Original Article

The Effect of the Combination of Ginseng, Tribulus Terrestris, and L-arginine on the Sexual Performance of Men with Erectile Dysfunction: a randomized, double-blind, parallel, and placebo-controlled clinical trial
1School of Pharmacy, Pharmaceutical Sciences Research Center, Research Institute for Health, Kermanshah University of Medical Sciences, Kermanshah, Iran
2Kermanshah University of Medical Sciences, Kermanshah, Iran
3School of Medicine Imam Reza Hospital Kermanshah University of Medical Sciences, Kermanshah, Iran
4School of Health, Medical Biology Research Center, Research Institute for Health Technology, Kermanshah University of Medical Sciences, Kermanshah, Iran
5Barij Essence Medicinal Plants Research Center, Kashan, Iran
6Social Determinants of Health (SDH) Research Center, Department of Biostatistics and Epidemiology, School of Public Health, Kashan University of Medical Sciences, Kashan, Iran
Correspondence to: Hojjat Baghshahi
Barij Essence Medicinal Plants Research Center, Mashhad Ardehal, Kashan 8715985131, Iran
Tel: +98-915-903-1196
E-mail: Baghshahi_h1989@yahoo.com
This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
J Pharmacopuncture 2024; 27(2): 82-90
Published June 30, 2024 https://doi.org/10.3831/KPI.2024.27.2.82
Copyright © The Korean Pharmacopuncture Institute.
Abstract
Methods: Over three months, 98 men with erectile dysfunction were randomly assigned to receive either 500 mg of herbal supplements or placebo pills. Each herbal tablet contained 100 mg of protodioscin, 35 mg of ginsenosides, and 250 mg of L-arginine.
Results: The results showed that the changes in the average scores of ILEF-5 within each group before and after the intervention indicated that all parameters related to the improvement of sexual function in patients with erectile dysfunction improved in the herbal treatment group (p < 0.001). The herbal group significantly improved IIEF-5 scores in non-diabetics (p < 0.05). However, there was no significant difference in the changes of IIEF-5 scores between the two intervention and control groups in diabetic patients.
Conclusion: In conclusion, ginseng, Tribulus terrestris, and L-arginine have properties that increase energy and strengthen sexual function, making them suitable for patients with sexual disorders.
Keywords
INTRODUCTION
Erectile dysfunction (ED) is one of the most common sexual disorders among men worldwide. It is defined as the inability to achieve or maintain an erection sufficient for satisfactory sexual performance [1]. The prevalence of ED increases with age and is more common in older men. However, it can also be a health concern among young men [2]. While ED is not a life-threatening disease [3], it is a psychological threat to patients and can impact various aspects of mental and physical health, as well as the quality of life [4, 5].
Penile erection is a complex physiological process that involves the coordination of multiple systems including the vascular, nervous, and endocrine systems [6]. Research has shown that nitric oxide released from parasympathetic neurons increases cyclic guanosine 3’,5’-cyclic monophosphate (cGMP) production. cGMP causes relaxation of cavernous smooth muscles and dilation of arterioles, resulting in increased penile blood flow and erection [7].
The enzyme, phosphodiesterase 5 (PDE-5), breaks down cGMP and causes an erection to subside [8]. Standard medications for improving penile erection work by inhibiting PDE-5, to maintain a high level of cGMP [9]. However, these medications can lead to resistance in some patients, increase the cost of care, and have side effects, such as headache, dizziness, indigestion, heartburn, flushing, and vasodilation [10, 11]. For these reasons, researchers are increasingly interested in finding alternatives [12]. Medicinal plants have been used for a long time in traditional medicine across different countries and cultures worldwide to enhance sexual function in both men and women. In recent years, numerous studies have investigated the properties of medicinal plants in reducing and treating ED [13-15].
This study aimed to investigate the combined effects of
MATERIALS AND METHODS
1. Plant collection
The
2. Extraction and preparation of extract
The extraction process involved grinding one kilogram of dried aerial parts of
3. Formulation preparation
The liquid extract was blended with L-arginine, microcrystalline cellulose (Avicel® PH-101), polyvinyl pyrrolidone, and other ingredients. Blending was performed for 10 minutes in a tumbler. After that, 1% magnesium stearate was added, and the mixture was stirred for an additional five minutes. Finally, the combination was compressed into tablets using a mono-punch tablet machine press, with an 18 mm-diameter oblong punch set.
4. Standardization
To standardize the composition of the tablets, protodioscin, a steroidal saponin found in
5. Method and features of the device
UV analysis was performed using a PerkinElmer UV spectrophotometer apparatus. A test tube filled with 5 mL of the sample solution and 5 mL of p-dimethylaminobenzaldehyde reagent was placed in a 58℃ water bath for two hours. The sample solutions were read at wavelengths ranging from 400 to 700 nm using the UV-Vis Spectrophotometer.
6. Study design
This study was conducted as a randomized, double-blind, parallel, and placebo-controlled clinical trial at the specialized clinic, Bustan, affiliated with Kermanshah University of Medical Sciences in Kermanshah, Iran. A total of 137 patients with ED, aged 38-64 years, were selected by a urology specialist who had been practicing medicine for approximately 12 years in Iran, and was interested in prescribing herbal medicines and their natural effects.
All participants were instructed not to change their current herbal supplement or diet during the study. The herbal tablets and placebo tablets were prepared in identical packages, sizes, shapes, and colors. The treatment group was instructed to take 500 mg of the herbal tablets (with at least 100 mg total saponin, 30 mg total ginsenosides, and 150 mg L-arginine in each tablet), twice daily after a meal, for three months, while the control group received placebo tablets and the same instructions. Before the study, the study purpose was explained to patients with ED and an informed consent to participate in the study was signed. The clinical features of the patients, including age, high blood pressure, diabetes, dyslipidemia, lower urinary tract disorders, drug usage, and side effects, were assessed in both groups. The IIEF-5 questionnaire (lower scores = a higher rate of ED) was completed by all participants. Additionally, the patients completed a questionnaire regarding their age, history of drug and alcohol use, underlying disorders (such as diabetes, high blood pressure, and genitourinary conditions), and previous consumption of other herbal compounds. Exclusion criteria included severe underlying disorders, simultaneous use of other drugs, and/or consumption of other interfering substances. Throughout the study, phone calls were made to facilitate communication with the participants and results were recorded. Three months after the start of the study, the IIEF-5 questionnaire was administered again to determine each participant’s sexual desire index. The five subdomains of this questionnaire were Q1: erectile function, Q2: orgasm function, Q3: sexual desire, Q4: sexual pleasure, and Q5: total satisfaction. The score for each subdomain ranged from 1 to 5.
7. Sample size
The sample size was calculated based on the results from examining the effect of
8. Size of randomized blocks
In this study, the 4-block randomization method was used. One individual, who was not involved in the recruitment and evaluation processes, created a random sequence using https://www.sealedenvelope.com, and 25 blocks of 4 were created. Another individual was responsible for blindly allocating participants to the different groups. All participants and investigators were blinded to the patient allocation process. The type of medicine was also unknown to the patients, physicians, drug delivery personnel, and data analysts. Only the pharmacists had access to the membership data of the groups.
9. Ethical considerations
This clinical trial was registered with the Iranian Registry of Clinical Trials (IRCT) under approval number IRCT20130722014106N8. Furthermore, this protocol was validated by the Kermanshah University of Medical Sciences Ethics Committee in Iran under code number IR.KUMS.REC.1399.568. All participants were aware of the protocol and provided written informed consent. All stages of proposal writing, implementation, data collection and analysis, and manuscript preparation were performed according to the checklist of the 4 Items for Reporting Randomized, Controlled Trials of Herbal Medicine Interventions guideline [21].
10. Statistical analysis
The statistical analyses were performed using SPSS Statistics, version 25 (IBM Corp, Armonk, NY, USA). The Kolmogorov-Smirnov test was conducted to assess the normality of the variables. The effects of each treatment group were assessed using the Wilcoxon signed-rank test and Fisher’s exact tests. The Chi-square test was used to compare qualitative variables, while the independent T and Mann-Whitney tests were applied for quantitative variables. Additionally, analysis of covariance (ANCOVA) was used to examine multivariate effects. A p-value less than 0.05 was considered statistically significant.
RESULTS
1. Standard curve
Each herbal pill contains 100 mg of protodioscin, 35 mg of ginsenosides, and 250 mg of L-arginine.
2. Formulation uniformity
Formulation uniformity was assessed by analyzing physical properties, such as color, appearance, mass uniformity, hardness, and dissolution test over a six-month period under accelerated conditions (75% humidity and 40℃). The results showed no significant changes throughout the storage period.
3. Microbial control
Microbial control tests conducted on the tablets at zero, third, and sixth months showed consistent results. The total aerobic microbial count and total yeast and mold counts were both N ≤ 10.
4. Eligible participants
Of the 137 eligible participants enrolled in the study, 17 men were excluded because they did not meet the inclusion criteria, while 6 other men declined to participate. The remaining 114 patients were randomly assigned to 2 groups: 1) the herbal medicine group (n = 57) and 2) the placebo group (n = 57). Finally, data from 49 participants in the herbal medicine group and 49 participants in the control group were analyzed (Fig. 1).
-
Figure 1.Consort flow diagram of the study.
5. Basic clinical features
Baseline characteristics were similar between the two groups, except for the ratio of patients with diabetes. Twelve participants in the herbal treatment group and 10 in the placebo group have diabetes (p = 0.628, Table 1).
-
Table 1 . Comparison of basic characteristics of the participants between the two groups before the intervention.
Variables Intervention group
(n = 49)Placebo group
(n = 49)p-value Age (year) (mean ± S.D) 51 ± 12.30 49.20 ± 10.63 0.439 Hypertension, n (%) Yes
No6 (12.2)
43 (87.8)7 (14.3)
42 (85.7)0.766 Diabetes, n (%) Yes
No12 (24.5)
37 (75.5)10 (20.4)
39 (79.6)0.628 Dyslipidemia, n (%) Yes
No2 (4.1)
47 (95.9)3 (6.1)
46 (93.9)0.695 Lower urinary tract diseases, n (%) Yes
No2 (4.1)
47 (95.9)1 (2)
48 (98)0.785 Drug abuse, n (%) Yes
No13 (26.5)
36 (73.5)11 (22.4)
38 (77.6)0.638 Reported Side effects, n (%) Yes
No8 (16.3)
41 (83.7)7 (14.3)
42 (85.7)0.779 p < 0.05 shows a statistical significant difference..
Changes in the average ILEF-5 scores before and after the intervention within each group indicated that all parameters that were indicative of sexual function improved in the herbal treatment group (p < 0.001). In contrast, none of the IIEF-5 questionnaire items showed a statistically significant change before and after treatment in the control group (Table 2).
-
Table 2 . Comparison of mean IIEF-5 scores before and after the intervention within each group.
Item Herbal (mean ± S.D) Placebo (mean ± S.D) Before After p-value Before After p-value Q1 2.02 ± 0.91 2.62 ± 1.07 < 0.001 1.80 ± 0.85 1.86 ± 0.85 0.083 Q2 2.30 ± 0.79 2.77 ± 0.94 < 0.001 2.17 ± 0.97 2.19 ± 0.98 0.317 Q3 2.17 ± 0.81 2.67 ± 0.99 < 0.001 2.43 ± 1.22 2.43 ± 1.22 N.S Q4 2.35 ± 1.12 2.82 ± 1.15 < 0.001 2.32 ± 1.23 2.36 ± 1.21 0.157 Q5 1.90 ± 1.00 3.07 ± 1.11 < 0.001 1.97 ± 0.99 2.08 ± 1.02 0.25 Total 10.75 ± 3.66 13.97 ± 4.72 < 0.001 10.71 ± 4.51 10.95 ± 4.54 0.37 N.SM, not significant; S.D, standard deviation..
The IIEF-5 questionnaire item scores between the herbal medicine and placebo groups did not differ before the intervention. However, after the intervention, the between-group comparisons of the mean IIEF-5 scores revealed that the parameters associated with ED significantly improve in the herbal group (Table 3). These results indicate that, on average, the herbal group reported a total score difference of 3.22 ± 2.42 after the intervention compared to before the intervention, while the placebo group had a difference of 0.23 ± 0.7 (p < 0.05) (Table 3).
-
Table 3 . Comparison of mean IIEF-5 scores before and after the intervention between groups.
Time Item Herbal
(mean ± S.D)Placebo
(mean ± S.D)p-value Before intervention Q1 2.02 ± 0.91 1.80 ± 0.85 0.264 Q2 2.30 ± 0.79 2.17 ± 0.97 0.716 Q3 2.17 ± 0.81 2.43 ± 1.22 0.414 Q4 2.35 ± 1.12 2.32 ± 1.23 0.776 Q5 1.90 ± 1.00 1.97 ± 0.99 0.677 Total 10.75 ± 3.66 10.71 ± 4.51 0.994 After intervention Q1 2.62 ± 1.07 1.86 ± 0.85 < 0.001 Q2 2.77 ± 0.94 2.19 ± 0.98 < 0.001 Q3 2.67 ± 0.99 2.43 ± 1.22 < 0.001 Q4 2.82 ± 1.15 2.36 ± 1.21 < 0.001 Q5 3.07 ± 1.11 2.08 ± 1.02 < 0.001 Total 2.62 ± 1.07 10.95 ± 4.54 < 0.001 Difference ΔbQ1 0.60 ± 0.63 0.06 ± 0.24 < 0.001 ΔQ2 0.47 ± 0.59 0.02 ± 0.14 < 0.001 ΔQ3 0.50 ± 0.59 0.00 ± 0.00c < 0.001 ΔQ4 0.47 ± 0.59 0.04 ± 0.20 < 0.001 ΔQ5 1.17 ± 0.74 0.10 ± 0.31 < 0.001 ΔTotal 3.22 ± 2.42 0.23 ± 0.70 < 0.001 S.D, standard deviation..
Table 4 compares the mean IIEF-5 scores for diabetic and non-diabetic individuals before and after the intervention. The findings show a significant difference between the two groups (diabetic vs. non-diabetic) for every item. In particular, the IIEF-5 scores increased significantly among the non-diabetics in the herbal treatment group (p < 0.05). The overall difference in IIEF-5 scores between the herbal and placebo groups was 3.27 ± 2.45 and 0.11 ± 0.52, respectively (p < 0.05). However, the IIEF-5 scores among patients with diabetes in the herbal and placebo groups did not significantly differ. Furthermore, 16.3% of patients in the intervention group and 14.3% in the control group reported at least one side effect and the difference was not statistically significant (p = 0.779).
-
Table 4 . Comparison of the mean IIEF-5 score for diabetic and non-diabetic individuals before and after the intervention.
Diabetic type Item Herbal
(mean ± S.D)Placebo
(mean ± S.D)p-value Non-diabetic n 37 39 - ΔQ1 0.59 ± 0.64 0.02 ± 0.16 < 0.001 ΔQ2 0.48 ± 0.60 0.00 ± 0.00 < 0.001 ΔQ3 0.51 ± 0.60 0.00 ± 0.00 < 0.001 ΔQ4 0.48 ± 0.60 0.02 ± 0.16 < 0.001 ΔQ5 1.18 ± 0.73 0.05 ± 0.23 < 0.001 ΔTotal 3.27 ± 2.45 0.11 ± 0.52 < 0.001 Diabetic n 12 10 - ΔQ1 0.66 ± 0.57 0.20 ± 0.42 0.140 ΔQ2 0.33 ± 0.57 0.10 ± 0.31 0.345 ΔQ3 0.33 ± 0.57 0.00 ± 0.00 0.068 ΔQ4 0.33 ± 0.57 0.10 ± 0.31 0.345 ΔQ5 1.00 ± 1.00 0.30 ± 0.48 0.169 ΔTotal 2.66 ± 2.30 0.70 ± 1.05 0.140 ΔQ = (Qafter intervention)– Qbefore intervention..
p < 0.05 shows a statistical significant difference..
DISCUSSION
ED is a complex disorder primarily caused by reduced nitric oxide formation due to impaired neural and endothelial function of the corpus cavernosum of the penis [22]. However, there are other pathophysiological mechanisms, such as high blood pressure, androgen deficiency, arteriosclerosis, high cholesterol levels, diabetes mellitus, prostate diseases, and anatomical deformation of the penis [23, 24]. Due to the negative consequences associated with chemical and hormonal drugs, the use of medicinal herbs and natural bioactive components to treat and lessen the severity of ED has attracted attention in recent years [12]. In this study, we investigated the combined effect of
Kamenov et al. (2017) reported that TT at a standardized dose, with 250 mg of the saponin furostanol, taken for 12 weeks, improved sexual function in men with mild to moderate ED. Importantly, TT was well tolerated by patients with ED [35]. Gauthaman et al. (2008) showed that an intravenous administration of TT extract increased plasma testosterone, dihydrotestosterone, and dehydroepiandrosterone sulfate in primates. An oral administration of TT extract in rabbits and rats also increased dihydrotestosterone levels. Protodioscin, a saponin-like compound found in TT, may trigger testosterone synthesis by the Leydig cells [36]. Administering TT to rabbits results in a rise in cAMP and a relaxing effect on the corpus cavernosum, suggesting that TT affects the erectile process through the NOS pathway [37]. Moreover, Zhang et al. (2019) demonstrated a reparative effect of impure saponins on the endothelial function of a type 2 diabetes mouse model. Furthermore, gross saponins of
A meta-analysis previously reported that arginine supplementation substantially increased IIEF sub-domain scores of overall satisfaction, sexual satisfaction, orgasmic function, and erectile function [39]. Furthermore, L-arginine significantly improved their erectile performance [40].
CONCLUSION
In conclusion, the combination of
LIMITATIONS
In this study, the IIEF-5 questionnaire was used to measure erectile function, which may be regarded as unideal. In the future, to improve study quality, erectile function should be assessed by measuring plasma hormones, especially free testosterone, blood flow in the internal pondal artery using Doppler ultrasound, and blood pressure in the genitals using penile thermography, as well as nighttime swelling of the genitals via prostate ultrasound, especially in males, aged over 50 years old.
SUPPLEMENTARY MATERIALS
Supplementary data is available at https://doi.org/10.3831/KPI.2024.27.2.82.
ACKNOWLEDGEMENTS
This study was conducted using Highsense Barij® tablets manufactured by Barij Essence Company in Iran, and this company was supported all financial support.
CONFLICTS OF INTEREST
The authors declare no conflicts of interest in this work.
References
- Adam DR, Alem MM. Erectile dysfunction: pharmacological pathways with understudied potentials. Biomedicines. 2022;11(1):46.
- Heruti R, Shochat T, Tekes-Manova D, Ashkenazi I, Justo D. Prevalence of erectile dysfunction among young adults: results of a large-scale survey. J Sex Med. 2004;1(3):284-91.
- Sin VJ, Anand GS, Koh HL. Botanical medicine and natural products used for erectile dysfunction. Sex Med Rev. 2021;9(4):568-92.
- Wang H, Zhao M, Zhang J, Yan B, Liu S, Zhao F, et al. The efficacy of acupuncture on patients with erectile dysfunction: a review. Evid Based Complement Alternat Med. 2022;2022:4807271.
- Shankhwar SN, Mahdi AA, Sharma AV, Pv K. A prospective clinical study of a prosexual nutrient: Nano Leo for evaluation of libido, erection, and orgasm in Indian men with erectile dysfunction. Evid Based Complement Alternat Med. 2020;2020:4598217.
- Sangiorgi G, Cereda A, Benedetto D, Bonanni M, Chiricolo G, Cota L, et al. Anatomy, pathophysiology, molecular mechanisms, and clinical management of erectile dysfunction in patients affected by coronary artery disease: a review. Biomedicines. 2021;9(4):432.
- Irwin GM. Erectile dysfunction. Prim Care. 2019;46(2):249-55.
- Castela Â, Costa C. Molecular mechanisms associated with diabetic endothelial-erectile dysfunction. Nat Rev Urol. 2016;13(5):266-74.
- Hatzimouratidis K, Salonia A, Adaikan G, Buvat J, Carrier S, El-Meliegy A, et al. Pharmacotherapy for erectile dysfunction: recommendations from the fourth International Consultation for Sexual Medicine (ICSM 2015). J Sex Med. 2016;13(4):465-88.
- Ückert S, Kuczyk MA, Oelke M. Phosphodiesterase inhibitors in clinical urology. Expert Rev Clin Pharmacol. 2013;6(3):323-32.
- Panahi Y, Akhavan A, Sahebkar A, Hosseini SM, Taghizadeh M, Akbari H, et al. Investigation of the effectiveness of Syzygium aromaticum, Lavandula angustifolia and Geranium robertianum essential oils in the treatment of acute external otitis: a comparative trial with ciprofloxacin. J Microbiol Immunol Infect. 2014;47(3):211-6.
- Masuku NP, Unuofin JO, Lebelo SL. Promising role of medicinal plants in the regulation and management of male erectile dysfunction. Biomed Pharmacother. 2020;130:110555.
- Chauhan NS, Sharma V, Dixit VK, Thakur M. A review on plants used for improvement of sexual performance and virility. Biomed Res Int. 2014;2014:868062.
- Taghizadeh M, Ostad SN, Asemi Z, Mahboubi M, Hejazi S, Sharafati-Chaleshtori R, et al. Sub-chronic oral toxicity of Cuminum cyminum L.'s essential oil in female Wistar rats. Regul Toxicol Pharmacol. 2017;88:138-43.
- Taghizadeh M, Farzin N, Taheri S, Mahlouji M, Akbari H, Karamali F, et al. The effect of dietary supplements containing green tea, capsaicin and ginger extracts on weight loss and metabolic profiles in overweight women: a randomized double-blind placebo-controlled clinical trial. Ann Nutr Metab. 2017;70(4):277-85.
- Zhang H, Abid S, Ahn JC, Mathiyalagan R, Kim YJ, Yang DC, et al. Characteristics of
Panax ginseng cultivars in Korea and China. Molecules. 2020;25(11):2635. - Kim JY, Lee HJ, Kim JS, Ryu JH. Induction of nitric oxide synthase by saponins of heat-processed ginseng. Biosci Biotechnol Biochem. 2005;69(5):891-5.
- Hossein M, Hossein A, Mohsen T, Jamileh J, Mohadese M, Mahnaz M. Evaluation of the effects of capsules containing Tribulus terrestris extract and L-carnitine on treatment of oligospermia in males. J Evol Med Dent Sci. 2018;7(29):3266-70.
- Gunarathne R, Nadeeshani H, Lu A, Li J, Zhang B, Ying T, et al. Potential nutraceutical use of
Tribulus terrestris L. in human health. Food Rev Int. 2022;39(8):5326-55. - Santos CA, Reis LO, Destro-Saade R, Luiza-Reis A, Fregonesi A. Tribulus terrestris versus placebo in the treatment of erectile dysfunction: a prospective, randomized, double blind study. Actas Urol Esp. 2014;38(4):244-8.
- Gagnier JJ, Boon H, Rochon P, Moher D, Barnes J, Bombardier C. Reporting randomized, controlled trials of herbal interventions: an elaborated CONSORT statement. Ann Intern Med. 2006;144(5):364-7.
- Zou H, Zhang X, Chen W, Tao Y, Li B, Liu H, et al. Vascular endothelium is the basic way for stem cells to treat erectile dysfunction: a bibliometric study. Cell Death Discov. 2023;9(1):143.
- Aversa A, Bruzziches R, Pili M, Spera G. Phosphodiesterase 5 inhibitors in the treatment of erectile dysfunction. Curr Pharm Des. 2006;12(27):3467-84.
- Papagiannopoulos D, Khare N, Nehra A. Evaluation of young men with organic erectile dysfunction. Asian J Androl. 2015;17(1):11-6.
- Jurys T, Burzynski B, Potyka A, Paradysz A. Post-radical prostatectomy erectile dysfunction assessed using the IIEF-5 questionnaire - a systematic literature review. Int J Sex Health. 2021;34(1):55-64.
- Su H, Lu Y, Ma C, Li H, Su X. Impact of atorvastatin on erectile dysfunction: a meta-analysis and systematic review. Andrologia. 2022;54(6):e14408.
- de Andrade E, de Mesquita AA, de Almeida Claro J, de Andrade PM, Ortiz V, Paranhos M, et al. Study of the efficacy of Korean Red Ginseng in the treatment of erectile dysfunction. Asian J Androl. 2007;9(2):241-4.
- Choi YD, Park CW, Jang J, Kim SH, Jeon HY, Kim WG, et al. Effects of Korean ginseng berry extract on sexual function in men with erectile dysfunction: a multicenter, placebo-controlled, double-blind clinical study. Int J Impot Res. 2013;25(2):45-50.
- Qi LW, Wang CZ, Yuan CS. Isolation and analysis of ginseng: advances and challenges. Nat Prod Rep. 2011;28(3):467-95.
- Yu J, Eto M, Akishita M, Kaneko A, Ouchi Y, Okabe T. Signaling pathway of nitric oxide production induced by ginsenoside Rb1 in human aortic endothelial cells: a possible involvement of androgen receptor. Biochem Biophys Res Commun. 2007;353(3):764-9.
- Leung KW, Cheng YK, Mak NK, Chan KK, Fan TP, Wong RN. Signaling pathway of ginsenoside-Rg1 leading to nitric oxide production in endothelial cells. FEBS Lett. 2006;580(13):3211-6.
- Wang X, Chu S, Qian T, Chen J, Zhang J. Ginsenoside Rg1 improves male copulatory behavior via nitric oxide/cyclic guanosine monophosphate pathway. J Sex Med. 2010;7(2 Pt 1):743-50.
- Kang YJ, Sohn JT, Chang KC. Relaxation of canine corporal smooth muscle relaxation by ginsenoside saponin Rg3 is independent from eNOS activation. Life Sci. 2005;77(1):74-84.
- Najafabadi BT, Jafarinia M, Ghamari K, Shokraee K, Tadayyon F, Akhondzadeh S. Vitamin E and ginseng combined supplement for treatment of male erectile dysfunction: a double-blind, placebo-controlled, randomized, clinical trial. Adv Integr Med. 2021;8(1):44-9.
- Kamenov Z, Fileva S, Kalinov K. Evaluation of the efficacy and safety of Tribulus terrestris in male sexual dysfunction - a prospective, randomized, double blinded, placebo-controlled clinical trial. Maturitas. 2015;81(1):P208.
- Gauthaman K, Ganesan AP. The hormonal effects of Tribulus terrestris and its role in the management of male erectile dysfunction--an evaluation using primates, rabbit and rat. Phytomedicine. 2008;15(1-2):44-54.
- Kam SC, Do JM, Choi JH, Jeon BT, Roh GS, Hyun JS. In vivo and in vitro animal investigation of the effect of a mixture of herbal extracts from Tribulus terrestris and Cornus officinalis on penile erection. J Sex Med. 2012;9(10):2544-51.
- Zhang H, Tong WT, Zhang CR, Li JL, Meng H, Yang HG, et al. Gross saponin of
Tribulus terrestris improves erectile dysfunction in type 2 diabetic rats by repairing the endothelial function of the penile corpus cavernosum. Diabetes Metab Syndr Obes. 2019;12:1705-1716. - Rhim HC, Kim MS, Park YJ, Choi WS, Park HK, Kim HG, et al. The potential role of arginine supplements on erectile dysfunction: a systemic review and meta-analysis. J Sex Med. 2019;16(2):223-34.
- Klotz T, Mathers MJ, Braun M, Bloch W, Engelmann U. Effectiveness of oral L-arginine in first-line treatment of erectile dysfunction in a controlled crossover study. Urol Int. 1999;63(4):220-3.
Related articles in JoP

Article
Original Article
J Pharmacopuncture 2024; 27(2): 82-90
Published online June 30, 2024 https://doi.org/10.3831/KPI.2024.27.2.82
Copyright © The Korean Pharmacopuncture Institute.
The Effect of the Combination of Ginseng, Tribulus Terrestris, and L-arginine on the Sexual Performance of Men with Erectile Dysfunction: a randomized, double-blind, parallel, and placebo-controlled clinical trial
Reza Tahvilian1 , Mohammad Amin Golesorkhi2
, Farajollah Parhoudeh3
, Fatemeh Heydarpour4
, Hossein Hosseini5
, Hojjat Baghshahi5*
, Hossein Akbari6
, Mohammad Reza Memarzadeh5
, Mehdi Mehran5
, Hosna Bagheri2
1School of Pharmacy, Pharmaceutical Sciences Research Center, Research Institute for Health, Kermanshah University of Medical Sciences, Kermanshah, Iran
2Kermanshah University of Medical Sciences, Kermanshah, Iran
3School of Medicine Imam Reza Hospital Kermanshah University of Medical Sciences, Kermanshah, Iran
4School of Health, Medical Biology Research Center, Research Institute for Health Technology, Kermanshah University of Medical Sciences, Kermanshah, Iran
5Barij Essence Medicinal Plants Research Center, Kashan, Iran
6Social Determinants of Health (SDH) Research Center, Department of Biostatistics and Epidemiology, School of Public Health, Kashan University of Medical Sciences, Kashan, Iran
Correspondence to:Hojjat Baghshahi
Barij Essence Medicinal Plants Research Center, Mashhad Ardehal, Kashan 8715985131, Iran
Tel: +98-915-903-1196
E-mail: Baghshahi_h1989@yahoo.com
This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Objectives: Nitric oxide is the most important mediator of penile erection after the onset of sexual excitement. It activates cyclic guanosine monophosphate (cGMP), increasing penile blood flow. Most pharmaceutical medications prevent enzyme phosphodiesterase type 5 (PDE-5) from breaking down cGMP, thus keeping its level high. However, due to the adverse effects of pharmacological therapies, herbal drugs that improve sexual function have gained attention recently. This study aimed to investigate the combined effects of ginseng, Tribulus terrestris, and L-arginine amino acid on the sexual performance of individuals with erectile dysfunction (ED) using the 5-item version of the International Index of Erectile Function (IIEF-5) questionnaire.
Methods: Over three months, 98 men with erectile dysfunction were randomly assigned to receive either 500 mg of herbal supplements or placebo pills. Each herbal tablet contained 100 mg of protodioscin, 35 mg of ginsenosides, and 250 mg of L-arginine.
Results: The results showed that the changes in the average scores of ILEF-5 within each group before and after the intervention indicated that all parameters related to the improvement of sexual function in patients with erectile dysfunction improved in the herbal treatment group (p < 0.001). The herbal group significantly improved IIEF-5 scores in non-diabetics (p < 0.05). However, there was no significant difference in the changes of IIEF-5 scores between the two intervention and control groups in diabetic patients.
Conclusion: In conclusion, ginseng, Tribulus terrestris, and L-arginine have properties that increase energy and strengthen sexual function, making them suitable for patients with sexual disorders.
Keywords: penile erection, herbal medicines, international index of erectile function, erectile dysfunction, traditional medicine
INTRODUCTION
Erectile dysfunction (ED) is one of the most common sexual disorders among men worldwide. It is defined as the inability to achieve or maintain an erection sufficient for satisfactory sexual performance [1]. The prevalence of ED increases with age and is more common in older men. However, it can also be a health concern among young men [2]. While ED is not a life-threatening disease [3], it is a psychological threat to patients and can impact various aspects of mental and physical health, as well as the quality of life [4, 5].
Penile erection is a complex physiological process that involves the coordination of multiple systems including the vascular, nervous, and endocrine systems [6]. Research has shown that nitric oxide released from parasympathetic neurons increases cyclic guanosine 3’,5’-cyclic monophosphate (cGMP) production. cGMP causes relaxation of cavernous smooth muscles and dilation of arterioles, resulting in increased penile blood flow and erection [7].
The enzyme, phosphodiesterase 5 (PDE-5), breaks down cGMP and causes an erection to subside [8]. Standard medications for improving penile erection work by inhibiting PDE-5, to maintain a high level of cGMP [9]. However, these medications can lead to resistance in some patients, increase the cost of care, and have side effects, such as headache, dizziness, indigestion, heartburn, flushing, and vasodilation [10, 11]. For these reasons, researchers are increasingly interested in finding alternatives [12]. Medicinal plants have been used for a long time in traditional medicine across different countries and cultures worldwide to enhance sexual function in both men and women. In recent years, numerous studies have investigated the properties of medicinal plants in reducing and treating ED [13-15].
This study aimed to investigate the combined effects of
MATERIALS AND METHODS
1. Plant collection
The
2. Extraction and preparation of extract
The extraction process involved grinding one kilogram of dried aerial parts of
3. Formulation preparation
The liquid extract was blended with L-arginine, microcrystalline cellulose (Avicel® PH-101), polyvinyl pyrrolidone, and other ingredients. Blending was performed for 10 minutes in a tumbler. After that, 1% magnesium stearate was added, and the mixture was stirred for an additional five minutes. Finally, the combination was compressed into tablets using a mono-punch tablet machine press, with an 18 mm-diameter oblong punch set.
4. Standardization
To standardize the composition of the tablets, protodioscin, a steroidal saponin found in
5. Method and features of the device
UV analysis was performed using a PerkinElmer UV spectrophotometer apparatus. A test tube filled with 5 mL of the sample solution and 5 mL of p-dimethylaminobenzaldehyde reagent was placed in a 58℃ water bath for two hours. The sample solutions were read at wavelengths ranging from 400 to 700 nm using the UV-Vis Spectrophotometer.
6. Study design
This study was conducted as a randomized, double-blind, parallel, and placebo-controlled clinical trial at the specialized clinic, Bustan, affiliated with Kermanshah University of Medical Sciences in Kermanshah, Iran. A total of 137 patients with ED, aged 38-64 years, were selected by a urology specialist who had been practicing medicine for approximately 12 years in Iran, and was interested in prescribing herbal medicines and their natural effects.
All participants were instructed not to change their current herbal supplement or diet during the study. The herbal tablets and placebo tablets were prepared in identical packages, sizes, shapes, and colors. The treatment group was instructed to take 500 mg of the herbal tablets (with at least 100 mg total saponin, 30 mg total ginsenosides, and 150 mg L-arginine in each tablet), twice daily after a meal, for three months, while the control group received placebo tablets and the same instructions. Before the study, the study purpose was explained to patients with ED and an informed consent to participate in the study was signed. The clinical features of the patients, including age, high blood pressure, diabetes, dyslipidemia, lower urinary tract disorders, drug usage, and side effects, were assessed in both groups. The IIEF-5 questionnaire (lower scores = a higher rate of ED) was completed by all participants. Additionally, the patients completed a questionnaire regarding their age, history of drug and alcohol use, underlying disorders (such as diabetes, high blood pressure, and genitourinary conditions), and previous consumption of other herbal compounds. Exclusion criteria included severe underlying disorders, simultaneous use of other drugs, and/or consumption of other interfering substances. Throughout the study, phone calls were made to facilitate communication with the participants and results were recorded. Three months after the start of the study, the IIEF-5 questionnaire was administered again to determine each participant’s sexual desire index. The five subdomains of this questionnaire were Q1: erectile function, Q2: orgasm function, Q3: sexual desire, Q4: sexual pleasure, and Q5: total satisfaction. The score for each subdomain ranged from 1 to 5.
7. Sample size
The sample size was calculated based on the results from examining the effect of
8. Size of randomized blocks
In this study, the 4-block randomization method was used. One individual, who was not involved in the recruitment and evaluation processes, created a random sequence using https://www.sealedenvelope.com, and 25 blocks of 4 were created. Another individual was responsible for blindly allocating participants to the different groups. All participants and investigators were blinded to the patient allocation process. The type of medicine was also unknown to the patients, physicians, drug delivery personnel, and data analysts. Only the pharmacists had access to the membership data of the groups.
9. Ethical considerations
This clinical trial was registered with the Iranian Registry of Clinical Trials (IRCT) under approval number IRCT20130722014106N8. Furthermore, this protocol was validated by the Kermanshah University of Medical Sciences Ethics Committee in Iran under code number IR.KUMS.REC.1399.568. All participants were aware of the protocol and provided written informed consent. All stages of proposal writing, implementation, data collection and analysis, and manuscript preparation were performed according to the checklist of the 4 Items for Reporting Randomized, Controlled Trials of Herbal Medicine Interventions guideline [21].
10. Statistical analysis
The statistical analyses were performed using SPSS Statistics, version 25 (IBM Corp, Armonk, NY, USA). The Kolmogorov-Smirnov test was conducted to assess the normality of the variables. The effects of each treatment group were assessed using the Wilcoxon signed-rank test and Fisher’s exact tests. The Chi-square test was used to compare qualitative variables, while the independent T and Mann-Whitney tests were applied for quantitative variables. Additionally, analysis of covariance (ANCOVA) was used to examine multivariate effects. A p-value less than 0.05 was considered statistically significant.
RESULTS
1. Standard curve
Each herbal pill contains 100 mg of protodioscin, 35 mg of ginsenosides, and 250 mg of L-arginine.
2. Formulation uniformity
Formulation uniformity was assessed by analyzing physical properties, such as color, appearance, mass uniformity, hardness, and dissolution test over a six-month period under accelerated conditions (75% humidity and 40℃). The results showed no significant changes throughout the storage period.
3. Microbial control
Microbial control tests conducted on the tablets at zero, third, and sixth months showed consistent results. The total aerobic microbial count and total yeast and mold counts were both N ≤ 10.
4. Eligible participants
Of the 137 eligible participants enrolled in the study, 17 men were excluded because they did not meet the inclusion criteria, while 6 other men declined to participate. The remaining 114 patients were randomly assigned to 2 groups: 1) the herbal medicine group (n = 57) and 2) the placebo group (n = 57). Finally, data from 49 participants in the herbal medicine group and 49 participants in the control group were analyzed (Fig. 1).
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Figure 1. Consort flow diagram of the study.
5. Basic clinical features
Baseline characteristics were similar between the two groups, except for the ratio of patients with diabetes. Twelve participants in the herbal treatment group and 10 in the placebo group have diabetes (p = 0.628, Table 1).
-
p < 0.05 shows a statistical significant difference..
&md=tbl&idx=1' data-target="#file-modal"">Table 1Comparison of basic characteristics of the participants between the two groups before the intervention.
Variables Intervention group
(n = 49)Placebo group
(n = 49)p-value Age (year) (mean ± S.D) 51 ± 12.30 49.20 ± 10.63 0.439 Hypertension, n (%) Yes
No6 (12.2)
43 (87.8)7 (14.3)
42 (85.7)0.766 Diabetes, n (%) Yes
No12 (24.5)
37 (75.5)10 (20.4)
39 (79.6)0.628 Dyslipidemia, n (%) Yes
No2 (4.1)
47 (95.9)3 (6.1)
46 (93.9)0.695 Lower urinary tract diseases, n (%) Yes
No2 (4.1)
47 (95.9)1 (2)
48 (98)0.785 Drug abuse, n (%) Yes
No13 (26.5)
36 (73.5)11 (22.4)
38 (77.6)0.638 Reported Side effects, n (%) Yes
No8 (16.3)
41 (83.7)7 (14.3)
42 (85.7)0.779 p < 0.05 shows a statistical significant difference..
Changes in the average ILEF-5 scores before and after the intervention within each group indicated that all parameters that were indicative of sexual function improved in the herbal treatment group (p < 0.001). In contrast, none of the IIEF-5 questionnaire items showed a statistically significant change before and after treatment in the control group (Table 2).
-
N.SM, not significant; S.D, standard deviation..
&md=tbl&idx=2' data-target="#file-modal"">Table 2Comparison of mean IIEF-5 scores before and after the intervention within each group.
Item Herbal (mean ± S.D) Placebo (mean ± S.D) Before After p-value Before After p-value Q1 2.02 ± 0.91 2.62 ± 1.07 < 0.001 1.80 ± 0.85 1.86 ± 0.85 0.083 Q2 2.30 ± 0.79 2.77 ± 0.94 < 0.001 2.17 ± 0.97 2.19 ± 0.98 0.317 Q3 2.17 ± 0.81 2.67 ± 0.99 < 0.001 2.43 ± 1.22 2.43 ± 1.22 N.S Q4 2.35 ± 1.12 2.82 ± 1.15 < 0.001 2.32 ± 1.23 2.36 ± 1.21 0.157 Q5 1.90 ± 1.00 3.07 ± 1.11 < 0.001 1.97 ± 0.99 2.08 ± 1.02 0.25 Total 10.75 ± 3.66 13.97 ± 4.72 < 0.001 10.71 ± 4.51 10.95 ± 4.54 0.37 N.SM, not significant; S.D, standard deviation..
The IIEF-5 questionnaire item scores between the herbal medicine and placebo groups did not differ before the intervention. However, after the intervention, the between-group comparisons of the mean IIEF-5 scores revealed that the parameters associated with ED significantly improve in the herbal group (Table 3). These results indicate that, on average, the herbal group reported a total score difference of 3.22 ± 2.42 after the intervention compared to before the intervention, while the placebo group had a difference of 0.23 ± 0.7 (p < 0.05) (Table 3).
-
&md=tbl&idx=3' data-target="#file-modal"">Table 3
Comparison of mean IIEF-5 scores before and after the intervention between groups.
Time Item Herbal
(mean ± S.D)Placebo
(mean ± S.D)p-value Before intervention Q1 2.02 ± 0.91 1.80 ± 0.85 0.264 Q2 2.30 ± 0.79 2.17 ± 0.97 0.716 Q3 2.17 ± 0.81 2.43 ± 1.22 0.414 Q4 2.35 ± 1.12 2.32 ± 1.23 0.776 Q5 1.90 ± 1.00 1.97 ± 0.99 0.677 Total 10.75 ± 3.66 10.71 ± 4.51 0.994 After intervention Q1 2.62 ± 1.07 1.86 ± 0.85 < 0.001 Q2 2.77 ± 0.94 2.19 ± 0.98 < 0.001 Q3 2.67 ± 0.99 2.43 ± 1.22 < 0.001 Q4 2.82 ± 1.15 2.36 ± 1.21 < 0.001 Q5 3.07 ± 1.11 2.08 ± 1.02 < 0.001 Total 2.62 ± 1.07 10.95 ± 4.54 < 0.001 Difference ΔbQ1 0.60 ± 0.63 0.06 ± 0.24 < 0.001 ΔQ2 0.47 ± 0.59 0.02 ± 0.14 < 0.001 ΔQ3 0.50 ± 0.59 0.00 ± 0.00c < 0.001 ΔQ4 0.47 ± 0.59 0.04 ± 0.20 < 0.001 ΔQ5 1.17 ± 0.74 0.10 ± 0.31 < 0.001 ΔTotal 3.22 ± 2.42 0.23 ± 0.70 < 0.001 S.D, standard deviation..
Table 4 compares the mean IIEF-5 scores for diabetic and non-diabetic individuals before and after the intervention. The findings show a significant difference between the two groups (diabetic vs. non-diabetic) for every item. In particular, the IIEF-5 scores increased significantly among the non-diabetics in the herbal treatment group (p < 0.05). The overall difference in IIEF-5 scores between the herbal and placebo groups was 3.27 ± 2.45 and 0.11 ± 0.52, respectively (p < 0.05). However, the IIEF-5 scores among patients with diabetes in the herbal and placebo groups did not significantly differ. Furthermore, 16.3% of patients in the intervention group and 14.3% in the control group reported at least one side effect and the difference was not statistically significant (p = 0.779).
-
ΔQ = (Qafter intervention)– Qbefore intervention..
&md=tbl&idx=4' data-target="#file-modal"">Table 4p < 0.05 shows a statistical significant difference..
Comparison of the mean IIEF-5 score for diabetic and non-diabetic individuals before and after the intervention.
Diabetic type Item Herbal
(mean ± S.D)Placebo
(mean ± S.D)p-value Non-diabetic n 37 39 - ΔQ1 0.59 ± 0.64 0.02 ± 0.16 < 0.001 ΔQ2 0.48 ± 0.60 0.00 ± 0.00 < 0.001 ΔQ3 0.51 ± 0.60 0.00 ± 0.00 < 0.001 ΔQ4 0.48 ± 0.60 0.02 ± 0.16 < 0.001 ΔQ5 1.18 ± 0.73 0.05 ± 0.23 < 0.001 ΔTotal 3.27 ± 2.45 0.11 ± 0.52 < 0.001 Diabetic n 12 10 - ΔQ1 0.66 ± 0.57 0.20 ± 0.42 0.140 ΔQ2 0.33 ± 0.57 0.10 ± 0.31 0.345 ΔQ3 0.33 ± 0.57 0.00 ± 0.00 0.068 ΔQ4 0.33 ± 0.57 0.10 ± 0.31 0.345 ΔQ5 1.00 ± 1.00 0.30 ± 0.48 0.169 ΔTotal 2.66 ± 2.30 0.70 ± 1.05 0.140 ΔQ = (Qafter intervention)– Qbefore intervention..
p < 0.05 shows a statistical significant difference..
DISCUSSION
ED is a complex disorder primarily caused by reduced nitric oxide formation due to impaired neural and endothelial function of the corpus cavernosum of the penis [22]. However, there are other pathophysiological mechanisms, such as high blood pressure, androgen deficiency, arteriosclerosis, high cholesterol levels, diabetes mellitus, prostate diseases, and anatomical deformation of the penis [23, 24]. Due to the negative consequences associated with chemical and hormonal drugs, the use of medicinal herbs and natural bioactive components to treat and lessen the severity of ED has attracted attention in recent years [12]. In this study, we investigated the combined effect of
Kamenov et al. (2017) reported that TT at a standardized dose, with 250 mg of the saponin furostanol, taken for 12 weeks, improved sexual function in men with mild to moderate ED. Importantly, TT was well tolerated by patients with ED [35]. Gauthaman et al. (2008) showed that an intravenous administration of TT extract increased plasma testosterone, dihydrotestosterone, and dehydroepiandrosterone sulfate in primates. An oral administration of TT extract in rabbits and rats also increased dihydrotestosterone levels. Protodioscin, a saponin-like compound found in TT, may trigger testosterone synthesis by the Leydig cells [36]. Administering TT to rabbits results in a rise in cAMP and a relaxing effect on the corpus cavernosum, suggesting that TT affects the erectile process through the NOS pathway [37]. Moreover, Zhang et al. (2019) demonstrated a reparative effect of impure saponins on the endothelial function of a type 2 diabetes mouse model. Furthermore, gross saponins of
A meta-analysis previously reported that arginine supplementation substantially increased IIEF sub-domain scores of overall satisfaction, sexual satisfaction, orgasmic function, and erectile function [39]. Furthermore, L-arginine significantly improved their erectile performance [40].
CONCLUSION
In conclusion, the combination of
LIMITATIONS
In this study, the IIEF-5 questionnaire was used to measure erectile function, which may be regarded as unideal. In the future, to improve study quality, erectile function should be assessed by measuring plasma hormones, especially free testosterone, blood flow in the internal pondal artery using Doppler ultrasound, and blood pressure in the genitals using penile thermography, as well as nighttime swelling of the genitals via prostate ultrasound, especially in males, aged over 50 years old.
SUPPLEMENTARY MATERIALS
Supplementary data is available at https://doi.org/10.3831/KPI.2024.27.2.82.
ACKNOWLEDGEMENTS
This study was conducted using Highsense Barij® tablets manufactured by Barij Essence Company in Iran, and this company was supported all financial support.
CONFLICTS OF INTEREST
The authors declare no conflicts of interest in this work.
Fig 1.

-
Table 1 . Comparison of basic characteristics of the participants between the two groups before the intervention.
Variables Intervention group
(n = 49)Placebo group
(n = 49)p-value Age (year) (mean ± S.D) 51 ± 12.30 49.20 ± 10.63 0.439 Hypertension, n (%) Yes
No6 (12.2)
43 (87.8)7 (14.3)
42 (85.7)0.766 Diabetes, n (%) Yes
No12 (24.5)
37 (75.5)10 (20.4)
39 (79.6)0.628 Dyslipidemia, n (%) Yes
No2 (4.1)
47 (95.9)3 (6.1)
46 (93.9)0.695 Lower urinary tract diseases, n (%) Yes
No2 (4.1)
47 (95.9)1 (2)
48 (98)0.785 Drug abuse, n (%) Yes
No13 (26.5)
36 (73.5)11 (22.4)
38 (77.6)0.638 Reported Side effects, n (%) Yes
No8 (16.3)
41 (83.7)7 (14.3)
42 (85.7)0.779 p < 0.05 shows a statistical significant difference..
-
Table 2 . Comparison of mean IIEF-5 scores before and after the intervention within each group.
Item Herbal (mean ± S.D) Placebo (mean ± S.D) Before After p-value Before After p-value Q1 2.02 ± 0.91 2.62 ± 1.07 < 0.001 1.80 ± 0.85 1.86 ± 0.85 0.083 Q2 2.30 ± 0.79 2.77 ± 0.94 < 0.001 2.17 ± 0.97 2.19 ± 0.98 0.317 Q3 2.17 ± 0.81 2.67 ± 0.99 < 0.001 2.43 ± 1.22 2.43 ± 1.22 N.S Q4 2.35 ± 1.12 2.82 ± 1.15 < 0.001 2.32 ± 1.23 2.36 ± 1.21 0.157 Q5 1.90 ± 1.00 3.07 ± 1.11 < 0.001 1.97 ± 0.99 2.08 ± 1.02 0.25 Total 10.75 ± 3.66 13.97 ± 4.72 < 0.001 10.71 ± 4.51 10.95 ± 4.54 0.37 N.SM, not significant; S.D, standard deviation..
-
Table 3 . Comparison of mean IIEF-5 scores before and after the intervention between groups.
Time Item Herbal
(mean ± S.D)Placebo
(mean ± S.D)p-value Before intervention Q1 2.02 ± 0.91 1.80 ± 0.85 0.264 Q2 2.30 ± 0.79 2.17 ± 0.97 0.716 Q3 2.17 ± 0.81 2.43 ± 1.22 0.414 Q4 2.35 ± 1.12 2.32 ± 1.23 0.776 Q5 1.90 ± 1.00 1.97 ± 0.99 0.677 Total 10.75 ± 3.66 10.71 ± 4.51 0.994 After intervention Q1 2.62 ± 1.07 1.86 ± 0.85 < 0.001 Q2 2.77 ± 0.94 2.19 ± 0.98 < 0.001 Q3 2.67 ± 0.99 2.43 ± 1.22 < 0.001 Q4 2.82 ± 1.15 2.36 ± 1.21 < 0.001 Q5 3.07 ± 1.11 2.08 ± 1.02 < 0.001 Total 2.62 ± 1.07 10.95 ± 4.54 < 0.001 Difference ΔbQ1 0.60 ± 0.63 0.06 ± 0.24 < 0.001 ΔQ2 0.47 ± 0.59 0.02 ± 0.14 < 0.001 ΔQ3 0.50 ± 0.59 0.00 ± 0.00c < 0.001 ΔQ4 0.47 ± 0.59 0.04 ± 0.20 < 0.001 ΔQ5 1.17 ± 0.74 0.10 ± 0.31 < 0.001 ΔTotal 3.22 ± 2.42 0.23 ± 0.70 < 0.001 S.D, standard deviation..
-
Table 4 . Comparison of the mean IIEF-5 score for diabetic and non-diabetic individuals before and after the intervention.
Diabetic type Item Herbal
(mean ± S.D)Placebo
(mean ± S.D)p-value Non-diabetic n 37 39 - ΔQ1 0.59 ± 0.64 0.02 ± 0.16 < 0.001 ΔQ2 0.48 ± 0.60 0.00 ± 0.00 < 0.001 ΔQ3 0.51 ± 0.60 0.00 ± 0.00 < 0.001 ΔQ4 0.48 ± 0.60 0.02 ± 0.16 < 0.001 ΔQ5 1.18 ± 0.73 0.05 ± 0.23 < 0.001 ΔTotal 3.27 ± 2.45 0.11 ± 0.52 < 0.001 Diabetic n 12 10 - ΔQ1 0.66 ± 0.57 0.20 ± 0.42 0.140 ΔQ2 0.33 ± 0.57 0.10 ± 0.31 0.345 ΔQ3 0.33 ± 0.57 0.00 ± 0.00 0.068 ΔQ4 0.33 ± 0.57 0.10 ± 0.31 0.345 ΔQ5 1.00 ± 1.00 0.30 ± 0.48 0.169 ΔTotal 2.66 ± 2.30 0.70 ± 1.05 0.140 ΔQ = (Qafter intervention)– Qbefore intervention..
p < 0.05 shows a statistical significant difference..
References
- Adam DR, Alem MM. Erectile dysfunction: pharmacological pathways with understudied potentials. Biomedicines. 2022;11(1):46.
- Heruti R, Shochat T, Tekes-Manova D, Ashkenazi I, Justo D. Prevalence of erectile dysfunction among young adults: results of a large-scale survey. J Sex Med. 2004;1(3):284-91.
- Sin VJ, Anand GS, Koh HL. Botanical medicine and natural products used for erectile dysfunction. Sex Med Rev. 2021;9(4):568-92.
- Wang H, Zhao M, Zhang J, Yan B, Liu S, Zhao F, et al. The efficacy of acupuncture on patients with erectile dysfunction: a review. Evid Based Complement Alternat Med. 2022;2022:4807271.
- Shankhwar SN, Mahdi AA, Sharma AV, Pv K. A prospective clinical study of a prosexual nutrient: Nano Leo for evaluation of libido, erection, and orgasm in Indian men with erectile dysfunction. Evid Based Complement Alternat Med. 2020;2020:4598217.
- Sangiorgi G, Cereda A, Benedetto D, Bonanni M, Chiricolo G, Cota L, et al. Anatomy, pathophysiology, molecular mechanisms, and clinical management of erectile dysfunction in patients affected by coronary artery disease: a review. Biomedicines. 2021;9(4):432.
- Irwin GM. Erectile dysfunction. Prim Care. 2019;46(2):249-55.
- Castela Â, Costa C. Molecular mechanisms associated with diabetic endothelial-erectile dysfunction. Nat Rev Urol. 2016;13(5):266-74.
- Hatzimouratidis K, Salonia A, Adaikan G, Buvat J, Carrier S, El-Meliegy A, et al. Pharmacotherapy for erectile dysfunction: recommendations from the fourth International Consultation for Sexual Medicine (ICSM 2015). J Sex Med. 2016;13(4):465-88.
- Ückert S, Kuczyk MA, Oelke M. Phosphodiesterase inhibitors in clinical urology. Expert Rev Clin Pharmacol. 2013;6(3):323-32.
- Panahi Y, Akhavan A, Sahebkar A, Hosseini SM, Taghizadeh M, Akbari H, et al. Investigation of the effectiveness of Syzygium aromaticum, Lavandula angustifolia and Geranium robertianum essential oils in the treatment of acute external otitis: a comparative trial with ciprofloxacin. J Microbiol Immunol Infect. 2014;47(3):211-6.
- Masuku NP, Unuofin JO, Lebelo SL. Promising role of medicinal plants in the regulation and management of male erectile dysfunction. Biomed Pharmacother. 2020;130:110555.
- Chauhan NS, Sharma V, Dixit VK, Thakur M. A review on plants used for improvement of sexual performance and virility. Biomed Res Int. 2014;2014:868062.
- Taghizadeh M, Ostad SN, Asemi Z, Mahboubi M, Hejazi S, Sharafati-Chaleshtori R, et al. Sub-chronic oral toxicity of Cuminum cyminum L.'s essential oil in female Wistar rats. Regul Toxicol Pharmacol. 2017;88:138-43.
- Taghizadeh M, Farzin N, Taheri S, Mahlouji M, Akbari H, Karamali F, et al. The effect of dietary supplements containing green tea, capsaicin and ginger extracts on weight loss and metabolic profiles in overweight women: a randomized double-blind placebo-controlled clinical trial. Ann Nutr Metab. 2017;70(4):277-85.
- Zhang H, Abid S, Ahn JC, Mathiyalagan R, Kim YJ, Yang DC, et al. Characteristics of
Panax ginseng cultivars in Korea and China. Molecules. 2020;25(11):2635. - Kim JY, Lee HJ, Kim JS, Ryu JH. Induction of nitric oxide synthase by saponins of heat-processed ginseng. Biosci Biotechnol Biochem. 2005;69(5):891-5.
- Hossein M, Hossein A, Mohsen T, Jamileh J, Mohadese M, Mahnaz M. Evaluation of the effects of capsules containing Tribulus terrestris extract and L-carnitine on treatment of oligospermia in males. J Evol Med Dent Sci. 2018;7(29):3266-70.
- Gunarathne R, Nadeeshani H, Lu A, Li J, Zhang B, Ying T, et al. Potential nutraceutical use of
Tribulus terrestris L. in human health. Food Rev Int. 2022;39(8):5326-55. - Santos CA, Reis LO, Destro-Saade R, Luiza-Reis A, Fregonesi A. Tribulus terrestris versus placebo in the treatment of erectile dysfunction: a prospective, randomized, double blind study. Actas Urol Esp. 2014;38(4):244-8.
- Gagnier JJ, Boon H, Rochon P, Moher D, Barnes J, Bombardier C. Reporting randomized, controlled trials of herbal interventions: an elaborated CONSORT statement. Ann Intern Med. 2006;144(5):364-7.
- Zou H, Zhang X, Chen W, Tao Y, Li B, Liu H, et al. Vascular endothelium is the basic way for stem cells to treat erectile dysfunction: a bibliometric study. Cell Death Discov. 2023;9(1):143.
- Aversa A, Bruzziches R, Pili M, Spera G. Phosphodiesterase 5 inhibitors in the treatment of erectile dysfunction. Curr Pharm Des. 2006;12(27):3467-84.
- Papagiannopoulos D, Khare N, Nehra A. Evaluation of young men with organic erectile dysfunction. Asian J Androl. 2015;17(1):11-6.
- Jurys T, Burzynski B, Potyka A, Paradysz A. Post-radical prostatectomy erectile dysfunction assessed using the IIEF-5 questionnaire - a systematic literature review. Int J Sex Health. 2021;34(1):55-64.
- Su H, Lu Y, Ma C, Li H, Su X. Impact of atorvastatin on erectile dysfunction: a meta-analysis and systematic review. Andrologia. 2022;54(6):e14408.
- de Andrade E, de Mesquita AA, de Almeida Claro J, de Andrade PM, Ortiz V, Paranhos M, et al. Study of the efficacy of Korean Red Ginseng in the treatment of erectile dysfunction. Asian J Androl. 2007;9(2):241-4.
- Choi YD, Park CW, Jang J, Kim SH, Jeon HY, Kim WG, et al. Effects of Korean ginseng berry extract on sexual function in men with erectile dysfunction: a multicenter, placebo-controlled, double-blind clinical study. Int J Impot Res. 2013;25(2):45-50.
- Qi LW, Wang CZ, Yuan CS. Isolation and analysis of ginseng: advances and challenges. Nat Prod Rep. 2011;28(3):467-95.
- Yu J, Eto M, Akishita M, Kaneko A, Ouchi Y, Okabe T. Signaling pathway of nitric oxide production induced by ginsenoside Rb1 in human aortic endothelial cells: a possible involvement of androgen receptor. Biochem Biophys Res Commun. 2007;353(3):764-9.
- Leung KW, Cheng YK, Mak NK, Chan KK, Fan TP, Wong RN. Signaling pathway of ginsenoside-Rg1 leading to nitric oxide production in endothelial cells. FEBS Lett. 2006;580(13):3211-6.
- Wang X, Chu S, Qian T, Chen J, Zhang J. Ginsenoside Rg1 improves male copulatory behavior via nitric oxide/cyclic guanosine monophosphate pathway. J Sex Med. 2010;7(2 Pt 1):743-50.
- Kang YJ, Sohn JT, Chang KC. Relaxation of canine corporal smooth muscle relaxation by ginsenoside saponin Rg3 is independent from eNOS activation. Life Sci. 2005;77(1):74-84.
- Najafabadi BT, Jafarinia M, Ghamari K, Shokraee K, Tadayyon F, Akhondzadeh S. Vitamin E and ginseng combined supplement for treatment of male erectile dysfunction: a double-blind, placebo-controlled, randomized, clinical trial. Adv Integr Med. 2021;8(1):44-9.
- Kamenov Z, Fileva S, Kalinov K. Evaluation of the efficacy and safety of Tribulus terrestris in male sexual dysfunction - a prospective, randomized, double blinded, placebo-controlled clinical trial. Maturitas. 2015;81(1):P208.
- Gauthaman K, Ganesan AP. The hormonal effects of Tribulus terrestris and its role in the management of male erectile dysfunction--an evaluation using primates, rabbit and rat. Phytomedicine. 2008;15(1-2):44-54.
- Kam SC, Do JM, Choi JH, Jeon BT, Roh GS, Hyun JS. In vivo and in vitro animal investigation of the effect of a mixture of herbal extracts from Tribulus terrestris and Cornus officinalis on penile erection. J Sex Med. 2012;9(10):2544-51.
- Zhang H, Tong WT, Zhang CR, Li JL, Meng H, Yang HG, et al. Gross saponin of
Tribulus terrestris improves erectile dysfunction in type 2 diabetic rats by repairing the endothelial function of the penile corpus cavernosum. Diabetes Metab Syndr Obes. 2019;12:1705-1716. - Rhim HC, Kim MS, Park YJ, Choi WS, Park HK, Kim HG, et al. The potential role of arginine supplements on erectile dysfunction: a systemic review and meta-analysis. J Sex Med. 2019;16(2):223-34.
- Klotz T, Mathers MJ, Braun M, Bloch W, Engelmann U. Effectiveness of oral L-arginine in first-line treatment of erectile dysfunction in a controlled crossover study. Urol Int. 1999;63(4):220-3.