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Pygeum

Scientific Name(s): Prunus africana (Hook. f.) Kalkm.
Common Name(s): African cherry, African plum, African prune, Pygeum, Red stinkwood

Medically reviewed by Drugs.com. Last updated on Mar 1, 2019.

Clinical Overview

Use

Pygeum has been used to improve symptoms of benign prostatic hyperplasia (BPH) and to improve sexual function. However, only studies comparing pygeum to placebo are available.

Dosing

Benign prostatic hyperplasia: 25 to 200 mg/day of P. africana extract standardized to 14% total sterols. The usual dosage is 100 mg/day in 6- to 8-week cycles.

Contraindications

Contraindications have not been identified.

Pregnancy/Lactation

Avoid use. Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

None well documented.

Adverse Reactions

GI irritation and headache have been reported.

Toxicology

A low incidence of toxicity has been demonstrated.

Scientific Family

  • Rosaceae

Botany

Pygeum (previously known as Pygeum africanum) is an evergreen tree native to African forest regions, Central and South American mountains, the Gulf of Guinea, and the Madagascar and Comoros islands.1 It can grow to 30 m in height.2 Its thick leaves are oblong in shape, dark green and glossy, and smell like almonds when crushed.3 Its flowers are small and white, and the fruit is a red berry that resembles a cherry when ripe. The bark has a hydrocyanic acid–like scent and is the part of the plant used for medicinal purposes; the bark can be red, brown, or gray, with red often indicating a younger tree and darker colors indicating an older tree.4, 5, 6 The bark also has the unique capability of regeneration as long as the vascular cambium is not destroyed.1

History

The hard wood of pygeum is valued in Africa and is often used to make wagons.4 Powdered pygeum bark has been used by African tribes to treat urinary problems.4, 6 Increased harvesting of pygeum has placed the tree at risk. Other Prunus spp. are being investigated for use as pygeum substitutes, with some success demonstrated in rats with induced BPH.7

Chemistry

The major bark components are fat-soluble compounds. Triterpenes are present (14%), including ursolic, oleanolic, and crataegolic acids. The lipid fraction contains fatty acids, which are 12 to 24 carbons in length. The ferulic acid esters are bound to n-tetracosanol and n-docosanol.6 N-docosanol has been used in some commercial products.6 Phytosterols present in pygeum include beta-sitosterol, beta-sitosterone, and campesterol.4, 5, 6, 8 Tannins have also been found in the plant.4 The highest activity is in the lipophilic extracts of the plant; these extracts are standardized to contain 14% triterpenes and 0.5% n-docosanol.6

Uses and Pharmacology

Prostatic effects

P. africana extract has been used in Europe for the treatment of enlarged prostate and may possess antiproliferative, anti-inflammatory, and antiestrogenic effects.9 Its benefits in BPH may be due to an ability to prevent the binding of dihydrotestosterone in the prostate gland and/or inhibit 5-alpha reductase and aromatase.3 Other proposed mechanisms include inactivation of androgen receptors via blocking of nuclear translocation; inhibition of cellular growth factors; anti-inflammatory activity via inhibition of 5-lipoxygenase; increases in bladder elasticity; histological modification of glandular cells; and inhibition of prolactin levels and consequently blocked accumulation of cholesterol in the prostate.2, 5, 10 Pygeum’s anti-inflammatory properties and ability to inhibit cellular growth factors and inactivate androgen receptors may be attributed to the active compounds N-N-butylbenzenesulfonamide and atraric acid.11 Pygeum may also exert protective effects in the bladder by reducing the deleterious effects of free radicals and degradative enzymes.1, 2

The ferulic acid ester components are responsible for pygeum's endocrine system activity. N-docosanol reduces leutinizing hormone, testosterone, and prolactin levels. Accumulation of testosterone within the prostate and subsequent conversion to the more potent form (dihydrotestosterone) is believed to be a major factor in prostatic hyperplasia. The phytoestrogenic action of P. africana extract markedly reduces the volume of prostatic hypertrophy.12 Fat-soluble components reduce cholesterol content in the prostate as well, decreasing accumulation of cholesterol metabolites.6

Beta-sitosterol may be responsible for pygeum’s effects against prostatic adenomas.3, 13 Specifically, beta-sitosterol may affect membrane structure and function of tumor and host tissues, signal transduction pathways that regulate tumor growth, and apoptosis.14

Animal and in vitro data

P. africana extract has demonstrated positive effects in animal hypophyseo-genito-adrenal axis and prostatic adenoma.15, 16 Pretreatment of rabbits with pygeum reduced partial outlet obstruction in bladder dysfunction secondary to BPH.17

Gland size reduction has also been reported. In one study, P. africana extract was a potent inhibitor of rat prostatic fibroblast proliferation.18 The extract also displays anti-inflammatory activity, which may affect gland size. In an in vitro study, P. africana extract inhibited growth of PC-3 (androgen insensitive) and LNCaP (androgen sensitive) cells at a 50% inhibitory concentration of 2.5 mcL/mL for both cell lines. In addition, P. africana extract induced apoptosis and downregulated estrogen receptor alpha protein expression in PC-3 cells and protein kinase C alpha protein expression in LNCaP cells. Beta-sitosterol inhibited growth of only LNCaP cells, not PC-3 cells.14

In vitro, the N-butylbenzene-sulfonamide (NBBS) component of P. africana exhibited antagonistic activity against human androgen receptors, which are known to control prostate growth; NBBS inhibited translocation of the receptors to the cell nucleus and inhibited growth of human prostate cancer cells.19

In a murine model, mice fed P. africana extract for 5 months experienced a significant reduction in the incidence of prostate cancer compared with mice fed casein (35% vs 62.5%, P=0.034).14

Clinical data

Most clinical trial results report improvement of BPH symptoms. Reduction in gland size and other parameters occur but are not as profound.6

In clinical trials, relief from BPH symptoms with use of P. africana extract has been documented.20, 21, 22, 23, 24, 25, 26, 27 The extract, in combination with mepartricin, was successful in treating urinary symptomatology in 22 subjects with varying stages of prostatic adenoma.22 In one study (N=74), all subjects treated with phytotherapy (containing an extract of either Sabal serrulatum or P. africana) or testosterone reported alleviation of obstructive bladder symptoms caused by BPH.23 In a placebo-controlled trial, P. africana extract improved symptoms of nocturnal frequency, difficulty in initiating urination, and bladder fullness compared with placebo.24 In a placebo-controlled, double-blind, multicenter evaluation (263 patients in 8 locations) in which 50 mg capsules of P. africana extract were given twice daily for 60 days, 66% of patients treated with P. africana extract (vs 31% of placebo patients) showed marked clinical improvement in micturition disorders.25 In another report, high-dose P. africana extract (200 mg/day) administered to 18 patients for 60 days improved urinary symptoms and sexual behavior.26 A combined extract of P. africana/Urtica dioica administered at half the standard dose was as safe and effective as the full dose (U. dioica 300 mg and P. africana extract 25 mg) and significantly reduced urine flow, residual urine, and nycturia in patients with BPH.27 In a 2013 sponsor-funded, phase 2, placebo-controlled, randomized clinical trial (N=57) conducted in men with BPH, a commercially available herbal formulation containing pumpkin seed oil, lycopene, saw palmetto, pygeum, and Epilobium parviflorum reduced median International Prostate Symptom Score, as well as daytime and nighttime urinary frequency. Improvements were progressive and were observed in several scores at 1 month and in all scores at 3 months.28

The 2013 European Association of Urology guidelines on the management of lower urinary tract symptoms in men discuss but do not make any specific recommendations regarding phytotherapy for the treatment of male lower urinary tract symptoms because of variability of products, lack of regulatory infrastructure, and variability in methodologies in the available literature.29 A meta-analysis conducted to determine the efficacy and safety of P. africana extract compared with placebo included 18 trials in men (N = 1,562) with a mean study duration of 64 days (range, 30 to122 days). Men receiving P. africana extract were twice as likely to report symptom improvement (relative risk [RR], 2.1; 95% confidence interval [CI], 1.4 to 3.1). A 19% reduction in nocturia, 24% reduction in residual urine volume, and 23% improvement in peak urine flow were noted in men receiving P. africana extract. Adverse effects and dropout rates were similar between the extract and placebo groups.30 In a study of 3 men with BPH undergoing prostatectomy and 3 men without BPH undergoing cystectomy, P. africana exerted antiproliferative and apoptotic effects against prostate fibroblasts and myofibroblasts but not smooth muscle cells.31

Macrophages (inflammatory cells) produce chemotactic mediators that may contribute to BPH development. One in vitro report suggested pygeum’s ability to antagonize 5-lipoxygenase metabolite production may contribute to its therapeutic activity on inflammatory components of BPH.32

Pygeum may help reverse sterility, which can be caused by insufficient prostatic secretions.4 In one study, P. africana extract increased prostate secretions in both rats and humans.33 It also improved seminal fluid composition.4 Thus by improving an underlying problem, P. africana extract may improve sexual function.6, 26

When P. africana extract was compared with saw palmetto in a double-blind trial, saw palmetto produced a greater reduction of symptoms and was better tolerated; however, P. africana extract may have greater effects on prostate secretion.6

In one study, men with chronic prostatitis were randomized to receive 15 days of an appropriate antibiotic (adjusted according to sensitivities) or an antibiotic plus 30 days of either saw palmetto 320 mg/day (n=51) or P. africana extract 200 mg/day (n=23), based on cost. The only statistically significant finding between the groups was regarding a lower chronic prostatitis symptom burden, according to National Institutes of Health Chronic Prostatitis Symptom Index questionnaire scores after the second follow-up visit, among patients receiving combination therapy compared to antibiotics alone.34

Other uses

In an in vitro study, P. africana extract exerted cytotoxic effects against head and neck cancer cell systems.35 In another in vitro study, P. africana extract exerted antibacterial activity against Staphylococcus aureus and methicillin-resistant S. aureus.36

Dosing

Benign prostatic hyperplasia

25 to 200 mg/day of P. africana extract standardized to 14% total sterols.25, 26, 27, 30, 37, 38, 39 The usual dosage is 100 mg/day in 6- to 8-week cycles.3

Pregnancy / Lactation

Avoid use. Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

None well documented.

Adverse Reactions

GI irritation (eg, nausea, constipation, diarrhea, stomach pain) has been documented, with only a small percentage of patients discontinuing therapy.1, 6 In one clinical trial (N=263), GI adverse effects occurred in 5 patients, with only 3 patients requiring discontinuation of treatment.25 In addition, pygeum may cause headache.1, 10 It is recommended that pygeum be taken only under physician supervision.4

Toxicology

A low incidence of toxicity has been demonstrated.

Index Terms

  • Pygeum africanum

References

1. Allkanjari O, Vitalone A. What do we know about phytotherapy of benign prostatic hyperplasia? Life Sci. 2015;126:42-56.25703069
2. Pagano E, Laudato M, Griffo M, Capasso R. Phytotherapy of benign prostatic hyperplasia. A minireview. Phytother Res. 2014;28(7):949-955.25165780
3. van Wyk BE, Wink M, eds. Medicinal Plants of the World: an Illustrated Scientific Guide to Important Medicinal Plants and Their Uses. 1st ed. Portland, OR: Timber Press Inc; 2004.
4. Chevallier A. Encyclopedia of Medicinal Plants. New York, NY: DK Publishing; 1996;257.
5. Bruneton J. Pharmacognosy, Phytochemistry, Medicinal Plants. Paris, France: Lavoisier Publishing; 1995;142.
6. Murray M. The Healing Power of Herbs. Rocklin, CA: Prima Publishing; 1995:286-293.
7. Jena AK, Vasisht K, Sharma N, Kaur R, Dhingra MS, Karan M. Amelioration of testosterone induced benign prostatic hyperplasia by Prunus species. J Ethnopharmacol. 2016;190:33-45.27235020
8. Longo R, Tira S. Steroidal and other components of Pygeum africanum bark. Farmaco Prat. 1983;38(7):287-292.6617830
9. Cheetham PJ. Role of complimentary therapy for male LUTS. Curr Urol Rep. 2013;14(6):606-613.24026362
10. Keehn A, Lowe FC. Complementary and alternative medications for benign prostatic hyperplasia. Can J Urol. 2015;22(suppl 1):18-23.26497340
11. Keehn A, Taylor J, Lowe FC. Phytotherapy for benign prostatic hyperplasia. Curr Urol Rep. 2016;17(17):53.27180172
12. Mathé G, et al. Orbach-Arbuoys S, Bizi E, Court B. The so-called phyto-estrogenic action of Pygeum africanum extract. Biomed Pharmacother. 1995;49(7-8):339-340.8562859
13. Russo G, Cimino S, Salamone C, et al. Potential efficacy of some African plants in benign prostatic hyperplasia and prostate cancer. Min Rev Med Chem. 2013;13:1564-1571.
14. Shenouda NS, Sakla MS, Newton LG, et al. Phytosterol Pygeuym africanum regulates prostate cancer in vitro and in vivo. Endocrine. 2007;31(1):72-81.17709901
15. Thieblot L, Berthelay S, Berthelay J. Preventive and curative action of a bark extract from an African plant, Pygeum africanum, on experimental prostatic adenoma in rats [in French]. Therapie. 1971;26(3):575-580.4107111
16. Thieblot L, Grizard G, Boucher D. Effect of V 1326 (active principle of bark extract) on hypophyseo-genito-adrenal axis in rats [in French]. Therapie. 1977;32(1):99-110.867342
17. Levin R, Levin SS, Zhao Y, Buttyan R. Cellular and molecular aspects of bladder hypertrophy. Eur Urol. 1997;32 (suppl 1):15-21.9218938
18. Yablonsky F, Nicolas V, Riffaud JP, Bellamy F. Antiproliferative effect of Pygeuym africanum extract on rat prostatic fibroblasts [published correction appears in J Urol. 1997;158(3, pt 1):889]. 1997;157:2381-2387.9146675
19. Papaioannou M, Schleich S, Roell D, et al. NBBS isolated from Pygeum africanum bark exhibits androgen antagonistic activity, inhibits AR nuclear translocation and prostate cancer cell growth. Invest New Drugs. 2010;28(6):729-743.19771394
20. Bassi P, Artibani W, De Luca V, Zattoni F, Lembo A. Standardized extract of Pygeum africanum in the treatment of benign prostatic hypertrophy. Controlled clinical study versus placebo [in Italian]. Minerva Urol Nefrol. 1987;39(1):45-50.2441479
21. Menchini-Fabris G, Giorgi P, Andreini F, Canale D, Paoli R, Sarteschi ML. New perspectives on the use of Pygeum africanum in prostato-bladder pathology [in Italian]. Arch Ital Urol Nefrol Androl. 1988;60(3):313-322.2975866
22. Casella G, Barbaro A. The role of mepartricin in the medical treatment of benign prostatic adenoma [in Italian]. Arch Sci Med. 1978;135(1):95-98.76466
23. Flamm J, Kiesswetter H, Englisch M. An urodynamic study of patients with benign prostatic hypertrophy treated conservatively with phytotherapy or testosterone (author’s transl) [in German]. Wien Klin Wochenschr. 1979;91(18):622-627.90434
24. DuFour B, Choquenet C, Revol M, Faure G, Jorest R. Controlled study of the effects of Pygeum africanum extract on the functional symptoms of prostatic adenoma [in French]. Ann Urol. 1984;18(3):193-195.6084978
25. Barlet A, Albrecht J, Aubert A, et al. Efficacy of Pygeum africanum extract in the medical therapy of urination disorders due to benign prostatic hyperplasia: evaluation of objective and subjective parameters. A placebo-controlled double-blind multicenter study [in German]. Wien Klin Wochenschr. 1990;102(22):667-673.1702916
26. Carani C, Salvioli V, Scuteri A, et al. Urological and sexual evaluation of treatment of benign prostatic disease using Pygeum africanum at high doses [in Italian]. Arch Ital Urol Nefrol Androl. 1991;63(3):341-345.1723220
27. Krzeski T, Kazón M, Borkowski A, Witeska A, Kuczera J. Combined extracts of Urtica dioica and Pygeum africanum in the treatment of benign prostatic hyperplasia: double-blind comparison of two doses. Clin Ther. 1993;15(6):1011-1020.7509261
28. Coulson S, Rao A, Beck SL, Steels E, Gramotnev H, Vitetta L.. A phase II randomised double-blind placebo-controlled clinical trial investigating the efficacy and safety of ProstateEZE Max: a herbal medicine preparation for the management of symptoms of benign prostatic hypertrophy. Complement Ther Med. 2013;21(3):172-179.23642948
29. Oelke M, Bachmann A, Descazeaud A, et al. EAU guidelines on the treatment and follow-up of non-neurogenic male lower urinary tract symptoms including benign prostatic obstruction. Eur Urol. 2013;64(1):118-1140.23541338
30. Wilt T, Ishani A, MacDonald R, Rutks I, Stark G. Pygeum africanum for benign prostatic hyperplasia. Cochrane Database Syst Rev. 2002;(1)CD001044.11869585
31. Quiles MT, Arbós MA, Fraga A, de Torres IM, Reventós J, Morote J. Antiproliferative and apoptotic effects of the herbal agent Pygeum africanum on cultured prostate stromal cells from patients with benign prostatic hyperplasia (BPH). Prostate. 2010;70(10):1044-1053.20503393
32. Paubert-Braquet M, Cave A, Hocquemiller R, et al. Effect of Pygeum africanum extract on A23187-stimulated production of lipoxygenase metabolite from human polymorphonuclear cells. J Lipid Mediat Cell Signal. 1994;9(3):285-290.7921787
33. Clavert A, Cranz C, Riffaud JP, Marquer C, Lacolle JY, Bollack C. Effects of an extract of the bark of Pygeuym afticanum (V.1326) on prostatic secretions in the rat and in the man [in French]. Ann Urol (Paris). 1986;20(5):341-343.3777880
34. Stamatiou KN, Moschouris H. A prospective interventional study in chronic prostatitis with emphasis to clinical features. Urol J. 2014;11(4):1829-1833.25194085
35. Schmidt M, Polednik C, Roller J, Hagen R. Cytotoxicity of herbal extracts used for treatment of prostatic disease on head and neck carcinoma cell lines and non-malignant mucosal cells. Oncol Rep. 2013;29(2):628-636.23165347
36. Mwitari PG, Ayeka PA, Ondicho J, Matu EN, Bii CC. Antimicrobial activity and probable mechanisms of action of medicinal plants of Kenya: Withania somnifera, Warbugia ugandensis, Prunus africana and Plectrunthus barbatus. PLoS ONE. 2013;8(6):e65619.23785437
37. Breza J, Dzurny O, Borowka A, et al. Efficacy and acceptablity of tadenan (Pygeum africanum extract) in the treatment of benign prostatic hyperplasia (BPH): a multicentre trial in central Europe. Curr Med Res Opin. 1998;14(3):127-139.9787978
38. Chatelain C, Autet W, Brackman F. Comparison of once and twice daily dosage forms of Pygeum africanum extract in patients with benign prostatic hyperplasia: a randomized, double-blind study, with long-term open label extension. Urology. 1999;54(3):473-478.10475357
39. Ishani A, MacDonald R, Nelson D, Rutks I, Wilt TJ. Pygeum africanum for the treatment of patients with benign prostatic hyperplasia: a systemic review and quantitative meta-analysis. Am J Med. 2000;109(8):654-664.11099686

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