Wednesday, 26 March 2014

Benign prostatic hyperplasia(BPH) in Herbs Points of View

 Kyle J. Norton

Benign prostatic hyperplasia(BPH) is defined as a condition of increased in the number of cells of prostate gland, causing partial, or sometimes virtually complete obstruction of the urinary tract. According to statistic, BPH commonly starts at age of 30 and symptoms usually can not be realized until age of 50. More than half of men between age of 60-70 are experience symptoms of BPH and only 10% are required treatment. Epidemiological studies, linking herbal medicine in reduced risk of benign prostate hyperplasia have produced certain positive results, but multi centers and large sample size studies are necessary to identify the principle ingredients to improve their validations.

1. Serenoa repens (Saw palmetto)
Saw Palmetto, is a small palm like tree of the genus in the genus Serenoa, belonging to the family, native to o southeastern North America. The herb has been used in The North American Seminole Indians for infertility, PMS, reproductive or urinary tract problems, urinary tract infections, stomach aches, indigestion and dysentery, etc. In rat study, a liposterolic extract of saw palmetto  showed to inhibited the contractions of prostate gland consistently with smooth muscle relaxant activity(1). In a total of 297 patients recruited, with 87 into the group TAM, 97 into the group SR and 81 into the group tamsulosin (TAM) + Serenoa repens (SR), SR and TAM treatment of BPH had showed to be efficacy as in alone, a combined therapy (TAM + SR) does not provide extra benefits(2). On the mRNA gene expression profiles of two representative models of BPH,  BPH1 cell line and primary stromal cells derived from BPH, lipidosterolic extract of Serenoa repens (LSESr) significantly altered gene expression patterns, categorized as part of proliferative, apoptotic, and inflammatory pathways(3). Unfortunately, a meta-analysis of two high quality long-term trials (n = 582), conducted by the,  showed no effect of Sere noa repens, at double and triple doses, in improving urinary flow measures or prostate size in men with lower urinary tract symptoms consistent with BPH(4).

2. Cuban royal palm
Cuban royal palm is a genus Roystonea, belonging to the family  Arecoideae, native to southern Florida, Mexico and parts of Central America and the northern
Caribbean. The roots of the tree has been used as a diuretic, and for treatment of diabetes. In rat study, 
D-004, a lipid extract from Cuban royal palm fruits incomparison of Saw palmetto and tamsulosin,
selective alpha(1A)-adrenoceptor antagonist, indicated that D-004 was moderately more effective
 than Saw palmetto, a phytotherapeutic standard used to treat BPH, but less effective than tamsulosin, a 
selective alpha(1A)-adrenoceptor antagonist(5).
Other study of the same by the Center of Natural Products from the National Center for Scientific
Research, showed that oral administration of D-004 for 14 days prevented the
increase of prostate size and the testosterone-induced prostate enlargement with in rodents(6)(7).

3. Prunus africana
Prunus africana. also known as Red Stinkwood, is a an evergreen tree,  genus Prunus, belonging to the family Rosaceae, native to the montane regions of Sub-Saharan Africa. The herb has been used in traditional medicine to treat fevers, malaria, wound dressing, arrow poison, stomach pain, purgative, kidney disease, appetite stimulant, gonorrhoea, and insanity(8).
Pygeum africanum extract, in a multicentre trial in central Europe, treatment found to be effective in changes in subjective scores, International Prostate Symptom Score (IPSS) and QoL, after the two-month period the extract also was highly statistically significant with mean improvements of 40% and 31% and with the overall result of a substantial improvement in QoL(9)(10). Although many evidences suggested that P. africanum modestly and significantly, improved urologic symptoms and flow measures, further research is needed using standardized preparations of P. africanum to determine its long-term effectiveness and ability to prevent complications associated with benign prostatic hyperplasia(11).

4. Green tea 
Green tea contains more amount of antioxidants than any drinks or food with the same volume, and is the leaves of Camellia sinensis, undergone minimal oxidation during processing, originated from China. Green tea has been a precious drink in traditional Chinese culture and used exceptional in socialization for more than 4000 thousand years. Because of their health benefits, they have been cultivated for commercial purposes all over the world. The levels or activity of androgen hormones are associated to the risk of BPH, green tea catechin, (-)epigallocatechin-3-gallate, exhibited its modulation of androgenic activity that may be useful for the treatment of various hormone-related abnormalities, such as benign prostatic hyperplasia(12). 5 alpha-reductase activity may be involved in the development of benign prostatic hyperplasia. The Ben May Institute for Cancer Research, and The Tang Center for Herbal Medicine Research study showed that green tea catechin (-)-epigallocatechin gallate (EGCG) is potent inhibition in cell-free and in replacement of the gallate ester in EGCG with long-chain fatty acids produced potent 5 alpha-reductase inhibitors(13). The study by the Oregon State University, also showed that in the study of male noble rats implanted with estradiol and testosterone divided into 4 dietary groups: control, soy, tea, or soy+tea, the combinartion of  soy and tea attenuated prostate malignancy by decreasing prostate hyperplasia(14). Also, green tea catechin, (-)epigallocatechin-3-gallate, according to Dr. Liao S., may be useful for the treatment of various hormone-related abnormalities, such as benign prostatic hyperplasia, due to its modulation of androgenic activity, possibly through increasing in testosterone metabolism, down-regulation of androgen receptors or activation of oestrogen receptors (15).

5. Licorice
Licorice (Glycyrrhiza Glabra) also known as sweetwood, is the genus Glycyrrhiza, belonging to the family Fabaceae, native to the Mediterranean and certain areas of Asia. The herb has been used in traditional medicine to treat skin diseases, coughs, constipation, bronchitis, inflammation, arthritis, etc. Glycyrrhiza glabra extract with doses of 150 and 300 mg/kg showed a significant reduction in prostate weight, total estosterone and VP epithelium/stroma ratio (V/V)(16).

6. Garlic
Garlic is a natural superfood healer for its natural antibiotic with antiviral, antifungal, anticoagulant and antiseptic properties. A multicenter case-control study of 1369 patients with BPH and 1451 controls, indicated an inverse association of intake of garlic related to the risk of BPH, consistent across age strata(17). Other researchers suggested that garlic potential in treating BPH due to its anti-inflammatory, anti-cancer and antioxidant effects as well as its effectiveness for the treatment of prostate cancer and relief of BPH symptoms(18).

7. Epilobium parviflorum
Epilobium parviflorum also known as Smallflower Hairy Willowherb, is a genus Epilobium, belonging to the family Onagraceae. The herb has been used in traditional medicine as an antioxidant and 
antiinflammatory agent and  in treating BPH, bladder and kidney, etc.
According to the study by Farmakognózia Intézet, willow-herb possess remarkable antioxidant and COX-inhibitory action and may be effective in treating benign prostatic hyperplasia (BPH)(19). Other study suggested a protective effect against benign prostatic hyperplasia (BPH), through inhibited oxidative damage, generated in fibroblast cells, decreased the PGE(2) release and inhibited COX-enzyme(20).

8. Urtica dioica
Sting Nettle is a flower plant in the genus Urtica, belonging tothe family Urticaceae, native to Europe, Africa, Asia, and North America.The herb has been used in traditional medicine as diuretic and laxative agent and to treat diarrhea and urinary disorders, to relieve pain, treat arthritis, asthma, bronchitis, sinusitis, etc.
In a 6-month, double-blind, placebo-controlled, randomized, partial crossover, comparative trial with placebo in 620 patients conducted by Shaheed Beheshti University of Medical Sciences, Urtica dioica showed to improve International Prostate Symptom Score (IPSS), the maximum urinary flow rate (Qmax), postvoid residual urine volume (PVR) and prostate size(21). Composition of 160 mg sabal fruit extract WS 1473 and 120 mg urtica root extract WS 1031 per capsule (PRO 160/120) found to improve  the amelioration of LUTS as measured by the I-PSS, obstructive and irritative urinary symptoms and in patients with moderate and severe symptoms of BPH(22)(23). Bazoton uno (459 mg dry extract of stinging nettle roots), in a study of a total of 246 patients, reduced irritative symptoms and BPS-associated complications due to the postulated antiphlogistic and antiproliferative effects(24).

9. Ginseng
Ginseng is a slow-growing perennial plants with fleshy roots, the genus Panax, belonging to the family Araliaceae. Depending to the climate where it grows, ginseng can be classified mainly into Panax ginseng Asian ginseng (root), Red ginseng, wild ginseng, American ginseng (root). Ginseng, one of the most popular herb has been used in human history in treating vary types of diseases. Panax ginseng or Red ginseng water extract and its chemical constituent 20(S)-Rg3 showed to inhibit testosterone-induced cell proliferation, arrested cell cycle by inducing p21 and p27, and induced apoptosis, through inhibition of testosterone-induced expression of human kallikrein-3 mRNA and activation of androgen receptor (AR)(25).

10. Rye (Secale cereal)
Rye (Secale cereal) is a grass in the genus Secale, belonging to the family Poaceae, native to the  central and eastern Turkey, and in adjacent areas. The herb has been used
in folk medicine as laxative due to its fibrous seed coat. Cernilton, isolated
from the rye-grass pollen Secale cereal, in randomized controlled trials or controlled clinical trials
comparing with placebo or other BPH medications in men with BPH showed a modestly
improves overall urologic symptoms including nocturia(26). In a 444 men enrolled in 2
placebo-controlled and 2 comparative trials lasting from 12 to 24 weeks, conducted by Department
of Veterans Affairs Coordinating Center,  Cernilton improved "self rated urinary symptoms", reduced
nocturia, but not improve urinary flow rates, residual volume or prostate size compared to placebo or
the comparative study agents(27). 

Taken altogether, without going into reviews, herbal medicine mentioned above may be effective in
reduced risk and treatment of Benign prostatic hyperplasia(BPH), but further studies are necessary to 
identify the
principle ingredients through comparison with Western medicine in use with large sample size and
multi centers involvement. As always, all articles written by Kyle J. Norton are for information &
education only, please consult your Doctor & Related field specialist before applying

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(1) Pharmacological characterization and chemical fractionation of a liposterolic extract of saw palmetto (Serenoa repens): Effects on rat prostate contractility by Chua T1, Eise NT2, Simpson JS3, Ventura S(PubMed)
(2) Does the addition of Serenoa repens to tamsulosin improve its therapeutical efficacy in benign prostatic hyperplasia? byArgirović A1, Argirović D2.(PubMed)
(3) Lipidosterolic extract of serenoa repens modulates the expression of inflammation related-genes in benign prostatic hyperplasia epithelial and stromal cells by Sirab N1, Robert G, Fasolo V, Descazeaud A, Vacherot F, Taille Ade L, Terry S.(PubMed)
(4) Serenoa repens for benign prostatic hyperplasia by Tacklind J1, Macdonald R, Rutks I, Stanke JU, Wilt TJ.(*PubMed)
(5) Effect of D-004, a lipid extract from the Cuban royal palm fruit, on atypical prostate hyperplasia induced by phenylephrine in rats by Arruzazabala ML1, Más R, Molina V, Noa M, Carbajal D, Mendoza N.(PubMed)
(6) Effect of D-004, a lipid extract from Cuban royal palm fruit, on histological changes of prostate hyperplasia induced with testosterone in rats by Noa M1, Arruzazabala ML, Carbajal D, Más R, Molina V.(PubMed)
(7) Preventive effects of D-004, a lipid extract from Cuban royal palm (Roystonea regia) fruits, on testosterone-induced prostate hyperplasia in intact and castrated rodents by Arruzazabala ML1, Carbajal D, Más R, Molina V, Rodríguez E, González V.(PubMed)
(8) Stewart KM."The African cherry (Prunus africana): can lessons be learned from an over-exploited medicinal tree?." [Review] Journal of Ethnopharmacology. 89(1):3-13, 2003 Nov.
(9)Efficacy and acceptability of tadenan (Pygeum africanum extract) in the treatment of benign prostatic hyperplasia (BPH): a multicentre trial in central Europe by Breza J1, Dzurny O, Borowka A, Hanus T, Petrik R, Blane G, Chadha-Boreham H.(PubMed)
(10) 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 by Chatelain C1, Autet W, Brackman F.(PubMed)
(11) Pygeum africanum for the treatment of patients with benign prostatic hyperplasia: a systematic review and quantitative meta-analysis by Ishani A1, MacDonald R, Nelson D, Rutks I, Wilt TJ.(PubMed)
(12) The medicinal action of androgens and green tea epigallocatechin gallate by Liao S.(PubMed)
(13) Structure-activity relationships for inhibition of human 5alpha-reductases by polyphenols by Hiipakka RA1, Zhang HZ, Dai W, Dai Q, Liao S.(PubMed)
(14) Dietary soy and tea mitigate chronic inflammation and prostate cancer via NFκB pathway in the Noble rat model by Hsu A1, Bruno RS, Löhr CV, Taylor AW, Dashwood RH, Bray TM, Ho E.(PubMed)
(15) The medicinal action of androgens and green tea epigallocatechin gallate by Liao S.(PubMed)
(16) Antiandrogenic activities of Glycyrrhiza glabra in male rats by Zamansoltani F1, Nassiri-Asl M, Sarookhani MR, Jahani-Hashemi H, Zangivand AA.(PubMed)
(17) Onion and garlic intake and the odds of benign prostatic hyperplasia by Galeone C1, Pelucchi C, Talamini R, Negri E, Dal Maso L, Montella M, Ramazzotti V, Franceschi S, La Vecchia C.(PubMed)
(18) Is garlic a promising food for benign prostatic hyperplasia and prostate cancer? by Devrim E1, Durak I.(PubMed)
(19) [Epilobium parviflorum--in vitro study of biological action].[Article in Hungarian] by Hevesi Tóth B1, Kéry A.(PubMed)
(20) Antioxidant and antiinflammatory effect of Epilobium parviflorum Schreb by Hevesi BT1, Houghton PJ, Habtemariam S, Kéry A.(PubMed)
(21) Urtica dioica for treatment of benign prostatic hyperplasia: a prospective, randomized, double-blind, placebo-controlled, crossover study by Safarinejad MR.(PubMed)
(22) Long-term efficacy and safety of a combination of sabal and urtica extract for lower urinary tract symptoms--a placebo-controlled, double-blind, multicenter trial by Lopatkin N1, Sivkov A, Walther C, Schläfke S, Medvedev A, Avdeichuk J, Golubev G, Melnik K, Elenberger N, Engelmann U.(PubMed)
(23) Efficacy and safety of a combination of Sabal and Urtica extract in lower urinary tract symptoms--long-term follow-up of a placebo-controlled, double-blind, multicenter trial by Lopatkin N1, Sivkov A, Schläfke S, Funk P, Medvedev A, Engelmann U.(PubMed)
(24) [Stinging nettle root extract (Bazoton-uno) in long term treatment of benign prostatic syndrome (BPS). Results of a randomized, double-blind, placebo controlled multicenter study after 12 months].

[Article in German] by Schneider T1, Rübben H.(PubMed)
(25) Red ginseng and 20(S)-Rg3 control testosterone-induced prostate hyperplasia by deregulating androgen receptor signaling by Bae JS1, Park HS, Park JW, Li SH, Chun YS.(PubMed)
(26) Cernilton for benign prostatic hyperplasia by Wilt T1, Mac Donald R, Ishani A, Rutks I, Stark G.(PubMed)
(27) systematic review of Cernilton for the treatment of benign prostatic hyperplasia by MacDonald R1, Ishani A, Rutks I, Wilt TJ.(PubMed)

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