4.93 ± 0.07, 4.85 ± 0.07 and 4.50 ± 0.05 days respectively. Conclusions Overall, these findings demonstrate that extracts from the six plant species exhibit varying bioactivity against the larvae and adult females of An. gambiae s.s. T. diversifolia and R. communis showed highest bioactivity against adult females An. gambiae and larvae while longevity of female An. gambiae s.s. decreased with exposure time to the two pure compounds.

This study aimed to investigate the antimitotic and antiproliferation activities of crude acetone-methanol and aqueous extracts of two marine molluscs commonly found in the Niger Delta region of Nigeria; T.fuscatus and P.aurita, against human cancerous cell lines (DU145, Hep-2, and HCC1395) cell lines in vitro. The antimitotic activity of the extracts was evaluated using Allium cepa root meristematic cells. Antiproliferative activity of the plant extracts against the cancerous cell lines was compared with normal cell line (VeroE6). Doxorubicin was used as a positive control. Gene expression studies using qPCR for the proapoptotic genes, CASP3, CASP8 and P53 were also carried out. The alcohol extract of T.fuscatus (TFAC) exhibited the most promising activity against all the cancer cell lines tested (DU145 IC(50) = 96.48 ± 1.36 μg/ml, HCC 1395 IC(50) = 61.44 ± 2.45 μg/ml, Hep2 IC(50) = 0.52 ± 0.36 μg/ml) and also had the highest selectivity index of 4.94, 7.78 and 921.97 for DU145, HCC 1395 and Hep-2 cells respectively. Furthermore, TFAC was the only extract that significantly upregulated the expression of caspase 3, caspase 8 and P53. Thus, these findings suggest potential exploitation of TFAC as an anticancer agent.