Pygeum africanum bark – Pruni africanae cortex (Prunus africana (Hook f.) Kalkm.)
|Latin name of the genus:||Pruni africanae cortex|
|Latin name of herbal substance:||Prunus africana (hook f.) kalkm.|
|Botanical name of plant:||Herbalref.com|
|English common name of herbal substance:||Pygeum africanum bark|
Latin name of the genus: Pruni africanae cortex
Botanical name of plant: Prunus africana (Hook f.) Kalkm.
English common name of herbal substance: Pygeum africanum bark
1.1. Description of the herbal substance(s), herbal preparation(s) or combinations thereof
Prunus africana (Hook f.) Kalkm. (syn: Pygeum africanum Hook f.) belongs to the Rosaceae family.
Pygeum africanum bark consists of the whole or cut, dried bark of the stems and branches of Prunus africana (Hook f.) Kalkm. (synonym: Pygeum africanum Hook f.). The material complies with the existing monograph of the European Pharmacopoeia (European Pharmacopoeia 1886: 2015)
Selected vernacular names: Pygeum, African plum tree, African prune, armaatet, bitter almond, Bitteramandel, chati, inkhokhokho,
The plant can be found in mountain forests of equatorial Africa: Angola, Cameroon, Ethiopia, Ghana, Kenya, Madagascar, Malawi, Mozambique, Congo, South Africa, Uganda, Tanzania, Zambia and Zimbabwe (Gruenwald et al. 2007; Bruneton 1999). An evergreen tree, usually
bony stone. Wood pale red, with strong cyanide smell when freshly cut. Owing to overexploitation and other factors, Prunus africana has been listed in Appendix II of the Convention on International Trade in Endangered Species of Wild Fauna and Flora. Darkening to rich dark red or
Plant material of interest is the dried trunk bark. Red to
The major components in the bark are fat soluble compounds: the main characteristic constituents are phytosterols (approximately 0.05%), e.g.
The proposed active constituents of a lipophilic extract of Pruni africanae cortex include docosanol (0.6%) and
Qualitative and quantitative analysis for the major constituents, docosanol and
Through bioactivity directed fractionation of the dichloromethane extract of pygeum africanum led to the isolation of
The request for information exchange concerning preparations from Prunus africana (Hook f.) Kalkm., Pruni africanae cortex, pygeum africanum bark revealed that a soft extract (DER
•Combinations of herbal substance(s) and/or herbal preparation(s) including a description of vitamin(s) and/or mineral(s) as ingredients of traditional combination herbal medicinal products assessed, where applicable.
1.2. Search and assessment methodology
The assessment is based on the sources mentioned in the list of references. Publications in other languages than English (at least abstract in English or other language available) were precluded from assessment.
Search engines used: Google; key words: Prunus africana (Hook f.) Kalkm., Pruni africanae cortex, Pygeum bark
Scientific databases: Scifinder, Scopus; search date 2014 and May 2015; key words: “pruni”, “Prunus africana”, Pruni africanae, Pygeum
Medical databases: Pubmed, Cochrane library; key words: “Prunus africana (Hook f.) Kalkm., Pruni africanae cortex, Pygeum bark”
Pharmacovigilance resources: Not applicable
Other resources: Library of the National Kapodistrian University of Athens (Pharmacy and Pharmacognosy library)
2. Data on medicinal use
2.1. Information about products on the market
2.1.1. Information about products on the market in the EU/EEA Member States
Information on medicinal products marketed in the EU/EEA
Products on the market
There is no product on the market in: Austria, Cyprus, Czech Republic, Estonia, Finland, Germany, Italy, Slovak Republic, Sweden, UK, while there are some combination products used as food supplements in Lithuania.
Italy: there was one product which is withdrawn with no well specified herbal preparation.
In Czech Republic, a product registered
Indication: Micturition disorders associated with benign prostatic hyperplasia. Posology: 1 capsule twice daily.
The marketing authorisations of above mentioned product were granted in the old legislative frame.
Moreover, there are the following marketed products in France, Greece and Poland:
Well established use
Indication: Treatment in miction moderate disorders connected with BHP
1)Soft extract; Solvent: stabilised chloroform; DER
Indication: Treatment in miction moderate disorders connected with benign prostatic hyperplasia (BPH). Posology: A capsule twice daily. A capsule contains 50 mg of extract. Duration of use:
6 weeks (+ 2 weeks) it can be renewed.
2)Soft extract; Solvent: methylene chloride; DER 200:1, since 2009
A capsule twice daily. A capsule contains 50 mg of extract. Duration of use: 6 weeks (+ 2 weeks) it can be renewed Soft extract. Solvent: methylene chloride, DER 200 (soft capsule) since 2009.
Indication: Treatment in micturition moderate disorders connected with BHP. A capsule twice daily. A capsule contains 50 mg of extract. Duration of use: 6 weeks (+ 2 weeks) it can be renewed.
Adverse reactions rarely: digestive disorders (nausea, constipation or diarrhoea)
Product 1) soft extract; Solvent: stabilised chloroform. DER
Indication (G04C): medicinal product for the relief of lower urinary tract symptoms related to BPH (such as nocturia, polyuria and urinary retention, etc). Posology: 3 capsules daily. Duration of use:
4)Two strengths of a soft extract were used; Pruni africanae corticis extractum siccum (DER 85- 250:1), extraction solvent: chloroform.
25 mg registered between
Indication: Moderate micturition disorders caused by prostate hyperthophy.
5)tablets, registered in
Prunus africana (=pygeum africanum), DER 200:1, extraction solvent: methylene chloride, corresponds to 6 mg of
Each tablet content: It contains 46 mg of extract of Prunus africana, cortex in the amount equivalent to 6 mg of
Indication: In men, adjunctive treating of urination disorders at an early stage of prostatic hyperplasia
The product cannot be used in patients with diagnosed prostate cancer.
Special warnings: Use of the product does not relieve the patient from the constant consultation with the urologist. The product does not affect the size of the prostate and only relieves symptoms associated with its hypertrophy.
If symptoms worsen or do not improve or if you notice blood in your urine, sudden retention of urine, it needs immediate consultation.
Table 1: Overview of data obtained from marketed medicinal products
This overview is not exhaustive. It is provided for information only and reflects the situation at the time when it was established.
Information on relevant combination medicinal products marketed in the EU/EEA
Combination product registered 1992 – 2003 – withdrawn on request of the MAH in 2003, the reason is not known, no pharmacovigilance action was taken on this product: Capsules containing a combination of Pruni africanae extractum (DER
Indication: for symptomatic treatment of early stages of benign prostatic hyperplasia. Posology: 2 capsules/day.
The marketing authorisations of above mentioned products were granted in the old legislative frame
Information on other products marketed in the EU/EEA (where relevant)
2.1.2. Information on products on the market outside the EU/EEA
2.2. Information on documented medicinal use and historical data from literature
The hard wood of pygeum africanum is valued in Africa. Powdered pygeum africanum bark is used by Africans natives to treat urinary problems (Bruneton 1999; DerMarderosian & Beutler 2005)
Prunus africana (Hook. f.) Kalkm. (syn. Pygeum africanum Hook. F.) commonly known as red stinkwood or bitter almond has traditionally been used for centuries by African traditional healers to treat genitourinary disorders. In the 1960s pygeum africanum came to the attention of French scientists who began to investigate its benefits in the treatment of BPH. The lipophilic extract of pygeum africanum bark has been used among the phytomedicines for BPH’s symptoms in Europe.
Pygeum africanum bark is used as an
ESCOP Monograph (Supplement 2009)
Pygeum bark (or a corresponding amount of extract) for: Symptomatic treatment of micturition disorders (dysuria, pollakiuria, nocturia, urine retention) in BPH stages I and II as defined by Aiken or stages II and III as defined by Vahlensieck.
The Review of natural products (DerMarderosian & Beutler 2005)
In France, pygeum africanum extract has become the primary course of treatment for enlarged prostate. Usual dosage of pygeum africanum extract is 100 mg/day in
PDR for Herbal Medicines (Gruenwald et al. 2007)
Fresh and dried seeds for: Irritable bladder and prostate complaints (this medication relieves only the symptoms associated with an enlarged prostate without reducing the enlargement).
WHO Monographs on selected medicinal plants Vol II (2009)
Treatment of lower urinary tract symptoms (LUTS) of BPH stages I and II, as defined by Alken (e.g. nocturia, polyuria and urinary retention), in cases where diagnosis of prostate cancer is negative.
In a recent review by Nicholson & Ricke 2011, about “Androgens and oestrogens in benign prostatic hyperplasia: Past, present and future” it is referred that plant extracts (pygeum bark) are extremely popular in the treatment of BPH, with American urologists estimating that up to 90% of newly referred patients with LUTS have tried or are using a form of alternative and complementary medicine, typically marketed as herbal prostate supplements. Extracts of the African evergreen tree pygeum africanum
are a popular ingredient in herbal prostate supplements, with a mechanism related to androgen signalling in BPH.
Table 2: Overview of historical data
2.3. Overall conclusions on medicinal use
On the basis of the information on traditional and current indications, and data from the overview of European market it is confirmed the existence of a marketed product, a herbal preparation (Soft extract; Solvent: stabilised chloroform; (DER
Traditional herbal medicinal product for the relief of lower urinary tract symptoms related to benign prostatic hyperplasia after serious conditions have been excluded by a medical doctor.
Table 3: Overview of evidence on period of medicinal use
3.1. Overview of available pharmacological data regarding the herbal substance(s), herbal preparation(s) and relevant constituents thereof
3.1.1. Primary pharmacodynamics
The phytosterols, especially
In vitro experiments
A lipophilic extract from pygeum africanum bark (200:1, methylene chloride; standardised to 13% sterols)
In tissue culture, ethanolic extracts (30%) of pygeum africanum inhibited the growth of
Recently, atraric acid (AA) and NBBS were isolated from a selective dichloromethane extract of pygeum africanum as two novel AR antagonistic compounds. The molecular mechanisms of AR inhibition were analysed and showed that AA isolated from bark material of pygeum africanum had
According to the authors, this study provided a molecular insight for AA as a natural
A lipophilic extract from pygeum africanum bark (not further confirmed) significantly inhibited the synthesis of
In vivo experiments
Influence on the prostate
lntragastric administration of a lipophilic extract from pygeum africanum bark to rats at 2 mg/kg body weight daily for
lntragastric administration of the extract to rats at 100 mg/kg daily for 3 days also increased prostate secretions (Clavert et al. 1986 in ESCOP 2009).
TRAMP (transgenic adenocarcinoma of the mouse prostate) mice fed pygeum africanum (ethanolic extracts (30%) of the plant) showed a significant reduction (P=0.034) in prostate cancer incidence (35%) compared to casein fed mice (62.5%) (Shenouda et al. 2007).
Influence on bladder function
A lipophilic extract of the crude drug administered intragastrically to rats inhibited spasms of the bladder induced by electroshock, phenylephrine, adenosine triphosphate and carbachol (WHO 2009). A reduction in
In a further experiment (intragastric
and prevented from day 3 the severity of contractile dysfunctions associated with partial outlet obstruction.
In another study, after 2 weeks of mild or severe partial outlet obstruction the extract was intragastrically administered to rabbits at 100 mg/kg/day for 3 weeks. In contrast to the previous experiments, the bladder weight of the verum group with severe outlet obstruction was lower than in the placebo group but still significantly higher (p<0.01) than in the control group. Contractile dysfunction and reduction in compliance were reversed in the mild outlet obstruction group, while in the severe outlet obstruction group contractile dysfunction was improved. Recent studies indicate that focal ischemia/reperfusion (I/R) can cause the contractile dysfunctions induced in animal models of partial bladder outlet obstruction. A
In a subsequent study rabbits received the extract intragastrically (100 mg/kg/day for 3 weeks) after 2 weeks of partial bladder outlet obstruction. Partial obstruction resulted in a significant increase in bladder weight compared to that of unobstructed animals (8.8 g versus 2.3 g; p<0.05). Obstructed rabbits in the verum group had significantly lower bladder weights than
micturition frequency and volume, but that only
A lipophilic extract from pygeum africanum bark, administered intragastrically at 400 mg/kg body weight, markedly reduced
Table 4: Overview of the main
3.1.2. Secondary pharmacodynamics
The effect of pygeum africanum (PA) extract on the proliferation of cultured human prostatic myofibroblasts and fibroblasts was investigated. Primary cultures of prostatic stromal cells were obtained from histologically confirmed human BPH by enzymatic digestion. Cell proliferation was measured by
Growth factors seem to play a role in the pathogenesis of BPH, in particular basic fibroblast growth factor
The activity of a lipophilic extract from pygeum bark on DNA synthesis was evaluated by measuring [‘H]thymidine incorporation into rat prostatic stromal cells. The extract inhibited the proliferation of both
As Prunus africana together with other plants (Withania somnifera, Warbugia ugandensis, and
Plectrunthus barbatus) are used traditionally in Kenya for treatment of cancer. Safety studies were carried using Cell Counting Kit 8 cell proliferation assay protocol. To evaluate extracts mechanisms of action,
A herbal mixture containing extracts of the herbs Dendranthema morifolium, Ganoderma lucidium,
Glycyrrhiza glabra, Isatis indigotica, Panax
herbs in the mixture, it has been exposed the head and neck cancer cell lines FADU, HLaC79 and its
The previous referred plant combination (pygeum together with Withania, Warbugia, and Plectrunthus barbatus) are used also in Kenya for treatment of microbial infections. A study was conducted on the effect of organic extracts of these plants on both bacterial and fungal strains, and their mechanisms of action. Extracts were evaluated through the disc diffusion assay. Bacteria and yeast test strains were cultured on
A chloroform extract from pygeum bark was fractionated by partitioning between solvents of varying polarity and by column chromatography. The inhibitory activity of the extract and fractions from it on ferrous
Oxidative stress in early diabetes induced bladder
In the diabetic rat bladder, early treatment with P. africana could effectively suppress oxidative stress (Wang 2010), also bladders of diabetic rats had reduced levels of hydroxyproline, TGF beta1, and bFGF following extract administration (Yongzhi 2008)
3.1.3. Safety pharmacology
No data available
3.1.4. Pharmacodynamic interactions
No data available
Experimental preclinical data presenting influence on urinary function,
3.2. Overview of available pharmacokinetic data regarding the herbal substance(s), herbal preparation(s) and relevant constituents thereof
No data available
Due to lack of data on pharmacokinetics, no general conclusions can be drawn.
3.3. Overview of available toxicological data regarding the herbal substance(s)/herbal preparation(s) and constituents thereof
3.3.1. Single dose toxicity
Single doses of the lipophilic (chloroform) extract administered intragastrically to mice and rats at up to 8 g/kg body weight were well tolerated (ESCOP 2009). Neither mortality nor signs of adverse effects were observed after oral administration of single doses of extract to mice at
3.3.2. Repeat dose toxicity
No adverse reactions were observed after daily intragastric administration of the extract to mice at 60 mg/kg or rats at 600 mg/kg bodyweight for 11 months (Bombardelli & Morazzoni 1997).
Oral administration of the extract to rats at up to 1 g/kg body weight daily for 8 weeks did not cause clinical or pathological signs of toxicity, but moderate rises were observed in serum alanine aminotransferase (ALAT) and blood urea nitrogen levels. At 3.3 g/kg daily for 6 days the extract caused marked clinical signs of toxicity, organ damage and a 50% mortality rate; the main lesions were hepatocellular degeneration and necrosis, diffuse nephrosis and myocardial degeneration, lymphocytic necrosis and neuronal degeneration. The morphological damage in these tissues caused a corresponding rise in blood biochemical parameters namely, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, creatine kinase and blood urea nitrogen. The target organs of toxicity of this extract are the liver, kidney and heart. Overt toxicity occurred only after the administration of multiple doses of 3.3 g/kg body weight. These findings confirmed the safety of the extract at therapeutic dosages, since signs of toxicity were observed only at very high dose levels (Andro & Riffaud 1995; Gathumbi et al. 2000, 2002; ESCOP 2009).
In vivo and in vitro mutagenicity studies on the extract indicated a complete absence of mutagenic and clastogenic potential (ESCOP 2009).
Dichloromethane and 90% methanol extracts of Prunus africana were investigated for mutagenic and antimutagenic effects in Salmonella microsome and micronucleus tests. Prunus africana extracts tested in the Salmonella typhimurium TA98 strain was not mutagenic and did not modify the effect of the mutagen
Dichloromethane and 90% methanol extracts were positive in the in vitro micronucleus test and in the alkaline Comet assay in human peripheral lymphocytes (Taylor et al. 2003), however, in a later review article (Verschaeve & van Staden 2008) the authors were of the opinion that positive results in these cellular tests caused by plant extracts may sometimes be artificial.
In conclusion, the genotoxicity studies gave variable results: the Ames test (strain TA98) gave uniformly negative results, whereas micronucleus test and the Comet assay gave both positive and negative results; especially the in vitro micronucleus test in human lymphocytes, extracts from P. africana significantly lowered the effect of the mutagen mitomycin C (MMC), where the extract alone was not genotoxic (Elgorashi et al. 2003;Taylor et al. 2003; Verschaeve 2004; Verschaeve & Van Staden 2008). In the in vitro micronucleus test in human lymphocytes, extracts from P. africana significantly lowered the effect of the mutagen mitomycin C (MMC), where the extract alone was not genotoxic (Verschaeve 2004).
No studies on carcinogenicity were found in the literature.
3.3.5. Reproductive and developmental toxicity
The pygeum bark extract at doses up to 80 mg/kg/day had no effect on fertility in male rats or rabbits (Andro & Riffaud 1995). The assays did not follow the International standards, hence were taken into consideration.
3.3.6. Local tolerance
No data available
3.3.7. Other special studies
No data available
Acute and chronic toxicity of the extract was low; signs of toxicity in liver, kidney and heart were observed only with very high doses. Genotoxicity studies gave variable results: the Ames test (strain TA98) gave uniformly negative results, whereas micronucleus test and the Comet assay gave both positive and negative results (Elgorashi et al. 2003; Reid et al. 2006; Taylor et al. 2003; Verschaeve
2004; Verschaeve & Van Staden 2008; ESCOP 2009). Thus, the use of the extracted is accepted as safe.
3.4. Overall conclusions on
Experimental preclinical data presenting influence on urinary function,
Tests on carcinogenicity have not been performed. Adequate tests on genotoxicity and reproductive toxicity have not been performed.
4. Clinical Data
4.1. Clinical pharmacology
4.1.1. Overview of pharmacodynamic data regarding the herbal substance(s)/preparation(s) including data on relevant constituents
No data available
4.1.2. Overview of pharmacokinetic data regarding the herbal substance(s)/preparation(s) including data on relevant constituents
There are no data available on human pharmacokinetics.
4.2. Clinical efficacy
No data available
4.2.1. Dose response studies
There are no specific data available on
4.2.2. Clinical studies (case studies and clinical trials)
Ishani et al. 2000: Trials were searched in computerised general and specialised databases (MEDLINE (1966 to 2000), EMBASE, Cochrane Library, Phytodok), by checking bibliographies, and by contacting relevant manufacturers and researchers. Main results:
A total of 18 randomised controlled trials involving 1562 men met inclusion criteria and were analysed. Only one of the studies reported a method of treatment allocation concealment, though 17 were double blinded. There were no studies comparing pygeum africanum bark to standard pharmacologic interventions such as
The mean study duration was quite short of only 64 days and not longer, and the daily dose of extract ranged from 75 to 200 mg. Data from 6
Although the duration of treatment was short, and study designs and types of reported outcome varied greatly, it was concluded that pygeum bark modestly but significantly (p<0.001 to p<0.05) improved urologic symptoms and flow measures.
Other clinical reviews, which assessed open as well as controlled studies, involved a total of 1310 patients, daily doses of
15 to 120 days. They all concluded that pygeum bark improved the symptoms and objective measures of BPH and was well tolerated (Bombardelli & Morazzoni 1997, lshani et al. 2000; ESCOP 2009,).
Chatelain et al. 1999: Two different daily dosage regimens for a lipophilic extract from pygeum bark were compared in a randomised study. Out of 235 BPH patients on commencement 209 completed a
108 patients). The primary efficacy parameter was the International Prostate Symptom Score (IPSS), a 40% or greater reduction from baseline being considered a significant improvement. Both treatments had similar efficacy after 2 months: in group A the IPSS decreased by 38%, the quality of life score improved by 28% and the maximum urinary flow rate increased by 16%; in group B the figures were 35%, 28% and 19%. In a subsequent
Methods: Patients with symptomatic benign prostatic hyperplasia (BPH) entered a
Results: 209 patients completed the comparative phase in compliance with the protocol; One hundred seventy four were included in the open phase. Both treatments had similar efficacy. IPSS (baseline 17 in both groups) improved by 38% in group A and 35% in group B. QOL improved by 28% in both groups. Qmax increased by 1.63 ml/s (16%) in group A and 2.02 ml/s (19%) in group B. After
12 months, the IPSS fell from 16 (baseline) to 9 (−46%). Half of the patients had an IPSS below 8.
Mean Qmax increased by 1.65 ml/s (15%). The safety profile was similar between groups and study phases. Pygeum africanum extract at 50 mg twice daily and 100 mg once daily proved equally effective and safe at a short period of 2 months and it was never repeated in any longer period study. Further improvements in efficacy with a satisfactory safety profile were documented after 12 months.
ESCOP 2009: In an older work the effect of Pygeum africanum (25 mg/capsule) was assayed on
Hutchinson et al. 2007: In a recent paper where were profiled the usage and effectiveness of various LUTS/BPH drugs in
medication, the majority (83% of those medicated) were prescribed only a single drug. Tamsulosin was the most commonly prescribed drug in all countries (38% of medicated cases), although with national variation from 24% in Poland to 70% in Italy. The
Significant improvements were seen in 43% of patients on phytotherapy with Pygeum africanum compared to 57% of those on finasteride and 68% on
Wilt and Ishani, 2011: The Cochrane
duration was quite short of about 64 days (range 30 – 122 days). Compared to men receiving placebo, P. africana provided a moderately improvement in the combined outcome of urologic symptoms and flow measures as assessed by an effect size defined by the difference of the mean change for each outcome divided by the pooled standard deviation for each outcome
Excluded studies had no control group : Breza 1998, Diz 1973, Grasset 1974, Greiner 1970, Grévy 1970,
In conclusion 12 clinical trials were made with soft extract; DER
Barlet 1990: Multicentre study. Double blinded (n=132). Treatment: Pygeum africanum extract 100 mg twice daily (n=131). Duration of 60 days. European men with symptomatic BPH. Significant improvement in nocturia (p<0.007) peak urine flow (p<0.02) residual volume (p<0.02) and overall symptom (p<0.001) in the verum group 5 patients stopped their treatment due to gastrointestinal problems.
Blitz et al. 1985 (ESCOP 2009; Wilt & Ishani the Cochrane analysis 2011): Double blinded. Control: placebo. Treatment: Pygeum africanum extract 100 mg daily. Duration of the study 60 days. Lost to
Bongi 1972 (ESCOP 2009; Wilt & Ishani the Cochrane analysis 2011): Double blinded. Control: placebo. Treatment: Pygeum africanum extract 75 mg daily. Duration of the study 60 days. Age range:
Donkervoort et al. 1977 (Wilt & Ishani the Cochrane analysis 2011): Double blinded. Control: placebo. Treatment: Pygeum africanum extract 75 mg daily 12 weeks. Patients were Dutch men with symptomatic BPH (n=20). Lost to
Dufour et al. 1984: Double blinded. Control: placebo (n=60). Treatment: Pygeum africanum extract 100 mg daily (n=60). Duration of the study 6 weeks (42 days). Lost to
Dutkiewicz 1996: (ESCOP 2009; Wilt & Ishani the Cochrane analysis 2011):
Frasseto et al. 1986 (Wilt & Ishani the Cochrane analysis 2011): Double blinded. Control: placebo (n=10). Treatment: Pygeum africanum extract 75 mg daily (n=10). Duration of the study 60 days. Age range:
Gagliardi 1983 (Wilt & Ishani the Cochrane analysis 2011): Double blinded. Control: Anti- inflammatory (not identified) (n=20). Treatment: Pygeum africanum extract 100 mg daily (n=20). Duration of the study 30 days. Age range:
Maver 1972 (Wilt & Ishani the Cochrane analysis 2011): Double blinded. Control: placebo (n=30). Treatment: Pygeum africanum extract 100 mg daily (n=30). Duration of the study 60 days. Age range:
Ranno et al. 1986 (Wilt & Ishani the Cochrane analysis 2011): Double blinded. Control: placebo (n=19). Treatment: Pygeum africanum extract 100 mg daily (n=20). Italian men with symptomatic BPH (n=39). Mean age: 70 years. Lost to
Rigatti et al. 1983 [Wilt & Ishani the Cochrane analysis 2011] Double blinded Control: NSAID (n=25). Treatment: Pygeum africanum extract 100 mg daily (n=24). Duration of the study 60 days. Italian men with symptomatic BPH (n=49). Lost to
Coulson et al. 2013: Recently in a clinical trial the efficacy and safety was evaluated of an orally dosed herbal preparation containing a mixture of Cucurbita pepo, Epilobium parviflorum, Pygeum africanum and Serenoa repens extracts as well as, lycopene, in the management of symptoms of medically diagnosed benign prostate hypertrophy (BPH).
Each commercially available
E. parviflorum extract (equivalent to 500 mg dry herb), lycopene (2.1 mg), Prunus africana (equivalent to 15 g dry stem, standardised to
The primary outcome measure was the international prostate specific score (IPSS) measured at baseline, 1, 2 and 3 months. The secondary outcomes were the specific questions of the IPSS and daytime and
There was a significant reduction in IPSS total median score in the active group of 36% as compared to 8% for the placebo group, during the
Descazeaud et al. 2015: In France, pygeum africanum extract (PAE) is among the
The guidance to physicians regarding LUTS associated with BPH, written in cooperation with the French society of Urology (AFU) (Descazeaud 2015) indicated BPH treatment options within its table 5 on page 409. These include alpha blockers and
In a review by Andro & Riffaud 1995, in total 12
volume, residual volume, nocturia, daytime frequency) to determine the efficacy of P. africana extract in alleviating BPH symptoms. Within the 12 reviewed studies, 358 evaluated patients received the proposed chloroform extract of P. africana whereas 359 received placebo. All 12 studies demonstrated efficacy of the extract compared to placebo – the review concluded that “pygeum africanum bark extract is
The placebo effect regarding miction problems can be quite large for men suffering from BPH (Dufour 1984) and a difference of objective measures within 2 months between extract and placebo group in a
Assessor’s comment: Although the placebo effect regarding miction problems can be quite large for men suffering from BPH and a study period of 2 months is short, the clinical studies could be taken into consideration for the plausibility of the use of Pruni africanae cortex.
In an older review of Andro & Riffaud 1995, results from an
Table 5: Clinical studies on humans
4.3. Clinical studies in special populations (e.g. elderly and children)
Not relevant as it is for use only of adults and elderly males.
4.4. Overall conclusions on clinical pharmacology and efficacy
Wilt & Ishani the Cochrane analysis 2011: A total of 18 randomised controlled trials involving 1562 men met inclusion criteria and were analysed. Only one of the studies reported a method of treatment allocation concealment, though 17 were double blinded.
There were no studies comparing pygeum africanum to standard pharmacologic interventions such as
The mean study duration was too short of mainly 64 days (range, 30 to 122 days), while several of the existing clinical studies did not report adequate results in a method that permitted proper meta- analysis.
Compared to men receiving placebo, pygeum africanum provided a moderately large improvement in the combined outcome of urologic symptoms and flow measures as assessed by an effect size defined by the difference of the mean change for each outcome divided by the pooled standard deviation for each outcome
Adverse effects due to pygeum africanum were mild and comparable to placebo.
The overall dropout rate was 12% and was similar between pygeum africanum (13%), placebo (11%) and other controls (8%).
Fourteen trials were excluded because they did not include a control (Anonymous 1973; Breza 1998; Diz 1973; Grasset 1974; Greiner 1970; Grévy 1970;
Twelve Clinical trials were made with Soft extract; DER
825 European men (from France, Italy, Poland, Netherlands) were participated, all of them with symptomatic BPH. The duration of the treatment was from
The final conclusions showed that preparation of pygeum africanum bark may be a useful treatment option for men with lower urinary symptoms consistent with BPH. However, the reviewed studies were small in size, were of short duration, used varied preparations and rarely reported outcomes using standardised validated measures of efficacy.
These trials should be of sufficient size and duration to detect important differences in clinically relevant endpoints and use standardised urologic symptom scale scores.
None of the “active comparison” arms have been conclusively demonstrated to be effective in treating symptomatic BPH.
5. Clinical Safety/Pharmacovigilance
5.1. Overview of toxicological/safety data from clinical trials in humans
No data available
5.2. Patient exposure
Aside from market presence and data from studies, there are no concrete data concerning patient exposure.
5.3. Adverse events, serious adverse events and deaths
Adverse events, serious adverse events and deaths have not been reported so far.
5.4. Laboratory findings
No data available
5.5. Safety in special populations and situations
No data available
5.5.1. Use in children and adolescents
Not relevant as it is for use only of adults and elderly males
Hypersensitivity to the active substance.
5.5.3. Special warnings and precautions for use
To ensure a safe use the following statement should be labelled:
If complaints worsen or if symptoms such as fever, spasms or blood in the urine, painful urination or urinary retention occur during the use of the medicinal product, a doctor should be consulted.
5.5.4. Drug interactions and other forms of interaction
Drug interactions from clinical trials or case studies have not been reported so far.
5.5.5. Fertility, pregnancy and lactation
No fertility data available.
Not relevant in use for pregnancy and lactation as it is for use only for adults and elderly males.
5.5.7. Effects on ability to drive or operate machinery or impairment of mental ability
No studies on the effect on the ability to drive and use machines have been performed.
5.5.8. Safety in other special situations
5.6. Overall conclusions on clinical safety
The common use of pygeum africanum bark proves not to be harmful. Thirteen of the eighteen studies provided information on specific adverse events. Adverse events due to pygeum africanum bark were generally mild in nature and comparable in frequency to placebo. The most frequently reported adverse events were gastrointestinal and occurred only among seven men in five trials. Overall, few side effects of gastrointestinal reactions due to the pygeum africanum bark preparations intake have been reported.
No serious adverse events or deaths as well as no drug interactions from clinical trials or case studies have been reported so far.
6. Overall conclusions
Pygeum africanum bark and herbal preparation (Soft extract; DER
There are no sufficient data from
Indication: Traditional herbal medicinal product for the relief of lower urinary tract symptoms related to BPH after serious conditions have been excluded by a medical doctor.
Posology; Adults and elderly: Single dose 50 mg / Daily dose 100 mg
No adequate fertility data available.
There is no relevant use in women, adolescents and children, as it is for use only for adults and elderly males.
Duration of use:
Method of administration: Oral use
Acute and chronic toxicity of the extract was low; signs of toxicity in liver, kidney and heart were observed only with very high doses.
No studies on carcinogenicity were found in the literature
Genotoxicity studies gave variable results: the Ames test (strain TA98) gave uniformly negative results, whereas micronucleus test and the Comet assay gave both positive and negative results (Elgorashi et al. 2003; Reid et al. 2006; Taylor et al. 2003; Verschaeve & Van Staden 2008).
Administration of pygeum africanum bark preparations can be regarded as safe, when using therapeutic doses. Rarely: digestive disorders (nausea, constipation or diarrhoea) have been reported.
Due to the lack of adequate data on genotoxicity, a European Union list entry is not supported.
No constituent with