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Entrepreneurial orientation among small and medium entreprises in selected rural areas of KwaZulu-Natal
No full textSubmitted in fulfilment of the requirements of the degree of Doctor of Philosophy Management Sciences
Specialising in Business Administration at the Durban University of Technology, Durban, South Africa, 2025.Small and medium enterprises (SMEs) in rural areas have been recognised on a
global scale as a significant employer and the cornerstone of prosperous
entrepreneurship, as they substantially boost national income, economic growth,
income redistribution, and inequality reduction, as well as commercial innovation of
any nation. However, Statistics South Africa reported a 0.2 percent decrease in the
country’s GDP in the 2023 third quarter, following a 0.5 percent increase in the
second quarter; and an almost 150 percent decrease in just a quarter earlier. This
study examined the critical factors of entrepreneurial orientation (EO), and how it
influenced the performance of SMEs in selected rural areas of KwaZulu-Natal (KZN).
The influence of EO and its dimensional variables of innovativeness, risk- taking,
proactiveness, autonomy, and competitive aggressiveness were investigated in
detail, in addition to how it assisted SMEs in rural areas of KZN to achieve growth.
Of particular importance is the study focus, as this was on both the uni- and multi-
dimensional constructs of EO, to determine whether each dimension, as well as the
overall entrepreneurial indicator, related effectively to the growth of SMEs operating
in the rural areas of KZN.
Many researchers have studied the factors that contribute to the smooth running of
SMEs in general. These factors include management skills, leadership ability, and
access to finance, as well as the availability of resources, the necessary
infrastructure, and raw materials, along with the economic climate, and government
regulations. However, despite extensive research in this field, a serious gap is left in
the body of knowledge, as no studies provide in-depth knowledge of EO among
SMEs in rural areas of KZN.
EO is known to instigate, develop and promote rural SMEs to prosper. Nonetheless,
theoretical models of the factors affecting EO and how they influence SME
performance in rural areas of KZN are lacking. This has created a further knowledge
gap; therefore, it can be argued this critical area of research has the potential to aid
in improving the current position of these SMEs. The high failure rate currently
observed in the SME sector, which may be attributed to a number of important issues
faced by South African rural SMEs, served as justification for the study.
Conducted in selected rural KZN areas, the study employed a quantitative research
method. The study population comprised rural SME owners-managers, selected using a non-probability, convenience sampling technique, while the researcher
developed a closed-ended questionnaire and used as the primary data collection
tool. Inferential and descriptive statistical data analysis was undertaken using the
SPSS (version 27.0) computer package.
The study found that, a number of issues negatively impacted rural SMEs, such as
the fact that most of their staff lacked formal training, they did not use modern
facilities to operate their businesses, their investment plans were hindered by a
persistent lack of funding, their local market was too small, and their infrastructure
was inadequate, making them face significant hurdles that negatively affect their EO
and performance. Unsustainable rural KZN SME growth was not only due to the
challenges faced but also from their EO, which negatively affected the abilities of the
owners-managers to implement innovations that could promote, support and sustain
SMME growth.
Consequently, the implications of this research will be the innovative growth owners-
managers of rural SMEs in KZN will achieve, when provided with a growth
framework and model, centred on the EO for sustained SME business continuity,
particularly in rural KZN areas. Government officials and other concerned parties will
also benefit from the study findings through improved comprehension of the factors
influencing the EO for sustainable SME continuity and development in rural KZN
areas. The study, therefore, sought to provide key insights into both the theoretical
and practical implications of EO among rural SMEs. In addition, a wide range of
suggestions and a theoretical framework are proposed for SME owners- managers,
public servants, and legislators to comprehend and implement in solving existing
rural SME problems, thereby encouraging the EO for rural SME owners- managers.
The suggested integrated EO framework comprises key components of an EO that
supports sustained rural SME business continuity and development. Consequently,
it is critical for owners-managers of rural SMEs to pay attention to these, as well as
additional, pertinent theories concerning EO for rural SME survival and growth.
These will help and direct them as they navigate a variety of obstacles in their
working environments.802 p
The role of performance management systems on the technical efficiency of academics in public higher education institutions in KwaZulu-Natal
No full textSubmitted in fulfilment of the requirement of the degree of Doctor of Philosophy in Human Resources Management, Durban University of Technology, Durban, South Africa, 2024.This study aimed to investigate the role of performance management systems on the
technical efficiency of academics in public higher education institutions in KwaZulu-Natal.
A cross-sectional study was conducted to assess the outcome and exposures of the
research participants simultaneously. The mixed methods approach was utilised to collect
and analyse the quantitative and qualitative data. The study involved academic staff at
the University of Zululand, University of KwaZulu-Natal and Durban University of
Technology. Questionnaires and interviews were used to collect primary data from the
research participants.
Quantitative data were collected from 170 respondents who were mobilised through
stratified sampling method, while the qualitative data were collected from 12 participants
through a purposive sampling approach. The quantitative data was analysed using SPSS,
27, whereas the qualitative data was analysed using NVivo, version 13. Statistically,
Pearson's correlation and linear regression were performed to assess the relationship
between performance management systems and technical efficiency among academics
in public higher education institutions in KwaZulu-Natal. The results showed that while
Pearson's correlation indicated a strong positive relationship between the performance
management system implementation and academic's technical efficiency, the linear
regression results showed no relationship between the implementation of the
performance management system and academic research efficiency. Pearson's and
linear regression results indicated no positive relationship between PMS implementation
and academic efficiency research. Moreover, Pearson's correlation and linear regression
results revealed no positive relationship between PMS implementation and teaching
within South African higher education institutions, and no positive correlation between the
implementation of PMS and other academic or service-related activities. By contrast, the
qualitative findings indicated that implementing a performance management system
impacted academics’ technical efficiency in terms of teaching and learning, other related
academic activities, and research and innovation. This study contributes to the body of knowledge by determining how performance
management systems impact academics’ technical efficiency in higher education
institutions. Theoretically, the study contributes to the theory and practice regarding
employees' perceived effectiveness of the performance management system toward
improving academics’ technical efficiency.
Assessing the responsiveness of journalism curricula to the labor market needs in South Africa : a systematic review
No full textThrough the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, this study evaluates the responsiveness of journalism curricula in South Africa to the evolving needs of the industry. Forty-six reviewed studies literature were retrieved for analysis. Findings indicate that while some institutions have incorporated digital media skills, critical thinking and ethics into their curricula, significant gaps remain in multimedia storytelling, data journalism, media entrepreneurship and AI tools in newsrooms. Furthermore, there is limited emphasis on practical work-integrated learning (WIL), leaving graduates underprepared for the fast-paced and highly competitive journalism labor market. The study recommends curriculum reforms that emphasize practical skills, industry partnerships and adaptabilit
Development of a sorghum and pearl millet-based instant breakfast cereal for the South African National School Nutrition Programme
No full textThesis submitted in fulfilment of the requirements of the degree of Master of Applied Science in Food and Nutrition, Durban University of Technology, Durban, South Africa, 2025.Background: The National School Nutrition Programme (NSNP) in South Africa was introduced
in 1994 to address hunger, malnutrition, and access to food among disadvantaged school children.
Many schools that access the NSNP are currently benefiting from sponsored breakfast
programmes funded by major food companies; however, the initiative is provided to a limited
number of schools. Despite these efforts, many learners start their day without breakfast, leading
to low energy and poor concentration levels, highlighting a gap in the current NSNP meal
provisioning structure. In 2024, the Department of Basic Education and National Treasury
pledged to implement breakfast provisioning as part of the NSNP. However, the rollout has been
delayed due to budget constraints and the limited range of breakfast options (maze-meal porridge)
provided by major food companies. The revival of indigenous grains can contribute to achieving
the Sustainable Development Goals (SDGs) focused on climate action, zero hunger, sustainable
consumption, and good health and well-being. Developing a nutritious and filling breakfast
porridge using indigenous grains could address hunger while providing learners with sustained
energy and thereby enable them to focus until their next meal.
Aim: This study aimed to develop a tasty, nutritious, and cost-effective breakfast cereal suitable
for the NSNP, using sorghum and pearl millet as the base ingredients.
Methodology: The study population consisted of learners aged 7-20 from four quintile 1-3
schools, two primary and two secondary schools, participating in the NSNP in the iLembe district
of KwaZulu-Natal. A breakfast needs assessment, and preference survey informed the food
product development process. Consent was obtained from 405 school learners to participate in the
breakfast needs and preference survey. A sensory acceptable breakfast porridge was developed
following the systematic steps of food product development using a 1:1 ratio of fermented sorghum
and pearl millet. A pure lactic acid bacteria (LAB) starter culture was isolated and used to ferment
the sorghum. To make the instant porridge, the fermented sorghum, pearl millet, and other
ingredients were then cooked, dried, grounded and packaged.
The developed instant porridge underwent sensory analysis throughout the product development
process using a 9-point hedonic rating scale. Consenting Food and Nutrition students experienced
in the sensory assessment process were used to analyse the sensory acceptability of the trial recipes during development. The instant porridge was also subjected to nutrient analysis, microbial, and
shelf-life testing. Thereafter, the instant porridge underwent a final sensory analysis using a 7-
point facial hedonic rating scale among 200 consenting learners aged 7-20 from the four
participating schools to assess the product’s sensory acceptability.
Results: The breakfast needs and preference survey showed that a significant percentage of the
school learners most times consumed breakfast (35.1%) or sometimes consumed breakfast (49.9%)
(p<0.00). It was found that most learners consumed breakfast inconsistently. Of the learners who
inconsistently consumed breakfast, 56.7% indicated that they often skipped breakfast due to lack
of time, whilst an alarming 30% said it was due to not having access to food. Primary school
learners received a breakfast porridge from the NSNP at school, whereas high school learners did
not. Popular breakfast cereals, such as Corn Flakes, All Bran Flakes and Weet-Bix, were preferred
by 53.3% (n=216) among the learners. Regarding preference for breakfast porridge flavours, a
significant percentage (40.2%) of the learners indicated that they preferred a chocolate-flavoured
breakfast cereal (p<0.001).
The porridge had a protein content of 10.1g/100g, dietary fibre (5.8g/1100g), vitamin B1
(0.37mg/100g), B3 (16.46mg/100g), phosphorus (3.15mg/100g), iron (3.81mg/100g) and zinc
(1.24mg/100g). The porridge was deemed microbiologically safe, and had a shelf-life of 12
months. Findings from the learner sensory assessment of the developed product by learners
indicated that learners rated the product as ‘good’ (35.0%, n=70), ‘super good’ (26.5%, n=53) and
‘really good’ (14.5%=29). While both boys and girls rated the developed breakfast cereal above
4, on average, boys (mean = 4.7) rated it significantly higher than girls (mean = 4.16), (p=0.002,
according to the t-test). However, there was no significant correlation between sensory scores
across grade and age groups.
Conclusion: The findings of the current study highlights and emphasises the need to address the
nutritional needs of NSNP learners by incorporating a breakfast component. The study identified
the preferred quality attributes of the breakfast cereal by the quintile 1-3 school learners. A
nutritious, cost-effective, fermented sorghum and pearl-millet porridge pocessing the preferred
quality attributes was developed. The developed porridge can supplement the recommended daily
allowance (RDA) shortfall of the NSNP and help achieve several SDGs for general health and well-being. By offering a nutritious breakfast option, the developed porridge can improve school
attendance and learners’ cognitive performance, contributing to their overall growth and
educational success. Sorghum and pearl millet, as indigenous grains, would play the role of an
affordable, readily available key base ingredients and hence vital and sustainable source foods for
improving the food and nutrition security of school learners accessing the NSNP.
3D mmWave MIMO channel modeling and reconstruction for street canyon and highrise scenarios
No full textThe use of millimeter-wave (mmWave) and full-dimensional multiple-input multiple-output (FD-MIMO) antenna systems for 3D wireless communication is being exploited for enhanced network capacity improvement in the ongoing fifth-generation (5G) deployment. For adequate assessment of competing air interface, random access channelization, and beam alignment procedures in mmWave systems, channel models for different use scenarios are necessary. A ray-tracing study was conducted with the use of a Wireless Insite ray tracing algorithm to characterize the mmWave channel in urban areas, using Lagos Island, Nigeria databases to predict measured statistics. These statistics include path loss, rms delay spread, angular spread of arrival, and departure in the azimuth and elevation domain. A 3GPP-style 3D mmWave channel is modeled and reconstructed, emphasizing the use of a ray tracer to determine elevation model parameters. Line of sight (LOS) and non-line of sight (NLOS) 3D models were developed for street canyon and high-rise scenario
An ERP implementation case study in the BRICs country South African BRICS South Africa economic tourism economic sector
No full textSouth Africa is one of the BRICS (Brazil, Russia, India, China and South Africa) nations that is changing the area of BRICS South Africa's economic in tourism. The current theory holds that demand for BRICS South Africa economic tourism initially rises, but then declines once a certain level of corruption reaches a certain threshold. As means of computerized data storage helps management with a complete vision for their performance. In this paper, the analysis of fake travel agent sites shows that the B&B businesses in Soweto and Durban are experiencing huge glitches. They also have a slow booking process because they use only cell phone calls and walk-ins for bookings, which results in slow business growth and unorganized transactions. This journal will focus on how to implement ERP to address these problems faced by this B&B, short stay, or rather provide a set of propositions on the designed website. Nevertheless, the centralized management of information from ERP can have a huge impact on the company's services. The study concludes that it is very important for travelers to have an online website to prevent being scammed online and always make sure travelers are safe and carried to their destinations without problems
Teachers and school social workers collaborating to support South African adolescents with psychosocial challenges
No full textThe strategies employed by teachers and school social workers are deemed pivotal in aiding adolescents grappling with psychosocial challenges. Despite the worldwide acknowledgment of the importance of comprehensive support for adolescent development, there exists an evident lack of inquiry into the approaches employed by these professionals in the context of South African public schools. This qualitative exploratory pilot study, conducted with teachers and school social workers (n = 6) from a bigger research project in two Gauteng District eleven schools, explores the perspectives of teachers and school social workers on supporting adolescents with psychosocial challenges. The thematic analysis confirmed that diverse approaches were used to support adolescents, the challenges faced by these professionals in their efforts to provide support, and existing and needed multidisciplinary collaborations in the school. The study recommends that a bigger research study be undertaken focusing on this current aim and multidisciplinary collaboration efforts in schools. It also argues that teachers need to be trained to identify adolescents with psychosocial challenges and school social workers need to be deployed in school settings
The effects of load shedding on MBA students’ learning at the Durban University of Technology in South Africa
No full textSubmitted in fulfilment of the requirements of the Master of Management Sciences specialising in Business Administration
at the Durban University of Technology, Durban, South Africa, 2025.Over the years electricity has been one of the biggest support structures in advancing teaching and learning for universities in South Africa. However, South African universities are currently inundated by several challenges including load shedding. Energy is considered the backbone of an economy's prosperity and progress and plays a crucial role in socio-economic development. Moreover, South Africa is facing an extreme shortage of electricity resulting in an energy crisis which has given rise to social and economic challenges that have threatened teaching and learning processes. This study aimed to determine the effect of load shedding on teaching and learning in the Durban University of Technology (DUT) MBA programme. This aim was achieved by using a qualitative research approach that involved the collection of data using interviews. Data was collected from a census of 35 participants consisting of MBA students and staff in the DUT MBA programme. The findings of this study indicated that widespread load shedding increases electronic resource access concerns. Students complained about frequent online learning platform stoppages, inadequate internet connections, and limited research and communication. Alternative power solution students face these challenges, which hinder academic progress and widen the gap. Interruptions upset students and lowered morale, hampering the DUT MBA teaching. The findings of this study contribute to the broader understanding of the impact of infrastructure-related challenges, such as load shedding, on the core activities at higher education institutions. While the specific context is the DUT MBA programme, the findings provide valuable insights that may be applicable to the education sector more broadly. The knowledge generated from this research can fill an important gap in the existing literature on the intersection of energy supply issues and the delivery of higher education. The findings of this study are also beneficial for both the academic and non-academic community at South African universities broadening the discussion around resourcing concerns in higher education.
Climate change modeling for water resources management : Tana Sub-Basin, Ethiopia
No full textSubmitted in the fulfillment of the requirements for the degree of Doctor of Engineering: Civil Engineering, Durban University of Technology, Durban, South Africa, 2025.This study, conducted in the Tana Sub-basin, Ethiopia, aimed to model the impact of climate
change on water resources management. The Soil and Water Assessment Tool (SWAT), SPI
generator, and RStudio were employed to conduct a comprehensive analysis of climate variability,
hydro-climatic extremes, and the impact of land use land cover change on water resources within
the region. The findings highlight the significant impacts of both climate variability and land use
land cover change on water resources management in the Tana Sub-basin. Changing climate
patterns and hydro-climatic extremes were identified as key factors posing increasing challenges
to water availability and sustainable management within the region.
In analyzing the variability and trends of climate parameters in the Tana Sub-basin, various
statistical methods and indices were employed to assess precipitation and temperature patterns.
The findings indicated a statistically non-significant increasing trend in rainfall across the Sub basin, with values ranging from 1.64 to 5.37 mm/year. With regard to temperature, an increase
was observed, but it was also not statistically significant. The seasonality index ranged between
0.87 and 1.03. In 36.69% of the Sub-basin, rainfall occurs in marked seasonal patterns with a long
dry season and the remaining 63.31% is concentrated in three or fewer months, indicating a
different rainfall distribution pattern. The assessment of precipitation concentration found that
57.5% of the rainfall data exhibited strong irregular concentration; 41.5% showed irregular
concentration, and 1% exhibited moderate concentration. This decreasing trend in projected mean
annual precipitation and increasing trend in temperature under the RCP4.5 and RCP8.5 scenarios
from 2020 to 2100 indicated significant changes in climate conditions in the Tana Sub-basin. In
conclusion, the study underscores the presence of climate change, variability, and trends in the
Tana Sub-basin, highlighting the need to align agricultural and water resource management
practices with the observed climate variability.
Hydro-climatic extremes in the Tana Sub-basin, including drought events, were investigated using
several statistical measures and tests including coefficient of variation, seasonality index,
precipitation concentration index, Mann-Kendall trend test, and Sen’s slope estimator. Three
categories of drought were identified: meteorological drought, agricultural drought, and
hydrological drought. The frequency of meteorological drought ranged from 1.05% to 10.04%,
agricultural drought from 1.26% to 12.21%, and hydrological drought from 0.21% to 14.5% in the
study area. The variability in drought occurrence indicates that certain areas and seasons in the
Tana Sub-basin are more susceptible to drought conditions than others. The observation of a
potential trend in drought and wet extent occurrences in the study area until 2100 suggests that it
may experience significant shifts in hydro-climatic patterns due to climate change. This highlights
the importance of considering both spatial and seasonal patterns when assessing drought risks and
implementing appropriate measures for water resource management and agricultural practices. In
conclusion, the study emphasizes the significance of understanding spatial and seasonal variations
in drought occurrence and aligning agricultural practices and water resource management
accordingly.
This study also assessed the impacts of land use land cover change on water resources using the
Soil and Water Assessment Tool. Three land use land cover maps (1986, 2000, and 2014) were
analyzed to assess and quantify the changes and their impact on water resources. The findings
indicated that changes in land use land cover have a significant impact on various components of
the water balance in the study area. Compared to the baseline year of 1986, the average annual
water yield increased by 14.88% and 12.6% in 2000 and 2014, respectively. Baseflow exhibited
an increase of 18.4% in 2000 but decreased by 7.16% in 2014. Surface runoff increased by 12%
and 16.16% in 2000 and 2014, respectively. Evapotranspiration decreased by 18.39% and 13.49%
in 2000 and 2014, respectively. The expansion of cultivated land and the decline of forestland and
grassland have implications for water resources and hydrological processes. The study thus
demonstrates that land use land cover changes in the Tana Sub-basin have significant implications
for surface runoff, water yield, evapotranspiration, and baseflow.
The analysis of water consumption by different sectors in the Sub-basin in 2020 indicated total
annual water consumption for irrigation and horticulture of approximately 555.76 and 46.52
MCM, respectively. Livestock consumes about 31.78 MCM annually. Urban and rural domestic
iii
water consumption is estimated to be around 22.03 and 33.43 MCM/year, respectively. The highest
water-consuming sectors in the Sub-basin are rainfed agriculture and hydropower, accounting for
more than 3,700 MCM annually. The projected increase in water demand, as indicated by the
estimated water requirements of 6079.01 MCM in 2025, 6423.99 MCM in 2030, and 7519.93
MCM in 2035, emphasizes the urgency of sustainable water resource management. The study
proposes adaptive strategy options for integrated water resource management as a crucial step in
addressing the scarcity of water and ensuring sustainable use of water resources in the area.
Assessing and updating water demand and available water resources are fundamental for informed
decision-making and effective management of water resources in the Tana Sub-basin.
Implementation of the adaptive strategy options outlined is essential to mitigate the challenges
posed by increasing water demand and consumption, ultimately contributing to sustainable
management of water resources in the region
Cheminformatics bioprospection and experimental validation of corn silk for interventive type 2 diabetes therapeutics
No full textSubmitted in fulfilment for the Degree of Master of Applied Science in Biotechnology, Durban University of Technology, Durban, South Africa, 2024.Diabetes mellitus (DM) is one of the oldest known human diseases, with type 2 diabetes
mellitus (T2DM) being the most prevalent form. Type 2 diabetes mellitus (T2DM) is
characterized by elevated blood glucose levels due to defective insulin production and/or
resistance to insulin. If left untreated, it can lead to severe complications affecting various
body systems. While synthetic medications are commonly used to treat T2DM, their
associated drawbacks, such as high cost, inaccessibility and side effects, mitigate their
application in managing T2DM. Consequently, there has been a growing interest in natural
products with antidiabetic potential. Natural products, including medicinal plants and plantderived products, have been used for centuries, and their active compounds continue to be
explored for therapeutic applications. For example, corn silk (CS), a waste material of corn
cultivation, possesses several therapeutic properties, including antidiabetic potential.
Although, studies reporting the promising hypoglycaemic potentials of CS exist, its exact
mechanism of action remains incompletely elucidated, a research gap that was fulfilled in
this study through metabolomics, cheminformatics bioprospection and in vitro
experimental validation.
To identify the constituents in CS, ultra-performance liquid chromatography-mass
spectrometry analysis and principal component analysis was performed on its three extracts
(aqueous, hydro-ethanolic and ethanolic) at two developmental growth stages (premature
and mature). A library consisting of 128 metabolites was generated from all the samples of
CS with qualitative and quantitative variations observed between the two growth stages of
CS and the type of solvent used for extraction. Specifically, the mature CS had a higher
abundance of most metabolites, with the hydro-ethanolic extract of CS being the most
metabolites-rich compared to the aqueous and ethanolic extracts of CS. These metabolites
were thereafter subjected to bioprospection against the therapeutic targets, such as enzymes
and genes implicated in the pathogenesis of T2DM using computational techniques.
The modulatory role of CS metabolites on six enzymes implicated in the pathogenesis of
T2DM and its secondary complication, particularly alpha-amylase (AA), alpha-glucosidase
(AG), aldose reductase (AR), dipeptidyl peptidase-4 (DPP-4), protein tyrosine phosphatase
1B (PTP1B) and sorbitol dehydrogenase (SDH), was analysed using molecular docking
complemented with molecular dynamics (MD) simulation. Molecular docking analysis
identified aesculin (-8.1 kcal/mol), austricin (-7.8 kcal/mol), (6E)-1-(4-hydroxyphenyl)-7-
phenylhepta-4,6-dien-3-one (-9.9 kcal/mol), (-)-11-hydroxy-9,10-dihydrojasmonic acid
11-beta-D-glucoside (-8.6 kcal/mol), phaseic acid (-6.0 kcal/mol), and erythronolide B (-
9.2 kcal/mol) as compounds with the most negative scores against AA, AG, AR, DPP-4,
PTP1B and SDH, respectively. However, a further insight into the binding free energy
(ΔGbind) calculations of the putative leads against each enzyme over a 150-ns simulation
period revealed that R-7-butyl-6,8-dihydroxy-3-[(3e)-pent-3-en-1-yl]-3,4-
dihydroisochromen-1-one (BHP), 1-O-vanilloyl-beta-D-glucose (VBJ), (-)-11-hydroxy9,10-dihydrojasmonic acid 11-beta-D-glucoside (HDJ), p-coumaroyl malic acid (CMA), 2-
hydroxydecanedioic acid (HDA), and (-)-11-hydroxy-9,10-dihydrojasmonic acid 11-beta-D-glucoside (HDJ) hold remarkable therapeutic promise as modulators of AA, AG, AR,
DPP-4, PTP1B, and SDH, respectively. The post-MD dynamic simulation analysis and
interaction plots in each case revealed the formation of thermodynamically stable
complexes suggestive of the putative leads as potential modulators of the respective
investigated enzymes and their possible applications in the management of T2DM and its
secondary complications. Density functional theory (DFT) analysis was used to determine
the molecular characteristics of the top ranked CS metabolites identified to modulate the
investigated enzyme targets. Although the lower energy gaps, higher softness and lower
chemical hardness of the metabolites did not correlate with their high negative binding free
energy (potentially due to the observed relative residue fluctuations and increased surface
area of the targets upon ligand binding), their electrophilicity indices which were above 1.5
electron volt (eV) alluded to their strong electrophilic potential. This highlights their ability
to interact with amino acids with nucleophilic side chains of the target enzymes that is
indicative of enhanced specificity and binding to the enzymes.
Subsequently, a network pharmacology study was conducted to elucidate the relationship
between CS constituents and signaling pathways implicated in T2DM. The analysis
identified the cAMP pathway as the central signaling pathway, with adenosine receptor A1
(ADORA1), hydroxycarboxylic acid receptor 2 (HCAR2) and gamma-aminobutyric acid
type B subunit 1 (GABBR1) as key therapeutic targets. Gallicynoic acid (-48.74 kcal/mol),
dodecanedioc acid (-34.53 kcal/mol), and tetradecanedioc acid (-36.80 kcal/mol) interacted
effectively with ADORA1, HCAR2, and GABBR1, respectively, relative to the reference
standards (metformin and resveratrol) and formed thermodynamically stable complexes, as
indicated by post-MD analysis results. These findings suggest the compounds as potential
drug candidates for T2DM through modulation of cAMP pathway genes. The cAMP
pathway is implicated in the pathogenesis of T2DM through various levels including
glucagon and epinephrine-stimulated cAMP production, increased glucose release from the
liver, modulation of insulin signaling, insulin resistance and the regulation of gut hormone
secretion, including glucagon-like peptide-1.
To complement and validate the results obtained through network pharmacology as a
further way of elucidating the mechanism of antidiabetic action of CS, experimental
validation employing the use of HepG2 cells was performed. The effect of different CS
formulations on HepG2 cells was firstly assessed using the 3-(4,5-dimethylthiazol-2-yl)-
2,5-diphenyltetrazolium bromide (MTT) viability and glucose consumption assays,
followed by real-time polymerase chain reaction (RT-qPCR) to understand the effect of CS
on the expression of ADORA1 and GABBR1, the top two target genes modulated by the CS
metabolites as identified by the network pharmacology study. For the MTT assay, CS
extracts at concentrations 75 – 100 µg/mL promoted viability of HepG2 cells, with the
ethanolic extract of the mature CS being the most viable relative to the controls (insulinand metformin-treated) and the untreated cells. Generally, higher HepG2 cell viability and
glucose uptake were observed following treatment with mature CS extracts compared to
premature CS. Specifically, the most significant and enhanced glucose uptake level was
observed with both normal and insulin-resistant HepG2 cells following treatment with the
aqueous extracts of mature CS extract compared to the controls. Furthermore, compared to the untreated cells, as well as insulin- and metformin-administered cells, treatment with CS
extracts remarkably inhibited the expression of ADORA1 and GABBR1 in insulin-resistant
HepG2 cells with the most prominent effect observed with the aqueous extract of premature
CS. These observation with the CS aqueous extracts may be attributed to their relatively
higher abundance of the profiled metabolites such as gallicynoic acid B and tetradecanedioc
acid, which were more than 40% each by composition in both the mature and premature
extracts. These findings regarding the high concentrations of gallicynoic acid B and
tetradecanedioc acid in CS aqueous extracts are not only significant in modulating the
expression of ADORA1 and GABBR1, resulting in increased glucose uptake in the treated
cells but consistent with the results of MD simulation that profiled the two compounds as
putative leads against the two most significant therapeutic targets in the cAMP signalling
pathway associated with T2DM. Overall, the findings from this study have contributed to
the elucidation of the mechanisms of antidiabetic action of CS metabolites which would be
vital in the development of CS as a therapeutic agent for the management of T2DM and its
associated secondary complications.