Table 3.
In vitro and in vivo studies regarding the efficacy of TT extracts in sexual disorders and their design evaluation.
| Herbal Drug and Subjects | Assay/Parameters | Outcome of Treated Group | Study Design Evaluation | Reference |
|---|---|---|---|---|
| In Vitro Studies | ||||
| Organ bath study of the corpus cavernosum from | Relaxation level | Concentration-dependent relaxation response | Part of the plant: NO | Kam et al. (2012) |
| male rabbits | Origin: NO | [64] | ||
| Phytochemical analysis: NO | ||||
| Control group: NO | ||||
| Appropriate Statistical analysis: YES | ||||
| Human sperm from 40 healthy volunteers | Motility analysis | Motility ↑ * after 60 minutes of incubation | Part of the plant: NO | Khaleghi et al. (2017) |
| TT extract | Sperm viability analysis | Viability ↑ * in a dose-dependent manner after 120 minutes of incubation | Origin: YES | [63] |
| Determination of DNA fragmentation | No effect on DNA fragmentation of human sperm in vitro | Phytochemical analysis: NO | ||
| Control group: YES | ||||
| Appropriate statistical analysis: YES | ||||
| In Vivo Animal Studies | ||||
| Male adult Sprague Dawley rats, castrated and normal | Sexual behavior studies: MF, IF, ML, IL, EL, PEI | Treatment of castrated rats (with testosterone or TT extract) showed increase in prostate weight and ICP that were statistically significant | Part of the plant: NCS | Gauthaman et al. (2002) |
| TT extract | ICP | Mild to moderate improvement of sexual behavior parameters | Origin: YES | [70] |
| Phytochemical analysis: NCS | ||||
| Control group: YES | ||||
| Positive control group: YES | ||||
| Appropriate statistical analysis: YES | ||||
| Male Sprague Dawley rats | ICP | ICP concentration-dependent increase in TT treated group* | Part of the plant: NCS | Kam et al. (2012) |
| TT extract, Cornus officinalis extract and a mixture of both | cAMP, cGMP in corpus cavernosum | cAMP ↑* in the group treated with the mixture | Origin: YES | [64] |
| cGMP no significant difference as compared with the control | Phytochemical analysis: NO | |||
| Control group: YES | ||||
| Positive control group: NO | ||||
| Appropriate statistical analysis: YES | ||||
| -Male rats | Morphometric analysis | Testicular weight ↑* | Origin: YES | Oliveira et al. (2015) |
| TT fruit extract and fractions | Gonadosomatic index | Gonadosomatic index increased in the group supplemented with ethanolic extract | Part of the plant: YES | [69] |
| Sperm quality analysis: motility, | -Nuclear, cytoplasmic, and individual volume of Leydig cells increased in supplementation with hexanic and aqueous fractions | Phytochemical analysis: NO | ||
| sperm count, | The extract influenced the spermatogenesis | Control group: YES | ||
| morphology, viability | Positive control group: NO | |||
| Appropriate statistical analysis: YES | ||||
| Male Wistar rats with STZ-induced diabetes (55 mg/kg) | Sperm characteristics, morphology | TT restored antioxidant enzyme activity in testis | Part of the plant: YES | Tag et al. (2015) |
| TT fruit extract | Body and genital organ weight | Improved lipid profile content in serum | Origin: YES | [85] |
| Serum testosterone, FSH, LPO level in testicular homogenate | TT treatment decreased testis tubular damage and restored it to normal morphology. | Phytochemical analysis: YES (identification reactions) | ||
| Activity of testicular SOD | Control group: YES | |||
| Testicular CAT activity | Positive control group: YES | |||
| GPx, GST | Appropriate statistical analysis: YES | |||
| Male Wistar rats with STZ-induced diabetes (50 mg/kg) | Testosterone | Sperm motility, sperm count, percentage of sperms with normal morphology ↑* | Part of the plant: YES | Ghanbari et al. (2016) |
| TT seed extract | Sperm analysis: morphology, count and motility | Testosterone ↑* | Origin: NO | [67] |
| Phytochemical analysis: NO | ||||
| Control group: YES | ||||
| Positive control group: NO | ||||
| Appropriate statistical analysis: YES | ||||
| Male Sprague Dawley rats | Time to exhaustion of over trained rats | Performance (time to exhaustion) ↑* | Origin: YES | Yin et al. (2016) |
| TT fruit extract (saponins >70%) | Serum testosterone, corticosterone, AR, IGF-1R in liver, gastrocnemius, and soleus | Increase in body weights, relative weights, and protein levels of gastrocnemius | Part of the plant: YES | [66] |
| Testosterone ↑* | Phytochemical analysis: YES (UHPLC-Q-TOF/MS) | |||
| AR ↑* | Control group: YES | |||
| IGF-1R ↓# | Appropriate Statistical analysis: YES | |||
| Adult male Swiss albino mice | SOD, CAT, GPx, | SOD, CAT, GST ↓# | Part of the plant: YES | Pavin et al. (2018) |
| TT fruit extract | GR, GST, GSH, 17β-HSD | GPx ↑# | Origin: YES | [65] |
| Plasma testosterone | 17β-HSD activity in treated group was not statistically significant different as compared with the control group | Phytochemical analysis: YES (UHPLC-Q-TOF/MS) | ||
| Semen analysis: | Testosterone ↑ | Control group: YES | ||
| motility, vigor, membrane integrity | Motility ↑# | Positive control group: YES | ||
| Histology of testes | No significant modifications in testicular architecture | Appropriate statistical analysis: YES | ||
| Male Wistar rats | Sperm analysis: sperm count, viability, motility | Testosterone, LH ↑* | Part of the plant: YES | Haghmorad |
| TT flower extract and | Serum testosterone, LH, FSH levels | All the treatment groups had higher number of Leydig, spermatogonia and spermatid cells | Origin: YES | et al. (2019) |
| Anacyclus Pyrethrum dried root extract | Histological analysis of Leydig and Sertoli cells, spermatogonia, and spermatid cell numbers measure | Phytochemical analysis: NO | [68] | |
| Control group: YES | ||||
| Positive control group: NO | ||||
| Appropriate statistical analysis: YES | ||||
| Sprague Dawley rats with type 2 diabetes induced with high-fat and high-sugar feeding and STZ (30 mg/kg) | ICP, MAP | ICP, ICP/MAP ↑ * | Part of the plant: NCS | Zhang et al. (2019) |
| Gross saponins of TT (GSTT) | eNOS expression level | Nitric oxide ↑* | Origin: YES | [86] |
| Nitric oxide level | ROS ↓* | Phytochemical analysis: NCS | ||
| cAMP expression level | No significant difference between the GSTT group and the sildenafil group in increasing cGMP levels | Control group: YES | ||
| ROS levels | Positive control group: YES | |||
| Appropriate statistical analysis: YES | ||||
| Clinical Studies | ||||
| 20–36-Year-old men | Testosterone, androstenedione, LH levels in the serum were measured before and after treatment (24, 72, 240, 408, and 576 h) | No significant difference between TT supplemented groups and the control in the serum testosterone, androstenedione, and LH | Part of the plant: YES | Neychev and Mitev (2005) |
| TT extract | Origin: YES | [76] | ||
| Phytochemical analysis or standardization: YES | ||||
| Placebo group: YES | ||||
| Randomization: YES | ||||
| Double-blind: NCS | ||||
| Appropriate statistical analysis: YES | ||||
| Australian elite male rugby league players | Strength, fat free mass | No significant changes | Part of the plant: NCS | Rogerson et al. (2007) |
| Urinary T/E ratio | No changes in urinary T/E ratio | Origin: YES | [77] | |
| Phytochemical analysis or standardization: YES | ||||
| Placebo group: YES | ||||
| Randomization: YES | ||||
| Double-blind: YES | ||||
| Appropriate statistical analysis: YES | ||||
| 20–22-Year-old athletes | CK, testosterone | CK ↑* | Part of the plant: NCS | Milasius et al. (2009) |
| TT capsules | Anaerobic alactic muscular power | Testosterone ↑* during the first half (10 days) of the experiment | Origin: NCS | [73] |
| Anaerobic alactic glycolytic power | Anaerobic alactic muscular power ↑* | Phytochemical analysis or standardization: NCS | ||
| Anaerobic alactic glycolytic power ↑* | Placebo group: YES | |||
| Randomization: NO | ||||
| Double-blind: NO | ||||
| Appropriate statistical analysis: YES | ||||
| Double-blind, randomized trial | IIEF, SQolM, | IIEF ↑* | Part of the plant: NCS | Iacono et al. (2012) |
| Male patients > sixty years with | Testosterone levels after 60 days of treatment, | SQolM ↑* | Origin: NCS | [74] |
| reduced libido, with or without erectile dysfunction (ED) | Side effects | TT level increased | Phytochemical analysis or standardization: NCS | |
| Treatment with “Tradamixina”, tadalafil | No side effects (headache, | Placebo group: NO | ||
| nasopharyngitis, | Randomization: YES | |||
| back pain, | Double-blind: YES | |||
| dizziness, | Appropriate statistical analysis: NO | |||
| dyspepsia) were observed | ||||
| Prospective, randomized, double-blind, placebo controlled study | IIEF and serum testosterone were obtained before randomization and after 30 days of study | No effects as compared with the placebo | Part of the plant: NO | Santos et al. (2014) |
| Healthy men, spontaneously complaining of ED, ≥40 years of age | Origin: NO | [72] | ||
| TT extract | Phytochemical analysis or standardization: NO | |||
| Placebo group: YES Randomization: YES | ||||
| Double-blind: YES | ||||
| Appropriate statistical analysis: YES | ||||
| Randomized, double-blind, placebo controlled clinical trial study | FSFI score | FSFI ↑* | Part of the plant: YES | Akhtari et al. (2014)[83] |
| Women with hypoactive sexual desire disorder | Origin: YES | |||
| TT leaves extract | Phytochemical analysis or standardization: NCS | |||
| Placebo group: YES | ||||
| Randomization: YES | ||||
| Double-blind: YES | ||||
| Appropriate statistical analysis: YES | ||||
| Prospective, randomized, double-blind, placebo controlled clinical trial | IIEF score | IIEF score ↑* | Part of the plant: YES | Kamenov et al. (2017) |
| Male with mild to moderate ED | GEQ responses | GEQ responses ↑* | Origin: YES | [71] |
| TT product: Tribestan®, | Phytochemical analysis or standardization: YES | |||
| 12-Week treatment period | Placebo group: YES | |||
| Randomization: YES | ||||
| Double-blind: YES | ||||
| Appropriate statistical analysis: YES | ||||
| Single-blind, placebo controlled, parallel study | MRS | Severity of menopausal transition sympt. ↓* | Part of the plant: YES | Fatima and Sultana (2017) |
| Perimenopausal women | Severity of menopausal transition symptoms | MRS ↓* | Origin: YES | [82] |
| TT fruit extract | Phytochemical analysis or standardization: NCS | |||
| Placebo group: YES | ||||
| Randomization: YES | ||||
| Double-blind: NO (single-blind) | ||||
| Appropriate statistical analysis: YES | ||||
| Prospective, randomized, double-blind, placebo controlled trial, | FSFI score | FSFI ↑* | Part of the plant: NCS | Vale et al. (2018) |
| Premenopausal women with diminished libido | QS-F score | QS-F ↑* | Origin: YES | [81] |
| TT extract | Serum testosterone | Serum testosterone ↑* | Phytochemical analysis or standardization: NCS | |
| Placebo group: YES | ||||
| Randomization: YES | ||||
| Double-blind: YES | ||||
| Appropriate statistical analysis: YES | ||||
MF, mount frequency; IF, intromission frequency; ML, mount latency; IL, intromission latency; EL, ejaculation latency; PEI, post-ejaculatory interval; ICP, intracavernous pressure; NCS, not clearly specified; cAMP, adenosine 3′,5′-cyclic monophosphate; cGMP, guanosine 3′,5′-cyclic monophosphate; FSH, follicle-stimulating hormone; LPO, lipid peroxidation; SOD, superoxide dismutase; CAT, catalase; GPx, glutathione peroxidase; GST, glutathione; S, transferase; AR, androgen receptor; IGF-1R, insulin growth factor 1 receptor; UHPLC-Q-TOF/MS, ultra-high performance liquid chromatography-quadrupole-time of flight mass spectrometry; GR, glutathione reductase; GSH, glutathione; 17β-HSD, 17β-hydroxysteroid dehydrogenase; LH, luteinizing hormone; MAP, mean arterial pressure; eNOS, endothelial nitric oxide synthase; urinary T/E ratio, urinary testosterone/epitestosterone (T/E) ratio; CK, creatine kinase; ED, erectile dysfunction; IIEF, International Index of Erectile Function; SQoLM, Sexual quality of life questionnaire male; FSFI, Female Sexual Function Index; GEQ, Global Efficacy Question; MRS, menopause rating scale; QS-F, Sexual Quotient Female Version; *, statistically significant difference as compared with the control/placebo; #, statistically significant difference as compared with the positive control group.