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Treatment of Erectile Dysfunction with Pycnogenol and L-arginine


Penile erection requires the relaxation of the cavernous smooth muscle, which is triggered by nitric oxide (NO). We investigated the possibility of overcoming erectile dysfunction (ED) by increasing the amounts of endogenous NO. For this purpose, we orally administered Pycnogenol, because it is known to increase production of NO by nitric oxide synthase together with L-arginine as a substrate for this enzyme. The study included 40 men, aged 25-45 years, without confirmed organic erectile dysfunction. Throughout the 3-month trial period, patients received 3 ampoules Sargenor a day, a drinkable solution of the dipeptide arginyl aspartate (equivalent to 1.7 g L-arginine per day). During the second month, patients were additionally supplemented with 40 mg Pycnogenol two times per day; during the third month, the daily dosage was increased to three 40-mg Pycnogenol tablets. We obtained a sexual function questionnaire and a sexual activity diary from each patient. After 1 month of treatment with L-arginine, a statistically nonsignificant number of 2 patients (5%) experienced a normal erection. Treatment with a combination of L-arginine and Pycnogenol for the following month increased the number of men with the restored sexual ability to 80%. Finally, after the third month of treatment, 92.5% of the men experienced a normal erection. We conclude that oral administration of L-arginine in combination with Pycnogenol causes a significant improvement in sexual function in men with ED without any side effects.

Source: Stanislavov, R., and V. Nikolova. “Treatment of erectile dysfunction with pycnogenol and L-arginine.” Journal of Sex &Marital Therapy 29.3 (2003): 207-213.

Effects of the nitric oxide synthase inhibitor NG‐nitro‐L‐arginine on the erectile response to cavernous nerve stimulation in the rabbit


Using a rabbit model, the involvement of the L‐arginine/nitric oxide pathway in penile erection was investigated. The mean basal intracavernous pressure was 21 cm H2O. Cavernous nerve stimulation (4–8 V, 20–30 Hz) increased the pressure to approximately 130 cm H2O. This response was highly reproducible and usually associated with full penile erection. The pressure increase could be quantified in terms of (1) the slope of the initial, ascending part of the pressure increase; (2) ΔP, which was defined as the maximal pressure obtained by the stimulation minus the basal pressure before the stimulation; (3) T90, which was defined as the time to reach 90 per cent of ΔP. Intrapenile administration of the L‐arginine/nitric oxide synthesis inhibitor NG‐nitro‐L‐arginine had no effect on systemic arterial blood pressure. However, NG‐nitro‐L‐arginine (0.22 and 2.19 mg), administered via the same route, abolished the erectile response induced by cavernous nerve stimulation; T90 increased and slope and ΔP decreased significantly. NG‐nitro‐D‐arginine (2.19), on the other hand, had no inhibitory effect. L‐arginine (21.07 mg), given either directly or after NG‐nitro‐L‐arginine had no consistent effect on the functional response to cavernous nerve stimulation.

The results suggest that pharmacologically induced effects on intracavernous pressure in the rabbit can be described quantitatively and that this model may be useful to study the mechanisms controlling penile erection in vivo. The pronounced inhibitory action of NG‐nitro‐L‐arginine demonstrates the important role of the arginine/nitric oxide pathway in mediating relaxation of penile smooth muscles necessary for erection.

Source: Holmquist, F., et al. “Effects of the nitric oxide synthase inhibitor NG‐nitro‐L‐arginine on the erectile response to cavernous nerve stimulation in the rabbit.” Acta physiologica Scandinavica 143.3 (1991): 299-304.

The effectiveness of oral L-arginine in first-line treatment of erectile dysfunction in a controlled crossover study


Background and Aims: Relaxation of cavernous smooth muscle is a parasympathetic and non-adrenergic, non-cholinergic mediated process which requires nitric oxide (NO). NO is synthesized from L-arginine by NO synthase (NOS). Some studies report good clinical results under oral L-arginine medication in the treatment of erectile dysfunction. We examined the effectiveness and safety of L-arginine in the treatment of mixed-type impotence. Methods: 32 patients (mean age 51.6 years) with mixed-type impotence diagnosed according to the results of sexual history and urological examination were enrolled in a randomized, placebo-controlled, crossover comparison of an oral placebo with 3 × 500 mg L-arginine/day. A validated questionnaire (KEED) was used to define the grade of impotence with a score. The treatment consisted of two 17-day courses (50 tablets). After a 7-day washout period, the patients who initially received the placebo for 17 days were switched to L-arginine and vice versa. We assessed the efficacy with the validated questionnaire at the end of each drug period. Results: 30 patients (94%) completed the whole treatment schedule. Five (17%) patients reported a significant improvement in erectile function at the end of the L-arginine phase and 6 (20%) patients after the placebo period. 17 (56%) patients showed little improvement with L-arginine and 13 (43%) with placebo. In 8 patients (27%) of the verum group, there was either no change in the ED score or even a slight worsening. No statistical difference in the impotence scores was found. No drug-related adverse effects occurred with L-arginine treatment. Conclusion: Oral L-arginine 3 × 500 mg/day is not better than placebo as a first-line treatment for mixed-type impotence.

Source: Klotz, T., et al. “Effectiveness of oral L-arginine in first-line treatment of erectile dysfunction in a controlled crossover study.” Urologia Internationalis 63.4 (1999): 220-223.

Efficacy and Safety of a Novel Combination of L-Arginine Glutamate and Yohimbine Hydrochloride: A New Oral Therapy for Erectile Dysfunction


Purpose: The goal of this double-blind, placebo-controlled, three-way crossover, randomized clinical trial was to compare the efficacy and safety of the combination of 6 g of L-arginine glutamate and 6 mg of yohimbine hydrochloride (AY) with that of 6 mg of yohimbine hydrochloride (YP) alone and that of placebo (PP) alone, for the treatment of erectile dysfunction (ED). Materials and Methods: Forty-five patients were included in this study. During each of the 2-week, crossover periods, the drug was administered orally, one to two hours before intended sexual intercourse. The primary endpoint was changed in the Erectile Function Domain score of the International Index of Erectile Function (IIEF). The secondary endpoints were patient and investigator assessments of treatment success.

Results: At the end of each treatment period, the Erectile Function Domain scores for AY, YP, and PP were 17.2±7.17, 15.4±6.49 and 14.1±6.56, respectively. The difference between AY and PP was statistically significant (p=0.006). When stratified according to baseline scores over 14, those patients with mild to moderate MED had a better Erectile Function Domain response to treatment (AY=22.2±4.99, YP=18.2±5.59, PP=16.9±6.91, respectively) than those with scores 14 and below (AY=12.4±5.48, YP=12.7±6.25, PP=11.4±5.02, respectively). Investigators’ and patients’ assessment of efficacy was significantly improved by YP over PP.

Conclusions: This pilot study shows that the on-demand oral administration of the L-arginine glutamate 6 g and 6 mg yohimbine combination is effective in improving erectile function in patients with mild to moderate ED. It appears to be a promising addition to first-line therapy for ED.

Source: Lebret, Thierry, et al. “Efficacy and safety of a novel combination of L-arginine glutamate and yohimbine hydrochloride: a new oral therapy for erectile dysfunction.” European Urology 41.6 (2002): 608-613.

Tongkat Ali (Eurycoma longifolia)

The In Vitro and In Vivo Anti-Cancer Activities of a Standardized Quassinoids Composition from Eurycoma longifolia on LNCaP Human Prostate Cancer Cells


We hypothesized that androgen could modulate CCL2 expression in hormone-responsive prostate cancer cells and thereby promote recruitment of monocytes. Dihydrotestosterone was found to induce a time-dependent (0-72 hours) and concentration-dependent (0-1 nmol/L) increase in CCL2 mRNA levels in androgen-responsive human prostate cancer cells (LNCaP). This increase in CCL2 mRNA corresponded with increased secretion of CCL2 protein. The effect of dihydrotestosterone was mediated through an androgen receptor (AR)-dependent pathway as small inhibitor RNA against AR negated the induction of CCL2. Both I3C and DIM inhibited promotional effects of dihydrotestosterone on CCL2 and migration.

Source: Tong KL, Chan KL, Abubakar S, Low BS, Ma HQ, Wong PF. “The In Vitro and In Vivo Anti-Cancer Activities of a Standardized Quassinoids Composition from Eurycoma longifolia on LNCaP Human Prostate Cancer Cells” PLoS One (2015) 10(3):e0121752.

Eurycomanone and eurycomanol from Eurycoma longifolia Jack as regulators of signaling pathways involved in proliferation, cell death, and inflammation

Eurycomanone and eurycomanol are two quassinoids from the roots of Eurycoma longifolia Jack. The aim of this study was to assess the bioactivity of these compounds in Jurkat and K562 human leukemia cell models compared to peripheral blood mononuclear cells from healthy donors. Both eurycomanone and eurycomanol inhibited Jurkat and K562 cell viability and proliferation without affecting healthy cells. Interestingly, eurycomanone inhibited NF-κB signaling through inhibition of IκBα phosphorylation and upstream mitogen-activated protein kinase (MAPK) signaling, but not eurycomanol. In conclusion, both quassinoids present differential toxicity towards leukemia cells, and the presence of the α,β-unsaturated ketone in eurycomanone could be prerequisite for the NF-κB inhibition.

Source: Hajjouli S, Chateauvieux S, Teiten MH, Orlikova B, Schumacher M, Dicato M, Choo CY, Diederich M. “Eurycomanone and eurycomanol from Eurycoma longifolia Jack as regulators of signaling pathways involved in proliferation, cell death, and inflammation” Molecules (2014) 19(9):14649-66.

Supplementation of Eurycoma longifolia Jack Extract for 6 Weeks Does Not Affect Urinary Testosterone: Epitestosterone Ratio, Liver and Renal Functions in Male Recreational Athletes

Supplementation of ElJ i.e. Physta(®) at a dosage of 400 mg/day for 6 weeks did not affect the urinary T: E ratio and hence will not breach any doping policies of the International Olympic Committee for the administration of exogenous testosterone or its precursor. In addition, the supplementation of ElJ at this dosage and duration was safe as it did adversely affect the liver and renal functions.

Source: Chen CK, Mohamad WM, Ooi FK, Ismail SB, Abdullah MR, George A. “Supplementation of Eurycoma longifolia Jack Extract for 6 Weeks Does Not Affect Urinary Testosterone: Epitestosterone Ratio, Liver and Renal Functions in Male Recreational Athletes” International Journal of Preventative Medicine (2014): 5(6):728-33.

Effects of a Proprietary Freeze-Dried Water Extract of Eurycoma longifolia (Physta) and Polygonum minus on Sexual Performance and Well-Being in Men: A Randomized, Double-Blind, Placebo-Controlled Study

Background. Methods. Outcome measures included validated questionnaires that aimed to evaluate erectile function, satisfaction with the intervention, sexual intercourse performance, erectile hardness, mood, and overall quality of life. Results. 12 subjects in the active group and 14 in the placebo group completed the study. Significant improvements were noted in scores for the Sexual Intercourse Attempt diary, Erection Hardness Scale, Sexual Health Inventory of Men, and Aging Male Symptom scale (P < 0.05 for all). Conclusion. Supplementation for twelve weeks with Polygonum minus and the proprietary Eurycoma longifolia extract, Physta, was well tolerated and more effective than placebo in enhancing sexual performance in healthy volunteers.

Source: Udani JK, George AA, Musthapa M, Pakdaman MN, Abas A. “Effects of a Proprietary Freeze-Dried Water Extract of Eurycoma longifolia (Physta) and Polygonum minus on Sexual Performance and Well-Being in Men: A Randomized, Double-Blind, Placebo-Controlled Study” Evidence-Based Complementary and Alternative Medicine (2014):179529.

Phytoandrogenic properties of Eurycoma longifolia as a natural alternative to testosterone replacement therapy

This significant decline in testosterone levels is further closely linked with medical conditions such as obesity, metabolic syndrome, diabetes or hypertension. Apart from the beneficial effects of TRT, significant adverse side effects have been described, and prostate cancer (PCa) as absolute contraindication is debated. Eurycoma longifolia (Tongkat Ali; TA) is a natural alternative to TRT and has been shown to restore serum testosterone levels, thus significantly improving sexual health. This includes significant positive effects on bone health and physical condition of patients.

Source: George A, Henkel R. “Phytoandrogenic properties of Eurycoma longifolia as a natural alternative to testosterone replacement therapy” Andrologia (2014): 46(7):708-21.

Evaluation of Acute 13-Week Subchronic Toxicity and Genotoxicity of the Powdered Root of Tongkat Ali (Eurycoma longifolia Jack)

Tongkat Ali (Eurycoma longifolia) is an indigenous traditional herb in Southern Asia. Its powdered root has been processed to produce health supplements, but no detailed toxicology report is available. In this study, neither mutagenicity nor clastogenicity was noted, and acute oral LD50 was more than 6 g/kg b.w. After 4-week subacute and 13-week subchronic exposure paradigms (0, 0.6, 1.2, and 2 g/kg b.w./day), adverse effects attributable to test compound were not observed with respect to body weight, hematology, serum biochemistry, urinalysis, macropathology, or histopathology. However, the treatment significantly reduced prothrombin time, partial thromboplastin time, blood urea nitrogen, creatinine, aspartate aminotransferase, creatine phosphate kinase, lactate dehydrogenase, and cholesterol levels, especially in males (P < 0.05). These changes were judged as pharmacological effects, and they are beneficial to health. The calculated acceptable daily intake (ADI) was up to 1.2 g/adult/day. This information will be useful for product development and safety management.

Source: Li CH, Liao JW, Liao PL, Huang WK, Tse LS, Lin CH, Kang JJ, Cheng YW. “Evaluation of Acute 13-Week Subchronic Toxicity and Genotoxicity of the Powdered Root of Tongkat Ali (Eurycoma longifolia Jack)” Evidence-Based Complementary and Alternative Medicine (2013):102987.

Eurycomanone, the major quassinoid in Eurycoma longifolia root extract increases spermatogenesis by inhibiting the activity of phosphodiesterase and aromatase in steroidogenesis

Eurycomanone enhanced testosterone steroidogenesis at the Leydig cells by inhibiting aromatase conversion of testosterone to estrogen, and at a high concentration may also involve phosphodiesterase inhibition. The quassinoid may be worthy for further development as a phytomedicine to treat testosterone-deficient idiopathic male infertility and sterility.

Source: Low BS, Choi SB, Abdul Wahab H, Das PK, Chan KL. “Eurycomanone, the major quassinoid in Eurycoma longifolia root extract increases spermatogenesis by inhibiting the activity of phosphodiesterase and aromatase in steroidogenesis” Journal of Ethnopharmacology (2013) 149(1):201-7.

Tongkat Ali as a potential herbal supplement for physically active male and female seniors–a pilot study

Thirteen physically active male and 12 physically active female seniors (57-72 years) were supplemented with 400-mg TA extract daily for 5 weeks. After treatment, hemoglobin, testosterone, and dehydroepiandrosterone concentrations, and the ratio of total testosterone/cortisol and muscle force remained significantly lower in female seniors than in male seniors. Treatment resulted in significant increases in total and free testosterone concentrations and muscular force in men and women. The study affirms the ergogenic benefit of TA through enhanced muscle strength.

Source: Henkel RR, Wang R, Bassett SH, Chen T, Liu N, Zhu Y, Tambi MI. “Tongkat Ali as a potential herbal supplement for physically active male and female seniors–a pilot study” Phytotherapy Research (2014) 28(4):544-50.

Randomized Clinical Trial on the Use of PHYSTA Freeze-Dried Water Extract of Eurycoma longifolia for the Improvement of Quality of Life and Sexual Well-Being in Men

A randomized, double-blind, placebo-controlled, parallel group study was carried out to investigate the clinical evidence of E. longifolia in men. Primary endpoints were the Quality of Life investigated by SF-36 questionnaire and Sexual Well-Being investigated by International Index of Erectile Function (IIEF) and Sexual Health Questionnaires (SHQ); Seminal Fluid Analysis (SFA), fat mass and safety profiles. The E. longifolia (EL) group significantly improved in the domain Physical Functioning of SF-36, from baseline to week 12 compared to placebo (P = 0.006) and in between group at week 12 (P = 0.028). All safety parameters were comparable to placebo.

Source: Ismail SB, Wan Mohammad WM, George A, Nik Hussain NH, Musthapa Kamal ZM, Liske E. “Randomized Clinical Trial on the Use of PHYSTA Freeze-Dried Water Extract of Eurycoma longifolia for the Improvement of Quality of Life and Sexual Well-Being in Men” Evidence-Based Complementary and Alternative Medicine (2012) :429268.

Eurycoma longifolia: Medicinal Plant in the Prevention and Treatment of Male Osteoporosis due to Androgen Deficiency

Osteoporosis in elderly men is now becoming an alarming health issue due to its relation with a higher mortality rate compared to osteoporosis in women. Androgen deficiency (hypogonadism) is one of the major factors of male osteoporosis and it can be treated with testosterone replacement therapy (TRT). However, one medicinal plant, Eurycoma longifolia Jack (EL), can be used as an alternative treatment to prevent and treat male osteoporosis without causing the side effects associated with TRT. EL exerts pro-androgenic effects that enhance testosterone level, as well as stimulate osteoblast proliferation and osteoclast apoptosis. This will maintain bone remodeling activity and reduce bone loss. Phytochemical components of EL may also prevent osteoporosis via its antioxidative property. Hence, EL has the potential as a complementary treatment for male osteoporosis.

Source: Mohd Effendy N, Mohamed N, Muhammad N, Naina Mohamad I, Shuid AN. “Eurycoma longifolia: Medicinal Plant in the Prevention and Treatment of Male Osteoporosis due to Androgen Deficiency” Evidence-Based Complementary and Alternative Medicine (2012):125761.

Effect of Eurycoma longifolia Jack (Tongkat Ali) extracts on human spermatozoa in vitro

A sample without addition of TA served as control. For washed spermatozoa, significant dose-dependent trends were found for vitality, total motility, acrosome reaction, and reactive oxygen species-positive spermatozoa. Contrary, the increase in the percentage of acrosome-reacted spermatozoa with increasing TA concentrations is very significant (P < 0.0001), and a significant difference (P=0.0069) to the control could even be recorded at 20 μg TA per ml. Results indicate that the TA extract has no deleterious effects on sperm functions at therapeutically used concentrations (<2.5 μg ml(-1) ). However, at very high concentrations, TA may have harmful effects in vitro.

Source: Erasmus N, Solomon MC, Fortuin KA, Henkel RR. “Effect of Eurycoma longifolia Jack (Tongkat Ali) extracts on human spermatozoa in vitro” Andrologia (2012): 44(5):308-14.

Standardized water-soluble extract of Eurycoma longifolia, Tongkat Ali, as a testosterone booster for managing men with late-onset hypogonadism?

Considering that human studies are not available, 76 of 320 patients suffering from late-onset hypogonadism (LOH) were given 200 mg of a standardized water-soluble extract of Tongkat Ali for 1 month. The Ageing Males’ Symptoms (AMS) according to the standardized rating scale and the serum testosterone concentration were taken. Results show that treatment of LOH patients with this Tongkat Ali extract significantly (P < 0.0001) improved the AMS score as well as the serum testosterone concentration.

Source: Tambi MI, Imran MK, Henkel RR. “Standardized water-soluble extract of Eurycoma longifolia, Tongkat Ali, as a testosterone booster for managing men with late-onset hypogonadism?” Andrologia. (2012): 44 Suppl 1:226-30.


Ginger and Testosterone *

Enhancing and protecting testosterone production is one target for many scientists because of its crucial role as a primary sex hormone in males. Several in vivo trials have utilized different dietary supplements and medicinal plants to enhance testosterone production in males. Since 1991, various in-vivo, as well as basic research studies, have discovered a link between ginger (Zingiber officinale) and testosterone. However, such a link has not yet been collectively reviewed. This review systematically discusses and summarizes the effect of ginger and ginger extracts on testosterone. To achieve this contribution, we searched the PubMed, Scopus, and Web of Science databases for English language articles (full texts or abstracts) from November 1991 through August 2018 using the keywords “ginger” and “Zingiber officinale” versus “testosterone”. Additionally, the references from related published articles were also reviewed, only if relevant. In conclusion, the mainstream of research that links ginger to testosterone demonstrated that ginger supplementation, particularly in oxidative stress conditions, enhances testosterone production in males. The mechanisms by which this occurs mainly by enhancing luteinizing hormone (LH) production, increasing the level of cholesterol in the testes, reducing oxidative stress and lipid peroxidation in the testes, enhancing the activity of the antioxidant enzymes, normalizing blood glucose, increasing blood flow in the testes, increasing testicular weight, and recycling testosterone receptors. However, the effect of ginger on testosterone is not yet confirmed in humans. Therefore, clinical studies in this context of research are imperative.

Source: Saleem Ali Banihani. “Ginger and Testosterone” Biomolecules (2018): 8(4): 119.

Effect of High Dose Ginger on Plasma Testosterone and Leutinising Hormone Levels in Male Rats after Lead Induced Toxicity *


Background: To study the effect of high dose ginger on plasma testosterone and leutinising hormone levels in male rats after lead induced toxicity.

Methods: In this quasi experimental study, 30 adult male Sprague Dawley rats were divided in two equal groups. Group A was given 0.3% lead acetate in drinking water and kept as lead control while the Group B was given a dose of 1.5gm/kg body weight ginger orally along with 0.3% lead for 42 consecutive days. Rats were then sacrificed and serum testosterone and LH levels were analyzed using ELISA technique. Data was expressed as mean±SD. P-values < 0.05 were considered as statistically significant.

Results: At the end of 42 days, mean serum testosterone level in Group A (control Group) was 2.2667 ± 0.45617ng/ml as compared to Group B (Experimental Group) 2.2667 ± 0.45617ng/ml and showed statistically insignificant change(p > 0.05). Comparison of mean serum LH levels in Group A (5.3200 ± 0.72526ng/ml)revealed statistically insignificant difference (p>0.05) as compared to Group B (5.7467 ± 0.70190ng/ml).

Conclusion: High dose ginger (>1gm/kg body weight) failed to enhance the suppressed testosterone level due to lead toxicity in male rats.

Source: Fatima Riaz, Kirn-e-Muneera, Muhammad Adnan Saeed “Effect of High Dose Ginger on Plasma Testosterone and Leutinising Hormone Levels in Male Rats after Lead Induced Toxicity” Journal of Rawalpindi Medical College (JRMC) (2017): 21(1): 90-92.

Antioxidant Effects of Some Ginger Constituents


The nonvolatile fraction of the dichloromethane extract of ginger rhizomes exhibited a strong antioxidative activity using linoleic acid as the substrate in ethanol‐phosphate buffer solution. The fraction was purified by chromatographic techniques to provide five gingerol related compounds and eight diarylheptanoids. Among them, 12 compounds exhibited higher activity than α‐tocopherol. The activity was probably dependent upon side chain structures and substitution patterns on the benzene ring.

Source: Kikuzaki, Hiroe, and Nobuji Nakatani. “Antioxidant effects of some ginger constituents.” Journal of food science 58.6 (1993): 1407-1410.

Ginger—An Herbal Medicinal Product with Broad Anti-Inflammatory Actions


The anti-inflammatory properties of ginger have been known and valued for centuries. During the past 25 years, many laboratories have provided scientific support for the long-held belief that ginger contains constituents with antiinflammatory properties. The original discovery of ginger’s inhibitory effects on prostaglandin biosynthesis in the early 1970s has been repeatedly confirmed. This discovery identified ginger as an herbal medicinal product that shares pharmacological properties with non-steroidal anti-inflammatory drugs. Ginger suppresses prostaglandin synthesis through inhibition of cyclooxygenase- 1 and cyclooxygenase-2. An important extension of this early work was the observation that ginger also suppresses leukotriene biosynthesis by inhibiting 5-lipoxygenase. This pharmacological property distinguishes ginger from nonsteroidal anti-inflammatory drugs. This discovery preceded the observation that dual inhibitors of cyclooxygenase and 5-lipoxygenase may have a better therapeutic profile and have fewer side effects than non-steroidal anti-inflammatory drugs. The characterization of the pharmacological properties of ginger entered a new phase with the discovery that a ginger extract (EV.EXT.77) derived from Zingiber officinale (family Zingiberaceae) and Alpina galanga (family Zingiberaceae) inhibits the induction of several genes involved in the inflammatory response. These include genes encoding cytokines, chemokines, and the inducible enzyme cyclooxygenase-2. This discovery provided the first evidence that ginger modulates biochemical pathways activated in chronic inflammation. Identification of the molecular targets of individual ginger constituents provides an opportunity to optimize and standardize ginger products with respect to their effects on specific biomarkers of inflammation. Such preparations will be useful for studies in experimental animals and humans.

Source: Grzanna, Reinhard, Lars Lindmark, and Carmelita G. Frondoza. “Ginger—an herbal medicinal product with broad anti-inflammatory actions.” Journal of medicinal food 8.2 (2005): 125-132.

Ginger and Turmeric

Dietary supplementation of ginger and turmeric improves reproductive function in hypertensive male rats *

Ginger [Zingiber officinale Roscoe (Zingiberaceae)] and turmeric [Curcuma longa Linn (Zingiberaceae)] rhizomes have been reportedly used in folk medicine for the treatment of hypertension. However, the prevention of its complication such as male infertility remains unexplored. Hence, the aim of the present study was to investigate the preventive effects of ginger and turmeric rhizomes on some biomarkers of male reproductive function in L-NAME-induced hypertensive rats. Male Wistar rats were divided into seven groups (n = 10): normotensive control rats; induced (L-NAME hypertensive) rats; hypertensive rats treated with atenolol (10 mg/kg/day); normotensive and hypertensive rats treated with 4% supplementation of turmeric or ginger, respectively. After 14 days of pre-treatment, the animals were induced with hypertension by oral administration of L-NAME (40 mg/kg/day). The results revealed significant decrease in serum total testosterone and epididymal sperm progressive motility without affecting sperm viability in hypertensive rats. Moreover, increased oxidative stress in the testes and epididymides of hypertensive rats was evidenced by significant decrease in total and non-protein thiol levels, glutathione S-transferase (GST) activity with concomitant increase in 2′,7′-dichlorofluorescein (DFCH) oxidation and thiobarbituric acid reactive substances (TBARS) production. Similarly, decreased testicular and epididymal NO level with concomitant elevation in arginase activity was observed in hypertensive rats. However, dietary supplementation with turmeric or ginger efficiently prevented these alterations in biomarkers of reproductive function in hypertensive rats. The inhibition of arginase activity and increase in NO and testosterone levels by both rhizomes could suggest possible mechanism of action for the prevention of male infertility in hypertension. Therefore, both rhizomes could be harnessed as functional foods to prevent hypertension-mediated male reproductive dysfunction.

Source: Ayodele Jacob Akinyemi, Isaac A. Adedara, Gustavo Roberto Thome, Vera Maria Morsch, Monique Tomazele Rovani, Lady Katerine Serrano Mujica, Thiago Duarte, Marta Duarte, Ganiyu Oboh, Maria Rosa Chitolina Schetinger. “Dietary supplementation of ginger and turmeric improves reproductive function in hypertensive male rats” Toxicology Reports (2015): 2: 1357–1366.

Ashwagandha Extract (Withania somnifera)

Examining the effect of Withania somnifera supplementation on muscle strength and recovery: a randomized controlled trial *


Background: Withania somnifera (ashwagandha) is a prominent herb in Ayurveda. This study was conducted to examine the possible effects of ashwagandha root extract consumption on muscle mass and strength in healthy young men engaged in resistance training.

Methods: In this 8-week, randomized, prospective, double-blind, placebo-controlled clinical study, 57 young male subjects (18–50 years old) with little experience in resistance training were randomized into treatment (29 subjects) and placebo (28 subjects) groups. Subjects in the treatment group consumed 300 mg of ashwagandha root extract twice daily, while the control group consumed starch placebos. Following baseline measurements, both groups of subjects underwent resistance training for 8 weeks and measurements were repeated at the end of week 8. The primary efficacy measure was muscle strength. The secondary efficacy measures were muscle size, body composition, serum testosterone levels and muscle recovery. Muscle strength was evaluated using the 1-RM load for the bench press and leg extension exercises. Muscle recovery was evaluated by using serum creatine kinase level as a marker of muscle injury from the effects of exercise.

Results: Compared to the placebo subjects, the group treated with ashwagandha had significantly greater increases in muscle strength on the bench-press exercise (Placebo: 26.4 kg, 95 % CI, 19.5, 33.3 vs. Ashwagandha: 46.0 kg, 95 % CI 36.6, 55.5; p = 0.001) and the leg-extension exercise (Placebo: 9.8 kg, 95 % CI, 7.2,12.3 vs. Ashwagandha: 14.5 kg, 95 % CI, 10.8,18.2; p = 0.04), and significantly greater muscle size increase at the arms (Placebo: 5.3 cm2, 95 % CI, 3.3,7.2 vs. Ashwagandha: 8.6 cm2, 95 % CI, 6.9,10.8; p = 0.01) and chest (Placebo: 1.4 cm, 95 % CI, 0.8, 2.0 vs. Ashwagandha: 3.3 cm, 95 % CI, 2.6, 4.1; p < 0.001). Compared to the placebo subjects, the subjects receiving ashwagandha also had significantly greater reduction of exercise-induced muscle damage as indicated by the stabilization of serum creatine kinase (Placebo: 1307.5 U/L, 95 % CI, 1202.8, 1412.1, vs. Ashwagandha: 1462.6 U/L, 95 % CI, 1366.2, 1559.1; p = 0.03), significantly greater increase in testosterone level (Placebo: 18.0 ng/dL, 95 % CI, -15.8, 51.8 vs. Ashwagandha: 96.2 ng/dL, 95 % CI, 54.7, 137.5; p = 0.004), and a significantly greater decrease in body fat percentage (Placebo: 1.5 %, 95 % CI, 0.4 %, 2.6 % vs. Ashwagandha: 3.5 %, 95 % CI, 2.0 %, 4.9 %; p = 0.03).

Conclusion: This study reports that ashwagandha supplementation is associated with significant increases in muscle mass and strength and suggests that ashwagandha supplementation may be useful in conjunction with a resistance training program.

Source: Sachin Wankhede, Deepak Langade, Kedar Joshi, Shymal R. Sinha, and Sauvik Bhattacharyya.“Examining the effect of Withania somnifera supplementation on muscle strength and recovery: a randomized controlled trial” Journal of International Society of Sports Nutrition 2015; 12: 43.

Dendrite extension by methanol extract of Ashwagandha (roots of Withania somnifera) in SK-N-SH cells


Extension of dendrites and axons in neurons may compensate for and repair damaged neuronal circuits in the dementia brain. Our aim in the present study was to explore drugs activating neurite outgrowth and regenerating the neuronal network. We found that the methanol extract of Ashwagandha (roots of Withania somnifera; 5 μg/ml) significantly increased the percentage of cells with neurites in human neuroblastoma SK-N-SH cells. The effect of the extract was dose- and time-dependent. mRNA levels of the dendritic markers MAP2 and PSD-95 by RT-PCR were found to be markedly increased by treatment with the extract, whereas those of the axonal marker Tau were not. Immunocytochemistry demonstrated the specific expression of MAP2 in neurites extended by the extract. These results suggest that the methanol extract of Ashwagandha promotes the formation of dendrites.

Source: Tohda, Chihiro, Tomoharu Kuboyama, and Katsuko Komatsu. “Dendrite extension by methanol extract of Ashwagandha (roots of Withania somnifera) in SK-N-SH cells.” Neuroreport 11.9 (2000): 1981-1985.

A Prospective, Randomized Double-Blind, Placebo-Controlled Study of Safety and Efficacy of a High-Concentration Full-Spectrum Extract of Ashwagandha Root in Reducing Stress and Anxiety in Adults


The findings of this study suggest that a high-concentration full-spectrum Ashwagandha root extract safely and effectively improves an individual’s resistance towards stress and thereby improves self-assessed quality of life.

Source: Chandrasekhar, K., Jyoti Kapoor, and Sridhar Anishetty. “A prospective, randomized double-blind, placebo-controlled study of safety and efficacy of a high-concentration full-spectrum extract of ashwagandha root in reducing stress and anxiety in adults.” Indian journal of psychological medicine 34.3 (2012): 255.

Clinical Evaluation of the Spermatogenic Activity of the Root Extract of Ashwagandha (Withania somnifera) in Oligospermic Males: A Pilot Study


Ashwagandha (Withania somnifera) has been described in traditional Indian Ayurvedic medicine as an aphrodisiac that can be used to treat male sexual dysfunction and infertility. This pilot study was conducted to evaluate the spermatogenic activity of Ashwagandha root extract in oligospermic patients. Forty-six male patients with oligospermia (sperm count < 20 million/mL semen) were enrolled and randomized either to treatment () with a full-spectrum root extract of Ashwagandha (675 mg/d in three doses for 90 days) or to placebo () in the same protocol. Semen parameters and serum hormone levels were estimated at the end of 90-day treatment. There was a 167% increase in sperm count (9.59 ± 4.37 × 106/mL to 25.61 ± 8.6 × 106/mL; ), 53% increase in semen volume (1.74 ± 0.58 mL to 2.76 ± 0.60 mL; ), and 57% increase in sperm motility (18.62 ± 6.11% to 29.19 ± 6.31%; ) on day 90 from baseline. The improvement in these parameters was minimal in the placebo-treated group. Furthermore, a significantly greater improvement and regulation were observed in serum hormone levels with the Ashwagandha treatment as compared to the placebo. The present study adds to the evidence on the therapeutic value of Ashwagandha (Withania somnifera), as attributed in Ayurveda for the treatment of oligospermia leading to infertility.

Source: Ambiye, Vijay R., et al. “Clinical evaluation of the spermatogenic activity of the root extract of Ashwagandha (Withania somnifera) in oligospermic males: a pilot study.” Evidence-Based Complementary and Alternative Medicine (2013).

Protective Role of Ashwagandha Leaf Extract and Its Component Withanone on Scopolamine-Induced Changes in the Brain and Brain-Derived Cells


Our study suggested that besides cholinergic blockade, scopolamine-induced memory loss may be associated with oxidative stress and Ashwagandha i-Extract, and withanone may serve as potential preventive and therapeutic agents for neurodegenerative disorders and hence warrant further molecular analyses. Source: Konar, Arpita, et al. “Protective role of Ashwagandha leaf extract and its component withanone on scopolamine-induced changes in the brain and brain-derived cells.” PloS one 6.11 (2011).

Turmeric (root)

Modulation of AKR1C2 by curcumin decreases testosterone production in prostate cancer *

Intratumoral androgen biosynthesis has been recognized as an essential factor of castration‐resistant prostate cancer. The present study investigated the effects of curcumin on the inhibition of intracrine androgen synthesis in prostate cancer. Human prostate cancer cell lines, LNCaP and 22Rv1 cells were incubated with or without curcumin after which cell proliferation was measured at 0, 24, 48 and 72 hours, respectively. Prostate tissues from the transgenic adenocarcinoma of the mouse prostate (TRAMP) model were obtained after 1‐month oral administration of 200 mg/kg/d curcumin. Testosterone and dihydrotestosterone concentrations in LNCaP prostate cancer cells were determined through LC‐MS/MSassay. Curcumin inhibited cell proliferation and induced apoptosis of prostate cancer cells in a dose‐dependent manner. Curcumin decreased the expression of steroidogenic acute regulatory proteins, CYP11A1 and HSD3B2 in prostate cancer cell lines, supporting the decrease of testosterone production. After 1‐month oral administration of curcumin, Aldo‐Keto reductase 1C2 (AKR1C2) expression was elevated. Simultaneously, decreased testosterone levels in the prostate tissues were observed in the TRAMP mice. Meanwhile, curcumin treatments considerably increased the expression of AKR1C2 in prostate cancer cell lines, supporting the decrease of dihydrotestosterone. Taken together, these results suggest that curcumin’s natural bioactive compounds could have potent anticancer properties due to suppression of androgen production, and this could have therapeutic effects on prostate cancer.

Source: Hisamitsu Ide, Yan Lu, Takahiro Noguchi, Satoru Muto, Hiroshi Okada, Suguru Kawato, Shigeo Horie. “Modulation of AKR1C2 by curcumin decreases testosterone production in prostate cancer” Cancer Science (2018): 109(4): 1230–1238.

A double-blind, placebo-controlled randomised trial evaluating the effect of a polyphenol-rich whole food supplement on PSA progression in men with prostate cancer—the UK NCRN Pomi-T study *

Background: Polyphenol-rich foods such as pomegranate, green tea, broccoli and turmeric have demonstrated anti-neoplastic effects in laboratory models involving angiogenesis, apoptosis and proliferation. Although some have been investigated in small, phase II studies, this combination has never been evaluated within an adequately powered randomised controlled trial.

Methods: In total, 199 men, average age 74 years, with localised prostate cancer, 60% managed with primary active surveillance (AS) or 40% with watchful waiting (WW) following previous interventions, were randomised (2:1) to receive an oral capsule containing a blend of pomegranate, green tea, broccoli and turmeric, or an identical placebo for 6 months.

Results: The median rise in PSA in the food supplement group (FSG) was 14.7% (95% confidence intervals (CIs) 3.4–36.7%), as opposed to 78.5% in the placebo group (PG) (95% CI 48.1–115.5%), difference 63.8% (P=0.0008). In all, 8.2% of men in the FSG and 27.7% in the PG opted to leave surveillance at the end of the intervention (χ2 P=0.014). There were no significant differences within the predetermined subgroups of age, Gleason grade, treatment category or body mass index. There were no differences in cholesterol, blood pressure, blood sugar, C-reactive protein or adverse events.

Conclusions: This study found a significant short-term, favourable effect on the percentage rise in PSA in men managed with AS and WW following ingestion of this well-tolerated, specific blend of concentrated foods. Its influence on decision-making suggests that this intervention is clinically meaningful, but further trials will evaluate longer term clinical effects, and other makers of disease progression.

Source: R. Thomas, M. Williams, H. Sharma, A. Chaudry, P. Bellamy. “A double-blind, placebo-controlled randomised trial evaluating the effect of a polyphenol-rich whole food supplement on PSA progression in men with prostate cancer—the UK NCRN Pomi-T study” Prostate Cancer and Prostatic Diseases (2014): volume 17, pages180–186.

Tribulus Terrestris

Tribulus terrestris extracts alleviate muscle damage and promote anaerobic performance of trained male boxers and its mechanisms: Roles of androgen, IGF-1, and IGF binding protein-3 *


Purpose: To investigate the effects of Tribulus terrestris (TT) extracts on muscle mass, muscle damage, and anaerobic performances of trained male boxers and its mechanisms: roles of plasma androgen, insulin growth factor 1 (IGF-1), and IGF-1 binding protein-3 (IGFBP-3).

Methods: Fifteen male boxers were divided into exercise group (E, n = 7) and exercise plus TT group (E + TT, n = 8). The 2 groups both undertook 3-week high-intensity and 3-week high-volume trainings separated by a 4-week rest. TT extracts (1250 mg/day) were orally administered by boxers in E + TT group. TT extract compositions were detected by UHPLC–Q-TOF/MS. Before and at the end of the 2 trainings, muscle mass, anaerobic performance, and blood indicators were explored.

Results: Compared with E group, decreases of plasma CK (1591.5 ± 909.6 U/L vs. 2719.9 ± 832.5 U/L) and IGFBP-3 (3075.5 ± 1072.5 ng/mL vs. 3950.8 ± 479.3 ng/mL) as well as increases of mean power (MP, 459.4 ± 122.3 W vs. 434.6 ± 69.5 W) and MP/body weight (MP/BW, 7.5 ± 0.9 W/kg vs. 7.1 ± 1.1 W/kg) were detected in E + TT group after a high-intensity training. For high-volume training, reduction of IGFBP-3 (2946.4 ± 974.1 ng/mL vs. 3632.7 ± 470.1 ng/mL) and increases of MP (508.7 ± 103.2 W vs. 477.8 ± 49.9 W) and MP/BW (8.2 ± 0.3 W/kg vs. 7.5 ± 0.9 W/kg) were detected in E + TT group, compared with E group. Muscle mass, blood levels of testosterone, dihydrotestosterone (DHT), and IGF-1 were not signifiantly changed between the 2 groups.

Conclusion: Taking 1250 mg capsules containing TT extracts did not change muscle mass and plasma levels of testosterone, DHT, and IGF-1 but significantly alleviated muscle damage and promoted anaerobic performance of trained male boxers, which may be related to the decrease of plasma IGFBP-3 rather than androgen in plasma.

Source: Yiming Ma, Zhicheng Guo, Xiaohui Wang. “Tribulus terrestris extracts alleviate muscle damage and promote anaerobic performance of trained male boxers and its mechanisms: Roles of androgen, IGF-1, and IGF binding protein-3” Journal of Sports and Health Science (2017): Volume 6, Issue 4, Pages 474-481.

Insights into Supplements with Tribulus Terrestris used by Athletes *

Herbal and nutritional supplements are more and more popular in the western population. One of them is an extract of an exotic plant, named Tribulus terrestris (TT). TT is a component of several supplements that are available over-the-counter and widely recommended, generally as enhancers of human vitality. TT is touted as a testosterone booster and remedy for impaired erectile function; therefore, it is targeted at physically active men, including male athletes. Based on the scientific literature describing the results of clinical trials, this review attempted to verify information on marketing TT with particular reference to the needs of athletes. It was found that there are few reliable data on the usefulness of TT in competitive sport. In humans, a TT extract used alone without additional components does not improve androgenic status or physical performance among athletes. The results of a few studies have showed that the combination of TT with other pharmacological components increases testosterone levels, but it was not discovered which components of the mixture contributed to that effect. TT contains several organic compounds including alkaloids and steroidal glycosides, of which pharmacological action in humans is not completely explained. One anti-doping study reported an incident with a TT supplement contaminated by a banned steroid. Toxicological studies regarding TT have been carried out on animals only, however, one accidental poisoning of a man was described. The Australian Institute of Sport does not recommend athletes’ usage of TT. So far, the published data concerning TT do not provide strong evidence for either usefulness or safe usage in sport.

Source: Andrzej Pokrywka, Zbigniew Obmiński, Jadwiga Malczewska-Lenczowska, Zbigniew Fijałek, Ewa Turek-Lepa, Ryszard Grucza. “Insights into Supplements with Tribulus Terrestris used by Athletes” Journal of Human Kinetics (2014): 41: 99–105.

Infertility, male

Botanical medicines

Panax ginseng (Chinese or Korean ginseng): Panax is effective in male infertility. Panax promotes growth of testes, increases sperm formation and testosterone levels, and increases sexual activity and mating behavior in studies with animals. Panax enhances nitric oxide production, which helps regulate capacitating process of sperm and acrosome reaction. Thus Panax improves fertilization sperm motility. Ginsenosides influence hypothalamic-pituitary-testicular axis, modulating stress-induced infertility or lowered testosterone from insufficient dehydroepiandrosterone (DHEA) synthesis. Panax may increase testosterone levels and sperm counts. Panax can be used for oligospermia, even with varicocele, and for improvement of erection and libido.

Pygeum africanum: improves fertility if diminished prostatic secretion plays significant role. It increases prostatic secretions and improves composition of seminal fluid by increasing total seminal fluid, alkaline phosphatase, and protein. It is most effective if alkaline phosphatase activity is reduced (<400 IU/cm3) with no evidence of inflammation or infection (no white blood cells or immunoglobulin A [IgA]). Lack of IgA in semen is a good indicator of potential clinical success. It improves capacity to achieve erection in patients with benign prostatic hypertrophy or prostatitis as determined by nocturnal penile tumescence. (Benign prostatic hypertrophy and prostatitis often are linked to erectile dysfunction and other sexual disturbances.)

Tribulus terrestris: Ayurvedic tonic and aphrodisiac; used in European folk medicine to increase sexual potency. Chief constituent: protodioscin, a steroidal saponin. Correct sourcing of Tribulus is critical to ensure its effectiveness. All scientific data and clinical outcomes are based on a leaf extract from Bulgaria, highest in protodioscin. Sources form other nations or plant parts may be less effective. In animal studies, Tribulus increased sex hormones (e.g., testosterone) and improved nitric oxide synthesis; however, these results have not been observed in some human studies. Explanation: differences in extract and plant parts and the fact that studies included healthy males with normal testosterone. Tribulus enhances male fertility by increasing sperm count, viability, and libido; however, study results are unclear.

Astragalus membranaceus: increases motility of sperm in semen. Astragalus increases motility of sperm in semen and motility of washed sperm, relevant to those seeking ART treatment.

Turnera diffusa (damiana): traditionally used for “its positive aphrodisiac effects, acting energetically on the genitourinary organs of both genders where it was highly indicated for sexual weakness and debility.” It is a stimulant tonic of sexual organs, especially during “enfeeblement of the central nervous system.” It is especially beneficial for sexual debility, erectile difficulty, and depression. Human studies are lacking. In male rats: damiana facilitates sexual behavior in rats with sexual dysfunction, reduces ejaculation latency, produces a restorative effect in sexual exhaustion, and hastens recovery. It suppresses aromatase activity, perhaps increasing levels of testosterone.

Mucuna pruriens (velvet bean): Ayurvedic medicine for enduranceagainst stress, resistance against infection, retardation of aging process, and improvement of male sexual function; it alleviates psychogenic impotence and unexplained infertility. M. pruriensseed powder helps fight stress-mediated poor semen quality. It is a restorative and invigorating tonic and aphrodisiac in infertile subjects. Mechanism: regulation of steroidogenesis and resulting improvements in semen quality. It improves testosterone, luteinizing hormone (LH), dopamine, adrenaline, and noradrenaline levels in infertile men and reduces FSH and prolactin (PRL). Sperm count and motility were also improved in infertile men.

Withania somnifera (Withania): has antistress and adaptogenic effects. At a dose of 5 g powdered root daily, Withania inhibited lipid peroxidation and improved sperm count and motility. It increased serum testosterone and LH and reduced follicle FSH and PRL, all beneficial effects in infertile men.

Source: Joseph E. Pizzorno, ND, Michael T. Murray, ND, Herb Joiner-Bey, ND. “Infertility, male” The Clinician’s Handbook of Natural Medicine (Third Edition), (2016): 521-546.

A review of traditional pharmacological uses, phytochemistry, and pharmacological activities of Tribulus terrestris *


Tribulus terrestris L. (TT) is an annual plant of the family Zygophyllaceae that has been used for generations to energize, vitalize, and improve sexual function and physical performance in men. The fruits and roots of TT have been used as a folk medicine for thousands of years in China, India, Sudan, and Pakistan. Numerous bioactive phytochemicals, such as saponins and flavonoids, have been isolated and identified from TT that are responsible alone or in combination for various pharmacological activities. This review provides a comprehensive overview of the traditional applications, phytochemistry, pharmacology and overuse of TT and provides evidence for better medicinal usage of TT.

Source: Wenyi Zhu, Yijie Du, Hong Meng, Yinmao Dong, and Li Li. “A review of traditional pharmacological uses, phytochemistry, and pharmacological activities of Tribulus terrestris” Chemistry Central Journal (2017): 11: 60.

Saponins in Tribulus terrestris – Chemistry and Bioactivity


Tribulus terrestris is a valuable herb known for its application in folk medicine in many parts of the world. Furostanol and spirostanol saponins of tigogenin, neotigogenin, gitogenin, neogitogenin, hecogenin, neo hecogenin, diosgenin, chlorogenin, ruscogenin and sarsasapogenin type are frequently found in this plant. Four sulphated saponins of tigogenin and diosgenin type are also isolated. Extracts and steroidal saponins have been found to possess various pharmacological activities. Preparations based on the saponin fraction of T. terrestris are used for treatment of infertility and libido disorders in men and women, as well as for treatment of cardiac diseases. Food supplements containing T. terrestris extracts are on sale in the USA and Europe with claims of a general stimulating action.

Source: Kostova, I., and D. Dinchev. “Saponins in Tribulus terrestris–chemistry and bioactivity.” Phytochemistry reviews 4.2-3 (2005): 111-137.

Phytopharmacological overview of Tribulus terrestris


Tribulus terrestris (family Zygophyllaceae), commonly known as Gokshur or Gokharu or puncture vine, has been used for a long time in both the Indian and Chinese systems of medicine for treatment of various kinds of diseases. Its various parts contain a variety of chemical constituents which are medicinally important, such as flavonoids, flavonol glycosides, steroidal saponins, and alkaloids. It has diuretic, aphrodisiac, antiurolithic, immunomodulatory, antidiabetic, absorption enhancing, hypolipidemic, cardiotonic, central nervous system, hepatoprotective, anti-inflammatory, analgesic, antispasmodic, anticancer, antibacterial, anthelmintic, larvicidal, and anticariogenic activities. For the last few decades or so, extensive research work has been done to prove its biological activities and the pharmacology of its extracts. The aim of this review is to create a database for further investigations of the discovered phytochemical and pharmacological properties of this plant to promote research. This will help in confirmation of its traditional use along with its value-added utility, eventually leading to higher revenues from the plant.

Source: Chhatre, Saurabh, et al. “Phytopharmacological overview of Tribulus terrestris.” Pharmacognosy reviews 8.15 (2014): 45.

Fenugreek (seed)

The Efficacy of Fenugreek Supplementation on Men’s Health: A Randomized Controlled Trial *

Brief Summary:

The problem: There is limited research on the use of herbal supplements in general, and fenugreek specifically, to improve male health, particularly to increase testosterone levels. As well, no located studies have examined the effects of fenugreek supplementation on healthy men’s health-related quality of life, anxiety levels, and body composition.

Relevant research examined the effects of fenugreek supplementation with healthy men aged between 43 and 70 years of age. The researchers found that both total serum testosterone and free testosterone increased compared to placebo after 12 weeks of active treatment. The researchers concluded that fenugreek supplementation was a safe and effective treatment for reducing symptoms of possible androgen deficiency, improves sexual function and increases serum testosterone in healthy middle-aged to older men. Another study found that fenugreek supplementation improved aging male symptoms and testosterone levels remained in a normal range in healthy men aged 25 to 45 years.

The importance of this study: The importance of this study is to help determine if fenugreek supplementation affects testosterone levels, body composition, health-related quality of life, anxiety, and aging symptoms in healthy men aged 21 – 45 years.

Source: Jacksonville University “The Efficacy of Fenugreek Supplementation on Men’s Health: A Randomized Controlled Trial” ClinicalTrials.gov (2018).

Fenugreek’s Effects on Hormone Changes and Sexual Function in Healthy Men *

Extract of Trigonella foenum-graecum seed reduces age-related symptoms

Design Double-blind, randomized, placebo-controlled trial conducted between February and November 2014 in Brisbane, Australia

Intervention The active treatment was standardized fenugreek (Trigonella foenum-graecum) seed extract at a dose of 600 mg/day.

Primary Outcome Measures Primary outcome measure was the change in the Aging Male Symptom questionnaire (AMS), a measure of possible androgen deficiency symptoms. Secondary outcome measures were sexual function and serum testosterone.

Participants Healthy middle age men (N=120). Subjects were excluded from the study if they

  • were diagnosed with erectile dysfunction or any physical disability that may limit sexual function,
  • had received any treatment/therapy (including testosterone or anabolic steroids) for any sexual disorder during last 6 months,
  • were being prescribed anticoagulation therapy,
  • were receiving levodopa for Parkinson’s disease or calcipotriene for psoriasis,
  • were diagnosed with severe renal and/or hepatic insufficiency,
  • were diagnosed with genital anatomical deformities or had any abnormal secondary sexual characteristics,
  • had uncontrolled diabetes mellitus,
  • had a history of spinal cord injury or major psychiatric disorder,
  • were diagnosed with prostate cancer or benign prostatic hypertrophy,
  • had an acute genitourinary disorder or history of genital surgery,
  • had a current or past history of chronic alcohol and/or drug abuse,
  • had a suspected or diagnosed chickpea allergy, or
  • were currently participating in another trial or had been in any other clinical trial during the last 30 days.

Key Findings: Both total testosterone (P < 0.001) and free testosterone (P=0.002) increased in the men who consumed fenugreek seed extract compared to the control group at week 12.

Additionally, fenugreek seed extract use was associated with favorable overall sexual function in the treatment group when compared to placebo when using the Derogatis Interview for Sexual Functioning-Self Report (P=0.006).

When numerous sexual sub-domains were analyzed further improvements were observed in the treatment group, especially sexual arousal (P=0.001), sexual drive/relationship (P=0.007), number of weekly erections from 1 per week to 2 to 3 per week (P=0.001), and sexual activity from 1 to 2 times per month to close to once a week (P=0.004). No changes were observed in the sub-domains of sexual cognition, sexual behavior, or orgasm.

Lastly, the AMS showed a significant difference across time (P < 0.001), and a significant difference between groups (P=0.013), for total AMS Score

There were no changes observed in BMI, waist/hip ratios, grip strength, DHEA-S, androstenedione, estradiol, or liver function after treatment with fenugreek seed extract. The herbal medicine was well tolerated, although it was associated with headache in <5% of subjects.

Source: Geovanni Espinosa, ND, LAc, CNS.“Fenugreek’s Effects on Hormone Changes and Sexual Function in Healthy Men” Natural Medicine Journal (2016) Vol. 8 Issue 10.

Testofen, a specialised Trigonella foenum-graecum seed extract reduces age-related symptoms of androgen decrease, increases testosterone levels and improves sexual function in healthy aging males in a double-blind randomised clinical study *


This study examined the effect of Testofen, a specialised Trigonella foenum-graecum seed extract on the symptoms of possible androgen deficiency, sexual function and serum androgen concentrations in healthy aging males. This was a double-blind, randomised, placebo-controlled trial involving 120 healthy men aged between 43 and 70 years of age. The active treatment was standardised Trigonella foenum-graecum seed extract at a dose of 600 mg/day for 12 weeks. The primary outcome measure was the change in the Aging Male Symptom questionnaire (AMS), a measure of possible androgen deficiency symptoms; secondary outcome measures were sexual function and serum testosterone. There was a significant decrease in AMS score over time and between the active and placebo groups. Sexual function improved, including number of morning erections and frequency of sexual activity. Both total serum testosterone and free testosterone increased compared to placebo after 12 weeks of active treatment. Trigonella foenum-graecum seed extract is a safe and effective treatment for reducing symptoms of possible androgen deficiency, improves sexual function and increases serum testosterone in healthy middle-aged and older men.

Source: Amanda Rao, Elizabeth Steels, Warrick J Inder, Suzanne Abraham, Luis Vitetta. “Testofen, a specialised Trigonella foenum-graecum seed extract reduces age-related symptoms of androgen decrease, increases testosterone levels and improves sexual function in healthy aging males in a double-blind randomised clinical study” Aging Male (2016): 19(2):134-42.

Beneficial effects of fenugreek glycoside supplementation in male subjects during resistance training: A randomized controlled pilot study *


Purpose: To evaluate the efficacy and safety of the glycoside fraction of fenugreek (Trigonella foenum-graecum) seeds (Fenu-FG) on physiological parameters related to muscle anabolism, androgenic hormones, and body fat in healthy male subjects during an 8-week resistance training program using a prospective, randomized, double-blind, placebo controlled design.

Methods: Sixty healthy male subjects were randomized to ingest capsules of Fenu-FG (1 capsule of 300 mg, twice per day) or the matching placebo at a 1:1 ratio. The subjects participated in a supervised 4-day per week resistance-training program for 8 weeks. The outcome measurements were recorded at recruitment (baseline) and at the end of the treatment (8 weeks). The efficacy outcome included serum testosterone (total and free) levels, muscle strength and repetitions to failure, metabolic markers for anabolic activity (serum creatinine and blood urea nitrogen), and % body fat. The standard safety measurements such as adverse events monitoring, vital signs, hematology, biochemistry, and urinalysis were performed.

Results: Fenu-FG supplementation demonstrated significant anabolic and androgenic activity as compared with the placebo. Fenu-FG treated subjects showed significant improvements in body fat without a reduction in muscle strength or repetitions to failure. The Fenu-FG supplementation was found to be safe and well-tolerated.

Conclusion: Fenu-FG supplementation showed beneficial effects in male subjects during resistance training without any clinical side effects.

Source: Sachin Wankhede, Vishwaraman Mohan, and Prasad Thakurdesai. “Beneficial effects of fenugreek glycoside supplementation in male subjects during resistance training: A randomized controlled pilot study” Journal of Sports and Health Science (2016): 176–182.

Trigonella foenum graecum (fenugreek) seed extract as an antineoplastic agent


The antineoplastic effect of Trigonella foenum graecum seed extract has been evaluated in the Ehrlich ascites carcinoma (EAC) model in Balb‐C mice. Intra‐peritoneal administration of the alcohol extract of the seed both before and after inoculation of EAC cells in mice produced more than 70% inhibition of tumour cell growth with respect to the control. Treatment with the extract was found to enhance both the peritoneal exudate cell and macrophage cell counts. The extract also produced a significant antiinflammatory effect. We report here the antiinflammatory and antineoplastic effects of Trigonella foenum graecum seed extract.

Source: Sur, P., et al. “Trigonella foenum graecum (fenugreek) seed extract as an antineoplastic agent.” Phytotherapy Research: An International Journal Devoted to Pharmacological and Toxicological Evaluation of Natural Product Derivatives 15.3 (2001): 257-259.

Effect of fenugreek seeds on blood glucose and serum lipids in type I diabetes


The effect of fenugreek seeds (Trigonella foenum graecum) on blood glucose and the serum lipid profile was evaluated in insulin-dependent (Type I) diabetic patients. Isocaloric diets with and without fenugreek were each given randomly for 10 d. Defatted fenugreek seed powder (100 g), divided into two equal doses, was incorporated into the diet and served during lunch and dinner. The fenugreek diet significantly reduced fasting blood sugar and improved the glucose tolerance test. There was a 54 per cent reduction in 24-h urinary glucose excretion. Serum total cholesterol, LDL and VLDL cholesterol and triglycerides were also significantly reduced. The HDL cholesterol fraction, however, remained unchanged. These results indicate the usefulness of fenugreek seeds in the management of diabetes.

Source: Sharma, R. D., T. C. Raghuram, and N. Sudhakar Rao. “Effect of fenugreek seeds on blood glucose and serum lipids in type I diabetes.” European Journal of Clinical Nutrition 44.4 (1990): 301-306.

Therapeutic Applications of Fenugreek


Fenugreek has a long history of medical uses in Ayurvedic and Chinese medicine, and has been used for numerous indications, including labor induction, aiding digestion, and as a general tonic to improve metabolism and health. Preliminary animal and human trials suggest possible hypoglycemic and antihyperlipidemic properties of oral fenugreek seed powder.

Source: Smith, Michael. “Therapeutic applications of fenugreek.” Alternative Medicine Review 8.1 (2003): 20-27.

Trigonella foenum graecum (fenugreek) seed powder improves glucose homeostasis in alloxan diabetic rat tissues by reversing the altered glycolytic, gluconeogenic and lipogenic enzymes


Trigonella foenum graecum (fenugreek) seed powder has been suggested to have potential antidiabetic effects. The effect of oral administration of Trigonella whole seed powder (5% in the diet) for 21 days on glycolytic, gluconeogenic and NADPlinked lipogenic enzymes were studied in liver and kidney tissues of alloxan-induced diabetic Wistar rats. Diabetic rats were characterised by a 4fold higher blood glucose level and a 0.7fold lower body weight compared to normal controls. The activities of the glycolytic enzymes were significantly lower in the diabetic liver and higher in the diabetic kidney. The activities of gluconeogenic enzymes were higher in both liver and kidney during diabetes, however the activities of the lipogenic enzymes were decreased in both tissues during diabetes. Trigonella seed powder treatment to diabetic rats for 21 days brought down the elevated fasting blood glucose levels to control levels. The altered enzyme activities were significantly restored to control values in both the liver and kidney after Trigonella seed powder treatment. The therapeutic role of Trigonella seed powder in type1 diabetes as exemplified in this study can be attributed to the change of glucose and lipid metabolising enzyme activities to normal values, thus stabilizing glucose homeostasis in the liver and kidney. These biochemical effects exerted by Trigonella seeds make it a possible new therapeutic in type1 diabetes.

Source: Raju, Jayadev, et al. “Trigonella foenum graecum (fenugreek) seed powder improves glucose homeostasis in alloxan diabetic rat tissues by reversing the altered glycolytic, gluconeogenic and lipogenic enzymes.” Molecular and cellular biochemistry 224.1-2 (2001): 45-51.

Epimedium (whole plant)

Erectogenic and Neurotrophic Effects of Icariin, a Purified Extract of Horny Goat Weed (Epimedium spp.) In Vitro and In Vivo *

Introduction: Epimedium species (aka horny goat weed) have been utilized for the treatment of erectile dysfunction in Traditional Chinese Medicine for many years. Icariin (ICA) is the active moiety of Epimedium species.

Aim: To evaluate the penile hemodynamic and tissue effects of ICA in cavernous nerve injured rats. We also studied the in vitro effects of ICA on cultured pelvic ganglia.

Methods: Rats were subjected to cavernous nerve injury and subsequently treated for 4 weeks with daily gavage feedings of a placebo solution of normal saline and Dimethyl sulfoxide (DMSO) vs. ICA dissolved in DMSO at doses of 1, 5, and 10 mg/kg. A separate group underwent a single dose of ICA 10 mg/kg 2 hours prior to functional testing. Functional testing with cavernous nerve stimulation and real-time assessment of intracavernous pressure (ICP) was performed at 4 weeks. After functional testing, penile tissue was procured for immunohistochemistry and molecular studies. In separate experiments, pelvic ganglia were excised from healthy rats and cultured in the presence of ICA, sildenafil, or placebo culture media.

Main Outcome: Measure Ratio of ICP and area under the curve (AUC) to mean arterial pressure (MAP) during cavernous nerve stimulation of subject rodents. We also assayed tissue expression of neuronal nitric oxide synthase (nNOS), eNOS: endothelial nitric oxide synthase (eNOS), calponin, and apoptosis via immunohistochemistry and Western blot. Serum testosterone and luteinizing hormone (LH) were assayed using enzyme-linked immunosorbant assay (ELISA). Differential length of neurite outgrowth was assessed in cultured pelvic ganglia.

Results: Rats treated with low-dose ICA demonstrated significantly higher ICP/MAP and AUC/MAP ratios compared with control and single-dose ICA animals. Immunohistochemistry and Western blot were revealing of significantly greater positivity for nNOS and calponin in penile tissues of all rats treated with ICA. ICA led to significantly greater neurite length in cultured specimens of pelvic ganglia.

Conclusion: ICA may have neurotrophic effects in addition to known phosphodiesterase type 5 inhibiting effects.

Source: Alan W. Shindel, MD, Zhong-Chen Xin, MD, Guiting Lin, MD, PhD, Thomas M. Fandel, MD, Yun-Ching Huang, MD, Lia Banie, BS, Benjamin N. Breyer, MD, Maurice M. Garcia, MD, Ching-Shwun Lin, PhD, Tom F. Lue, MD. “Erectogenic and Neurotrophic Effects of Icariin, a Purified Extract of Horny Goat Weed (Epimedium spp.) In Vitro and In Vivo” Journal of Sexual Medicine (2010): 7(4 Pt 1): 1518–1528.

Effects of Icariin on Reproductive Functions in Male Rats *

The present study investigated the effects and potential mechanism(s) of action of icariin on the reproductive functions of male rats. Adult rats were treated orally with icariin at doses of 0 (control), 50, 100, or 200 mg/kg body weight for 35 consecutive days. The results show that icariin had virtually no effect on the body weight or organ coefficients of the testes or epididymides. However, 100 mg/kg icariin significantly increased epididymal sperm counts. In addition, 50 and 100 mg/kg icariin significantly increased testosterone levels. Real-time PCR suggests icariin may be involved in testosterone production via mRNA expression regulation of genes such as peripheral type benzodiazepine receptor (PBR) and steroidogenic acute regulatory protein (StAR). Furthermore, 100 mg/kg icariin treatment also affected follicle stimulating hormone receptor (FSHR) and claudin-11 mRNA expression in Sertoli cells. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels were measured in the testes; 50 and 100 mg/kg icariin treatment improved antioxidative capacity, while 200 mg/kg icariin treatment upregulated oxidative stress. These results collectively suggest that icariin within a certain dose range is beneficial to male reproductive functions; meanwhile, higher doses of icariin may damage reproductive functions by increasing oxidative stress in the testes.

Source: Maoxin Chen, Jie Hao, Qiaozhen Yang, Gang Li. “Effects of Icariin on Reproductive Functions in Male Rats” Molecules (2014) Jul; 19(7): 9502–9514.

The testosterone mimetic properties of icariin *


Aim: To evaluate the testosterone mimetic properties of icariin.

Methods: Forty-eight healthy male Sprague-Dawley rats at the age of 15 months were randomly divided into four groups with 12 rats each: the control group (C), the model group (M), the icariin group (ICA) and the testosterone group (T). The reproductive system was damaged by cyclophosphamide (intraperitoneal injection, 20 mg/kg x day) for 5 consecutive days for groups M, ICA and T, at the sixth day, ICA (gastric gavage, 200 mg/kg x day) for the ICA group and sterandryl (subcutaneous injection, 5 mg/rat . day) for the T group for 7 consecutive days, respectively. The levels of serum testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), serum bone Gla-protein (BGP) and tartrate-resistant acid phosphatase activity in serum (StrACP) were determined. The histological changes of the testis and the penis were observed by microscope with hematoxylin-eosin (HE) staining and terminal deoxynucleotidyl transferase biotin-dUTP-X nick end labeling (TUNEL), respectively.

Results: (1) Icariin improved the condition of reproductive organs and increased the circulating levels of testosterone. (2) Icariin treatment also improved the steady-state serum BGP and might have promoted bone formation. At the same time, it decreased the serum levels of StrACP and might have reduced the bone resorption. (3) Icarrin suppressed the extent of apoptosis of penile cavernosal smooth muscle cells.

Conclusion: Icariin has testosterone mimetic properties and has therapeutic potential in the management of hypoandrogenism.

Source: Zhen-Bao Zhang, Qing-Tao Yang. “The testosterone mimetic properties of icariin” Asian Journal of Andrology (2006): 601-5.

Flavonoids from Epimedium wanshanense


A novel flavonol glycoside named wanepimedoside A was isolated from the whole plant of Epimedium wanshanense, along with fifteen known flavonoids, anhydroicaritin, desmethylanhydroicaritin, icarisid I and II, quercetin, ikarisoside A and B, sagittatoside B, 2″-O-rhamnosylicarisid II, icariin, 2″-O-rhamnosylikarisoside A, epimedin B, epimedin C, and diphylloside A and B.

Source: Li, Wen-Kui, Ru-Yi Zhang, and Xiao Pei-Gen. “Flavonoids from Epimedium wanshanense.” Phytochemistry 43.2 (1996): 527-530.

The genus Epimedium: An ethnopharmacological and phytochemical review


Epimedium (Berberidaceae), is a genus of about 52 species in the family Berberidaceae, which also known as Rowdy Lamb Herb, Xianlinpi, Barrenwort, Bishop’s Hat, Fairy Wings, Horny Goat Weed, and Yangheye or Yin Yang Huo (Chinese: ). Many plants have been proven to possess efficacy on sexual dysfunction and osteoporosis in traditional Chinese medicine (TCM). The paper reviews the ethnopharmacology, the biological activities and the correlated chemical compounds of Epimedium species. More than 260 compounds have been isolated; among them prenyl-flavonoids are the major constituents and also important chemotaxonomic markers. Modern pharmacology studies and clinical practice demonstrated that Epimedium and its active compounds possess wide pharmacological actions, especially in strengthening yang, hormone regulation, anti-osteoporosis, immunological function modulation, anti-oxidation and anti-tumor, anti-aging, anti-atherosclerosis and anti-depressant activities. Currently, effective monomeric compounds or active parts have been screened for pharmacological activity from Epimedium in vivo and in vitro.

Source: Ma, Huiping, et al. “The genus Epimedium: an ethnopharmacological and phytochemical review.” Journal of ethnopharmacology 134.3 (2011): 519-541.

Altitudinal variation in pharmacologically active compounds of wild and cultivated populations of Epimedium elatum


Epimedium is a well known genus of Chinese pharmacopoeia, possessing various medicinal properties such as aphrodisiac, antioxidant, immunomodulatory, vasodilatory, hepatoprotective, cardioprotective, antidepressant, anticancerous and antiosteoporosis activities. The active principle has been found to be its flavonoid glycosides, especially Icariin and Icariside-II. In the present study, Epimedium elatum, the only species of this genus growing in Indian subcontinent and endemic to Kashmir Himalayas, has been studied for its active principle content at different habitats. The plants were collected from wild populations (W-I W-II &W-III) growing at three different sites of different altitudes and cultivated at low altitudes of Central Kashmir. After two years, the plants from wild populations as well as cultivated populations were collected, shade dried, grinded and prepared for HPLC analysis. The results showed that the content of active principles in leaves vary significantly between plants growing at different habitats. The Icariin and Icariside-II yield (per plant) of wild populations significantly increased with a decrease in altitude of habitat. Cultivated populations growing at higher altitude had significantly more yield than all other populations, except the W-III. The content of active principles as a percentage of leaf dry mass increased with increase in altitude. However, the harvest index of wild populations showed a decreasing trend with increasing altitude. The content of active principles as a percentage of dry mass of whole plant was comparable in all the habitats, including the cultivated populations. The present study suggests that Epimedium plants cultivated at lower altitudes are equally or more productive in terms of Icariin and Icariside-II content than that of wild plants growing at higher altitudes.

Source: Arief, Zargar Mohmad, Abdul Sami Shawl, and Abid Hussain Munshi. “Altitudinal variation in pharmacologically active compounds of wild and cultivated populations of Epimedium elatum.” Journal of applied research on medicinal and aromatic plants 3.2 (2016): 48-51.


Oral l ‐citrulline supplementation improves erectile function and penile structure in castrated rats *


Objectives: To investigate the efficacy of oral l ‐citrulline for erectile dysfunction and penile structure disruption in a rat model.

Methods: Male W istar‐ST rats aged 15 weeks were randomly divided into three groups as follows: sham‐operated rats (control group), surgically castrated rats (castrated group) and surgically castrated rats subsequently treated with 2% l ‐citrulline water (castrated + l ‐citrulline). At 4 weeks postoperative, erectile function was assessed based on intracavernous pressure changes, followed by electrostimulation of cavernous nerves and calculation of maximum intracavernous pressure/mean arterial pressure. Penile structure was evaluated by M asson’s trichrome staining and the smooth muscle‐to‐collagen ratio was calculated. The serum bioavailable testosterone, l ‐arginine, l ‐citrulline, NG ,NG ‐dimethylarginine and nitrogen oxide levels were evaluated.

Results: The bioavailable testosterone concentrations were decreased in the castrated and castrated + l ‐citrulline groups compared with the control group at 4 weeks after surgery. The intracavernous pressure‐to‐mean arterial pressure and smooth muscle‐to‐collagen ratios were significantly decreased in the castrated group compared with the control group, but significantly increased in the castrated + l ‐citrulline group compared with the castrated group. The serum l ‐citrulline, l ‐arginine and NG, NG ‐dimethylarginine levels, and the l ‐arginine‐to‐NG, NG ‐dimethylarginine ratios were significantly increased in the castrated + l ‐citrulline group compared with the castrated group. The serum nitrogen oxide levels were increased in the castrated + l ‐citrulline group compared with the castrated group.

Conclusion: Oral l ‐citrulline can improve the erectile response to electric stimulation of cavernous nerve and penile structure in castrated rats.

Source: Yuji Hotta, Arufumi Shiota, Tomoya Kataoka, Marina Motonari, Yasuhiro Maeda, Masahiko Morita, Kazunori Kimura. “Oral l ‐citrulline supplementation improves erectile function and penile structure in castrated rats” International Journal of Urology (2013).

Effects of Methanolic Extract of Citrullus lanatus Seed on Experimentally Induced Prostatic Hyperplasia *


Aims: To investigate the effects of methanolic extract of Citrullus lanatus seed (MECLS) on experimentally induced benign prostate hyperplasia.

Study design: Animal model of experimentally induced prostatic hyperplasia.

Place and Duration of Study: Department of Anatomy, Faculty of Basic Medical Sciences, Ikenne Campus, Ikenne, Ogun State, Nigeria, between May 2010 and August 2010.

Methodology: Twenty adult male Wistar rats weighing about 135-180g were randomly divided into four groups of five animals each. Group I, Normal control (NC) was given corn oil as placebo 1g/Kg BW; Group II, Hormone treated control (HTC), Groups III, and IV hormone and extract treated (HTEC), received continuous dosage of 300µg and 80µg of testosterone (T) and estradiol (E2) respectively on alternate days for three weeks subcutaneously in the inguinal region while the extract treated received an additional 2g/Kg BW (low dose) and 4g/Kg BW (high dose) of extract orally for 4 weeks after the successful induction of prostate enlargement. Immediately after induction some animals were randomly selected and sacrificed for gross inspection of prostate enlargement and sperm count evaluation, these procedures were repeated again after four weeks of extract treatment. Portion of the prostate were taken and processed routinely for paraffin embedding and stained with H&E.

Results: Hormone treatment did not affect the body weight of the animals; however it caused a significant decrease in the weight of the testes and rendered all the rats azoospermia. In addition, treatment with extracts caused a significant decrease in the enlarged prostate, seminal vesicle and testes sizes in a dose related manner (P<0.05) compared to the hormone treated control. Histological examination of prostate revealed that the methanolic extract caused significant changes in its histo-architecture. There was an increase in the fibromuscular layer, decrease in prostatic acini size, shrinkage of epithelium, and no infolding of the epithelium into the lumen, rather, it appeared flat compared to the very distinct columnar epithelium of the hormone treated control and conspicuousness of the acini. The extracts further caused a dose dependent reduction in the prostates weight. PSA level was significantly lowered in both HTEC at low and high doses (P < 0.05) in dose dependent manner.

Conclusion: Administration of MECLS for one month reduced the prostate size significantly (P < 0.05), both at high and low dose, but could not restore the initial size of shrunken testes and severe oligospermia caused by the hormones. The histological studies clearly establish MECLS as a potential candidate in management of androgen dependent conditions like benign prostate hyperplasia.

Source: Olamide, A. A., Olayemi, O. O., Demetrius, O. O., Olatoye, O. J., & Kehinde, A. A. “Effects of Methanolic Extract of Citrullus lanatus Seed on Experimentally Induced Prostatic Hyperplasia” European Journal of Medicinal Plants (2011). 1(4), 171-179.

The metabolism of L-arginine and its significance for the biosynthesis of endothelium-derived relaxing factor: cultured endothelial cells recycle L-citrulline to L-arginine


We have investigated the mechanism by which cultured endothelial cells generate L-arginine (L-Arg), the substrate for the biosynthesis of endothelium-derived relaxing factor. When Arg-depleted endothelial cells were incubated in Krebs’ solution for 60 min, L-Arg levels were significantly (9.7-fold) elevated. The generation of L-Arg coincided with a substantial decrease (90%) in intracellular L-glutamine (L-Gln), whereas all other amino acids were virtually unaffected. Changes in calcium, pH, or oxygen tension had no effect on L-Arg generation, which was, however, prevented when the cells were incubated in culture medium containing L-Gln. L-Arg generated by endothelial cells labeled with L-[14C]Arg was derived from an unlabeled intracellular source, for the specific activity of the intracellular L-Arg pool decreased substantially (8.8-fold) over 60 min. Arg-depleted endothelial cells did not form urea or metabolize L-ornithine but converted L-citrulline (L-Cit) to L-Arg possibly via formation of L-argininosuccinic acid. Nondepleted cells stimulated with the calcium ionophore A23187 showed only a transient accumulation of L-Cit, indicating that L-Cit is recycled to L-Arg during the biosynthesis of endothelium-derived relaxing factor. The generation of L-Arg by Arg-depleted endothelial cells was partially (45%) blocked by protease inhibitors, and various Arg-containing dipeptides were rapidly cleaved to yield L-Arg. Thus, cultured endothelial cells recycle L-Cit to L-Arg and possibly liberate peptidyl L-Arg. The Arg-Cit cycle appears to be the equivalent in the endothelial cell to the formation of urea by the liver. The biosynthesis of endothelium-derived relaxing factor may, therefore, not only produce a powerful vasodilator but also relieve the endothelial cell of excess nitrogen.

Source: Hecker, Markus, et al. “The metabolism of L-arginine and its significance for the biosynthesis of endothelium-derived relaxing factor: cultured endothelial cells recycle L-citrulline to L-arginine.” Proceedings of the National Academy of Sciences 87.21 (1990): 8612-8616.

Endothelial cells metabolize NG-monomethyl-L-arginine to L-citrulline and subsequently to L-arginine


NG-monomethyl-L-arginine (MeArg) inhibits the release of endothelium-derived relaxing factor (EDRF) from endothelial cells (EC) and the formation of nitric oxide (NO) from L-arginine (Arg) in EC and activated macrophages. We have compared the inhibitory potency of MeArg to that of Nω-nitro-L-arginine (NO2Arg), a more potent inhibitor of EDRF synthesis in vitro. NO2Arg (100 μM) was significantly more potent than MeArg in inhibiting the endothelium-dependent relaxation of rabbit aorta induced by acetylcholine. MeArg and NO2Arg (10 and 30 μM) also inhibited the release of EDRF from bovine aortic cultured EC. In the anaesthetized rat in vivo, the pressor effect of NO2Arg (3 and 10 mg kg−1) was significantly larger and longer lasting than that of MeArg. These differences in potency could be due to the extensive metabolism of MeArg but not NO2Arg to L-citrulline (Cit) and subsequently to Arg by EC. The enzyme responsible for the conversion of MeArg to Cit had the characteristics of a novel deiminase, NG,NG-dimethylarginine dimethylaminohydrolase, recently isolated from rat kidney.

Source: Hecker, Markus, et al. “Endothelial cells metabolize NG-monomethyl-L-arginine to L-citrulline and subsequently to L-arginine.” Biochemical and biophysical research communications 167.3 (1990): 1037-1043.

Oral L-Citrulline Supplementation Improves Erection Hardness in Men With Mild Erectile Dysfunction


Although less effective than phosphodiesterase type-5 enzyme inhibitors, at least in the short term, L-citrulline supplementation has been proved to be safe and psychologically well accepted by patients. Its role as an alternative treatment for mild to moderate ED, particularly in patients with a psychologically fear of phosphodiesterase type-5 enzyme inhibitors, deserves further research.

Source: Cormio, Luigi, et al. “Oral L-citrulline supplementation improves erection hardness in men with mild erectile dysfunction.” Urology 77.1 (2011): 119-122.


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