On this page you will find statements that are made and scientific claims/medical journal publications which can back up those statements and substantiate the claims made.

Resveratrol can inhibit the release of estrogen at the aromatase

1. The Red Wine Polyphenol Resveratrol Displays Bilevel Inhibition on Aromatase in Breast Cancer Cells Yun Wang, et al. Toxicol. Sci., Jul 2006; 92: 71 – 77. http://toxsci.oxfordjournals.org/content/92/1/71.abstract

  • Because of its structural resemblance to estrogen, resveratrol’s agonistic and antagonistic properties on estrogen receptor have been examined and demonstrated. Resveratrol inhibited the aromatase activity with an IC50 value of 25μM. The present study illustrated that pharmacological dosage of resveratrol inhibited aromatase at both the enzyme and mRNA levels.

Resveratrol can increase sperm count and testosterone

1. The Red Wine Polyphenol Resveratrol Displays Bilevel Inhibition on Aromatase in Breast Cancer Cells
Yun Wang, et al.
Toxicol. Sci., Jul 2006; 92: 71 – 77. http://www.ncbi.nlm.nih.gov/pubmed/15795430

  • trans-Resveratrol was reported to have health benefits including anticarcinogenic effects and protection against cardiovascular disease. One of the mechanisms by which it exerts its action is through modulating the estrogen response systems. Because estrogen is involved in male reproductive biology, we investigated the effect of trans-resveratrol on testis and spermatogenesis. Adult male rats were divided into 2 groups. The treated group was administered by gavage 20 mg/(kg . d) of trans-resveratrol suspended in 10 g/L of carboxymethylcellulose for 90 d, whereas the control group received only carboxymethylcellulose during the same period. The relative weight of testes did not differ between the groups. However, the diameter of the seminiferous tubules was significantly reduced from 437.5 +/- 0.1 mum in the controls to 310.9 +/- 0.1 mum in the resveratrol-treated rats. This decrease was accompanied by a significant increase in tubular density, from 3.20 +/- 0.18 in controls to 6.58 +/- 0.18 tubules/mm(2) in the treated group. Moreover, sperm counts were significantly greater in the resveratrol-treated rats (24.8 +/- 3.30 x 10(7)) than in the control group (14.1 +/- 0.80 x 10(7)), but sperm quality did not differ. Serum concentrations of gonadotrophins and testosterone were significantly higher in the resveratrol-treated group. We identified a novel activity of trans-resveratrol. The daily oral administration of this phytochemical to adult male rats enhanced sperm production by stimulating the hypothalamic-pituitary-gonadal axis, without inducing adverse effects.

Resveratrol can increase testosterone, sperm count and sperm mobility

2. trans-Resveratrol relaxes the corpus cavernosum ex vivo and enhances testosterone levels and sperm quality in vivo.
S Shin, et al.
Arch Pharm Res, Jan 2008; 31(1): 83-7. http://www.ncbi.nlm.nih.gov/pubmed/18277612

  • We examined the effects of trans-resveratrol on male reproductive functions; ex-vivo penile erection and in-vivo sperm counts and quality. For the ex-vivo study, the relaxation effects of resveratrol on isolated New Zealand white rabbit corpus cavernosum, precontracted by phenylephrine (5×10(-5) M) were measured. The in-vivo study measured reproductive organ weights, blood testosterone levels, testicular histopathology, sperm counts, as well as the epididymal sperm motility and deformity of male ICR mice given an oral dose of resveratrol (50 mg/ kg) for 28 days. Resveratrol elicited a concentration-dependent relaxing effect on corpus cavernosum, leading to a median effective concentration (EC50) of 0.29 mg/mL. Repeated treatment with resveratrol (50 mg/kg) did not cause an increase in body weight, reproductive organ weight or testicular microscopic findings; however, resveratrol did elicit an increase in blood testosterone concentration, testicular sperm counts and epididymal sperm motility by 51.6%, 15.8% and 23.3%, respectively, without influence on sperm deformity. In conclusion, we propose that resveratrol has a positive effect on male reproductive function by triggering a penile erection, as well as enhancing blood testosterone levels, testicular sperm counts, and epididymal sperm motility.

Benzoflavone can inhibit estrogen synthetise At the aromatase

1. Inhibition of human estrogen synthetase (aromatase) by flavones
JT Kellis, Jr et al.
Science, Sep 1984; 225: 1032 – 1034. http://www.ncbi.nlm.nih.gov/pubmed/6474163

  • Several naturally occurring and synthetic flavones were found to inhibit the aromatization of androstenedione and testosterone to estrogens catalyzed by human placental and ovarian microsomes. These flavones include (in order of decreasing potency) 7,8-benzoflavone, chrysin, apigenin, flavone, flavanone, and quercetin; 5,6-benzoflavone was not inhibitory. 7,8-Benzoflavone and chrysin were potent competitive inhibitors and induced spectral changes in the aromatase cytochrome P-450 indicative of substrate displacement. Flavones may thus compete with steroids in their interaction with certain monooxygenases and thereby alter steroid hormone metabolism.

Benzoflavone has:
Aphrodisiac, libido enhancing properties
Can prevent the metabolic degradation of testosterone
Upregulates blood – testosterone levels in the body
Can be used in the management of:
morphine addiction

1. Drug/substance reversal effects of a novel trisubstituted benzoflavone moiety (BZF) isolated from Passiflora incarnata Linn. —a brief perspective
KAMALDEEP DHAWAN et al. http://www.ncbi.nlm.nih.gov/pubmed/14690874

  • The present work is a mini-review of the author’s original work on the plant Passiflora incarnata Linn., which is used in several parts of the world as a traditional medicine for the management of anxiety, insomnia, epilepsy and morphine addiction. A tri-substituted benzoflavone moiety (BZF) has been isolated from the bioactive methanol extract of this plant, which has been proposed in the author’s earlier work to be responsible for the biological activities of this plant. The BZF moiety has exhibited significantly encouraging results in the reversal of tolerance and dependence of several addiction-prone psychotropic drugs, including morphine, nicotine, ethanol, diazepam and delta-9-tetrahydrocannabinol, during earlier pharmacological studies conducted by the author. In addition to this, the BZF moiety has exhibited aphrodisiac, libido-enhancing and virility-enhancing properties in 2-year-old male rats. When administered concomitantly with nicotine, ethanol and delta-9-tetrahydrocannabinol for 30 days in male rats, the BZF also prevented the drug-induced decline in sexuality in male rats. Because the BZF moiety isolated from P. incarnata is a tri-substituted derivative of alpha-naphthoflavone (7,8-benzoflavone), a well-known aromatase-enzyme inhibitor, the mode of action of BZF has been postulated to be a neurosteroidal mechanism vide in which the BZF moiety prevents the metabolic degradation of testosterone and upregulates blood – testosterone levels in the body. As several flavonoids (e.g. chrysin, apigenin) and other phytoconstituents also possess aromatase-inhibiting properties, and the IC50 value of such phytomoieties is the main factor determining their biochemical efficacy, by altering their chemical structures to attain a desirable IC50 value new insights in medical therapeutics can be attained, keeping in view the menace of drug abuse worldwide.

Benzoflavone increases libido

2. Aphrodisiac activity of methanol extract of leaves of Passiflora incarnata Linn in mice.
K Dhawan, et al.
Phytother Res, Apr 2003; 17(4): 401-3. http://www.ncbi.nlm.nih.gov/pubmed/12722149

  • The aphrodisiac properties of the methanol extract of leaves of Passiflora incarnata Linn. have been evaluated in mice by observing the mounting behaviour. The methanol extract of P. incarnata exhibited significant aphrodisiac behaviour in male mice at all doses, i.e. 75, 100 and 150 mg/kg. Amongst these, the highest activity was observed with the 100 mg/kg dose when the mountings were calculated about 95 min after the administration of the test extracts.

Benzoflavone can positively effect libido, fertility, and sperm count

1. Prevention of chronic alcohol and nicotine-induced azospermia, sterility and decreased libido, by a novel tri-substituted benzoflavone moiety from Passiflora incarnata Linneaus in healthy male rats.
K Dhawan and et al.
Life Sci, Nov 2002; 71(26): 3059-69. http://www.ncbi.nlm.nih.gov/pubmed/12408873

  • Excessive long term consumption of alcohol and nicotine have serious detrimental effects upon the libido, fertility, and sperm count in male species. The present work describes the beneficial effects of a novel tri-substituted benzoflavone moiety (BZF) isolated from Passiflora incarnata Linneaus, the phyto-chemical isolation, spectroscopic elucidation, and multifarious biological activities of which have recently been reported by the authors. The BZF moiety has been reported to increase libido, sperm count, and sexual fertility in 2 years old male rats at 10 mg/kg, po dose, in the one of our previous studies. Presently, the BZF moiety has been evaluated against chronic ethanol- and nicotine-induced decrease in libido, sexual fertility and mating efficiency in healthy male rats. The male rats were given ethanol (3 g/kg, po) A, nicotine (2 mg/kg, sc) N, alcohol-nicotine combinations (AN) alone, and also with 10 mg/kg po dose of BZF (concurrent administrations). These treatments were given for 30 days. At the end of treatments, it was observed that rat groups A, N, and AN had no libido (evaluated by mounting behaviour), declined sperm count, and consequently no mating efficiency or fertility (upon pairing with pro-estrus female rats). However, the rats which were given 10 mg/kg BZF along-with nicotine (NP group), alcohol (AP group), and alcohol-nicotine combination (ANP) exhibited significant libido-oriented mounting behaviour, increased sperm count (significantly comparable to the control group), and increased fertilization potential. The rats having decreased sperm count, libido and fertilization potential due to chronic administration of alcohol, nicotine and alcohol-nicotine combinations, i.e., rats of A, N, and AN groups were again subdivided and were given 10 mg/kg BZF for 7 days. This treatment confirmed that BZF speeds up the restoration of sexuality in rats upon cessation of the administration of substances like alcohol, nicotine and alcohol-nicotine combinations, which have severe detrimental effects upon male sexuality, fertility and vigour. BZF, the strongest inhibitor of aromatase enzyme, when administered concurrently with substances like alcohol and nicotine restores sexual virility, libido and vigour in male rats by maintaining the blood-testosterone levels to be high.

Benzoflavone can inhibit the conversion of androgens into estrogens and why isoflavones are not as powerful at inhibiting aromatase than flavones

1. Molecular basis of the inhibition of human aromatase (estrogen synthetase) by flavone and isoflavone phytoestrogens: A site-directed mutagenesis study.
Kao YC, et al.
Environ Health Perspect 1998;106:85-92 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1533021/

  • Flavone and isoflavone phytoestrogens are plant chemicals and are known to be competitive inhibitors of cytochrome P450 aromatase with respect to the androgen substrate. Aromatase is the enzyme that converts androgen to estrogen; therefore, these plant chemicals are thought to be capable of modifying the estrogen level in women. In this study, the inhibition profiles of four flavones [chrysin (5, 7-dihydroxyflavone), 7,8-dihydroxyflavone, baicalein (5,6,7-trihydroxyflavone), and galangin (3,5,7-trihydroxyflavone)], two isoflavones [genistein (4,5,7-trihydroxyisoflavone) and biochanin A (5,7-dihydroxy-4-methoxyisoflavone)], one flavanone [naringenin (4, 5,7-trihydroxyflavanone)], and one naphthoflavone (alpha-naphthoflavone) on the wild-type and six human aromatase mutants (I133Y, P308F, D309A, T310S, I395F, and I474Y) were determined. In combination with computer modeling, the binding characteristics and the structure requirement for flavone and isoflavone phytoestrogens to inhibit human aromatase were obtained. These compounds were found to bind to the active site of aromatase in an orientation in which rings A and C mimic rings D and C of the androgen substrate, respectively. This study also provides a molecular basis as to why isoflavones are significantly poorer inhibitors of aromatase than flavones.

Benzoflavone can reduce anxiety in humans

1. Preoperative Oral Passiflora Incarnata Reduces Anxiety in Ambulatory Surgery Patients: A Double-Blind, Placebo-Controlled Study
Ali Movafegh, et al.
Anesth. Analg., Jun 2008; 106: 1728 – 1732. http://www.ncbi.nlm.nih.gov/pubmed/18499602

  • Many patients have preoperative anxiety; therefore, the development of a strong anxiolytic with minimal psychomotor impairment for premedication may be desirable.
  • In this study, 60 patients were randomized into two groups to receive either oral Passiflora incarnata (500 mg, Passipy IranDarouk) (n = 30) or placebo (n = 30) as premedication, 90 min before surgery. A numerical rating scale (NRS) was used for each patient to assess anxiety and sedation before, and 10, 30, 60, and 90 min after premedication. Psychomotor function was assessed with the Trieger Dot Test and the Digit-Symbol Substitution Test at arrival in the operating room, 30 and 90 min after tracheal extubation. The time interval between arrival in the postanesthesia care unit and discharge to home (discharge time) was recorded for each patient.
  • The demographic characteristics of patients, ASA physical status, duration of surgery, basal NRS score, sedation at the preset time intervals, and discharge time were similar in the two groups. The NRS anxiety scores were significantly lower in the passiflora group than in the control group (P < 0.001). There were no significant differences in psychological variables in the postanesthesia care unit and recovery of psychomotor function was comparable in both groups.
  • In outpatient surgery, administration of oral Passiflora incarnata as a premedication reduces anxiety without inducing sedation.

These last 2 extracts may be hard to understand but they prove that benzoflavone is a modulator of the GABA(b) receptor and that GABA(b) receptor agonists reverses the negative feedback effect of testosterone on gonadotropin-releasing hormone and luteinizing hormone secretion

Benzoflavone is modulator of the GABA(b) receptor complex

1. Modulation of the γ-aminobutyric acid (GABA) system by Passiflora incarnata L.
Kurt Appel, Thorsten Rose, Bernd Fiebich, Thomas Kammler, Christine Hoffmann, Gabriele Weiss,* http://www.ncbi.nlm.nih.gov/pubmed/21089181

  • Passiflora incarnata L. (Passifloraceae) is important in herbal medicine for treating anxiety or nervousness, Generalized Anxiety Disorder (GAD), symptoms of opiate withdrawal, insomnia, neuralgia, convulsion, spasmodic asthma, ADHD, palpitations, cardiac rhythm abnormalities, hypertension, sexual dysfunction and menopause. However, the mechanism of action is still under discussion. Despite gaps in our understanding of neurophysiological processes, it is increasingly being recognized that dysfunction of the GABA system is implicated in many neuropsychiatric conditions, including anxiety and depressive disorders. Therefore, the in vitro effects of a dry extract of Passiflora incarnata (sole active ingredient in Pascoflair® 425 mg) on the GABA system were investigated. The extract inhibited [(3) H]-GABA uptake into rat cortical synaptosomes but had no effect on GABA release and GABA transaminase activity. Passiflora incarnata inhibited concentration dependently the binding of [(3) H]- SR95531 to GABA(A) -receptors and of [(3) H]-CGP 54626 to GABA(B) -receptors. Using the [(35) S]-GTPγS binding assay Passiflora could be classified as an antagonist of the GABA(B) receptor. In contrast, the ethanol- and the benzodiazepine-site of the GABA(A) -receptor were not affected by this extract. In conclusion, the first evidence was shown that numerous pharmacological effects of Passiflora incarnata are mediated via modulation of the GABA system including affinity to GABA(A) and GABA(B) receptors, and effects on GABA uptake.

GABA(b) receptor agonist can reverses the negative feedback effect of testosterone on GNRH and LH secretion

1. A gamma-aminobutyric acidB agonist reverses the negative feedback effect of testosterone on gonadotropin-releasing hormone and luteinizing hormone secretion in the male sheep.
Endocrinology. 2000 Nov;141(11):3940-5. http://www.ncbi.nlm.nih.gov/pubmed/11089523

  • Infusion of baclofen, a GABA(B) agonist, into the medial basal hypothalamus (MBH) of castrated rams rapidly increases LH pulse amplitude without altering pulse frequency. The objectives of this study were to determine whether baclofen infusion increased LH in testosterone (T)-treated and intact rams, the increased LH was due to increased GnRH release, and FSH secretion also was increased. In the first experiment we tested the main effects and interaction of baclofen and T on FSH and LH pulse patterns in castrated rams (n = 7). In the second experiment we determined whether baclofen affected GnRH and LH pulses in intact males. Microdialysis guide cannulae were implanted bilaterally into the MBH. After recovery of the animal from surgery, the MBH was perfused using concentric microdialysis probes (2-mm tip) with artificial cerebrospinal fluid (aCSF) for a 3-h control period followed by either aCSF or 1 mM baclofen for 4 h. Blood samples were taken at 10-min intervals. T suppressed mean LH concentrations (10.4 +/- 1.3 vs. 3.3 +/- 1.3 ng/ml) such that LH pulses were undetectable in some T-treated animals during the control period. The change (control period vs. drug infusion period) in mean LH was greater in response to baclofen than in response to aCSF and was not altered by T. The baclofen x T interaction was nonsignificant. Mean FSH was decreased by T, but was not altered by baclofen. In the second experiment hypophyseal portal blood was collected coincident with microdialysis. Infusion of baclofen into the MBH of intact males (n = 7) resulted within 1 h in the onset of frequent and robust GnRH pulses (0.10/h before baclofen vs. 1.57/h after baclofen) that were followed either immediately or gradually by coincident LH pulses. One interpretation is that baclofen acts downstream of the site of action of T. GABA(B) receptors may regulate pulse amplitude in both the presence and absence of T and regulate pulse frequency by modulating the inhibitory effect of T.