**1. Introduction**

Infertility is a reproductive health disease defined by the failure to achieve a pregnancy after 12 months or more of regular unprotected sexual intercourse [1]. Male factor infertility can contribute between 30 and 50% to this condition and may arise from several factors such as physiological, systemic pathologies, genetic abnormalities, environmental pollution, and oxidative stress (OS) [2, 3].

OS is described as an imbalance between the production of reactive oxygen species (ROS) and their removal or reducing agents called antioxidants [4]. This state of OS potentially leads to the damage of biomolecules such as proteins, nucleic acids, and lipids [4]. In recent years, OS has become more prevalent and has significantly contributed to abnormal sperm morphology [5–8] and sperm quality

and quantity [6, 7, 9]. In the testes, OS is capable of disrupting the steroidogenic capacity of Leydig cells as well as the spermatogenesis process [10]. Spermatozoa contain polyunsaturated fats (PUFAs) and limited cytoplasm antioxidant enzymes [11] and are susceptible to oxidative attack. The free radical attack can induce lipid peroxidation (LPO) and DNA fragmentation, disrupting both sperm development and motility [2, 11].

Numerous disorders of the male reproductive system such as cancer, varicocele, cryptorchidism, testicular torsion of the spermatic cords, and diabetes have been associated with male infertility due to OS caused by the uncompensated hyperproduction of ROS [12]. The OS derived from diabetic mellitus (DM) may affect the male reproductive function [11]. Diabetes mellitus is a group of metabolic conditions that are characterized by high glucose levels (hyperglycemia) caused by abnormal insulin secretion/insulin deficiency, abnormal insulin action, or both. It has been demonstrated that diabetes has a direct effect on male fertility [13]. OS in diabetic patients develops from pathways including the nonenzymatic, enzymatic, and mitochondrial signaling pathways [12–14]. Although the problems arising from DM have been widely investigated, the mechanisms responsible for the male reproductive dysfunction are still poorly understood [15]. In hyperglycemic patients, glucose undergoes autoxidation and reacts with proteins leading to the development of Amadori products and advanced glycosylation end products (AGEs). In hyperglycemia, there is enhanced metabolism of glucose through the polyol (sorbitol) pathway, which also results in the enhanced production of superoxide [11, 16]. Another enzymatic generation of ROS is via the mitochondrial respiratory chain through the oxidative phosphorylative process where electrons are transferred from electron carriers NADH and FADH2, through four complexes in the inner mitochondrial membrane, to oxygen, generating ATP in the process [17]. Hyperglycemic conditions disturb endothelial cells, and ROS are produced which participate in the development of diabetic complications. There are enzymatic overproductions of ROS in diabetes through NADPH oxidase that enhance O2 <sup>−</sup> [18].

Diabetes-related OS, endocrine disorders, and neuropathy may contribute to the reproductive impairment by causing sexual function alterations including testicular function and epididymal sperm transit [19]. Moreover, under OS condition the protective effects of testicular and epididymal antioxidant enzymes decline [6, 20].

Many artificial and natural agents possessing antioxidant properties, such as dietary antioxidants, may be of great importance as additional protective measures and have been proposed to prevent and/or treat oxidative damage induced by DM [6]. The use of derivatives of plant materials might be important and effective because they are less toxic and affordable as well as minimize side effects or risks caused by other options [20]. Phytochemicals are considered strong natural antioxidants and play an important role in healthcare systems [6]. They have adaptive characteristics to respond to stress and help regulate the interconnected endocrine, immune, and nervous systems [6]. Moreover, ethnobotanical research, literature reviews, and experimental studies reported the beneficial effect of plant materials which have been used many years ago in prevention and treatment of diabetes as well as its complications [20]. More than 1200 flowering plants have been claimed to possess antidiabetic properties [22–24]. These properties have been found to be present in different parts of plants such as the aerial parts, bark, flowers, roots, seeds, leaves, bulbs, tubers, and/or the whole plant [22–24].

*Garcinia kola* (*G. kola*), commonly referred to as bitter kola, is one of such plants that has been widely used in ethnomedicine [25]. The therapeutic and medicinal values of *Garcinia kola* are the subject of many studies, and several researchers have described their functional health benefits [5, 26–30] *G. kola* is an angiosperm plant that belongs to the family of Guttiferae (Clusiaceae) [5, 28–30]. It adapts and grows

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**Figure 2.**

**Figure 1.**

*Potential Antioxidative Effects of Kolaviron on Reproductive Function in Streptozotocin-Induced…*

Moreover, phytochemical screening of *Garcinia kola* seed showed the presence of polyphenol compound, which is a bioflavonoid Kolaviron (KV). This extract was found in a 2:2:1 ratio of bioflavonoid GB1, GB2, and kola flavanone [21] (**Figure 2**). Polyphenolic compounds are composed of three benzene rings with hydroxyl (OH)

KV, extract from *G. kola* nut, has shown great potential for use in therapeutic medicine against many health-threatening chronic diseases of the liver and reproductive system and diabetes [5, 25–30]. It is widely used in traditional medicine in southern Nigeria for the treatment of different conditions associated with increased OS [5]. KV is known to possess antihyperglycemic effects in normal and alloxanand streptozotocin (STZ)-induced diabetic animals [21, 25]. Moreover, KV has elicited strong antioxidant activity in in vivo and in vitro models [33]. This property is due to the high flavonoid (bioflavonoids) contents which are able to terminate the

up in moist lowland forest and subtropical or tropical region. *Garcinia kola* tree is up to 14 m high and produces brown nut-like seeds (**Figure 1**). *G. kola* is highly valued in African countries such as Nigeria, Benin, Cameroon, Democratic Republic of Congo, Ivory Coast, Gabon, Ghana, Liberia, Senegal, and Sierra Leone. These

countries used *G. kola* seeds as source of food and medication [5].

groups which preserve antioxidant activity [31, 32] (**Figure 2**).

free radical chain reactions in response to OS [33].

*Garcinia kola tree (A) and its brown seeds (B).*

*Chemical structure of KV isolated from Garcinia kola seed.*

*DOI: http://dx.doi.org/10.5772/intechopen.84822*

*Potential Antioxidative Effects of Kolaviron on Reproductive Function in Streptozotocin-Induced… DOI: http://dx.doi.org/10.5772/intechopen.84822*

up in moist lowland forest and subtropical or tropical region. *Garcinia kola* tree is up to 14 m high and produces brown nut-like seeds (**Figure 1**). *G. kola* is highly valued in African countries such as Nigeria, Benin, Cameroon, Democratic Republic of Congo, Ivory Coast, Gabon, Ghana, Liberia, Senegal, and Sierra Leone. These countries used *G. kola* seeds as source of food and medication [5].

Moreover, phytochemical screening of *Garcinia kola* seed showed the presence of polyphenol compound, which is a bioflavonoid Kolaviron (KV). This extract was found in a 2:2:1 ratio of bioflavonoid GB1, GB2, and kola flavanone [21] (**Figure 2**). Polyphenolic compounds are composed of three benzene rings with hydroxyl (OH) groups which preserve antioxidant activity [31, 32] (**Figure 2**).

KV, extract from *G. kola* nut, has shown great potential for use in therapeutic medicine against many health-threatening chronic diseases of the liver and reproductive system and diabetes [5, 25–30]. It is widely used in traditional medicine in southern Nigeria for the treatment of different conditions associated with increased OS [5]. KV is known to possess antihyperglycemic effects in normal and alloxanand streptozotocin (STZ)-induced diabetic animals [21, 25]. Moreover, KV has elicited strong antioxidant activity in in vivo and in vitro models [33]. This property is due to the high flavonoid (bioflavonoids) contents which are able to terminate the free radical chain reactions in response to OS [33].

**Figure 1.** *Garcinia kola tree (A) and its brown seeds (B).*

**Figure 2.**

*Chemical structure of KV isolated from Garcinia kola seed.*

*Antioxidants*

and motility [2, 11].

and quantity [6, 7, 9]. In the testes, OS is capable of disrupting the steroidogenic capacity of Leydig cells as well as the spermatogenesis process [10]. Spermatozoa contain polyunsaturated fats (PUFAs) and limited cytoplasm antioxidant enzymes [11] and are susceptible to oxidative attack. The free radical attack can induce lipid peroxidation (LPO) and DNA fragmentation, disrupting both sperm development

Numerous disorders of the male reproductive system such as cancer, varicocele, cryptorchidism, testicular torsion of the spermatic cords, and diabetes have been associated with male infertility due to OS caused by the uncompensated hyperproduction of ROS [12]. The OS derived from diabetic mellitus (DM) may affect the male reproductive function [11]. Diabetes mellitus is a group of metabolic conditions that are characterized by high glucose levels (hyperglycemia) caused by abnormal insulin secretion/insulin deficiency, abnormal insulin action, or both. It has been demonstrated that diabetes has a direct effect on male fertility [13]. OS in diabetic patients develops from pathways including the nonenzymatic, enzymatic, and mitochondrial signaling pathways [12–14]. Although the problems arising from DM have been widely investigated, the mechanisms responsible for the male reproductive dysfunction are still poorly understood [15]. In hyperglycemic patients, glucose undergoes autoxidation and reacts with proteins leading to the development of Amadori products and advanced glycosylation end products (AGEs). In hyperglycemia, there is enhanced metabolism of glucose through the polyol (sorbitol) pathway, which also results in the enhanced production of superoxide [11, 16]. Another enzymatic generation of ROS is via the mitochondrial respiratory chain through the oxidative phosphorylative process where electrons are transferred from electron carriers NADH and FADH2, through four complexes in the inner mitochondrial membrane, to oxygen, generating ATP in the process [17]. Hyperglycemic conditions disturb endothelial cells, and ROS are produced which participate in the development of diabetic complications. There are enzymatic overproductions of

Diabetes-related OS, endocrine disorders, and neuropathy may contribute to the reproductive impairment by causing sexual function alterations including testicular function and epididymal sperm transit [19]. Moreover, under OS condition the protective effects of testicular and epididymal antioxidant enzymes decline [6, 20]. Many artificial and natural agents possessing antioxidant properties, such as dietary antioxidants, may be of great importance as additional protective measures and have been proposed to prevent and/or treat oxidative damage induced by DM [6]. The use of derivatives of plant materials might be important and effective because they are less toxic and affordable as well as minimize side effects or risks caused by other options [20]. Phytochemicals are considered strong natural antioxidants and play an important role in healthcare systems [6]. They have adaptive characteristics to respond to stress and help regulate the interconnected endocrine, immune, and nervous systems [6]. Moreover, ethnobotanical research, literature reviews, and experimental studies reported the beneficial effect of plant materials which have been used many years ago in prevention and treatment of diabetes as well as its complications [20]. More than 1200 flowering plants have been claimed to possess antidiabetic properties [22–24]. These properties have been found to be present in different parts of plants such as the aerial parts, bark, flowers, roots,

*Garcinia kola* (*G. kola*), commonly referred to as bitter kola, is one of such plants that has been widely used in ethnomedicine [25]. The therapeutic and medicinal values of *Garcinia kola* are the subject of many studies, and several researchers have described their functional health benefits [5, 26–30] *G. kola* is an angiosperm plant that belongs to the family of Guttiferae (Clusiaceae) [5, 28–30]. It adapts and grows

<sup>−</sup> [18].

ROS in diabetes through NADPH oxidase that enhance O2

seeds, leaves, bulbs, tubers, and/or the whole plant [22–24].

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This study was therefore designed to evaluate any potential effects of KV in boosting testicular and epididymal antioxidant status in STZ-induced diabetic Wistar rats.
