Exploring the use of phytotherapy in benign prostatic hyperplasia [BPH]: a systematic review

2.1 Search strategies

A comprehensive literature search of published works on phytotherapy for the management of BPH was systematically undertaken on the PubMed, Web of Science (WoS), and Scopus databases up to June 20, 2024. The following search terms were used: “natural product”, plants, foods, supplements, nutraceuticals, “benign prostatic hyperplasia”, management, amelioration, treatment, therapy, and remedy. Boolean operators; AND/OR/NOT, were used to develop search strategies according to the specifications of each of the databases according to the search strategy formulation methods reported by Refs. 26–28. The search was restricted to peer-reviewed literature published in English. The paper selection process was conducted in conformity with the Preferred Reporting Items for Systematic Reviews and Meta-analyses [PRISMA] 2020 guideline,²⁹ as reportedby.³⁰

2.2 Selection criteria, and data extraction

The following inclusion criteria were applied for articles to be selected for the study: studies involving preclinical models of BPH, interventions specifically targeting plant or plant-based therapy, studies reporting quantitative outcomes related to BPH treatment and ameliorations, peer-reviewed articles published in English, studies with clear methodology and reporting of the administration and plant-based products. The exclusion criteria set for the screening and selection included: studies not focusing on BPH, and studies lacking preclinical models of BPH. Human studies were to be excluded, non-English publications, studies lacking clear reporting of outcomes or methodology, review articles, editorials, commentaries, and conference abstracts.

The data extraction extracted from each of the included studies is: name of the plant or plant-based product, plant part [for plant extract], method of extraction [for plant extract], category [supplement, capsule, plant-extract, etc.], year of publication, method of induction, BPH model [e.g. rat, droso, mice, rabbit, etc], duration of treatment, nature of the study [protective or therapeutic].

3.1 Search results

The search identified a total of 694 articles: comprising 201 articles from WoS, 334 from Scopus and 159 articles from PubMed. The articles were transferred to Rayyan digital platform for assessment and selection for the systematic review methodology.³¹ Using the platform, 494 duplicate were detected from the entries, leading to the deletion of 291 articles, whereas 163 articles were resolved. With other articles that have only single entries, a total of 403 articles were screened via title/abstract consideration, and full text screening sequentially, in accordance to the eligibility criteria. Ultimately, only 84 publications were examined in the study, having met the eligibility requirements [ Figure 1].

Figure 1. PRISMA flow chart for study selection.

3.2 Study characteristics

Several natural products and plant extracts were studied for their potential role in managing benign prostatic hyperplasia [BPH]. These included purple rice,³² and Couroupita guianensis Aubl., ³³ Epilobium angustifolium, ^34,35 green tea, soybean, and camellia oil,³⁶ Panax ginseng and bee-pollen,³⁷ and saw palmetto^38,39 ( Table 1 and refer extended data Table 2).¹⁴⁴ Other notable plants included Brassica campestris L. pollen,⁴⁰ Melandrii Herba, ³⁷ Croton membranaceus, ⁴¹ and Caesalpinia bonduc.⁴² Additionally, plants like Cistanches salsa, ⁴³ Withania coagulans, ⁴⁴ Cucurbitacin E glucoside, ⁴⁵ Moringa peregrina, ⁴⁶ and Antrodan⁴⁷ were also analyzed for their therapeutic properties in treating BPH [ Table 1 and extended data Table 2]. Other samples included Lycopene and Curcumin,⁴⁰ funtumia Africana and Abutilon Mauritianium leaves⁴⁸ Spermacoce radiata and Hypselodelphys poggeana, ⁴⁸ and Pygeum africanum⁴⁹ [ Table 1 and extended data Table 2].

The types of extracts used varied widely depending on the plant. For instance, fractionation was used for purple rice³² while in many studies the ethanolic extracts were applied [ Table 1]. Studies using ethanolic extract include those of Brassica campestris L pollen,⁴⁰ Melandrii herba,³⁷ Cistanches salsa,⁵⁰ and Moringa peregrina⁵¹ Aqueous extracts were also common, as seen with Panax ginseng,³⁷ Pygeum africanum, ⁵² and Alginate Oligosaccharide⁵³ [ Table 1]. Some studies used more specific combinations like Lycopene and Curcumin,⁴⁰ while others used supercritical fluid extraction, such as in the study of Saw palmetto oil.⁵⁴ Unique extracts like cucurbitacin E glucoside,⁴⁵ Curcuma oil,⁵⁵ and phenolic extracts from date seeds⁵⁶ were also explored [ Table 1 and extended data Table 2].

3.3 Evaluation methods and mechanisms of action reported in the included studies

Various evaluation methods were used in these studies, reflecting a diversity of approaches to studying bioactive compounds. Western blot analysis was employed in studies of Couroupita guianensis Aubl., ³³ Saw palmetto,⁵⁴ and Cinnamomum cassia and Rosa laevigata.³³ Biochemical analysis was utilized in studies of Epilobium angustifolium L⁵⁷ and Panax ginseng.³⁷ Additionally, histopathological examination was frequently performed, as seen in studies with Croton membranaceus, ⁵⁸ Caesalpinia bonduc,⁴² Brassica napus L, ⁵⁹ and Pao Pereira Extract.⁶⁰ Moreover, LC/MS-QTOF and ELISA tests were used to analyze compounds in some studies, such as with Juglans regia, ⁶¹ while immunohistochemistry was utilized in the study of Panax ginseng and bee-pollen.³⁷

The mechanisms of action reported in the included studies have been presented in Table 1. Purple rice³² exhibited protective effects against testosterone-induced BPH in rats, while Couroupita guianensis Aubl.³³ suppressed BPH-related biomarkers and improved the prostate index. Epilobium angustifolium L⁵⁷ extracts demonstrated an inhibitory effect on prostate enlargement, although the specific mechanisms were not elaborated. The combination of green tea, soybean, and camellia oil³⁶ inhibited the DHT-AR complex and macrophage inflammation, showcasing their anti-inflammatory potential.

In the case of Panax ginseng and bee-pollen,³⁷ the aqueous extract was found to reduce prostate weights and DHT levels while decreasing prostatic epithelial hyperplasia. Similarly, saw palmetto oil⁵⁴ regulated inflammatory and apoptotic proteins in BPH rats. Another example was Croton membranaceus, where extracts acted as alpha-1 blockers and 5α-reductase inhibitors,⁶² while Caesalpinia bonduc⁴² inhibited DHT formation via 5α-reductase, leading to reduced BPH symptoms. Furthermore, curcumin and lycopene⁴⁰ were shown to inhibit inflammatory factors and regulate hormone levels associated with BPH. Similarly, Pygeum africanum⁴⁹ exhibited anti-androgenic effects by inhibiting fibroblast proliferation. Lastly, the study of Phellodendri chinensis cortex and Anemarrhenae rhizoma⁴⁹ showed these compounds' ability to reverse metabolite imbalances associated with BPH, while Moringa peregrina⁵¹ exerted anti-inflammatory, anti-proliferative, and anti-angiogenic effects on BPH tissues.

3.4 Oxidative, Apoptotic, and Prostate Biomarkers

Figure 2. Oxidative, Apoptotic, and Prostrate Biomarkers.

3.5 Inflammatory biomarkers associated with BPH

Figure 3 shows the association of inflammatory markers with BPH. Elevated levels of TNF-α, IL-1β, IL-6, IL-8, COX-2, iNOS, in untreated BPH models and poorly managed clinical trials highlight the role of inflammation in the disease progression. Treatment with anti-inflammatory phytochemicals [e.g., phytosterols from Urtica dioica or essential oils from Artemisia judaica] reduces these cytokine levels, relieving BPH symptoms.^22,67 Similarly, NF-κB activation, a hallmark of chronic inflammation, is suppressed by bioactive compounds in plants like Curcuma longa and Epilobium angustifolium.^68,69 This inhibition reduces inflammatory signaling and limits tissue proliferation in the prostate. Lower inflammatory markers after phytotherapy correlate with symptom improvement, such as reduced prostate volume and enhanced urinary flow. Studies on Cucurbita pepo and Panax ginseng support these outcomes.^24,37

Figure 3. Inflammatory biomarkers associated with BPH.

3.6 List of plants investigated

Extended data Table 3¹⁴⁴ shows plants studied for their therapeutic roles to manage Benign Prostatic Hyperplasia [BPH]. Table 3 lists the plants used according to their scientific names, English names, families, parts used, and country of origin.

Plant families and species diversity

All the listed plants are of different botanical families: Moringaceae, Brassicaceae, Araceae, Annonaceae, Cucurbitaceae, Fabaceae, and Urticaceae. Notably, the most predominant family was the Moringaceae family, for example, Moringa peregrina, which reduces inflammation, cell growth, and angiogenesis in BPH tissues.⁵¹ Another is Annona muricata from the Annonaceae family, which stops 5α-reductase and lowers PSA levels and prostatic hyperplasia.⁶⁴ Again, Lepidium meyenii [Red Maca] and Cucurbita pepo [pumpkin] from the Brassicaceae family are known to have hormonal and prostate health effects,^24,70 while Urtica dioica from the Urticaceae family also stops 5α-reductase activity and has a strong anti-androgen effect.²² The variety of plants used in phytotherapy shows the different ways they can target pathways related to BPH, such as androgen signaling, inflammation, and oxidative stress.

Plant parts utilized

The parts used in research reflect the concentration of bioactive compounds. Researchers have studied a variety of plant parts, including leaves, seeds, fruits, tubers, whole plants, and even the stem itself. This variation is due to the different phytochemical profiles in different plant tissues.

Leaves: For instance, Urtica dioica [stinging nettle] leaves are rich in phytosterols and essential fatty acids, which exhibit anti-inflammatory effects,⁷¹ while purple rice leaves have protective effects against testosterone-induced BPH in rats.⁷²

Seeds: Cucurbita pepo [pumpkin] seeds are a traditional remedy for urinary issues, containing phytosterols and tocopherols that reduce prostate growth,⁷³ while Glycine max [soybean] inhibits the DHT-AR complex and macrophage inflammation, showcasing their anti-inflammatory potential.⁷⁴

Roots and Tubers: Plants like Colocasia esculenta [Cocoyam] offer high antioxidant potential, making them useful for reducing oxidative stress associated with BPH.⁷⁵

Fruits: Kigelia africana prevents and reverses testosterone-induced prostatic hyperplasia,⁷⁶ while Xylopia aethiopica [spice tree] possesses a protective effect against BPH in rats.⁷⁷

Whole plant: Lepidium meyenii [red maca] modulates inflammatory pathways in BPH,⁷⁰ while Croton membranaceus [croton plant] extracts act as alpha-1 blockers and 5α-reductase inhibitors.⁶⁶

Geographical Relevance

The plants listed originate from various geographical locations. The geographical spread of plants emphasizes their accessibility and ethnopharmacological importance. This also indicates a global interest in utilizing phytotherapy for BPH management. Notable examples include:

Africa: Colocasia esculenta [cocoyam, from Nigeria] and Annona muricata [Soursop, from Nigeria] are widely used in traditional African medicine for urinary and prostate health.⁷⁸

Asia: Plants such as Lepidium meyenii [Red Maca, from Peru] and Panax ginseng [from Korea] highlight phytotherapy practices in traditional Peru and Korean medicine.³⁷

Europe: Epilobium angustifolium [Rosebay Willowherb, from Poland] and Epilobium angustifolium [Rosebay Willowherb, from Italy] are known anti-inflammatory agents used in European herbal medicine.^79,80

3.7 Families of plants investigated

Distribution across botanical families

Figure 4 showcases the diversity of plant families contributing to BPH treatment research, with notable representation from:

Figure 4. Families of plants investigated.

Figure 5. Risk of bias analysis of the included articles.

Urticaceae: for instance, Urtica dioica, which is known for inhibiting 5α-reductase and reducing DHT levels.⁸¹

Brassicaceae: example Lepidium meyenii [Red Maca], which modulates hormonal balance and inflammation.⁷⁰

Asteraceae: for instance, Taraxaci herba [Dandelion], reduces prostate weights and lowers serum testosterone and DHT levels.⁸²

Moringaceae: example, Moringa peregrine which exerts anti-inflammatory, anti-proliferative, and anti-angiogenic effects on BPH tissues.⁸³

Annonaceae: notably, Annona muricata which inhibits 5α-reductase, reducing PSA levels and prostatic hyperplasia⁷⁸

3.8 Risk of bias analysis

The Risk of Bias Visualization [robvis] tool was used in this systematic review to methodically assess and display any potential biases in the included papers.

4.1 Diversity of species and plant families

The plants reviewed in this work belong to a wide range of botanical families, demonstrating the vast biological diversity explored for managing BPH. Notable families include: Arecaceae [Palm Family] such as plants like Serenoa repens [Saw Palmetto] and Phoenix dactylifera [Date]. These are known for their anti-androgenic and anti-inflammatory effects.^91,92 Brassicaceae [Mustard Family], which includes plants like Lepidium meyenii [Red Maca]^93,94 and Cucurbita pepo [pumpkin].²⁴ These plants modulate hormonal balance and inflammation.^24,70 Furthermore, the Urticaceae [Nettle Family], include Urtica dioica [Stinging Nettle], a well-known inhibitor of 5α-reductase.^22,81,95 Moringaceae [the horseradish Family], which Includes Moringa peregrine.⁸³ They have been reported to exhibit anti-inflammatory and anti-angiogenic effects on prostate tissues.^83,96 Another is Annona muricata from the Annonaceae family, which stops 5α-reductase and lowers PSA levels and prostatic hyperplasia.⁷⁸ The variety of plants used in phytotherapy shows the different ways they can target pathways related to BPH, such as androgen signaling, inflammation, and oxidative stress. Notably, this diversity highlights the wide array of bioactive compounds across plant families, such as phytosterols, polyphenols, and essential fatty acids, which target BPH’s underlying mechanisms.

4.2 Geographical distribution

The plants reviewed in this study, originate from diverse geographical regions, underscoring the accessibility and ethnopharmacological significance of BPH treatments across cultures. This also indicates a global interest in utilizing phytotherapy for BPH management. Notable examples include; Africa, where plants like Annona muricata [Soursop], Xylopia aethiopica [Spice Tree], and Colocasia esculenta [cocoyam, from Nigeria],⁷⁸ are commonly used in traditional African medicine for urinary and prostate health.^78,97 Other areas include Asia, which features plants like Panax ginseng [Korean Ginseng] and Epilobium angustifolium [Rosebay Willowherb],^33,79,98 reflecting the integration of traditional Chinese and Korean medicine into BPH management and Europe with Plants like Epilobium angustifolium from Poland and Italy indicates the role of herbal medicine in European traditions.^79,80 Another location and culture where these herbs are used is America, having plants such as Cucurbita pepo [Pumpkin Seed] and Lycopene from tomatoes,⁷³ showcasing the focus on nutraceuticals in North and South America. The wide geographical representation indicates the universal burden of BPH and the global interest in accessible and sustainable phytotherapeutic solutions.

4.3 Parts of plants utilized

The parts used in the research reflect the concentration of bioactive compounds. Researchers have studied a variety of plant parts, including leaves, seeds, fruits, tubers, whole plants, and even the stem itself. This variation is due to the different phytochemical profiles in various plant tissues. The Leaves of Urtica dioica [stinging nettle] have rich concentrations of phytosterols and essential fatty acids, which exhibit anti-inflammatory effects,⁸¹ while purple rice leaves have protective effects against testosterone-induced BPH in rats.⁹⁹ The Seeds of Cucurbita pepo [pumpkin] is a traditional remedy for urinary issues, containing phytosterols and tocopherols that reduce prostate growth,⁷³ while Glycine max [soybean] inhibits the DHT-AR complex and macrophage inflammation, showcasing their anti-inflammatory potential.⁷⁴ The roots and tubers of plants like Colocasia esculenta [Cocoyam] offer high antioxidant potential, making them useful for reducing oxidative stress associated with BPH,¹⁰⁰ while the fruits of Kigelia africana prevent and reverses testosterone-induced prostatic hyperplasia.⁷⁶ Xylopia aethiopica [spice tree] possesses a protective effect against BPH in rats.⁷⁷ Notably, the whole plant parts have been used for some studies. The whole plant parts of plants like Lepidium meyenii [red maca] modulate inflammatory pathways in BPH 170⁷⁰ while Croton membranaceus [croton plant] extracts act as alpha-1 blockers and 5α-reductase inhibitors.⁶⁶ Cistanches salsa has been recorded to have a combined anti-inflammatory and anti-proliferative effects.¹⁰¹

4.4 Mechanisms of action

The plant investigated, characteristics, and mechanism of action of the plants for BPH treatment are shown in Table 1 and extended data Table 2. The studies reviewed revealed multiple mechanisms through which these phytochemicals exert their therapeutic effects. These include hormonal Modulation, Anti-Inflammatory capacity, antioxidative mechanism, and apoptotic regulation. Many compounds inhibit 5α-reductase, reducing dihydrotestosterone [DHT] levels, a key factor in BPH pathogenesis Phytotherapeutic agents operate through diverse mechanisms that directly target the pathophysiological aspects of BPH.^59,102 Examples include saw palmetto and Pygeum africanum. Anti-Inflammchemicals such as curcumin and Lycopene demonstrated inhibition of inflammatory cytokines [e.g., TNF-α, IL-1β, IL-6], which are elevated in BPH. The numerous plants and phyto-substances studied in this review exert their therapeutic effects via one or more of the above mechanisms of action.

Several clinical trials have evaluated the efficacy of phototherapy in managing BPH symptoms. Saw palmetto, for instance, has been widely studied, with findings indicating its ability to improve urinary flow rates and reduce LUTS. A meta-analysis comparing saw palmetto with placebo found significant symptom improvement with fewer side effects than conventional medications.¹⁰³ Extracts such as saw palmetto [Serenoa repens] are rich in fatty acids and phytosterols, which inhibit the enzyme 5-alpha-reductase, reducing dihydrotestosterone [DHT] levels. DHT plays a pivotal role in prostate growth, and its inhibition can significantly curb prostate enlargement.⁶⁵ Additionally, these agents exhibit anti-inflammatory effects by downregulating pro-inflammatory cytokines and reducing oxidative stress, both of which are implicated in prostate tissue hyperplasia.

Despite these findings, variability in study design and outcomes presents challenges. Some studies demonstrate negligible differences between phytotherapeutic agents and placebos, underscoring the need for robust and standardized research. Differences in extraction methods, dosages, and patient populations contribute to the heterogeneity of results. Other agents, like pygeum [Prunus africana], [Cinnamomum cassia and Rosa laevigata] act as anti-androgens and reduce cholesterol accumulation in the prostate, which is linked to glandular hyperplasia. The obstructive symptoms of BPH are lessened by the anti-inflammatory properties of pygeum bark [Prunus africana]. Rats' prostate stromal cells' basal growth is inhibited by the bark when it is stimulated by TPA [tissue plasminogen activator], bFGF, EGF, IGF-I, and PDBu [phorbol 12,13-butyrate] [Csikós et al.,2021]. Stinging nettle [Urtica dioica] demonstrates estrogen-modulating properties and also inhibits sodium-potassium ATPase activity in the prostate cells, helping to regulate cellular activity.⁸¹ The multi-faceted actions of these compounds make them particularly appealing as therapeutic agents. According to studies on animals, U. dioica's flavonoid concentration significantly reduces platelet aggregation and enhances the lipid profile.^104,105 Additionally, it was discovered that the stinging nettle methanol extract dramatically reduced the experimentally induced prostate development.¹⁰⁶

Cucurbita pepo [pumpkin]: Pumpkin seed extract's therapeutic benefits include alleviating the symptoms of lower urinary tract ailments, prostate abnormalities, and urinary tract disorders.¹⁰⁷ Pumpkin seed extracts may mitigate testosterone-induced hypertrophy by blocking the rise in prostate weight and protein synthesis brought on by testosterone and prazosin Furthermore, 10 g of pumpkin extract per day has tonic effects on the bladder and urethra.^108,109 The effects of pumpkin seed oil were assessed in a clinical investigation including more than 2000 males with BPH. For 12 weeks, the patients took 500–1000 mg of the oil daily. Consequently, the medication reduced the IPSS by 41.4%, and over 96% of patients experienced no negative side effects, suggesting that pumpkin seed oil greatly reduced patients' urinary dysfunction.¹¹⁰ Pumpkin seed oil enhances the antioxidative defense system, reducing oxidative stress markers, while compounds such as Juglans regulate hyperplastic prostate tissues, aiding in volume reduction. Purple rice³² exhibited protective effects against testosterone-induced BPH in rats, while Couroupita guianensis Aubl.¹¹¹ suppressed BPH-related biomarkers and improved the prostate index. Epilobium angustifolium L¹¹² extracts demonstrated an inhibitory effect on prostate enlargement, although the specific mechanisms were not elaborated. In the case of Panax ginseng and bee-pollen,³⁷ the aqueous extract was found to reduce prostate weights and DHT levels while decreasing prostatic epithelial hyperplasia. Similarly, Saw palmetto oil⁸⁸ regulated inflammatory and apoptotic proteins in BPH rats. Another example was Croton membranaceus, where extracts acted as alpha-1 blockers and 5α-reductase inhibitors,⁶⁶ while Caesalpinia bonduc⁴² inhibited DHT formation via 5α-reductase, leading to reduced BPH symptoms. Furthermore, curcumin and lycopene⁹⁰ were shown to inhibit inflammatory factors and regulate hormone levels associated with BPH. Lastly, the study of Phellodendri chinensis cortex and Anemarrhenae rhizoma¹¹³ showed these compounds' ability to reverse metabolite imbalances associated with BPH, while Moringa peregrina⁸³ exerted anti-inflammatory, anti-proliferative, and anti-angiogenic effects on BPH tissues. Pygeum africanum⁸⁹ exhibited anti-androgenic effects by inhibiting fibroblast proliferation.

4.5 Plants targeting androgen signaling and 5α-reductase activity

Several plants exert their therapeutic effects by targeting androgen signaling, particularly by inhibiting 5α-reductase, a key factor in BPH progression. Serenoa repens [Saw Palmetto] has been widely studied for its ability to inhibit 5α-reductase, reduce DHT levels, and alleviate urinary symptoms.¹¹⁴ Its anti-inflammatory properties further enhance its therapeutic profile.^65,88 These findings suggest that Serenoa repens could be a primary candidate for phytotherapy in BPH, especially for patients seeking non-invasive treatments. Pygeum africanum [African Cherry] is known for reducing urinary frequency and residual urine, this plant demonstrates anti-androgenic effects through the inhibition of fibroblast proliferation and DHT production.⁸⁹ These properties make Pygeum africanum suitable for managing both symptoms and underlying causes of BPH. Urtica dioica [Nettle Root] plant complements Serenoa repens in combination therapies by inhibiting sex hormone binding to prostate receptors, thereby limiting prostate growth.²² Such synergies highlight the potential for combination therapies to enhance efficacy.

4.6 Plants with anti-inflammatory properties

Elevated levels of TNF-α, IL-1β, IL-6, IL-8, COX-2, iNOS, in untreated BPH models and poorly managed clinical trials highlight the role of inflammation in the disease progression. Chronic inflammation is a critical factor in BPH progression. Treatment with anti-inflammatory phytochemicals [e.g., phytosterols from Urtica dioica or essential oils from Artemisia judaica] reduces these cytokine levels, relieving BPH symptoms.^22,115 Similarly, NF-κB activation, a hallmark of chronic inflammation, is suppressed by bioactive compounds in plants like Curcuma longa and Epilobium angustifolium.^33,116 This inhibition reduces inflammatory signaling and limits tissue proliferation in the prostate. Lower inflammatory markers after phytotherapy correlate with symptom improvement, such as reduced prostate volume and enhanced urinary flow. Plants with anti-inflammatory properties offer an alternative or complementary approach to conventional treatments. Studies on Cucurbita pepo and Panax ginseng support these outcomes.^24,37 Curcuma longa [Turmeric] and Cucurbita pepo [Pumpkin Seed] are both very common plants that contain bioactive compounds like curcumin and phytosterols, which reduce pro-inflammatory cytokines and inhibit macrophage-driven inflammation.^73,90 These effects correlate with improved urinary symptoms and reduced prostate size, suggesting their potential as adjunctive treatments in BPH management. Epilobium angustifolium [Rosebay Willowherb] plant inhibits DHT-induced androgen receptor translocation and decreases prostate-specific antigen [PSA] levels, emphasizing its dual anti-inflammatory and androgen-regulating effects.¹¹⁶ Similarly, Pygeum africanum⁸⁹ exhibited anti-androgenic effects by inhibiting fibroblast proliferation. The combination of green tea, soybean, and camellia oil³⁶ inhibited the DHT-AR complex and macrophage inflammation, showcasing their anti-inflammatory potential.

4.7 Plants with antioxidant properties

Oxidative stress contributes to the pathogenesis of BPH by inducing cellular damage and inflammation. Several plants reviewed show promise in counteracting oxidative stress. Lycopene [Tomato Extract] and Curcumin, both restore oxidative balance by reducing malondialdehyde [MDA] levels, a marker of lipid peroxidation. This protective effect mitigates BPH symptoms and slows disease progression.⁹⁰ While Annona muricata [Soursop] plant’s antioxidant activity, mediated by its ability to inhibit 5α-reductase, positions it as a promising candidate for managing BPH.⁷⁸

4.8 Phytotherapy with multi-modal effects

Several plants demonstrate a combination of anti-androgenic, anti-inflammatory, and antioxidant activities, making them highly versatile. Croton membranaceus act as an alpha-1 blocker and 5α-reductase inhibitor. This plant addresses multiple pathways involved in BPH pathogenesis. Clinical studies show significant symptom improvement, supporting its potential for broader clinical applications.^14,66,86 Cistanches salsa and Moringa peregrina plants exhibit anti-inflammatory, anti-proliferative, and anti-angiogenic effects on prostate tissues, emphasizing their role in both symptom management and disease modification.^83,101 While Serenoa repens [Saw Palmetto] derived from the saw palmetto fruit, is one of the most widely used phytotherapeutic agents for BPH. Its lipid extracts inhibit 5α-reductase, reducing DHT levels and mitigating prostate enlargement. Numerous clinical trials have shown significant improvements in IPSS and peak urinary flow rates.^117–119 Despite its popularity, recent studies suggest its effects may be equivalent to placebo in certain settings, underscoring the need for more rigorous investigations.

Saw Palmetto [Serenoa repens] - Saw palmetto remains a common therapy for BPH. Extracts derived through supercritical fluid extraction regulated inflammatory and apoptotic proteins in BPH models, reducing PSA and prostate volume 29.¹²⁰ The dual mechanism of 5α-reductase inhibition and androgen receptor antagonism underscores its role as a natural alternative to conventional medications.¹²¹

Pygeum africanum [African Plum] - Pygeum africanum has been extensively studied for its role in BPH management.^89,122,123 Extracts from its bark exhibit multiple mechanisms of action, including inhibition of oxidative stress, inhibition of fibroblast proliferation, modulation of androgen receptor activity, and reduction of prostatic inflammation.¹²³ Pygeum inhibits the activity of growth factors and reduces androgen receptor binding, resulting in prostate size reduction and improved urinary symptoms.¹²² Meta-analyses have demonstrated moderate improvements in urinary flow and nocturia reduction.^14,124 However, variations in study designs and treatment durations warrant further research to validate its therapeutic potential.

Purple Rice [Oryza sativa] - Purple rice has demonstrated protective effects against testosterone-induced benign prostatic hyperplasia [BPH] in animal models.³² The crude ethanolic extract of purple rice modulated oxidative stress and reduced inflammation in the prostate tissue. These effects are attributed to the bioactive anthocyanins present in purple rice, which act as potent antioxidants. Key findings included the reduction of prostate size and the suppression of pro-inflammatory cytokines such as TNF-α and IL-6anensis

Couroupita guianensis Aubl., has shown promising results in regulating BPH biomarkers.¹¹¹ Using western blot analysis, studies revealed that extracts from this plant improved the prostate index and reduced the levels of prostate-specific antigen [PSA] and androgen receptor expression.¹¹¹ These effects highlight its potential as an anti-inflammatory and anti-proliferative agent in managing BPH.

Cucurbita pepo [Pumpkin] - Cucurbita pepo, commonly known as pumpkin, is extensively used in managing BPH symptoms.¹²⁵ The seeds contain bioactive compounds such as phytosterols, which exert antiandrogenic effects by inhibiting 5α-reductase and preventing the conversion of testosterone to dihydrotestosterone [DHT].⁷³ Clinical trials have demonstrated significant improvements in urinary flow rates and reductions in prostate volume following pumpkin seed extract administration.^126,127 However, the variability in extraction methods and dosages across studies highlights the need for standardized formulations to optimize its therapeutic potential.

Cucurbitacin E Glucoside - Cucurbitacin E glucoside, a triterpenoid compound, exhibits potent anti-inflammatory and antiproliferative effects, making it a promising agent for BPH management.⁴⁵ Studies have demonstrated its ability to inhibit the NF-κB signaling pathway, which reduces the production of pro-inflammatory cytokines like TNF-α and IL-6.^45,128 Additionally, its role in oxidative stress regulation is evident through its capacity to enhance superoxide dismutase [SOD] activity and decrease malondialdehyde [MDA] levels, key oxidative biomarkers associated with BPH progression.⁴⁵

Epilobium ang [Fireweed] - Fireweed extracts have been traditionally used in European medicine for prostate health. The ethyl acetate and n-butanol extracts were found to inhibit DHT-induced androgen receptor translocation, reducing PSA levels.¹¹² The bioactive polyphenols and flavonoids in Epilobium angustifolium contribute to its anti-inflammatory and anti-androgenic effects, making it a viable candidate for phytotherapy in BPH management.

Green Tea, Soybean, and a combination of green tea extract, soybean, and camellia japonica oil demonstrated synergistic effects in inhibiting the DHT-androgen receptor complex and suppressing macrophage-mediated inflammation.^129,130 This blend reduced oxidative stress markers, including MDA and SOD levels, while improving apoptotic regulation via caspase activation.¹³⁰ This combination therapy highlights the potential benefits of integrating multiple plant compounds for comprehensive BPH management.

Panax Ginseng and Bee Pollen - Panax ginseng and bee pollen, has shown significant efficacy in reducing prostate weights and DHT levels while ameliorating prostatic epithelial hyperplasia.¹⁴ Immunohistochemistry and biochemical analyses revealed the anti-inflammatory and anti-androgenic properties of these extracts, mediated through the downregulation of androgen receptor pathways and pro-inflammatory cytokines.¹³¹

Urtica dioica [Stinging Nettle] - Urtor its anti-inflammatory properties and ability to inhibit SHBG binding, thereby reducing the proliferation of prostate cells.⁸¹ While randomized controlled trials demonstrate significant symptom relief and reductions in IPSS scores,¹³² its weak inhibition of 5α-reductase and limited influence on prostate size suggest it may be more effective in combination therapies.

Brassica campestris L. Pollen - Ethanol-refined extracts of Brassica camplen have demonstrated improvements in BPH symptoms. This extract has been reported to act as an antioxidant, reducing ROS levels and enhancing apoptotic markers such as Bax and caspase-3.⁴⁰ Additionally, it modulates androgen receptor pathways, contributing to the reduction of prostatic hyperplasia.

Caesalpinia bonduc - Seed extracts of Caesalpinia bonduc exhibit significant anti-andrities by inhibiting 5α-reductase.⁴² This action reduces DHT formation, leading to a decrease in prostate volume and inflammation. LC/MS-QTOF analyses confirmed the presence of bioactive compounds responsible for these therapeutic effects.¹³³ Cistanches salsa—Ethanol extracts of Cistanches salsa were shown to improve BPH symptoms by regulating stress and enhancing apoptotic markers. The pro-apoptotic effects are mediated through caspase-3 activation and downregulation of Bcl-2, reducing prostate size and improving urinary symptoms.¹⁰¹ Withania coagulans - Withania coagulans, also known as vegetable rennet, has potent anti-inflammatory and apopin BPH management. Studies revealed its ability to inhibit pro-inflammatory cytokines such as IL-6 and TNF-α while enhancing apoptotic pathways, thereby mitigating prostatic hyperplasia.¹³⁴

Moringa peregrine - Moringa peregrina, known for its rich antioxidant profile, contains bioactive compounds such as quercetin and kaempferol [m These compounds reduce oxidative stress by scavenging free radicals and upregulating endogenous antioxidant enzymes.⁸³ The plant also exhibits significant anti-inflammatory properties by modulating the expression of cyclooxygenase [COX] enzymes and reducing the levels of prostaglandins, which are elevated in BPH. Clinical and preclinical evaluations indicate its potential in decreasing prostate volume and alleviating LUTS symptoms.

Antrodan - Antrodan, a polysaccharide derived from the Antrodia cinnamomea mushroom, has been studied for its anti-inflammatory and apoptotic properties in BPH treatment.⁵¹ It inhibits inflammatory mediators, such as interleukins [IL-1β, IL-6] and TNF-α, by downregulating the MAPK pathway. Furthermore, Antrodan induces apoptosis in hyperplastic prostate cells by activating caspases and modulating the Bcl-2/Bax ratio, crucial apoptotic biomarkers.¹³⁵

Lycopene and Curcumin - Lycopene, a carotenoid found in tomatoes, and curcumin, a polyphenol derived from turmeric, have synergistic effects in managing BPH.⁹⁰ Lycopene reduces oxidative stress by neutralizing reactive oxygen species [ROS], while curcumin inhibits inflammation by suppressing the NF-κB pathway.^50,136 Both compounds have been shown to downregulate prostate-specific antigen [PSA] levels and reduce prostate volume.⁹⁰ Their antioxidant properties also contribute to decreased levels of MDA and increased activity of SOD and catalase.

Funtumia africana and Abutilon mauritianium Leaves - These plants are traditionally used for their anti-inflammatory and antioxidant properties. Bioactive compounds in Funtumia africana, such as alkaloids and flavonoids, inhibit pro-inflammatory cytokines and reduce oxidative damage in prostate tissue.⁴⁸ Similarly, Abutilon mauritianium leaves contain phenolic compounds that enhance antioxidant defenses and modulate apoptotic pathways, aiding in prostate health restoration.⁴⁸

Spermacoce radiata and Hypselodelphys poggeana - The combined use of Spermacoce radiata and Hypselodelphys poggeana has shown potential in reducing BPH symptoms.⁴⁸ These plants possess bioactive compounds that inhibit 5α-reductase activity, thereby reducing DHT levels. Additionally, their anti-inflammatory effects are mediated through the suppression of COX-2 expression and the reduction of inflammatory biomarkers like TNF-α.

Other Phytotherapeutics - Several other plants, including Urtica dioica [stinging nettle] and Secale cereale [rye grass pollen], have shown promise in managing BPH symptoms.^14,137 Urtica dioica exerts its effects by inhibiting inflammatory pathways and androgen receptors,¹³⁸ while Secale cereale enhances urinary flow and reduces residual volume through anti-inflammatory and anti-androgenic mechanisms.^139,140 While these agents are supported by clinical evidence, their inclusion in combination therapies warrants further exploration to optimize efficacy. Additional plants such as Secan] and Serenoa repens [saw palmetto] have been investigated for BPH management. Rye grass pollen demonstrates anti-inflammatory and antiandrogenic activities, while saw palmetto inhibits 5α-reductase. Although these agents show promise, most studies emphasize the need for larger, long-term trials to validate their efficacy.

4.9 Limitations and controversies

While the promise of phytotherapy is clear, several limitations in the reviewed studies warrant discussion

Controversies also exist regarding the efficacy of certain phytotherapies. While some studies report significant improvements in urinary symptoms and prostate size reduction, others find no better outcomes than placebo [Ulbricht, 2016]. For example, although Saw palmetto has been extensively studied, its efficacy remains debated, highlighting the need for more rigorous research to resolve these inconsistencies [Yamada et al., 2022].

4.10 Integration into clinical practice

The conventional care of BPH is supplemented by phytotherapy. Phytotherapeutic substances provide a feasible and less harmful option for patients with mild to moderate symptoms who prefer natural treatments. The absence of standardized products, however, forces practitioners to rely on higher-ups, validated supplements. Phytotherapy may also be helpful when combined with traditional therapies, especially for patients who want to reduce their symptoms without experiencing worsening adverse effects.

4.11 Implications for future research

Phytotherapy offers a viable alternative to conventional treatments, particularly in regions with limited access to healthcare resources. However, the lack of standardization in extraction processes and dosages, coupled with a paucity of high-quality clinical trials, limits its integration into evidence-based practice.^141,142 Future research should prioritize harmonizing methodologies and exploring combination therapies to maximize efficacy.

The diverse mechanisms and bioactive compounds of these plants highlight their potential for tailored therapies in BPH management. Plants like Serenoa repens and Pygeum africanum could serve as front-line treatments, especially for mild to moderate cases.^65,89,143 Anti-inflammatory and antioxidant-rich plants, such as Curcuma longa and Lycopene, may act as supportive therapies, reducing reliance on conventional drugs and mitigating side effects. Moreover, emerging therapies like Croton membranaceus suggest opportunities for integrative approaches that combine multiple therapeutic pathways.

However, standardization in extraction methods, dosages, and clinical protocols remains essential to harness these plants' full potential. This synthesis underscores the need for large-scale clinical trials to validate these findings and establish phytotherapy as a cornerstone in the holistic management of BPH.

4.12 Knowledge gaps and research opportunities

Despite the promising potential of phytotherapy, significant gaps remain in our understanding of its mechanisms, efficacy, and long-term safety. Many studies reviewed were preclinical, relying on animal models, with limited human clinical trials to validate their findings.^32,111 The variability in extraction methods and dosages further complicates the standardization of these treatments, making it difficult to draw firm conclusions or develop universal guidelines for their use.

Future research should prioritize:

Investigating the synergistic effects of combining phytotherapy with conventional treatments, which may offer enhanced outcomes while minimizing side effects.