Browsing by Author "Dokunmu, Titilope M"

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    Acute oral toxicity and antimalarial studies of 7-[(7-methoxy- 4,5-dihydro-1H-benzo[g]indazol-3-yl)carbonyl]-2-phenyl- 5,6,7,8-tetrahydropyrazolo[1,5-a]pyrido[4,3-d]pyrimidin-9 (1H)-one in mouse models
    (Scientific African, 2024) Oladejo, David O; Dokunmu, Titilope M; Tebamifor, Mercy E; Omunagbe, Mercy B; Okafor, Esther O; Iweala, Emeka Joshua
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    Anticancer Activity of Ethyl Acetate Fraction and Ethanol Leaf Extract of Olax subscorpioidea against DMBA-Induced Female Rats
    (Tropical Journal of Natural Product Research, 2024) Adelegan, Ayodeji A.; Talabi, Azeem A.; Dokunmu, Titilope M; Iweala, Emeka Eze Joshua
    Breast cancer continues to be a major contributor to cancer-related deaths in developing nations. Olax subscorpioidea is used in Nigerian traditional medicine as a treatment for cancer. The study examined the effects of Olax subscorpioidea's ethyl acetate fraction (OSEA) and ethanol leaf extract (OSE) on 7,12-Dimethylbenz(α)anthracene (DMBA)-induced breast cancer in female Sprague-Dawley rats. The anticancer, antioxidant and anti-inflammatory activities of the extracts were evaluated using established procedures. The study involved 40 female Sprague-Dawley rats with an average weight of 110 ± 20 g. The rats were given a dose of 80 mg/kg of DMBA to stimulate proliferation. Subsequently, OSEA, OSE (250 mg/kg BW), and tamoxifen (6.6 mg/kg BW) were administered. The trial spanned a duration of 22 weeks. The study evaluated the impact of the treatment on various aspects such as body weight, organ weight, liver and kidney function, oxidative stress indicators, oestrogen levels, Interleukin 6 (IL-6), Cancer antigen 153 (CA-153), and mammary tissue histology. It was found that body weight, Superoxide dismutase (SOD), Reduced glutathione (GSH), liver enzymes, and renal function increased significantly with OSEA and OSE therapy. The levels of oestrogen, IL-6, CA-153, and Malondialdehyde (MDA) decreased significantly. The histological study revealed that OSEA and OSE had a positive impact on acini normalisation and the inhibition of breast ductal cell growth. The study found that OSEA and OSE demonstrated promising effects against cancer, as well as antioxidant and anti-inflammatory properties, in rats with DMBA-induced breast cancer. The results offer scientific support for the traditional use of Olax subscorpioidea as a potential natural remedy for breast cancer.
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    Gene expression levels and inhibitory effect of 7-[(7-methoxy- 4,5-dihydro-1H-benzo[g]indazol-3-yl)carbonyl]-2-phenyl- 5,6,7,8-tetrahydropyrazolo[1,5-a]pyrido[4,3-d]Pyrimidin-9 (1H)-one (MCL) against AP2-I and BDP1 in malaria experimental models
    (Scientific African, 2024) Oladejo, David O; Anzaku, Dorathy O; Mamudu, Collins O; Elugbadebo, Temitope; Dokunmu, Titilope M; Adebiyi, Ezekiel F; Iweala, Emeka Joshua
    Resistance to antimalarial drugs leads a global recurrence of malaria, posing a significant challenge to malaria control. This study aimed to assess gene expression and resistance profiles in clinical isolates, and validate the inhibitory effect of MCL compound against PbAP2-I and PbBDP1 genes in vivo. Malaria prevalence rate throughout the clinical study period stood at 12.24%. Blood samples were obtained from 182 malaria outpatients and 30 P. berghei-infected mice treated with varying MCL concentrations. DNA and RNA were extracted. PfAP2-I, PfBDP1, PfMDR1, and PfK13 genes were amplified using Real-time qPCR and sequenced for mutation profiling. Relative gene expression of AP2-I and BDP1 genes in P. falciparum and P. berghei-treated mice was carried out by Reverse-transcription PCR. The data were analyzed using ANOVA at P<0.05 indicating a significant difference. Relative gene expression results from clinical isolates showed PfAP2-I and PfBDP1 are highly expressed in the trophozoite and schizont stages. The clinical isolates show conserved nucleotide sequences for PfAP2-I, PfBDP1, and PfK13 genes compared to the 3D7 strain. However, Asn86Tyr mutation implicated in antimalarial drug resistance and Leu1312Iso mutation not previously reported to be associated with antimalarial drug resistance were observed for the PfMDR1 gene. MCL inhibited the expression of PbAP2-I (by 4.52 and 8.08 folds) and PbBDP1 (by 37.92 and 79.07 folds) at 40μM and 50μM concentrations after a 7-day, single oral daily dose. Our findings validate MCL’s inhibitory activity against AP2-I and BDP1 genes, hence representing potential new targets of antimalarial therapy for controlling malaria parasite invasion.