Browsing by Author "Koketsu, M."

Now showing 1 - 6 of 6
  • Item
    Cholinergic inhibition and antioxidant potential of Gongronema latifolium benth leaf in neurodegeneration: experimental and in silico study
    (2024) Gyebi, G.A.; Ejoh, J.C.; Ogunyemi, O.M.; Afolabi, S.O.; Ibrahim, I.M.; Anyanwu, G.O.; Koketsu, M.
  • Item
    Comparative Antileukemic Activity of a Tetranorditerpene Isolated from Polyalthia longifolia Leaves and the Derivative against Human Leukemia HL-60 cells
    (Japan Oil Chemists’ Society., 2017) Afolabi, S.; Olorundare, O.; Ninomiya, M.; Babatunde, A.; Mukhtar, H.; Koketsu, M.
    Abstract: The discovery of potent cytotoxic isolates from botanicals provides an opportunity to explore this viable tool for cancer chemoprevention. The antileukemic potential of clerodane diterpene from Polyalthia longifolia leaves has already been established. However, in this present study, utilizing chromatographic techniques we report for the first time, the isolation of a rare tetranorditerpene (compound 1) from P. longifolia. The structure of compound 1 was elucidated and confirmed by spectrophotometric data. UPLCMS analysis was conducted on the methanolic extract, ethyl acetate fraction, and isolated tetranorditerpene showed that the tetranorditerpene is one of the major constituents of the plant with a retention time of 30.78 min. In addition, a methyl ester derivative (compound 2) of the isolated tetranorditerpene was synthesized. Using the CCK-8 assay, we compared the cytotoxic potential of isolated tetranorditerpene (1) and methyl ester derivative (2) with the previously isolated clerodane diterpenes. Our results showed that the methyl ester derivative (2) displayed the highest inhibitory activity against human leukemia HL-60 cells. The isolated tetranorditerpene (1) did not exhibit significant inhibitory effect against HL-60 cells. Morphological examination indicated chromatin condensation and nuclear fragmentation suggesting induction of apoptosis in compound 2 treated HL-60 cells. The methyl esterification of the isolated tetranorditerpene (1) conferred on it a significant level of antileukemic activity suggesting the possibility of a synergistic relationship between pure compound isolation and synthetic reaction in the discovery of new chemopreventive agents.
  • Item
    Iloneoside, an antimalarial pregnane glycoside isolated from Gongronema latifolium leaf, potentiates the activity of chloroquine against multidrug resistant Plasmodium falciparum
    (Elsevier, 2022-03) Adebayo, J. O.; Ceravolo, I. P.; Gyebi, G.A.; Olorundare, O. E.; Babatunde, A. S.; Penna-Coutinho, J. P.; Koketsu, M.; Krettli, A. U.
    The rapid spread of drug resistant malaria parasites has necessitated the search for novel antimalarials and chemosensitizers capable of reversing drug resistance in the parasites. A number of studies have revealed the resistance reversal activities of pregnane glycosides and the antimalarial activity of a pregnane glycoside obtained from Gongronema species. However, the pregnane (2) and pregnane glycosides (1, 3–4) isolated from Gongronema latifolium leaf have not been evaluated for these activities. This study was therefore carried out to evaluate the antiplasmodial and chloroquine resistance reversal activities of a pregnane and three pregnane glycosides isolated from G. latifolium leaf in vitro. The compounds were evaluated for their inhibitory activities against P. falciparum 3D7 (a chloroquine-sensitive strain) and P. falciparum W2 (a chloroquine-resistant clone) in vitro. The activities of chloroquine in separate combination with each of the compounds against P. falciparum W2 were also evaluated. Moreover, the interaction of the active compounds (1 and 4) with selected P. falciparum proteins (PfProteins) were evaluated in silico. The results revealed that only 1 and 4 were active against P. falciparum 3D7 and P. falciparum W2. Also, 2 and 3 did not exhibit chloroquine resistance reversal activity. Activity of chloroquine against P. falciparum W2 was potentiated by 1 by 3200% at concentrations higher than 0.625 μg/mL. Also, 1 and 4 demonstrated similar binding patterns and higher binding tendencies to the selected PfProteins compared to chloroquine. Thus, 1 (iloneoside) is an antimalarial pregnane glycoside which can potentiate the activity of chloroquine against multidrug resistant P. falciparum.
  • Item
    Iloneoside, an antimalarial pregnane glycoside isolated from Gongronema latifolium leaf, potentiates the activity of chloroquine against multidrug resistant Plasmodium falciparum
    (Elsevier, 2022-03) Adebayo, J. O.; Ceravolo, I. P.; Gyebi, G.A.; Olorundare, O. E.; Babatunde, A. S.; Penna-Coutinho, J. P.; Koketsu, M.; Krettli, A. U.
    The rapid spread of drug resistant malaria parasites has necessitated the search for novel antimalarials and chemosensitizers capable of reversing drug resistance in the parasites. A number of studies have revealed the resistance reversal activities of pregnane glycosides and the antimalarial activity of a pregnane glycoside obtained from Gongronema species. However, the pregnane (2) and pregnane glycosides (1, 3–4) isolated from Gongronema latifolium leaf have not been evaluated for these activities. This study was therefore carried out to evaluate the antiplasmodial and chloroquine resistance reversal activities of a pregnane and three pregnane glycosides isolated from G. latifolium leaf in vitro. The compounds were evaluated for their inhibitory activities against P. falciparum 3D7 (a chloroquine-sensitive strain) and P. falciparum W2 (a chloroquine-resistant clone) in vitro. The activities of chloroquine in separate combination with each of the compounds against P. falciparum W2 were also evaluated. Moreover, the interaction of the active compounds (1 and 4) with selected P. falciparum proteins (PfProteins) were evaluated in silico. The results revealed that only 1 and 4 were active against P. falciparum 3D7 and P. falciparum W2. Also, 2 and 3 did not exhibit chloroquine resistance reversal activity. Activity of chloroquine against P. falciparum W2 was potentiated by 1 by 3200% at concentrations higher than 0.625 μg/mL. Also, 1 and 4 demonstrated similar binding patterns and higher binding tendencies to the selected PfProteins compared to chloroquine. Thus, 1 (iloneoside) is an antimalarial pregnane glycoside which can potentiate the activity of chloroquine against multidrug resistant P. falciparum.
  • Item
    Iloneoside: a cytotoxic ditigloylated pregnane glycoside from the leaves of Gongronema latifolium Benth.
    (Taylor & Francis., 2018) Gyebi, G.A.,; Adebayo, J.O.,; Olorundare, O.E.,; Pardede, A.,; Ninomiya, M.,; Afolabi, O. S.,; Babatunde, A.S.,; Koketsu, M.
    Gongronema latifolium Benth (Asclepiadaceae) is an edible-green-leafy vegetable with known medicinal value. A chemical investigation of the 80% methanolic extract of the leaves led to the isolation of a new pregnane glycoside: iloneoside (3-O-[6-deoxy-3-O-methyl-β-D-allopyranosyl-(1→14)-β-D-oleandropyranosyl]-11,12-di-O-tigloyl-17β-marsdenin), together with four known constituents. Their chemical structures were determined by spectroscopic analysis. The isolates were tested for their in vitro growth inhibitory activity against human leukemia HL-60 cells. Iloneoside was the most active and gave apoptotic response. Molecular docking analysis demonstrated that iloneoside could be accommodated within hot spots of anti-apoptotic protein Bcl-2. These results suggest G. latifolium as a reliable source of potent anticancer compounds.
  • Item
    Polyalthia longifolia extract triggers ER stress in prostate cancer cells concomitant with induction of apoptosis: insights from in vitro and in vivo studies
    (Hindawi publishers, 2019) Afolabi, Saheed O.; Olorundare, Olufunke E.; Babatunde, A.; Albrecht, R.M.; Koketsu, M.; Syed, Deeba N.; Mukhtar, Hassan
    Plant-based therapies are being explored to prevent or treat several cancer types. The antioxidant properties of Polyalthia longifolia plant are well established. In our previous work, we demonstrated the presence of cytotoxic compounds in the methanol extract of Polyalthia longifolia (MEP) with potent activity against human leukemia cells. In the present study, we evaluated the efficacy of MEP against prostate cancer (PCa) and established the molecular basis of its effect in in vitro and in vivo models. We observed that MEP treatment resulted in a significant decrease in the growth and viability of PCa cells, associated with arrest in the G1/S phase of the cell cycle. Apoptosis was confirmed as the primary mode of MEP-induced cell death through activation of the intrinsic apoptotic machinery. Proteomic and biochemical studies identified BiP as an important target of MEP with the activation of the ER stress pathway, as a potential mechanism driving MEP-induced apoptosis. The extract exhibited strong efficacy in the PCa xenograft mouse model with significant inhibition of tumor growth and reduced tumor burden. Taken together, our findings indicate that MEP-induced apoptosis in PCa cells concomitant with the activation of the ER stress pathways results in the inhibition of tumor growth, in vitro and in vivo. Our studies provide initial evidence of the efficacy of MEP against PCa and advocate for in-depth studies in other preclinical models for its possible use in clinical settings.