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Evaluation of antioxidant potential, anti-inflammatory effect and the mechanisms of action of phenolic compounds from South African indigenous plants used in the management of diabetes-related male infertility
Author(s)
Nethengwe, Murendeni
Date Issued
2024
Type
Thesis
Publisher
Cape Peninsula University of Technology
Abstract
Diabetes mellitus (DM) is a chronic metabolic disease characterised by hyperglycaemia. The
rise in mortality associated with DM is attributed to the complications driven by prolonged
hyperglycaemia which leads to excessive production of free radicals. The imbalance in the
level of free radicals causes oxidative stress and inflammation. Hyperglycaemic-induced
oxidative stress and inflammation have previously been shown to cause damage and a
significant impact on male sub-/infertility by reducing sperm parameters such as sperm
motility, sperm DNA and mitochondrial membrane integrity, and sperm capacitation. Over the
years, these diabetic complications have been treated with conventional drugs, however, the
adverse effects associated with their long usage have necessitated searching for safe and
effective treatment that targets the pathological pathways leading to diabetic-related male
infertility. Therefore, the present study identified potential medicinal plants (Androstachys
johnsonii and Garcinia livingstonei) used in traditional medicine for the treatment of DM-related
male infertility and investigated their effects in the amelioration of reproductive dysfunction
linked to hyperglycaemia. The study is premised on the hypothesis that phenolic-rich South
African medicinal plants could exhibit some antidiabetic effects, and attenuate oxidative stress
and inflammation in the semen of diabetic individuals with male infertility. The medicinal plants
were identified in the first phase of the study, and the plant extracts were prepared. Preliminary
studies were conducted to determine the hypoglycaemic, anti-inflammatory, and antioxidant
properties of the plant extract. The plant extracts were tested on sperm cells induced with
hyperglycaemia in vitro. Normal sperm cells were collected from 25 male individuals. Each
sample was divided into a normal group sample, hyperglycaeimia-induced sample, and a
sample induced with hyperglycaemia and treated with the plant extract. Phenolic compounds
that could be responsible for the biological activities were identified from the plant extracts and
among which, flavonoids were majorly abundant in both plant extracts. The results
demonstrated high antioxidant capacity in both plant extracts through the determination of
ferric reducing antioxidant power (FRAP), Trolox equivalent antioxidant capacity (TEAC), and 2,2-diphenyl-1-pycrylhydrazyl (DPPH). Also, the extracts exhibited significant (P<0.05) α-
glucosidase inhibitory activity higher than acarbose. Both extracts displayed anti-inflammatory
effects significantly (P<0.05), depending on the concentration of the plant extract. While no
cell toxicity on C3A hepatocarcinoma cells was observed with all test concentrations of G.
livingstonei, the highest concentration (250 μg/mL) of the A. johnsonii extract showed cell
toxicity. Hyperglycaemia induction led to a significant (P<0.05) increase in the production of
ROS, which was significantly reduced after exposure to both plant extracts. Both catalase and
superoxide dismutase (SOD) activities remained unchanged after hyperglycaemia induction
and treatment with both plant extracts. Induction of hyperglycaemia led to the decline of sperm
parameters: motility, vitality, DNA integrity, mitochondrial membrane potential, capacitation,
and acrosome reaction. Treatment with G. livingstonei led to increasing in all tested sperm
parameters, with the lowest concentration exhibiting maximum protective effects. The
administration of the A. johnsonii extract on hyperglycaemic cells also led to an increase in all,
with the highest concentration (1 μg/mL) leading to the highest protective effects. The findings
of this study show that both medicinal plants have potential therapeutic effects to ameliorate
oxidative stress-causing hyperglycemia in human semen. The results of this study revealed
that both A. johnsonii and G. livingstonei can potentially reduce glucose levels, and exhibit
protective effects on the sperm cells of males with DM. However, further studies in vitro and
in vivo are necessary to understand the safe and effective optimum concentrations, and other
mechanisms of action through which the plant extracts exhibit their effects in the treatment of
diabetic complications.
rise in mortality associated with DM is attributed to the complications driven by prolonged
hyperglycaemia which leads to excessive production of free radicals. The imbalance in the
level of free radicals causes oxidative stress and inflammation. Hyperglycaemic-induced
oxidative stress and inflammation have previously been shown to cause damage and a
significant impact on male sub-/infertility by reducing sperm parameters such as sperm
motility, sperm DNA and mitochondrial membrane integrity, and sperm capacitation. Over the
years, these diabetic complications have been treated with conventional drugs, however, the
adverse effects associated with their long usage have necessitated searching for safe and
effective treatment that targets the pathological pathways leading to diabetic-related male
infertility. Therefore, the present study identified potential medicinal plants (Androstachys
johnsonii and Garcinia livingstonei) used in traditional medicine for the treatment of DM-related
male infertility and investigated their effects in the amelioration of reproductive dysfunction
linked to hyperglycaemia. The study is premised on the hypothesis that phenolic-rich South
African medicinal plants could exhibit some antidiabetic effects, and attenuate oxidative stress
and inflammation in the semen of diabetic individuals with male infertility. The medicinal plants
were identified in the first phase of the study, and the plant extracts were prepared. Preliminary
studies were conducted to determine the hypoglycaemic, anti-inflammatory, and antioxidant
properties of the plant extract. The plant extracts were tested on sperm cells induced with
hyperglycaemia in vitro. Normal sperm cells were collected from 25 male individuals. Each
sample was divided into a normal group sample, hyperglycaeimia-induced sample, and a
sample induced with hyperglycaemia and treated with the plant extract. Phenolic compounds
that could be responsible for the biological activities were identified from the plant extracts and
among which, flavonoids were majorly abundant in both plant extracts. The results
demonstrated high antioxidant capacity in both plant extracts through the determination of
ferric reducing antioxidant power (FRAP), Trolox equivalent antioxidant capacity (TEAC), and 2,2-diphenyl-1-pycrylhydrazyl (DPPH). Also, the extracts exhibited significant (P<0.05) α-
glucosidase inhibitory activity higher than acarbose. Both extracts displayed anti-inflammatory
effects significantly (P<0.05), depending on the concentration of the plant extract. While no
cell toxicity on C3A hepatocarcinoma cells was observed with all test concentrations of G.
livingstonei, the highest concentration (250 μg/mL) of the A. johnsonii extract showed cell
toxicity. Hyperglycaemia induction led to a significant (P<0.05) increase in the production of
ROS, which was significantly reduced after exposure to both plant extracts. Both catalase and
superoxide dismutase (SOD) activities remained unchanged after hyperglycaemia induction
and treatment with both plant extracts. Induction of hyperglycaemia led to the decline of sperm
parameters: motility, vitality, DNA integrity, mitochondrial membrane potential, capacitation,
and acrosome reaction. Treatment with G. livingstonei led to increasing in all tested sperm
parameters, with the lowest concentration exhibiting maximum protective effects. The
administration of the A. johnsonii extract on hyperglycaemic cells also led to an increase in all,
with the highest concentration (1 μg/mL) leading to the highest protective effects. The findings
of this study show that both medicinal plants have potential therapeutic effects to ameliorate
oxidative stress-causing hyperglycemia in human semen. The results of this study revealed
that both A. johnsonii and G. livingstonei can potentially reduce glucose levels, and exhibit
protective effects on the sperm cells of males with DM. However, further studies in vitro and
in vivo are necessary to understand the safe and effective optimum concentrations, and other
mechanisms of action through which the plant extracts exhibit their effects in the treatment of
diabetic complications.
Additional information
Thesis (DPhil (Biomedical Sciences))--Cape Peninsula University of Technology, 2024
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