TABLE 2.
Botanical drugs without phosphodiesterase-5 inhibitory activity.
| Botanical drugs | Type of study | Study subject | Intervention measure | Therapeutic effects | Adverse events | Mechanism of action Sin et al. (2021) |
|---|---|---|---|---|---|---|
| Lepidium meyenii (Maca) | Double-blind randomized parallel placebo | >40 years men with AMS score ≥27 | 1,000 mg of Maca, two pills at a time, three times per day for 12 weeks before food intake | AMS, IIEF, ADAM, total and free testosterone levels improved. Al-Rehaily et al. (2015) | Gastrointestinal disorders | Nil |
| Double-blind randomized placebo | 31∼41 years patients with mild ED | 1,200 mg Maca dry extract two times daily for 12 weeks | IIEF-5 score improved. Psychological, physical and social performance-related SAT-P improved. Kim et al. (1998) | None | ||
| Double-blind randomized placebo parallel | 21∼56 years healthy men | 3 tablets of 500 mg each of gelatinized Maca per day (Maca 1.5 g) for 12 weeks, or 6 daily tablets of gelatinized Maca (3,000 mg) for 12 weeks | Sexual desire improved, and not because of changes in mood or serum testosterone and oestradiol levels. Lin and Gou, (2013) | Not mentioned | ||
| Double-blind randomized placebo cross-over | Experienced and endurance trained male cyclists, mean age 30 ± 7 years old | 5 capsules per day (each containing 400 mg L. meyenii root’s extract) for 2 weeks and 1 week washout period | Self-rated sexual desire score improved. Li et al. (2014) | Not mentioned | ||
| Rosa damascena | Double-blind randomized placebo | 18∼45 years patients with opioid-dependency and treated with metha-done maintenance therapy and have sexual dysfunction as side-effect | 2 mL/day and contained 17 mg citronellol of essential oil of R. damascena for 8 weeks | Sexual dysfunction decreased, and serum testosterone increased. No consistent relation between them. Chen and Lee, (1995) | Not mentioned | Nil |
| Double-blind randomized placebo | Patients treated with an SSRI and suffering from major depressive disorders and SSRI-I SD | 2 mL of verum daily (17 mg citronellol of essential oil of R. damascena) for 8 weeks | Sexual dysfunction improved, and depression symptoms reduced as sexual dysfunction improved. Wang et al. (2010) | None | ||
| Crocus sativus | Double-blind randomized placebo | 18∼45 years male patients with major depressive disorder stabilized on fluoxetine and fluoxetine-related sexual dysfunction | Saffron capsule 15 mg twice per day for 4 weeks | Erectile function, intercourse satisfaction, and IIEF total scores improved | 1) Nausea | Increase in cGMP levels |
| 2) Daytime drowsiness | ||||||
| 3) Decreased appetite | ||||||
| 4) Dry mouth | ||||||
| 5) Nervousness | ||||||
| 6) Restlessness | ||||||
| 7) Morning drowsiness | ||||||
| 8) Increased appetite | ||||||
| Double-blind randomized placebo parallel | 40∼76 years patients with ED and diabet | Rub a pea-sized amount of the gel containing 1% C. sativus on penis half an hour before a sexual intercourse | Erectile dysfunction improved. Ying et al. (2018) | None | ||
| Open-label study | 26∼62 years patients with ED | 1 tablet (200 mg C. sativus per tablet)every morning for 9 days, 2 tablets on day 10 | IIEF-15 improved. NPT test improved. Cho et al. (2013) | Not mentioned | ||
| Randomized open-label cross-over | 27∼60 years patients with ED | Saffron (30 mg, the extract of C. sativus) twice daily for 12 weeks, 2-week washout phase and then on-demand 50-mg sildenafil | No significant improvements in the IIEF sexual function domains, SEP questions and EDITS scores. Leitao et al. (2021) | 1) Headache | ||
| 2) Flushing | ||||||
| 3) Dyspepsia | ||||||
| (Less than sidenafil) | ||||||
| Panax ginseng | Double-blind randomized placebo parallel multicenter | Patients with mild-to-moderate ED | 4 tablets of SKGB (350 mg ginseng berry extract per tablet), daily, for 8 weeks | The total and each of the individual domain scores of IIEF-15 increased. PEDT scores improved. Ismail et al. (2012) | None | 1) Regulate L-arginine/NO pathway, act as an NO donor to cause relaxation 2) regulate the NO/cGMP pathway, restore the corpus cavernosum endothelial function 3) inhibit oxidative stress, restore Akt activity, protect endothelial and smooth muscle cells (diabetes-induced ED) 4) enhance NO release from corpus cavernosum endothelial and nerve cell 5) increase serum testosterone levels 6) activate large conductance Ca2+-activate K+ (BKCa) channels in corporal smooth muscle cells 7) decrease HIF-1α expression in hypoxia state 8) increase eNOS expression 9) inhibit PDE5A |
| Double-blind randomized placebo | 33∼79 years patients with ED | 1,000 mg of TMGE twice a day for 8 weeks | IIEF-15 total score and every individual domain of IIEF-5 improved. Kamenov et al. (2017) | Minor headaches | ||
| Double-blind randomized placebo | 26∼70 years patients with mild or mild to moderate ED | 1,000 mg Korean Red Ginseng (KRG) 3 times daily for 12 weeks | IIEF-5 total score, and scores on rigidity, penetration, maintenance improved. Roaiah et al. (2016) | Headache Insomnia | ||
| Trigonella foenum‐graecum | Double-blind randomized placebo | 25∼52 years healthy men | 2 tablets per day (600 mg Testofen, a standardized T. foenum‐graecum extract, per day)for 6 weeks | DISF‐SR total scores and all four DISF-SR domains improved. GamalEl Din et al. (2019) | Slight stomach discomfort without food intake | Increase testosterone, LH, and FSH levels and decrease GnRH levels |
| Double-blind randomized placebo | 43∼70 years healthy men | T. foenum-graecum seed extract (Testofen) at a dose of 600 mg/day for 12 weeks | AMS score improved | Dizziness headache | ||
| Sexual function, including number of morning erections and frequency of sexual activity improved | ||||||
| Both total and free serum testosterone increased. Santos et al. (2014) | ||||||
| Pistacia vera | Prospective study | 38∼59 years patients with ED for at least 12 months | 100 g pistachio nuts at lunch diet for 3 weeks | Mean peak systolic velocity values, IIEF-15 total scores and all five IIEF-5 domains improved | None | Nil |
| TC and LDL levels decreased, HDL level increased. Cortes-Gonzalez et al. (2010) | ||||||
| Withania somnifera (Ashwagandha) | Single-blind randomized placebo parallel | 18∼60 years patients with psychogenic ED and serum testosterone levels over 239 ng/dL | 4 Ashwagandha tablets (500 mg each) thrice a day after food for 60 days | Both Ashwagandha and placebo provided no relief in psychogenic ED. Cherdshewasart and Nimsakul, (1008) | Not mentioned | Activating the Nrf2/HO-1 pathway, inhibit NF-κB levels, and increase serum testosterone levels |
PDE5, phosphodiesterase-5; AMS, Aging Males’ Symptoms scale; IIEF, international index for erectile function; ADAM, androgen deficiency of aging males; ED, erectile dysfunction; SAT-P, satisfaction profile; SSRI, selective serotonin reuptake inhibitor; SSRI-I SD, selective serotonin reuptake inhibitor induced sexual dysfunction; NPT, nocturnal penile tumescence; SEP, sexual encounter profile; EDITS, erectile dysfunction inventory of treatment satisfaction; cGMP, cyclic guanosine monophosphate; SKGB, standardized Korean ginseng berry; PEDT, premature ejaculation diagnostic tool; TMGE, tissue-cultured mountain ginseng extract; NO, nitric oxide; HIF-1α, hypoxia inducible factor-1α; eNOS, endothelial nitric oxide synthase; DISF‐SR, Derogatis Interview for Sexual Functioning-Self Report; LH, luteinizing hormone; FSH, follicle-stimulating hormone; GnRH, gonadotropin releasing hormone; TC, total cholesterol; LDL, low density lipoprotein; HDL, high density lipoprotein; Nrf2, nuclear factor-erythroid 2-related factor 2; HO-1, heme oxygenase-1; NF-κB, nuclear factor kappa-B.