ASSESSMENT OF BIOACTIVE CONSTITUENTS AND ANTIDIABETIC ACTIVITIES OF Nauclea latifolia Sm. AND Terminalia catappa L. LEAF EXTRACTS

Iheagwam, Franklyn N (2020) ASSESSMENT OF BIOACTIVE CONSTITUENTS AND ANTIDIABETIC ACTIVITIES OF Nauclea latifolia Sm. AND Terminalia catappa L. LEAF EXTRACTS. ["eprint_fieldopt_thesis_type_phd" not defined] thesis, Covenant University, Canaanland Ota..

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Abstract

Nauclea latifolia (NL) and Terminalia catappa (TC) leaves are used by locals in Nigeria to treat diabetes. However, there is paucity of scientific data on the antidiabetic activities and molecular mechanisms of action of these plants; hence, the set objectives of this research work. Samples of NL and TC leaves were collected from Ibadan in Oyo State and Ota in Ogun State, respectively, and identified. Aqueous (A) and ethanol (E) crude extracts of the plants were prepared for the analyses. Phytochemical analyses, in silico simulation, in vitro antidiabetic and membrane stabilising assessments were carried out using standard methods. Phytoconstituent assessment of NL and TC leaves using gas chromatography-mass spectroscopy (GC-MS) revealed the presence of 50 and 38 different phytochemicals, respectively. These were categorized as alcohols, alkaloids, carbohydrates, hydrocarbons, carboxylic acids, phenolics, fatty acids, terpenes/terpenoids and pyrethrin. The leaves possessed ferric-reducing power, total antioxidant activity, 2,2-diphenyl-1-picrylhydrazyl, hydrogen peroxide radical scavenging activities and membrane-stabilizing potential comparable with synthetic antioxidants such as butylated hydroxytoluene, ascorbic acid and ibuprofen. They also exhibited significant (p<0.05) inhibitory property on α-amylase and α-glucosidase with IC50 values comparable with acarbose. For the inhibitory kinetics, NL extracts (NLE and NLA) exhibited uncompetitive and competitive inhibition on α-glucosidase and α-amylase, respectively, while TC extracts (TCA and TCE) exhibited a mixed inhibition on α-amylase. However, TCA and TCE exhibited non-competitive and mixed-mode of inhibition, respectively on α-glucosidase. TCA showed significantly (p<0.05) higher in vitro antidiabetic activity than the other extracts and was subjected to in vivo toxicological and antidiabetic evaluation. In acute toxicity studies, the LD50 of TCA was > 5000 mg/kg b.wt with no significant (p>0.05) changes in general behaviour and mortality. The sub-acute toxicological evaluation at the experimental doses revealed no significant (p>0.05) alteration in the weight, biochemical, haematological and histopathological indices of the experimental animals. The induction of diabetes in high-fat diet/low dose streptozotocin-induced diabetic rats led to a loss of weight, initiation of systemic and organ oxidative stress, plasma and organ dyslipidaemia, liver and kidney dysfunction as well as observed abnormal level in other diabetes-related parameters. Upon 28-day repeated administration of TCA, these observed systemic and organ anomaly were significantly (p<0.05) reversed to levels that are comparable to glibenclamide administration. In silico studies of 18 compounds selected from GC-MS identified phytoconstituents of the plants revealed four compounds (n-hexadecanoic acid, vitamin E, ethyl-α-d-glucopyranoside and phytol) that were potent DPP-IV, α-glucosidase and α-amylase inhibitors comparable to saxagliptin, alogliptin and acarbose. These four compounds also exhibited promising oral bioavailability, pharmacokinetics and toxicity profile. In conclusion, these plant extracts possess antidiabetic activities and do not elicit an adverse toxic effect at the doses tested. It also displays various mechanisms at which these plant extracts as well as their phytoconstituents elicit their antidiabetic action. Further studies are required to establish the antidiabetic potential and mechanism of action of ethyl-α-d-glucopyranoside and novel bioactive compounds from N. latifolia and T. catappa leaves.

Item Type:	Thesis (["eprint_fieldopt_thesis_type_phd" not defined])
Uncontrolled Keywords:	Nauclea latifolia, Terminalia catappa, Antidiabetic activity, Mechanism of action, Toxicological evaluation
Subjects:	Q Science > QH Natural history > QH301 Biology
Divisions:	UNSPECIFIED
Depositing User:	Mrs Patricia Nwokealisi
Date Deposited:	06 Oct 2020 10:41
Last Modified:	08 Oct 2020 09:45
URI:	http://eprints.covenantuniversity.edu.ng/id/eprint/13635

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