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Glut4 translocation augmentation effects of medicinal plants traditionally used for the management of type II diabetes mellitus

Thesis (M. Sc. (Biochemistry)) --University of Limpopo, 2017 / Diabetes mellitus is a chronic metabolic disorder characterised by perpetual
hyperglycaemia. Various oral pharmacological theraputic management strategies
currently exist but are too expensive and having a host of undesirable side effects.
Therefore people resort to the use of traditional medicinal plants as they offer a cost
effective and readily available health care avenue. Despite the wide-spread use of
traditional medicinal plants, several worrisome concerns about their effectiveness,
clinical modes of action and safety have been raised.
Leaves of five selected plants (Toona celliata, Seriphium plumosum, Schkuhria
pinnata, Olea africana, Opuntia ficus-indica) were collected from Mankweng area,
Capricon Local Municipality, Limpopo province, South Africa. Ground plant materials
were exhaustively extracted by maceration in methanol, acetone or hexane. The
presence of different plant secondary metabolites in the crude extracts was
determined using various standard chemical tests and thin layer chromatography
(TLC). A myriad of compounds which represented various secondary plant
metabolites groups were observed on the TLC plates and were best resolved in the
non-polar (BEA) and intermediate (CEF) mobile phases. The total phenolic content
and total flavonoids of the different extracts were determined spectrophotometrically
using the Folin-Ciocalteu`s phenol reagent method and Aluminium chloride
colorimetric assay respectively. The plants contained comparatively higher amounts
of total phenolic compounds as compared to the flavonoids. The antiglycation activity
of the plant extracts were determined using the bovine serum albumin assay. The
acetone extract of Seriphium plumosum (SPlA) exhibited the most glycation
inhibitory activity among all the examined extracts, as it resulted in 2,22% glycation.
The antioxidant potential of each of the different extracts was quantitatively
determined spectrophotometrically using the 2, 2-diphenyl-1-picrylhydrazyl (DPPH)
free radical scavenging assay and the ferric ion reducing power assay. The methanol
extract of Seriphium plumosum showed the best antioxidant activity among all the
extracts in this study. It exhibited the lowest EC50 values of 0.72 mg/ml and 2.31
mg/ml for the DPPH scavenging activity and the ferric reducing power assay
respectively. The cytotoxicity profiles of the different plant extracts on C2C12 cell line
were determined using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium
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bromide (MTT) assay. It was concluded that since the all the extracts investigated
had CC50 values greater than 50 μg/ml they were generally non-toxic. The amount of
glucose taken up by differentiated C2C12 cells was quantified using the glucose
uptake assay. Treatment of the C2C12 cells with the hexane extract of Seriphium
plumosum resulted in the best glucose utilisation effect of 35,77% which was higher
than that of insulin which was 26,06% after 6 hours. The translocation assay was
used to determine the effect of the plant extract on GLUT4 translocation while the
expression of various mitogen activated protein kinases in the cells was determined
using the human MAPK profiler assay. It was established that treatment with
Seriphium plumosum hexane extract resulted in increased GLUT4 translocation from
the intracellular vesicular stores to the cell surface membrane. The increase in
GLUT4 translocation may have resulted from the upregulation of expression of
phosphorylated Akt-1, Akt-2, GSK3β, ERK1, ERK2 p70S kinase and MKK3 under
the influence of Seriphium plumosum hexane extract.
The study documents a probable insulin-mimetic activity of the hexane extract of
Seriphium plumosum. This activity may be responsible for its hypoglycaemic
capability and may occur via the augmentation of proximal mitogen activated protein
kinases involved in the GLUT4 translocation pathway. Further investigations need to
be conducted to ascertain this novel finding which may help provide a cost-effective
and readily available antidiabetic therapeutic agent. / National Research Foundation (NRF)

Identiferoai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:ul/oai:ulspace.ul.ac.za:10386/4278
Date January 2017
CreatorsBeseni, Brian Kudakwashe
ContributorsMokgotho, M. P., Bagka, V. P.
Source SetsSouth African National ETD Portal
LanguageEnglish
Detected LanguageEnglish
TypeThesis
Formatxvii, [144] leaves
RelationPDF

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