Terminalia catappa aqueous leaf extract reverses insulin resistance, improves glucose transport and activates PI3K/AKT signalling in high fat/streptozotocin-induced diabetic rats

Iheagwam, Franklyn Nonso; Iheagwam, Olawumi Toyin; Onuoha, Michael Kemjika; Ogunlana, Olubanke Olujoke; Chinedu, Shalom Nwodo

doi:10.1038/s41598-022-15114-9

Cited by 19 publications

(25 citation statements)

References 61 publications

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“…To evaluate the medicinal potentials of this species, the majority of studies have focused on physiochemical and biological characteristics of the leaf. T. catappa leaf have been shown for its high potential in treatment diabetes using aqueous extract (11,12), protection of human skin fibroblasts from oxidative stress using methanol extract (13), inhibition of metastasis of oral, lung and brain cancer (14)(15)(16). Both aqueous extract and ethanol of T. catappa leaf exhibited antioxidant activity, probably due to significant amount of polyphenolic and flavonoid contents (17)(18)(19)(20).…”

Section: Introductionmentioning

confidence: 99%

Physiochemical properties, antibacterial and antioxidant activities of Terminalia catappa seed oils from two extracting processes

et al. 2022

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Terminalia catappa is a widespread medium tree species in many tropical countries. While the majority of the studies up to date focuses on the aerial part of the plant such as leaf, stem bark and fruit, information about the phytochemical property as well as the biological property of the edible seed is still scarce. This study was the first to explore the fatty acid composition, antibacterial and antioxidant activities of the seed oil from T. catappa grown in Vietnam. The results showed that both the hot-pressed and cold-pressed oils contained a high level of unsaturated fatty acids such as oleic (~32%) and linoleic acids (28.38%-29.2%), as well as saturated fatty acids such as palmitic acid (~33.3%-33.61%). The presence of eicosadienoic acid in T. catappa seed oils was reported in this study for the first time. These oils displayed antibacterial activity against 5 out of 12 tested strains such as Bacillus cereus, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Vibrio parahaemolyticus. The antioxidant activity of the oils was also recorded by DPPH radical scavenging assays with IC50 values of 950 µg/ml and 2529 µg/ml for cold-pressed oil and hot-pressed oil respectively. This study has provided promising extracting methods and resulted in oils that could be good candidates for developing food sources with valuable fatty acids, antioxidant and antibacterial capacities against both Gram-positive and negative bacteria in the human diet.

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Section: Introductionmentioning

confidence: 99%

Physiochemical properties, antibacterial and antioxidant activities of Terminalia catappa seed oils from two extracting processes

et al. 2022

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“…The PI3K-AKT pathway is involved in the regulation of cell proliferation, differentiation, apoptosis and glucose transport (47)(48)(49)(50). The main biological functions of miR-29a target genes are also focused on these aspects, so there may be an association between the two.…”

Section: Discussionmentioning

confidence: 99%

Effect of miR‑29a‑3p in exosomes on glioma cells by regulating the PI3K/AKT/HIF‑1α pathway

2023

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Exosomes secreted by glioma cells can carry a number of bioactive molecules. As the most abundant noncoding RNA in exosomes, microRNAs (miRNAs) are involved in signaling between tumor cells in a number of ways. In addition, hypoxia is an important feature of the microenvironment of most tumors. The present study investigated the effect of miR-29a-3p in glioma exosomes on the proliferation and apoptosis levels of U251 glioma cells under hypoxia. Qualitative PCR results showed that the expression level of miR-29a-3p in plasma exosomes of glioma patients was lower than that of normal subjects. By conducting hypoxia experiments in vitro on U251 glioma cells, it was found that the expression level of miR-29a-3p decreased following hypoxia, while overexpression of miR-29a-3p significantly decreased the proliferation of U251 glioma cells and promoted apoptosis by inhibiting the expression of the antiapoptotic marker Bcl-2 and increasing the expression of the proapoptotic marker Bax The potential targets of miR-29a-3p were predicted by online tools and validated by a dual-luciferase gene reporter assay. miR-29a-3p was found to target and regulate PI3K, which in turn inhibited the activity of the PI3K-AKT pathway, thereby reducing the expression of hypoxia inducible factor (HIF)-1α protein. Furthermore, the effects of miR-29a-3p on proliferation and apoptosis in glioma cells in those processes could be reversed by the PI3K-AKT agonist Recilisib. In addition, the inhibitory effect of miR-29a-3p on the PI3K/AKT/HIF-1α regulatory axis could cause a decrease in the expression levels of pyruvate dehydrogenase kinase-1 and pyruvate dehydrogenase kinase-2 and eventually lead to a reduction in glycolysis in U251 glioma cells. Similarly, Recilisib slowed the inhibitory effect of miR-29a-3p on glycolysis and glycolysis-related molecules. The results of this study tentatively confirm that miR-29a-3p carried by exosomes can be used as a novel diagnostic marker and a potential inhibitory molecule for glioma cells, providing a new theoretical and experimental basis for the precise clinical treatment of glioma.

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“…Also, diabetes can further result in heart attacks, stroke, and lower limb amputation. Diabetes needs to be treated with drugs that are more efficient and less toxic for patients [3] . Biguanides and metformin are a group of oral antihyperglycemic drugs that work by preventing the production of glucose in the liver, improving the body‘s sensitivity to insulin, and reducing the amount of sugar absorbed by the intestines [4–6] .…”

Section: Introductionmentioning

confidence: 99%

“…Diabetes needs to be treated with drugs that are more efficient and less toxic for patients. [3] Biguanides and metformin are a group of oral antihyperglycemic drugs that work by preventing the production of glucose in the liver, improving the body's sensitivity to insulin, and reducing the amount of sugar absorbed by the intestines. [4][5][6] They also stimulate an enzyme (AMPK) which helps cells respond more effectively to insulin and take in glucose from the blood.…”

Section: Introductionmentioning

confidence: 99%

Modelling of Tungsten (C₅₉W), Osmium (C₅₉O_s), and Platinum (C₅₉Pt) Doped Fullerenes for Drug Delivery of Biguanides (BNG) and Metformin (MET): DFT Perspective

et al. 2023

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Owing to the vast range of exciting ideas and chances for the diagnosis and treatment of diabetes, the number of people with the disease has increased significantly in both developed and developing nations, with the greatest burden typically falling on indigenous people and socially disadvantaged groups. Nanostructures, however, have drawn a lot of interest because of their capacity to specifically target diabetes cells without damaging healthy cells. Herein, the potential of fullerene (C60) surface doped with C59Os, C59W, and C59Pt is explored as drug delivery systems for biguanides and metformin using density functional theory (DFT) computation at the M06‐2X/Gen/LanL2DZ/6‐311++G(d,p) level of theory. Interestingly, results obtained in this investigation specify that metformin interacts with both the doped and updoped surfaces more strongly than biguanides. Fascinatingly, the energy gap obtained from frontier molecular orbital (FMO) accounted for the significant reactivity and stability strength in the following order: MET@C59W>MET@C59Pt>MET@C59Os>MET@C60, whereas BGN@C59 W>BGN@C59Pt>BGN@C59Os>BGN@C60. Substantially, hydrogen bonding was found to be crucial in the interactions between the drug molecules and all doped and undoped surfaces through non‐covalent interaction (NCI) and quantum theory of atoms in molecules (QTAIM). Also worth mentioning is the complexes′ propensity for forward electron transfer, which is aided by their severe electronegative values, thus explicating that the doped surfaces are a preferable carrier for both metformin and biguanides. Although, theoretically, it follows that doped surfaces are promising drug delivery targets most notably for metformin.

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Terminalia catappa aqueous leaf extract reverses insulin resistance, improves glucose transport and activates PI3K/AKT signalling in high fat/streptozotocin-induced diabetic rats

Cited by 19 publications

References 61 publications

Physiochemical properties, antibacterial and antioxidant activities of Terminalia catappa seed oils from two extracting processes

Physiochemical properties, antibacterial and antioxidant activities of Terminalia catappa seed oils from two extracting processes

Effect of miR‑29a‑3p in exosomes on glioma cells by regulating the PI3K/AKT/HIF‑1α pathway

Modelling of Tungsten (C₅₉W), Osmium (C₅₉O_s), and Platinum (C₅₉Pt) Doped Fullerenes for Drug Delivery of Biguanides (BNG) and Metformin (MET): DFT Perspective

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Terminalia catappa aqueous leaf extract reverses insulin resistance, improves glucose transport and activates PI3K/AKT signalling in high fat/streptozotocin-induced diabetic rats

Cited by 19 publications

References 61 publications

Physiochemical properties, antibacterial and antioxidant activities of Terminalia catappa seed oils from two extracting processes

Physiochemical properties, antibacterial and antioxidant activities of Terminalia catappa seed oils from two extracting processes

Effect of miR‑29a‑3p in exosomes on glioma cells by regulating the PI3K/AKT/HIF‑1α pathway

Modelling of Tungsten (C59W), Osmium (C59Os), and Platinum (C59Pt) Doped Fullerenes for Drug Delivery of Biguanides (BNG) and Metformin (MET): DFT Perspective

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Modelling of Tungsten (C₅₉W), Osmium (C₅₉O_s), and Platinum (C₅₉Pt) Doped Fullerenes for Drug Delivery of Biguanides (BNG) and Metformin (MET): DFT Perspective