**3. Buchu and the reproductive system**

The benefits of Buchu may be applied to treat ailments of the reproductive system. As previously sited, Buchu is used as a urinary tract antiseptic and as an anti-inflammatory agent [2], thereby reducing the inflammation seen in UTI's and treating infections of the urethra and prostate. Buchu has many direct and indirect effects on the reproductive system via its ability to act as a diuretic, an anti-oxidant, anti-microbial and an anti-inflammatory agent. The ability of Buchu to do this will be looked at in more detail below, focussing on its actions in Benign Prostatic Hypertrophy/Hyperplasia (BPH), prostatitis, in UTI's and on male fertility.

### **3.1. Benign prostatic hypertrophy/hyperplasia**

BPH is the non-malignant enlargement of the prostate, and is the most common benign tumour in men over the age of 60 [17]. BPH has many predisposing factors, which include age, ethnicity, medical and family history and lifestyle factors such as cigarette smoking [17]. Men who have suffered from chronic diseases such as hypertension, coronary artery disease and diabetes mellitus are at risk of developing BPH [17].

The prostate is an exocrine gland [18] composed of fibromuscular tissue in a network of glands embedded in stroma [19]. Androgens are essential to growth of the prostate during early development, purberty and aging [20]. Androgens do not essentially cause BPH, but have been found to play a role in hypertrophy of the prostate along with other factors such as aging, diet, an increase in inflammatory mediators, hormones and oxidative stress [19].

BPH is characterised by nodular overgrowth of the epithelium and fibromuscular tissue [18] of the prostate, with the differentiation of fibroblasts into myofibroblasts being the hallmark of tissue remodelling [18] in the disease. Increased deposition of collagen in the ultrastruscture of the penis and the loss of smooth muscle causes urethral obstruction [21], causing a list of clinical symptoms related to urinary tract obstruction.

The pathophysiology of BPH is multifaceted, with local and endocrine factors being involved [17]. One of the main instigators is age-related changes to sex steroid hormone levels which leads to alterations in the metabolism of androgens locally. This disrupts the growth factor signalling pathways which interact with the stroma/epithelium, promoting tissue remodelling, leading to an increase in the size of the prostate [17]. The remodelled epithelium has an altered production of cytokines and chemoattractants, which encourages inflammation of the prostate and the production of ROS and RNS. With the increased proliferation of stromal and fibro‐ muscular cells comes an increased demand of nutrition and oxygen to be delivered to the prostate [17]. This leads to local tissue hypoxia, promoting neovascularisation to cope with the increased demand for blood flow, and the production of ROS [17]. The increase in ROS leads to further fibroblast to myofibroblast differentiation, perpetuating the cell proliferation cycle and resulting in a further increase in prostate volume.

Buchu, is hepatotoxic [2]. It has been found to reduce the levels of glutathione, a substance used by the liver in several detoxification steps [2], which would allow the accumulation of toxins within the liver. The depletion of glutathione and the excess amounts of pulegone found at high dosages lead to hepatocellular necrosis. Care should thus be taken when Buchu is consumed to ensure that the maximal therapeutic benefits are acquired, without any of the

The benefits of Buchu may be applied to treat ailments of the reproductive system. As previously sited, Buchu is used as a urinary tract antiseptic and as an anti-inflammatory agent [2], thereby reducing the inflammation seen in UTI's and treating infections of the urethra and prostate. Buchu has many direct and indirect effects on the reproductive system via its ability to act as a diuretic, an anti-oxidant, anti-microbial and an anti-inflammatory agent. The ability of Buchu to do this will be looked at in more detail below, focussing on its actions in Benign

BPH is the non-malignant enlargement of the prostate, and is the most common benign tumour in men over the age of 60 [17]. BPH has many predisposing factors, which include age, ethnicity, medical and family history and lifestyle factors such as cigarette smoking [17]. Men who have suffered from chronic diseases such as hypertension, coronary artery disease and

The prostate is an exocrine gland [18] composed of fibromuscular tissue in a network of glands embedded in stroma [19]. Androgens are essential to growth of the prostate during early development, purberty and aging [20]. Androgens do not essentially cause BPH, but have been found to play a role in hypertrophy of the prostate along with other factors such as aging, diet,

BPH is characterised by nodular overgrowth of the epithelium and fibromuscular tissue [18] of the prostate, with the differentiation of fibroblasts into myofibroblasts being the hallmark of tissue remodelling [18] in the disease. Increased deposition of collagen in the ultrastruscture of the penis and the loss of smooth muscle causes urethral obstruction [21], causing a list of

The pathophysiology of BPH is multifaceted, with local and endocrine factors being involved [17]. One of the main instigators is age-related changes to sex steroid hormone levels which leads to alterations in the metabolism of androgens locally. This disrupts the growth factor signalling pathways which interact with the stroma/epithelium, promoting tissue remodelling, leading to an increase in the size of the prostate [17]. The remodelled epithelium has an altered production of cytokines and chemoattractants, which encourages inflammation of the prostate and the production of ROS and RNS. With the increased proliferation of stromal and fibro‐

an increase in inflammatory mediators, hormones and oxidative stress [19].

Prostatic Hypertrophy/Hyperplasia (BPH), prostatitis, in UTI's and on male fertility.

unwanted toxic effects.

300 Antioxidant-Antidiabetic Agents and Human Health

**3. Buchu and the reproductive system**

**3.1. Benign prostatic hypertrophy/hyperplasia**

diabetes mellitus are at risk of developing BPH [17].

clinical symptoms related to urinary tract obstruction.

The roles of other steroidal hormones [20] have been proposed in the pathophysiology of BPH. The reason for this stemmed from the finding that prostatic cells continue to grow, even in the face of declining androgen levels [23]. This led to the rationale that other factors being secreted by the testes may stimulate growth or even sensitize cells of the prostate to the actions of androgens [23]. As men age, the increase in their body weight increases the amount of adipose tissue within the body, leading to an increase in circulating oestrogen levels [24]. This is evident in the levels of free estradiol found circulating in the bloodstream, which remains constant due to the age-related increases in body weight [25, 26]. Adipose tissue causes increased secretion of the enzyme aromatase, which stimulates the conversion of androgen to oestrogen. Increased circulating oestrogen levels stimulate the increased proliferation of cells seen in BPH as oestrogens have been found to increase the number of prostatic epithelial and stromal cells [27, 29]. Oestrogen also has an indirect effect on the increase in prostate volume through its role in mediating the alterations in other circulating serum hormones [20].

The changes seen in androgen levels with age disrupt the interaction of growth factors with prostate cells [22]. The growth of prostate cells is enhanced by the production of growth factors, which are supplied to the prostate via circulation [17] or locally through autocrine production by stromal cells [18]. The locally produced growth factors control cell differentiation and proliferation, and matrix protein production through a network that is interactive, providing for a negative feedback control mechanism that controls normal cell growth [18]. Any disrup‐ tion in this network leads to abnormal proliferation and stromal hyperplasia [18], which manifects as BPH. Stromal cell proliferation is enhanced by fibroblast growth factors (FGF 1 and 9), insulin-like growth factors (IGF I and II) and transforming growth factor β (TGFβ1) [18]. Expression of these growth factors is upregulated in BPH and are a mechanism which may be altered to reduce accumulation of prostatic cells.

The prostate is located at the neck of the bladder, enveloping the urethra [17]. This location plays a role in the obstructive symptoms seen in patients with BPH, which also correlate with the size of the prostate [17]. There are two components of prostatic enlargement that play a role in obstruction of the bladder outlet which lead to lower urinary tract symptoms, namely static and dynamic [17].

The static component is related to enlargement of the prostate which is attributed to the nodular proliferation classically seen in benign prostatic hypertrophy and hyperplasia [17]. This component accounts for the symptoms related to obstruction of the lower urinary tract seen in cases of BPH. The dynamic component related to the tone of prostatic smooth muscle [17]. Smooth muscle accounts for a rather large percentage of prostatic volume in BPH [17]. These provide binding sites for α1-adrenoreceptors, making the prostate susceptible to changes in adrenoreceptor signalling. α-adrenergic signalling has a significant influence on survival of stromal cells of the prostate and on the activity of smooth muscle cells in the prostate and the rest of the body [17]. α-adrenergic signalling alters expression of TGFβ1 and extracellular matix turnover [18].

and growth of infectious agents, which ultimately leads to further stimulation of the inflam‐

Buchu – The Multi-Purpose Ethnomedicinally Important Specie and Its Benefits in the Reproductive System

Inflammation of the prostate increases the risk of urinary retention, which suggests that the

Prostatic inflammation is a possible target for the prevention and treatment of BPH. Phyto‐ therapy has become a popular treatment modality for BPH, and the anti-inflammatory properties of Buchu may be applied to help alleviate inflammation found in BPH. The presence of essential oils and limonene in buchu oil can inhibit the synthesis of leukotrienes by blocking

and maintenance of inflammatory processes, thereby limiting an infection and preventing its

strengthen connective tissue, reducing inflammation and any downstream effects that it may have. The reduction in inflammation can assist in reducing inflammation-induced damage seen in prostatic tissue, putting an end to chronic would healing that is activated to repair the cells damaged by inflammatory processes. It will also diminish inflammation-based tissue

Oxidative stress is a condition caused by the imbalance between free radicals and free radical scavengers [15]. Free radicals are molecules with one or more unpaired electron(s) [36] that are highly reactive, attacking nearby stable molecules to gain an electron [15]. The molecule from which the electron was acquired becomes damaged, and it itself may initiate events that lead to damage of surrounding cells [37]. Free radicals are present at physiological concentra‐ tions which help maintain homeostasis via their actions as signal transducers [38]. Free radicals come in two common forms, i.e. ROS and RNS [15]. ROS include the superoxide ion, hydrogen peroxide, the peroxyl and the hydroxyl radical [39]. Reactive nitrogen species include nitric oxide, nitrous oxide, peroxynitrite, peroxynitrous acid and the nitroxyl anion, and are considered to be a subsection of ROS [39]. Free radical scavengers are known as antioxidants, and these assist in keeping free radicals at physiologically homeostatic levels [15]. By doing this, they help to prevent any pathological effects that may be activated by the development of oxidative stress, where ROS exceed the number of antioxidants due to increased ROS,

The body produces ROS on a daily basis via metabolic processes that occur in a normal cell [40]. ROS are generated endogenously by mitochondria and through metabolic and inflam‐ matory processes, but are also introduced into the body via external sources [40]. Physiological levels of ROS are essential to the regulation of many biological processes [40]. Increased generation of ROS is related to tissue injury and DNA damage, which are processes found in cellular proliferation, aging, infections and mutations in mitochondrial DNA [40]. Increased levels of ROS have also been associated with neoplastic transformation, abnormal cell

remodelling and prevent further enlargement of the prostate.

. Buchu can also prevent the attachment of bacteria to internal surfaces, inhibiting

. The flavonoids found in buchu may also modulate of inflammation and

. This will reduce inflammation by preventing the initiation

http://dx.doi.org/10.5772/57233

303

inflammatory processes occurring in BPH lead to lower urinary tract symptoms [19].

matory response [19].

progression2

biofilm formation2

synthesis of the enzyme 5-LOX2

**3.3. Oxidative stress in BPH**

decreased levels of antioxidants, or both [15].

proliferation and growth [40].

BPH presents clinically with lower urinary tract symptoms such as frequent urination, nocturia (frequent urination at night), the feeling of a full bladder even after voiding, post urination dribbling, weak urine stream and difficulty initiating urination [30]. It is associated with serious morbidity and may lead to complications which include acute urinary retention, and a reduction in the quality of life [17].

### **3.2. Inflammation in BPH**

A substantial number of inflammatory cells and pro-inflammatory cytokines have been found to be involved in prostatic cell proliferation [19]. The prostate is generally populated by a small amount of T and B lymphocytes, mast cells and macrophages [19]. These are chronically activated in BPH and release pro-inflammatory cytokines such as Interleuken 2( IL-2), Interferon gamma (IFN-γ) and TGFβ, which stimulate growth of the fibromuscular stroma [19]. Cytokines released by neighbouring cells stimulate the release of cyclo-oxygenase 2 (COX-2) in prostatic epithelial cells, increasing the cell turnover within the prostate [31, 32].

The local hypoxia stimulated by high cell turnover in BPH brings about the release of ROS which act as inflammatory mediators, causing enlargement of the prostate via stimulating differentiation of fibroblasts to myofibroblasts [33]. Local hypoxia also stimulates the release of growth factors and cytokines by stromal cells, including IL-8, vascular endothelial growth factors, fibroblast growth factors (FGF-2 and 7) and TGFβ [19]. TGFβ regulates stromal cell proliferation and differentiation in BPH, and is a key factor in the control of prostatic growth by androgens [34].

The prostate gland's immune response is mainly a cell mediated one, with regulatory T cells found in the stromal tissue and cytotoxic T cells in the gland's epithelia [35]. The accumulation of activated lymphocytes seen in inflammation of the prostate contributes to the development of BPH by causing tissue destruction and subsequent tissue rebuilding [20]. The cytokines produced may drive growth factor production leading to angiogenesis and cell proliferation as a "wound healing" mechanism [20]. The damage induced by inflammation of the prostate is thus a chronic process of wound healing where the excessive proliferation of prostatic cells leads to a cyclic reactivation of inflammation within the prostate [20]. This hyperproliferation and wound healing leads to the formation of prostatic nodules seen in benign prostatic hypertrophy/hyperplasia [19]. Inflammation leads to prostatic enlargement by stimulating growth of the prostate directly or indirectly by reducing apoptosis [19].

Whilst the mechanism of how inflammation leads to the pathogenesis of BPH is well under‐ stood, the origin of the inflammation is not as clearly understood [19]. Numerous aetiologies have been brought forward, including bacterial infections, an autoimmune response, urine reflux combined with chemical inflammation, hormones, diet and any combination of these [19]. The origin thus seems to be multifactorial [19]. It has been proposed that constant injury to epithelial cells leads to the loss of its function as an effective barrier, facilitating the passage and growth of infectious agents, which ultimately leads to further stimulation of the inflam‐ matory response [19].

Inflammation of the prostate increases the risk of urinary retention, which suggests that the inflammatory processes occurring in BPH lead to lower urinary tract symptoms [19].

Prostatic inflammation is a possible target for the prevention and treatment of BPH. Phyto‐ therapy has become a popular treatment modality for BPH, and the anti-inflammatory properties of Buchu may be applied to help alleviate inflammation found in BPH. The presence of essential oils and limonene in buchu oil can inhibit the synthesis of leukotrienes by blocking synthesis of the enzyme 5-LOX2 . This will reduce inflammation by preventing the initiation and maintenance of inflammatory processes, thereby limiting an infection and preventing its progression2 . Buchu can also prevent the attachment of bacteria to internal surfaces, inhibiting biofilm formation2 . The flavonoids found in buchu may also modulate of inflammation and strengthen connective tissue, reducing inflammation and any downstream effects that it may have. The reduction in inflammation can assist in reducing inflammation-induced damage seen in prostatic tissue, putting an end to chronic would healing that is activated to repair the cells damaged by inflammatory processes. It will also diminish inflammation-based tissue remodelling and prevent further enlargement of the prostate.

#### **3.3. Oxidative stress in BPH**

rest of the body [17]. α-adrenergic signalling alters expression of TGFβ1 and extracellular matix

BPH presents clinically with lower urinary tract symptoms such as frequent urination, nocturia (frequent urination at night), the feeling of a full bladder even after voiding, post urination dribbling, weak urine stream and difficulty initiating urination [30]. It is associated with serious morbidity and may lead to complications which include acute urinary retention, and

A substantial number of inflammatory cells and pro-inflammatory cytokines have been found to be involved in prostatic cell proliferation [19]. The prostate is generally populated by a small amount of T and B lymphocytes, mast cells and macrophages [19]. These are chronically activated in BPH and release pro-inflammatory cytokines such as Interleuken 2( IL-2), Interferon gamma (IFN-γ) and TGFβ, which stimulate growth of the fibromuscular stroma [19]. Cytokines released by neighbouring cells stimulate the release of cyclo-oxygenase 2 (COX-2) in prostatic epithelial cells, increasing the cell turnover within the prostate [31, 32].

The local hypoxia stimulated by high cell turnover in BPH brings about the release of ROS which act as inflammatory mediators, causing enlargement of the prostate via stimulating differentiation of fibroblasts to myofibroblasts [33]. Local hypoxia also stimulates the release of growth factors and cytokines by stromal cells, including IL-8, vascular endothelial growth factors, fibroblast growth factors (FGF-2 and 7) and TGFβ [19]. TGFβ regulates stromal cell proliferation and differentiation in BPH, and is a key factor in the control of prostatic growth

The prostate gland's immune response is mainly a cell mediated one, with regulatory T cells found in the stromal tissue and cytotoxic T cells in the gland's epithelia [35]. The accumulation of activated lymphocytes seen in inflammation of the prostate contributes to the development of BPH by causing tissue destruction and subsequent tissue rebuilding [20]. The cytokines produced may drive growth factor production leading to angiogenesis and cell proliferation as a "wound healing" mechanism [20]. The damage induced by inflammation of the prostate is thus a chronic process of wound healing where the excessive proliferation of prostatic cells leads to a cyclic reactivation of inflammation within the prostate [20]. This hyperproliferation and wound healing leads to the formation of prostatic nodules seen in benign prostatic hypertrophy/hyperplasia [19]. Inflammation leads to prostatic enlargement by stimulating

Whilst the mechanism of how inflammation leads to the pathogenesis of BPH is well under‐ stood, the origin of the inflammation is not as clearly understood [19]. Numerous aetiologies have been brought forward, including bacterial infections, an autoimmune response, urine reflux combined with chemical inflammation, hormones, diet and any combination of these [19]. The origin thus seems to be multifactorial [19]. It has been proposed that constant injury to epithelial cells leads to the loss of its function as an effective barrier, facilitating the passage

growth of the prostate directly or indirectly by reducing apoptosis [19].

turnover [18].

a reduction in the quality of life [17].

302 Antioxidant-Antidiabetic Agents and Human Health

**3.2. Inflammation in BPH**

by androgens [34].

Oxidative stress is a condition caused by the imbalance between free radicals and free radical scavengers [15]. Free radicals are molecules with one or more unpaired electron(s) [36] that are highly reactive, attacking nearby stable molecules to gain an electron [15]. The molecule from which the electron was acquired becomes damaged, and it itself may initiate events that lead to damage of surrounding cells [37]. Free radicals are present at physiological concentra‐ tions which help maintain homeostasis via their actions as signal transducers [38]. Free radicals come in two common forms, i.e. ROS and RNS [15]. ROS include the superoxide ion, hydrogen peroxide, the peroxyl and the hydroxyl radical [39]. Reactive nitrogen species include nitric oxide, nitrous oxide, peroxynitrite, peroxynitrous acid and the nitroxyl anion, and are considered to be a subsection of ROS [39]. Free radical scavengers are known as antioxidants, and these assist in keeping free radicals at physiologically homeostatic levels [15]. By doing this, they help to prevent any pathological effects that may be activated by the development of oxidative stress, where ROS exceed the number of antioxidants due to increased ROS, decreased levels of antioxidants, or both [15].

The body produces ROS on a daily basis via metabolic processes that occur in a normal cell [40]. ROS are generated endogenously by mitochondria and through metabolic and inflam‐ matory processes, but are also introduced into the body via external sources [40]. Physiological levels of ROS are essential to the regulation of many biological processes [40]. Increased generation of ROS is related to tissue injury and DNA damage, which are processes found in cellular proliferation, aging, infections and mutations in mitochondrial DNA [40]. Increased levels of ROS have also been associated with neoplastic transformation, abnormal cell proliferation and growth [40].

Androgens have been found to increase oxidative stress in the prostate gland [41]. Pathological levels of ROS bring about lipid peroxidation, apoptosis and DNA damage [15]. Lipid peroxi‐ dation is one of the main signs of oxidative damage, and has been found to stimulate alterations in membrane structure and has been linked to enzyme inactivation [41]. ROS cause this by abstracting a hydrogen atom from side chains of fatty acids in the cell membrane, initiating lipid peroxidation which has been found to enhance carcinigenesis [41].

**4. Urinary tract infections**

which is known to have bactericidal activity [45].

prostatitis) [46].

smooth muscle [2

in erectile dysfunction.

UTI's have a varied incidence that is dependent on age, sex and predisposing factors [45]. UTI's are an uncommon occurrence in healthy young men, but incidence does increase with an

Buchu – The Multi-Purpose Ethnomedicinally Important Specie and Its Benefits in the Reproductive System

http://dx.doi.org/10.5772/57233

305

The most common cause of UTI'sare bacteria, the most common being Escherichia coli, Klebsiella pneumonia, enterococci and Staphylococcus epidermidis, to name a few [45]. Bacteria causing UTI'sin men have been found to reach the urinary tract via an ascending route [45]. The bacterial flora found around the region of the anus is a reservoir for potential pathogens of the urinary tract [45]. Invasion of the urinary tract is lead by colonisation of the opening of the urethra, followed by adhesion and attachment to the epithelial lining of the urethra, with growth of bacteria on the urethral surface leading to ascension of bacteria into the urinary tract [45]. Invasion of the urethra by bacteria is difficult in men due to the distance between the opening of the urethra and the perianal region where the bacteria causing UTI'sare known to reside, the length of the urethra and the presence of prostatic fluid in the urethra,

Co-infection of the prostate in patients with UTI'sis unknown [45], but a mechanism has been suggested. Reflux of urine into ducts of the prostate lead to the retrograde transfer of bacteria from the urethra into the prostate, bringing about infection of the prostate gland (bacterial

Men with UTI'sare usually predisposed to them by functional or structural abnormalities [47, 49]. Lesions of the urinary tract which predispose men to UTI'sinclude bladder outlet obstruc‐ tion, bladder stones, stricture of the urethra, cancer of the bladder and kidney stones [50].

Signs and symptoms of UTI'sinclude frequency, pain on urination, flank pain and/or costo-

Lower UTI'sare related to erectile dysfunction and BPH [51]. This interaction may be affected by extraneous variables such as diabetes, aging and coronary artery diseases such as athero‐ sclerosis, but it was found to be independent of these variables when the co-morbidities were controlled for [51]; the association between lower UTI's(UTI) and erectile dysfunction remains. Men who are found to have more severe lower UTI's have more severe erectile dysfunction [51]. The mechanism that gives rise to this interaction is obstruction of the urethra which is propagated by collagen deposition in the penile ultrastructure and the subsequent loss of

Buchu has been found to have antimicrobial activity against bacteria that cause urinary tract

Flavonoids found in buchu may modulate inflammation and strengthen connective tissue. They may be used in the acute and long-term use for chronic or recurrent UTI, reducing the symptoms caused by UTI's [52]. The diuretic actions of Buchu will also assist in the reduction of inflammation by helping to flush bacteria out of the urinary tract through its ability to

infections, i.e. Staphylococcus aureus and Klebsiella pneumonia.

. The loss of smooth muscle leads to the reduction in erectile tissue, resulting

vertebral angle tenderness, which is tenderness in the area overlying the kidney [45].

increase in age due to predisposing factors and urological abnormalities [45].

Intracellular changes in the levels of ROS occur during proliferative, apoptotic and senescent processes, which can lead to the activation of signalling pathways [40]. As mentioned previ‐ ously, changes in tissue oxygenation during these processes causes and upregulation of cytokines and growth factors, which trigger prostatic cell proliferation, prostatic growth and inflammation. These processes themselves are a source of oxidative stress, which then leads to further proliferation and the initiation a chronic inflammation. The presence of ROS is thus an essential component in the pathogenesis of BPH when present at high levels within the prostate. This will help reduce ROS levels to physiologically homeostatic levels, allowing them to carry out their functions as signal transducers without activating any pathological mecha‐ nisms.

Endogenous antioxidant levels decrease with age [42], and this is compounded by other agerelated changes which ultimately lead to the manifestation of BPH. Oxidative stress can lead to cell mutations, which may lead to carcinogenesis and remodelling of the gland's internal structure [43]. BPH is an alternative, benign pathway of unregulated prostatic growth which is encouraged by inflammatory mediators and increased oxidative stress [41]. Management of oxidative stress is thus an imperative step in the management of BPH [41].

Management of oxidative stress is also an important factor in the prevention and treatment of BPH [41]. Buchu is an antioxidant-rich natural remedy that may be used to reduce oxidative stress. The polyphenolics contained within the plant scavenge free radicals, allowing them to act as anti-oxidants1 . The hydrogen donating ability of the phenolic groups1 will help reduce the bulid up of ROS. By donating hydrogen groups, these polyphenolics will stabilise free radicals, preventing them from attacking nearby cells to acquire it.

An increase in free radicals stimulates cyclooxygenase(COX) [44], a key enzyme in initiantion of the inflammatory process. Increase COX activity stimulates the production of an array of pro-inflammatory substances called prostaglandins. In patients with BPH and prostatitis there is an increased production of cyclooxygenase 2 (COX-2) and a reduction in the levels of prostaglandin E1 [44]. Free radical scavengers, particularly hydroxyl radical scavengers, suppress the over expression of COX and prostaglandin synthesis [44]. Ethanolis extracts of Buchu (Agathosma betulina) possess an inhibitory effect on COX-2 synthesis [44]. This inhibition will, as a consequence, suppress the inflammatory response and reduce hypertro‐ phy/hyperplasia and inflammation of the prostate, which is the goal of antioxidant treatment.

Reducing levels of ROS allows Buchu to interrupt the pathogenesis of BPH by reducing tissue injury, DNA damage, neoplastic transformation, and activation of growth factors that lead to abnormal cell proliferation and growth [40]. A diet rich in antioxidants such as vitamins A, C and E may also be prescribed to work in unison with Buchu to reduce oxidative stress.
