Next Article in Journal
Different Classes of Phytohormones Act Synergistically to Enhance the Growth, Lipid and DHA Biosynthetic Capacity of Aurantiochytrium sp. SW1
Previous Article in Journal
Cerebellar Cells Self-Assemble into Functional Organoids on Synthetic, Chemically Crosslinked ECM-Mimicking Peptide Hydrogels
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:

A Comprehensive Review of the Phytochemical, Pharmacological, and Toxicological Properties of Tribulus terrestris L.

Ruxandra Ștefănescu
Amelia Tero-Vescan
Ancuța Negroiu
Elena Aurică
1 and
Camil-Eugen Vari
Department of Pharmacognosy and Phytotherapy, Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540139 Targu Mures, Romania
Department of Biochemistry, Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540139 Targu Mures, Romania
Department of Pharmacology and Clinical Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540139 Targu Mures, Romania
Author to whom correspondence should be addressed.
Biomolecules 2020, 10(5), 752;
Submission received: 13 March 2020 / Revised: 2 May 2020 / Accepted: 5 May 2020 / Published: 12 May 2020


The general spread of Tribulus terrestris L. (South Africa, Australia, Europe, and India), the high content of active ingredients (in particular sterol saponins, as well as flavonoids, tannins, terpenoids, phenol carboxylic acids, and alkaloids), and its frequent uses in folk medicine, and as food supplements highlight the importance of evaluating its phytopharmacological properties. There are miscellaneous hypotheses that the species could have a high potential for the prevention and improvement of various human conditions such as infertility, low sexual desire, diabetes, and inflammatory diseases. Worldwide, numerous herbal supplements are commercialized with indications mostly to improve libido, sexual performance in both sexes, and athletic performance. Phytochemical studies have shown great disparities in the content of active substances (in particular the concentration of furostanol and spirostanol saponoside, considered to be the predominant active ingredients related to the therapeutic action). Thus, studies of experimental pharmacology (in vitro studies and animal models in vivo) and clinical pharmacology (efficacy and safety clinical trials) have sometimes led to divergent results; moreover, the presumed pharmacodynamic mechanisms have yet to be confirmed by molecular biology studies. Given the differences observed in the composition, the plant organ used to obtain the extract, the need for selective extraction methods which are targeted at the class of phytocompounds, and the standardization of T. terrestris extracts is an absolute necessity. This review aims to highlight the phytochemical, pharmacological, and toxicological properties of T. terrestris, with a focus on the contradictory results obtained by the studies conducted worldwide.

1. Introduction

Tribulus terrestris (TT) is a plant that grows especially in South Africa, Australia, India, and Europe. It is part of the Zygophyllaceae family, a widespread family with 25 genera and about 250 species. TT is a crawling herbal plant that generally grows in arid climates and sandy soils and grows up to one meter high. The name Tribulus comes from the Greek name “tribolos” which means spike fruit. The fruits are used in traditional Chinese medicine (TCM), in Ayurvedic medicine in India, and traditional medicine in Bulgaria for the treatment of different conditions [1]. In addition, the fruits have monographs in the Japanese Pharmacopoeia, 16th Ed. (2012), Korean Pharmacopoeia, 9th Ed. (2007), Pharmacopoeia of China (2005), and Siddha Pharmacopoeia India, Vol. 1 (2008) (taxonomy validated in Many compounds with a variety of biological properties and chemical structures have been identified in TT extract, especially steroidal saponins, flavonoids, tannins, terpenoids, polyphenol carboxylic acids, and alkaloids. The composition of TT extract depends on various factors such as the extraction method and whether roots, leaves, or fruits have been used.
Furthermore, the composition and biological activity of TT depends on growth conditions, including soil quality, but also the harvesting period [2]. As shown by Dinchev et al. [3], the highest content of saponins in the aerial parts was met during the preflowering and flowering periods. However, a correlation could not be found between the geographical and ecological conditions and the chemical composition. Nevertheless, remarkable variations (different concentrations in compounds as well as the absence of some compounds) were noticed between samples collected from the same country [4]. Worldwide, there are many pharmaceutical preparations and herbal supplements that contain extracts standardized in steroidal saponins. These are mainly indicated in libido disorders for both males and females, erectile dysfunction, and abnormal sperm motility, but data from the literature are somewhat controversial regarding the efficacy of TT extracts in such disorders [5]. Increased consumption of TT supplements has also been observed in athletes as they continually seek natural sources for boosting their performance.
Several reviews have been published in recent years. Table 1 comprises all the reviews related to TT found in the scientific literature.
This review presents the most important phytochemical and pharmacological data with an emphasis on the prominent information related to the chemical composition, pharmacological studies, mechanisms of action, and toxicological data.
The information on TT was compiled via an electronic search of the following major scientific databases: Science Direct, PubMed, Web of Science, and Scopus, from 2000 to 2020. Whenever the published data were relevant for the present review, the search was extended to 1982 (identification of compounds in different organs and toxicological reports). The query was supplemented by searching the reference lists of papers included in the first selection. The search terms were as follows: “Tribulus terrestris” alone or in combination with “chemistry”, “pharmacology”, “effects”, and “toxicity”. For this review, only full-text articles written in the English language were taken into consideration. Unpublished results or grey literature were not included and only pharmacological actions that demonstrated effects both in vitro and in vivo were discussed in the present review.

2. Chemical Composition

TT fruits contain important secondary metabolites such as saponins, polyphenolic compounds, and alkaloids. The steroidal saponins are mainly furostanol and spirostanol type (Figure 1). The furostanol saponins are believed to be biogenetic precursors of the spiro analogs. To date, over 70 different compounds have been identified in TT (Table 2).
Studies have revealed that the composition is strictly linked with the origin of the plant, and hence with climatic conditions.
Geographical regions significantly influence the composition of herbal drugs. Dinchev et al. [3] detected prototribestin only in the samples collected from Bulgaria, Turkey, Greece, Macedonia, Iran, and Serbia, but no protodioscin was detected in the samples collected from Vietnam and India. It appeared that this compound could be a marker for the European variety of TT [3]. Lazarova et al. [4] demonstrated that there were considerable differences between the samples collected from the same country; dioscin was not detected in some samples collected from Bulgaria, and the concentrations of the compounds also varied widely. The obtained result could be correlated with the methods used for extraction because furostanol bidesmosides were transformed into their spirostanol monodesmosides analogs during extraction. Lazarova et al. [4] performed the extraction by sonication for 15 min, using 50% aqueous acetonitrile as a solvent, but as shown by Sarvin et al. [18], a longer extraction time (60 min) gave a better yield. The β-Carboline indole alkaloids, i.e., harman, harmine, and harmalol were isolated from fruits, leaves, stems, and roots, but harmaline was only isolated from the roots, stem, and leaves [44]. As can be seen in Table 2, the concentration of protodioscin, prototribestin, dioscin, tribestin, and tribulosin varies within very wide limits depending on the origin of the plant. Differences are noticed between the different organs of the plant. These significant variations in TT composition explain the opposite pharmacological effects obtained in the performed studies. In Figure 2 are presented the chemical structures of the main compounds found in TT, other than the steroidal compounds.

3. Pharmacological Properties

3.1. Pharmacokinetic Properties of TT Main Compounds

Protodioscin is the dominant component in TT fruits and is considered to be the main pharmacologically active steroidal saponin [3]. Studies regarding the pharmacokinetic characteristics of protodioscin have contradictory results. For example, a recent study published by Zhang et al. [52] concluded that protodioscin had low bioavailability in vivo. However, the same group of authors has shown that after the administration of an extract from Dioscorea, the pharmacokinetic profile of protodioscin revealed good bioavailability [53]. Despite multiple in vivo studies with TT, very little is known about the pharmacokinetics of the therapeutically active compounds. There are, however, pharmacokinetic studies for protodioscin and dioscin after the administration of different Dioscorea sp. extracts [53,54]. Saponins, due to their amphiphilic molecule, have membrane permeabilizing properties, thus, they could increase the absorption of other compounds. This property is of great importance because toxic effects could appear in patients with multiple conditions who undergo chronic treatments.

3.2. Antioxidant Activity

Production of reactive oxygen species (ROS) in the body and their correlation with the incidence of chronic diseases has been largely described in the scientific literature and is already a fact.
TT extracts contain flavonoids and polyphenol carboxylic acids. The antioxidant activity of these compounds has been convincingly confirmed, based on their ability to donate hydrogen. Polyphenols are capable of scavenging hydroxyl (HO), peroxyl (RO2), and superoxide (O2•−) radicals [55].
Nevertheless, the effect of flavonoids varies and is strictly linked to their chemical characteristics and functional groups. Lower scavenging effects were noticed on singlet oxygen, and only for flavonones and phenolic acids [56]. In vitro determinations have proven that TT extracts have antioxidant activity determined using DPPH, ABTS, and FRAP methods. The reported concentration of polyphenols ranges from 0.6% to 3% and the content in flavonoids ranges from 0.04% to 0.5% [57,58]. It has been shown that when fractionated extracts were tested for their antioxidant activity, the ethyl acetate fraction had the strongest DPPH free radical scavenging activity, and the responsible compounds from this fraction were 4,5-di-p-cis-coumaroylquinic acid, and 4,5-di-p-trans-coumaroylquinic acid [27].
Dutt-Roy et al. [59] observed in an in vivo study that the treatment with TT extracts (part of the plant not specified, ethanol extraction, origin India) increased the activities of catalase and superoxide dismutase, and decreased the malondialdehyde (MDA) concentration. These effects were noticed in diabetic rats and in rats with depression induced by para-chlorophenylalanine (a selective and irreversible inhibitor of tryptophan hydroxylase) [59]. Catalase breaks down hydrogen peroxide (H2O2) to water and oxygen, and it has an essential role in the protection of cells from ROS. Superoxide dismutase catalyzes the transformation of superoxide anion free radical (O2) into oxygen (O2) and H2O2 [60]. MDA is a marker of oxidative stress and is one of the final products of polyunsaturated fatty acids (PUFAs) peroxidation [61].
Studies have shown that STZ-induced diabetes increased oxidative stress, and apparently, TT extracts (plant origin UAE, 70% ethanolic extract) were capable of modulating oxidative stress markers (MDA and GSH) [62].

3.3. Sexual Disorders

On the basis of the widespread societal presumption that natural compounds are active in erectile dysfunction, but lack the side effects specific to compounds obtained by chemical synthesis (e.g., phosphodiesterase-5 inhibitors such as sildenafil, tadalafil, etc.), they are often preferred and used for extended periods. Various products containing TT extracts are widely utilized for this purpose, mainly due to the advertising of supplements for professional athletes, based on the alleged effect of testosterone boosting. Existing data in the literature, resulting from in vitro experiments, by analyzing animal models (preclinical studies) and evaluating endpoints from clinical trials on subjects with erectile dysfunction are presented below.

3.3.1. In Vitro Experiments

The main objective of in vitro studies was to evaluate the quality of semen (morphology and viability). In vitro incubation of human spermatozoa with TT extract (origin Iran, part of the plant used not specified, extraction with water) had a beneficial effect on motility and viability. These findings suggest that TT extracts could be further used in the preparation of spermatozoa before in vitro fertilization [63]. An organ bath study of the corpus cavernosum (CC) from rabbits showed that TT extract (origin Korea) produced a concentration-dependent relaxation response. The authors suggested that because the location of action was in the endothelium, the relaxation effect appeared via the NOS pathway [64].

3.3.2. Preclinical Experimental Studies (Animal Models)

Preclinical studies have focused on animal models of human diseases that affect spermatogenesis and androgen secretion (cytotoxic medication that affects the gonads, castration, and diabetes); the effect of TT extracts on spermatogenesis and gonadal steroidogenesis in healthy male subjects, whether or not subjected to standardized physical exertion has also been evaluated.
In adult male Swiss albino mice with reproductive damage induced by cyclophosphamide, TT showed an improvement of epididymal sperm characteristics (motility) and an increase in testosterone levels as compared with the control group [65]. Extracts with TT administered to trained rats (fruit extract, China >70% saponins), diabetic rats (seed extract, Iran), healthy male rats (flowers, Iran) led to a significant increase in testosterone levels as compared with the control [66,67,68]. In healthy Wistar rats, a 70-day supplementation with TT extract influenced spermatogenesis, as shown by the changes in the tubular compartment of the testes (increase in the total tube length, tubular volume, and height of the seminiferous epithelium) [69]. In healthy male rats, a significantly increased testosterone level was confirmed as compared with the control group and positive effects on sexual parameters [68]. The TT extracts (origin Bulgaria) improved sexual behavior in castrated rats (mount frequency, intromission frequency, mount latency, intromission latency, ejaculation latency, and post-ejaculatory interval) [70].

3.3.3. Clinical Trials

The analysis of available clinical trials on the effectiveness of TT extracts in men highlights two categories of primary endpoints as follows: Some studies set as their main goal the evaluation of efficacy in erectile dysfunction (erection quality and libido intensity) and others evaluated the change in the basal secretion of testosterone at the end of the study with the initial values of the subjects serving as the control. However, the available studies did not shed light on the controversy regarding the real efficacy of TT. On the one hand, due to the divergent results (when the quantified parameter could be determined accurately such as testosterone and dihydrotestosterone, pituitary gonadotropin levels, etc.); on the other hand, due to the subjective evaluation (especially if the endpoints were based on the self-evaluation of the subjects’ standardized questionnaires such as the International Index of Erectile Function (IIEF), Questionnaire and Global Efficacy Question (GEQ).
Recently, Kamenov et al. [71] evaluated the efficacy and safety of a standardized extract (Tribestan®, Sopharma AD-coated tablets containing 250 mg of dry extract equivalent to furostanol saponins not less than 112.5 mg) for the treatment of men with mild to moderate erectile dysfunction and with or without hypoactive sexual desire disorder in a prospective, phase IV, randomized, double-blind, placebo controlled clinical trial in parallel groups. The characteristics of the study can be summarized as follows: dose of three coated tablets per day; sample size of 90 subjects in each group (treated vs. placebo); duration of 12 weeks; primary endpoint, the change in IIEF score at the end of the treatment. The authors showed a significant improvement in erection, libido, and orgasmic function in the treated group, in the absence of any difference in the profile of side effects as compared with the placebo [71].
Santos et al. [72] conducted a prospective, randomized, double-blind study on patients with erectile dysfunction. The treated group received 400 mg of TT extract. There were no significant differences noticed between the placebo and the treated group. The origin of the plant or the method of extraction were not specified.
In contrast to these data, two studies confirmed the beneficial effects after treatment with pharmaceutical products containing TT and other components. The first study showed that after 20 days of supplementation with the dietary supplement “Tribulus”, anaerobic muscle power and serum testosterone increased significantly in young men [73]. The other double-blind placebo controlled study in older men with a history of erectile dysfunction and lower levels of total and free testosterone showed high efficacy of a preparation containing TT. The product, called “Tradamixin”, consisted of TT, Alga Eckonia, D-glucosamine, and N-acetyl-glucosamine, was given daily for two months, and improved libido in elderly men and increased testosterone. It should be noted, however, that in both experiments, there was no certainty that a particular component would have caused those biological benefits or if TT contributed to those effects [74].
In a study conducted on male boxers, the administration of a TT supplement (with >40% saponins) produced no effect on plasma testosterone and dihydrotestosterone. Although the results were inconclusive, the authors suggested that a possible mechanism of action for TT compounds could be related to insulin-like growth factor (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP-3). IGF-1 is a growth hormone that showed the capacity of elevating skeletal muscles and preventing age-related loss of muscle mass [35].
Additionally, IGF improves insulin signaling, which could explain the beneficial effects obtained with TT extracts in diabetes, but the exact mechanism of action is not fully known [75].
The booster effects of TT extracts have been confirmed by some authors, both in experimental research and in clinical studies, as shown above, but are questioned by others. The available data on the mechanisms underlying the use in sexual disorders can be summarized as follows (Figure 3): steroidal saponins from TT increase the endogenous testosterone levels, due to an indirect action, i.e., the LH-type action of the steroidal saponosides or a weak androgenic agonist type action [13], but these mechanisms are denied by others [76,77]. Luteinizing hormone (LH) regulates the expression of 17β-hydroxysteroid dehydrogenase, which is the enzyme that transforms androstenedione into testosterone [78]. In addition, the antioxidant effect could contribute to the booster action of TT, knowing that oxidative stress is linked to endothelial dysfunction. Nitric oxide mediates the formation of cyclic guanosine monophosphate (cGMP); this mechanism could promote erection by vasodilation and increased blood supply to the corpora cavernosa [64,79]. In oxidative stress, the reactive oxygen species and advanced end glycation products react with nitric oxide in the vasculature forming reactive nitrogen species, contributing to the pathogenesis of erectile dysfunction [80]. Furthermore, different studies have shown that TT extracts are efficient in women with sexual disorders by having a favorable action in clinical trials on hypoactive sexual desire in women, as well as in the control of menopausal transition symptoms [81,82,83].
Given the testosterone boosting action of the extract, research has been performed to evaluate if the consumption of TT extracts could influence the doping tests of athletes regarding the urinary testosterone/epitestosterone TS/ET ratio limit of 4:1 (World Anti-Doping Agency) [84].
The in vitro and in vivo studies are briefly presented in Table 3, where pharmacological actions related to sexual disorders have been evaluated.

3.4. Antibacterial Activity

There are several in vitro studies that have revealed the antibacterial potency of TT total or fractionated extracts on Gram-negative and Gram-positive bacterial strains. Among the Gram-positive bacteria, facultative anaerobe strains such as Staphylococcus aureus, Streptoccocus mutans, Streptococcus sanguinis, Actinomyces viscosus, Enteroccocus faecalis, and Bacillus subtilis were susceptible and among the Gram-negative bacteria Escherichia coli, Salmonella typhi, Proteus mirabilis, and Klebsiella pneumoniae were susceptible [87,88,89,90,91,92]. It is still unclear which components are responsible for the antibacterial activity, but alkaloids contribute to the general antibacterial effect of the total extracts [88]. The antibacterial effects of saponins are well documented and the mechanism of action is based on the destruction of the cell membrane, leading to cell death (bactericidal effect), probably due to their amphiphilic nature and their surfactant properties. In addition, it was noticed that saponins could modulate ion channels, influencing the membrane potential [93,94]. Kianbakht and Jahaniani [92] found that the antibacterial activity of extract from TT roots was lower than the activity of the extracts obtained from the fruits and stems plus leaves. Although the authors did not provide a phytochemical profile of the extracts, we have shown in Table 2 that furostanol and spirostanol saponins were mainly identified and quantified in the aerial parts of TT rather than in the roots. However, alkaloids were identified in all organs. These results suggest that the antibacterial activity of TT is correlated mostly with the saponin content. Flavonoid fractions from TT leaves and fruits have also been proven to have antibacterial activity against E. coli, Salmonella, Staphylococcus aureus, and Streptococcus [39,40].
A recently published paper demonstrated the quorum quenching activity of TT (origin India) root extracts on Chromobacterium violaceum, Serratia marcescens, and Pseudomonas aeruginosa strains. The main compound was found to be ß-1, 5-O-dibenzoyl ribofuranose [51].

3.5. Antihyperglycemic Effect

3.5.1. In Vitro Determinations

Studies conducted with extracts from TT have been shown to inhibit the activity of alpha-glucosidase and alpha-amylase in vitro. Alpha-glucosidase and alpha-amylase are enzymes involved in the hydrolysis of carbohydrates. Alpha-amylase breaks down the oligosaccharides into disaccharides and alpha-glucosidase breaks down the disaccharides into absorbable monosaccharides. Inhibition of the activity of these enzymes has been proven to reduce postprandial hyperglycemia in diabetic patients. The TT extracts exhibited a relatively higher inhibition capacity on alpha-amylase than on that of alpha-glucosidase [95]. The activity of the total extract was higher than the activity of isolated saponin, meaning that there are other constituents in the TT extract that act synergistically. As reported by Song et al., cinnamic acid amides also have the capacity to inhibit the activity of alpha-glucosidase [36]. Ponnusamy et al. [96] concluded that TT had a lower capacity of inhibition of the activity of alpha-glucosidase as compared with other extracts.

3.5.2. Preclinical Studies

In vivo animal studies are in concordance with the in vitro studies, as it was shown that the saponins from TT administered to rats were able to delay the postprandial hyperglycemia by inhibiting alpha-glucosidase [97]. Studies on diabetic rats and glucose-loaded rabbits have shown that TT extracts are also capable of reducing fasting blood glucose levels, which suggests that the active compounds have multiple mechanisms of action [98,99,100]. Although the majority of the preclinical research for TT extracts was conducted on diabetic rats in order to evaluate the effect on different complications caused by diabetes, mostly related to sexual disorders, all studies reported the antihyperglycemic effect of TT extracts [67,85,86]. Diosgenin was shown to promote insulin secretion and influence beta cell regeneration in STZ-induced diabetes in rats through PPARγ activation in adipose tissue and oxidative stress modulation [101,102]. Stimulation of PPARγ nuclear receptors as a likely mechanism of the antihyperglycemic effect of diosgenin could explain the insulin-sensitizing action by altering the free fatty acid/glucose ratio by facilitating their intracellular uptake into muscle and adipose tissue. Intracellular uptake of both glucose and free fatty acids could be the consequence of stimulating the expression of GLUT-4 (glucose transporter 4) and CD36 (cluster of differentiation 36 or fatty acid translocase) as a result of PPARγ receptor activation (Figure 4).
Alkaloids could act synergistically with the steroidal saponins, as it was shown that imidazolidine derivatives stimulate insulin secretion by activation of imidazoline receptor type 3 binding sites in the pancreatic beta cells [103].

3.5.3. Clinical Studies

Samani et al. [104] conducted a double-blind, randomized placebo controlled clinical trial that included ninety-eight women. The study concluded that TT extract significantly lowered the blood glucose level of diabetic patients as compared with the placebo group. Another study conducted by Ramteke et al. [105] included 100 patients with diabetes mellitus and microalbuminuria. The results showed that the group treated with an ayurvedic preparation that contained TT had significantly lower blood glucose after the treatment as compared with the initial blood glucose level and the microalbuminuria was also reduced.
Recent research suggests that there is a correlation between testosterone levels and type 2 diabetes and that low testosterone levels in men predict a high risk of type 2 diabetes [106]. The direct and indirect androgenic action of TT extracts could also contribute to the improvement in the glycemic profile of diabetic patients, as it is known that androgens increase carbohydrate tolerance and promote glycogenesis [107].
Table 4 summarizes the most relevant results obtained in pharmacological studies related to the antihyperglycemic effect of TT.

3.6. Anti-Inflammatory Properties

3.6.1. In Vitro Studies

Several studies have demonstrated that extracts of TT have anti-inflammatory activities. The primary mechanisms involved are thought to be downregulation of inflammatory pathway protein NFκB [46]. The extract used was standardized in tribulusterine (aqueous extract with 0.54 mg% tribulusterine, origin India, part of the plant used not specified). Because the protein NFκB is also a mediator of cell cycle and cell survival, it has been shown that TT extracts can induce apoptosis in human liver cancer cells by inhibiting the NFκB signaling pathway (aqueous extract from fruits, origin Korea) [108]. Research has also shown that the extracts have an anti-inflammatory effect even in the topical application by affecting modulation of the calcium channels Orai-1 and TRPV3, as well as by inhibiting mast cell activation (ethanolic extract from fruits, origin Korea) [43]. The only compound identified in TT extract was rutin. Lee et al. [48] assessed the anti-inflammatory effects of tribulusamide D isolated from the fruits of TT in an in vitro study (origin Korea). They suggested that the effect occurred through the downregulation of enzymes responsible for the production of cytokines and inflammatory mediators. Hong et al. [109], demonstrated that TT fruits extract (origin Korea) inhibited the COX-2 activity. Other in vitro studies have shown that TT extracts have anti-inflammatory effects [39,110].

3.6.2. In Vivo Studies

Animal experiments have confirmed the anti-inflammatory effects demonstrated in vitro. Mohammed et al. [111] showed that the methanolic extract from the aerial parts of TT (origin Sudan) and the chloroformic fraction had significant anti-inflammatory effects in rat paw edema induced with carrageenan as compared with the untreated group. The anti-inflammatory effect of a flavonoid fraction from TT leaves was also evaluated in an ear swelling model induced by xylene in mice. The study demonstrated that the flavonoid fraction reduced the swelling degree in a dose-dependent manner [39]. Qiu et al. [112] tested terrestrosin D on bleomycin-induced inflammation in mice. They concluded that TT administration suppressed the inflammatory and fibrotic changes induced by bleomycin in the lungs.

3.7. Action on the Central Nervous System

The β-Carboline indole alkaloids are known to be monoamine oxidase inhibitors (MAOIs), primarily MAO-A, as they prevent biogenic amine from binding to the active site of the MAO molecule and undergoing deamination. Consequently, their presence in TT is thought to have been responsible for the unusual locomotory disturbance in sheep that grazed in areas with TT [45,113]. If this action is maintained in humans, special precautions should be taken in patients under treatment with monoamine oxidase inhibitors.
In several studies, the neuroprotective effect has been demonstrated and several mechanisms of action have been proposed. Chaudary et al. [114] demonstrated the neuroprotective effect of TT extracts (fruits part of the plant, origin Pakistan) in aluminum chloride-induced Alzheimer’s disease in rats. Biochemical and behavioral parameters improvement were connected with the antioxidant activity of the extract and also with the chelating properties of flavonoids. Song et al. [115] evaluated the anticonvulsant effect of protodioscin on a pilocarpine-induced convulsion model in mice and suggested that the effect was modulated through the GABAergic system.
Part of the previously mentioned effects of TT extracts is mediated through the central nervous system, and therefore are not included in the present section. These include the modulation of pituitary gonadotropin secretion. The toxic effects observed in sheep also involve the modulation of the GABAergic and dopaminergic system and are further presented.

3.8. Toxicological Studies

3.8.1. In Vitro Studies

Evaluation of toxicological effects in vitro has demonstrated that TT extracts (part of the plant not specified, origin Turkey) have estrogenic and genotoxic effects [116].

3.8.2. Preclinical Experimental Studies (Animal Models)

Hepatogenous photosensitivity appeared after 11 days in sheep fed with a mixture of TT and alfalfa (Medicago sativa). The symptoms included depression, jaundice, weight loss, conjunctivitis, and also the reddening of the muzzle, nose, ears, and eyelids [117]. The study conducted by Gandhi et al. [118], on diabetic rats, was inconclusive with respect to the nephrotoxic effects of TT extract (50 mg hydroalcoholic extract/kg with 45% saponins). Although an improvement in kidney function was expected after the treatment, no improvement was noticed [118]. Bourke [119] reported that a specific, irreversible, asymmetrical locomotor disorder appeared in sheep that ingested large quantities of TT. Administration of levodopa to the affected and nonaffected sheep, followed by the removal of the striatum and the quantification of dopamine and 3,4-dihydroxyphenylacetic acid, led the author to the conclusion that chronic intake of large quantities of TT caused a malfunction of the striatal presynaptic receptor, affecting the nigrostriatal pathway. The same author, along with other scientists, continued the research in this field and indicated harmane and norharmane as two possible neurotoxins [45].
Acute and subacute toxicity tests were performed by Hemalatha and Hari [120] with butanolic extract from TT fruits (origin India). No signs of significant toxicity were noticed. Also, El-Shaibany et al. [100] concluded that there were no toxic symptoms, deaths or behavioral changes in an acute toxicity study in rabbits treated with TT aerial parts extract (origin Yemen).

3.8.3. Case Reports

Talasaz et al. [121] reported a severe case of nephrotoxicity in a 28-year-old man, after the consumption of TT water. There is also a published case presentation in which a 36-year-old man, who consumed a herbal supplement based on a TT extract, was diagnosed with a 72-hour priapism [122]. It was presumed that the priapism was caused by TT supplement, and no further analysis of the supplement was performed; therefore, a pertinent conclusion cannot be drawn regarding this side effect, i.e., if it was caused by the extract found in the supplement or by an unknown compound with which the supplement was impurified. Another reported case of toxicity caused by consumption of TT supplements was that of a 30-year-old male, diagnosed with hyperbilirubinemia, cholestasis, and bilirubin-induced toxic acute tubular necrosis [123]. As in the previous case, the analysis of the supplement was not performed.
The toxicity of TT extracts has not been fully evaluated, and the toxic compounds have not been properly identified.
With respect to the reported cases of toxicity, no clinical trial in which TT-based products were administered, have reported these side effects. Particular attention should be given to the herbal supplements, and an elaborate analysis should be performed in order to identify the toxic compounds. There is a constant risk of adulteration of food supplements, primarily when these are used for their anabolic effects. There is also the possibility of trace metal accumulation in herbal drugs. A single research article was found that analyzed the content of some essential and trace elements in TT organs [124]. Although the results did not indicate toxic concentrations in the samples, a routine analysis of these elements should be performed for the food supplements. Antinutritional factors (hydrocyanic acid, phytate, nitrate, and oxalate) in TT leaves were also identified [125]. Seven compounds (listed in Table 5) from TT have a toxicological profile in the U.S. National Library of Medicine [126]. Harmine was the only compound found to have a complete toxicological profile. Effects of toxic doses are tremor, sleepiness, nausea or vomiting (man), excitement, mydriasis, dyspnea and ataxia (rabbit), and excitements (mouse).
Considering all of the above information, a complete analysis of the supplements should be performed when a toxicity case is reported.

4. Conclusions

Different phytochemical profiles of the herbal drugs from TT, highlighted both in the concentration of the main active compounds and in the absence of some active compounds, explain the major differences in the therapeutic effects reported over the years in the literature. The main pharmacological research on TT has been focused on sexual disorders, but other important effects have been demonstrated in vitro and in vivo studies, i.e., anti-hyperglycaemic, anti-inflammatory, antioxidant, and antibacterial. Toxicological studies, although limited, have highlighted the risk of nephrotoxicity following the administration of TT supplements. However, additional studies are needed to determine some of the still unknown molecular mechanisms of action of the therapeutic active compounds found in Tribulus extracts. Although TT has been extensively researched, further studies are needed in order to clarify important aspects such as a more accurate correlation between the phytochemical and pharmacological profiles, pharmacokinetic studies of the most important compounds, as well as the evaluation of possible pharmacokinetic and pharmacodynamic interactions with other compounds. Researchers should provide full information on the plant origin and the tested organ. Methods for standardization are necessary in order to achieve reproducible results. To date, it seems that the chemical compounds found in TT are capable of activating multiple pathways, hence, the various effects.

Author Contributions

Writing—original draft preparation, R.Ș., A.N., and E.A.; writing—review and editing, R.Ș., A.T.-V., and C.-E.V.; visualization, R.Ș., A.T.-V., and C.-E.V.; funding acquisition, R.Ș. All authors have read and agreed to the published version of the manuscript


This research was supported by a project funded by the Internal Research Grants of the University of Medicine and Pharmacy of Targu Mureş, Romania (grant contract for execution of research projects no. 15609/10/29.12.2017).


This research was supported by a project funded by the Internal Research Grants of the University of Medicine and Pharmacy of Targu Mureş, Romania (grant contract for execution of research projects no. 15609/10/29.12.2017). The authors would like to thank Mr. Adrian Naznean for the English language revision of the manuscript.

Conflicts of Interest

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.


  1. Pokrywka, A.; Obmiński, Z.; Malczewska-Lenczowska, J.; Fijałek, Z.; Turek-Lepa, E.; Grucza, R. Insights into Supplements with Tribulus Terrestris used by Athletes. J. Hum. Kinet. 2014, 41, 99–105. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  2. Neychev, V.; Mitev, V. Pro-sexual and androgen enhancing effects of Tribulus terrestris L.: Fact or Fiction. J. Ethnopharmacol. 2016, 179, 345–355. [Google Scholar] [CrossRef]
  3. Dinchev, D.; Janda, B.; Evstatieva, L.; Oleszek, W.; Aslani, M.R.; Kostova, I. Distribution of steroidal saponins in Tribulus terrestris from different geographical regions. Phytochemistry 2008, 69, 176–186. [Google Scholar] [CrossRef] [PubMed]
  4. Lazarova, I.; Ivanova, A.; Mechkarova, P.; Peev, D.; Valyovska, N. Intraspecific variability of biologically active compounds of different populations of Tribulus terrestris L. (Zygophyllaceae) in South Bulgaria. Biotechnol. Biotechnol. Equip. 2011, 25, 2352–2356. [Google Scholar] [CrossRef] [Green Version]
  5. GamalEl Din, S.F. Role of Tribulus terrestris in Male Infertility: Is It Real or Fiction? J. Diet. Suppl. 2018, 15, 1010–1013. [Google Scholar] [CrossRef]
  6. Kostova, I.; Dinchev, D. Saponins in Tribulus terrestris—Chemistry and bioactivity. Phytochem. Rev. 2005, 4, 111–137. [Google Scholar] [CrossRef]
  7. Hashim, S.; Bakht, T.; Bahadar Marwat, K.; Jan, A. Medicinal properties, phytochemistry and pharmacology of Tribulus terrestris L. (Zygophyllaceae). Pakistan J. Bot. 2014, 46, 399–404. [Google Scholar]
  8. Chhatre, S.; Nesari, T.; Kanchan, D.; Somani, G.; Sathaye, S. Phytopharmacological overview of Tribulus terrestris. Pharmacogn. Rev. 2014, 8, 45–51. [Google Scholar] [CrossRef] [Green Version]
  9. Yanala, S.R.; Sathyanarayana, D.; Kannan, K. A recent phytochemical review—Fruits of Tribulus terrestris linn. J. Pharm. Sci. Res. 2016, 8, 132–140. [Google Scholar]
  10. Sivapalan, S.R. Biological and pharmacological studies of Tribulus terrestris Linn- A review. Int. J. Multidiscip. Res. Dev. 2016, 3, 257–265. [Google Scholar]
  11. Zhu, W.; Du, Y.; Meng, H.; Dong, Y.; Li, L. A review of traditional pharmacological uses, phytochemistry, and pharmacological activities of Tribulus terrestris. Chem. Cent. J. 2017, 11, 1–16. [Google Scholar] [CrossRef] [Green Version]
  12. Azam, F.; Munier, S.; Abbas, G. A review on advancements in ethnomedicine and phytochemistry of Tribulus terrestris – a plant with multiple health benefits. Int. J. Biosci. 2019, 14, 21–37. [Google Scholar]
  13. Sanagoo, S.; Sadeghzadeh Oskouei, B.; Gassab Abdollahi, N.; Salehi-Pourmehr, H.; Hazhir, N.; Farshbaf-Khalili, A. Effect of Tribulus terrestris L. on sperm parameters in men with idiopathic infertility: A systematic review. Complement. Ther. Med. 2019, 42, 95–103. [Google Scholar] [CrossRef]
  14. Semerdjieva, I.B.; Zheljazkov, V.D. Chemical Constituents, Biological Properties, and Uses of Tribulus terrestris: A Review. Nat. Prod. Commun. 2019, 14, 1–26. [Google Scholar] [CrossRef] [Green Version]
  15. Meena, P.; Anand, A.; Vishal, K. A comprehensive overview of Gokshura (Tribulus terrestris Linn.). J. Ayurveda Integr. Med. Sci. 2019, 4, 205–211. [Google Scholar]
  16. De Combarieu, E.; Fuzzati, N.; Lovati, M.; Mercalli, E. Furostanol saponins from Tribulus terrestris. Fitoterapia 2003, 74, 583–591. [Google Scholar] [CrossRef]
  17. Ganzera, M.; Bedir, E.; Khan, I.A. Determination of steroidal saponins in Tribulus terrestris by reversed-phase high-performance liquid chromatography and evaporative light scattering detection. J. Pharm. Sci. 2001, 90, 1752–1758. [Google Scholar] [CrossRef]
  18. Sarvin, B.; Stekolshchikova, E.; Rodin, I.; Stavrianidi, A.; Shpigun, O. Optimization and comparison of different techniques for complete extraction of saponins from T. terrestris. J. Appl. Res. Med. Aromat. Plants 2018, 8, 75–82. [Google Scholar] [CrossRef]
  19. Kostova, I.; Dinchev, D.; Rentsch, G.H.; Dimitrov, V.; Ivanova, A. Two new sulfated furostanol saponins from Tribulus terrestris. Zeitschrift fur Naturforsch. - Sect. C J. Biosci. 2002, 57, 33–38. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  20. Huang, J.W.; Tan, C.H.; Jiang, S.H.; Zhu, D.Y. Terrestrinins A and B, two new steroid saponins from Tribulus terrestris. J. Asian Nat. Prod. Res. 2003, 5, 285–290. [Google Scholar] [CrossRef] [PubMed]
  21. Skhirtladze, A.; Nebieridze, V.; Benidze, M.; Kemertelidze, E.; Ganzera, M. Furostanol glycosides from the roots of Tribulus terrestris L. Bull. Georg. Natl. Acad. Sci. 2017, 11, 122–126. [Google Scholar]
  22. Zhang, C.; Wang, S.; Guo, F.; Ma, T.; Zhang, L.; Sun, L.; Wang, Y.; Zhang, X. Analysis of variations in the contents of steroidal saponins in Fructus Tribuli during stir-frying treatment. Biomed. Chromatogr. 2020, 34, e4794. [Google Scholar] [CrossRef] [PubMed]
  23. Zheng, W.; Wang, F.; Zhao, Y.; Sun, X.; Kang, L.; Fan, Z.; Qiao, L.; Yan, R.; Liu, S.; Ma, B. Rapid Characterization of Constituents in Tribulus terrestris from Different Habitats by UHPLC/Q-TOF MS. J. Am. Soc. Mass Spectrom. 2017, 28, 2302–2318. [Google Scholar] [CrossRef] [PubMed]
  24. Wang, Z.F.; Wang, B.B.; Zhao, Y.; Wang, F.X.; Sun, Y.; Guo, R.J.; Song, X.B.; Xin, H.L.; Sun, X.G. Furostanol and Spirostanol Saponins from Tribulus terrestris. Molecules 2016, 21, 429. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  25. Xu, Y.J.; Xu, T.H.; Liu, Y.; Xie, S.X.; Si, Y.S.; Xu, D.M. Two new steroidal glucosides from Tribulus terrestris L. J. Asian Nat. Prod. Res. 2009, 11, 548–553. [Google Scholar] [CrossRef]
  26. Bedir, E.; Khan, I.A. New steroidal glycosides from the fruits of Tribulus terrestris. J. Nat. Prod. 2000, 63, 1699–1701. [Google Scholar] [CrossRef]
  27. Hammoda, H.M.; Ghazy, N.M.; Harraz, F.M.; Radwan, M.M.; ElSohly, M.A.; Abdallah, I.I. Chemical constituents from Tribulus terrestris and screening of their antioxidant activity. Phytochemistry 2013, 92, 153–159. [Google Scholar] [CrossRef]
  28. Ivanova, A.; Serly, J.; Dinchev, D.; Ocsovszki, I.; Kostova, I.; Molnar, J. Screening of some saponins and phenolic components of Tribulus terrestris and Smilax excelsa as MDR modulators. In Vivo (Brooklyn). 2009, 23, 545–550. [Google Scholar]
  29. Miles, C.O.; Wilkins, A.L.; Munday, S.C.; Flåøyen, A.; Holland, P.T.; Smith, B.L. Identification of Insoluble Salts of the β-d-Glucuronides of Episarsasapogenin and Epismilagenin in the Bile of Lambs with Alveld and Examination of Narthecium ossifragum, Tribulus terrestris, and Panicum miliaceum for Sapogenins. J. Agric. Food Chem. 1993, 41, 914–917. [Google Scholar] [CrossRef]
  30. Burda, N.Y.; Zhuravel, I.O.; Dababneh, M.F.; Fedchenkova, Y.A. Analysis of diosgenin and phenol compounds in Tribulus terrestris L. Pharmacia 2019, 66, 41–44. [Google Scholar] [CrossRef]
  31. Vaidya, V.; Kondalkar, P.; Shinde, M.; Gotmare, S. HPTLC fingerprinting for simultaneous quantification of harmine, kaempferol, diosgenin and oleic acid in the fruit extract of Tribulus terrestris and its formulation. Int. J. Pharm. Sci. Res. 2018, 9, 3066–3074. [Google Scholar]
  32. Deepak, M.; Dipankar, G.; Prashanth, D.; Asha, M.K.; Amit, A.; Venkataraman, B.V. Tribulosin and β-sitosterol-D-glucoside, the anthelmintic principles of Tribulus terrestris. Phytomedicine 2002, 9, 753–756. [Google Scholar] [CrossRef] [PubMed]
  33. Xu, Y.X.; Chen, H.S.; Liu, W.Y.; Gu, Z.B.; Liang, H.Q. Two sapogenins from Tribulus terrestris. Phytochemistry 1998, 49, 199–201. [Google Scholar] [CrossRef]
  34. Wu, T.S.; Shi, L.S.; Kuo, S.C. Alkaloids and other constituents from Tribulus terrestris. Phytochemistry 1999, 50, 1411–1415. [Google Scholar] [CrossRef]
  35. Ma, Y.; Guo, Z.; Wang, X. Tribulus terrestris extracts alleviate muscle damage and promote anaerobic performance of trained male boxers and its mechanisms: Roles of androgen, IGF-1, and IGF binding protein-3. J. Sport Heal. Sci. 2017, 6, 474–481. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  36. Song, Y.H.; Kim, D.W.; Curtis-Long, M.J.; Park, C.; Son, M.; Kim, J.Y.; Yuk, H.J.; Lee, K.W.; Park, K.H. Cinnamic acid amides from Tribulus terrestris displaying uncompetitive a-glucosidase inhibition. Eur. J. Med. Chem. 2016, 114, 201–208. [Google Scholar] [CrossRef]
  37. Li, J.X.; Shi, Q.; Xiong, Q.B.; Prasain, J.K.; Tezuka, Y.; Hareyama, T.; Wang, Z.T.; Tanaka, K.; Namba, T.; Kadota, S. Tribulusamide A and B, new hepatoprotective lignanamides from the fruits of Tribulus terrestris: Indications of cytoprotective activity in murine hepatocyte culture. Planta Med. 1998, 64, 628–631. [Google Scholar] [CrossRef]
  38. Bhutani, S.P.; Chibber, S.S.; Seshadri, T.R. Flavonoids of the fruits and leaves of Tribulus terrestris: Constitution of tribuloside. Phytochemistry 1969, 8, 299–303. [Google Scholar] [CrossRef]
  39. Tian, C.; Chang, Y.; Zhang, Z.; Wang, H.; Xiao, S.; Cui, C.; Liu, M. Extraction technology, component analysis, antioxidant, antibacterial, analgesic and anti-inflammatory activities of flavonoids fraction from Tribulus terrestris L. leaves. Heliyon 2019, 5, e02234. [Google Scholar] [CrossRef] [Green Version]
  40. Tian, C.; Zhang, Z.; Wang, H.; Guo, Y.; Zhao, J.; Liu, M. Extraction technology, component analysis, and in vitro antioxidant and antibacterial activities of total flavonoids and fatty acids from Tribulus terrestris L. fruits. Biomed. Chromatogr. 2019, 33, 4. [Google Scholar] [CrossRef]
  41. Louveaux, A.; Jay, M.; Hadi, O.T.M.E.; Roux, G. Variability in flavonoid compounds of four Tribulus species: Does it play a role in their identification by desert locust Schistocerca gregaria? J. Chem. Ecol. 1998, 24, 1465–1481. [Google Scholar] [CrossRef]
  42. Kumar, A. Comparative and quantitative determination of quercetin and other flavonoids in North Indian populations of Tribulus terrestris Linn, by HPLC. Int. J. Pharma Bio Sci. 2012, 3, 69–79. [Google Scholar]
  43. Kang, S.Y.; Jung, H.W.; Nam, J.H.; Kim, W.K.; Kang, J.S.; Kim, Y.H.; Cho, C.W.; Cho, C.W.; Park, Y.K.; Bae, H.S. Effects of the Fruit Extract of Tribulus terrestris on Skin Inflammation in Mice with Oxazolone-Induced Atopic Dermatitis through Regulation of Calcium Channels, Orai-1 and TRPV3, and Mast Cell Activation. Evidence-based Complement. Altern. Med. 2017, 2017, 1–12. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  44. Tosun, F.; Tanker, M.; Tosun, A. Alkaloids of Tribulus terrestris L. Growing in Turkey. Fabad J. Pharm. Sci. 1994, 19, 149–151. [Google Scholar]
  45. Bourke, C.; Stevens, G.; Carrigan, M. Locomotor effects in sheep of alkaloids identified in Australian Tribulus terrestris. Aust. Vet. J. 1992, 69, 163–165. [Google Scholar] [CrossRef]
  46. Ranjithkumar, R.; Alhadidi, Q.; Shah, Z.A.; Ramanathan, M. Tribulusterine Containing Tribulus terrestris Extract Exhibited Neuroprotection Through Attenuating Stress Kinases Mediated Inflammatory Mechanism: In Vitro and In Vivo Studies. Neurochem. Res. 2019, 44, 1228–1242. [Google Scholar] [CrossRef]
  47. Ko, H.J.; Ahn, E.K.; Oh, J.S. N-trans-q-caffeoyl tyramine isolated from Tribulus terrestris exerts anti-inflammatory effects in lipopolysaccharide-stimulated RAW 264.7 cells. Int. J. Mol. Med. 2015, 36, 1042–1048. [Google Scholar] [CrossRef] [Green Version]
  48. Lee, H.H.; Ahn, E.K.; Hong, S.S.; Oh, J.S. Anti-inflammatory effect of Tribulusamide D isolated from Tribulus terrestris in lipopolysaccharide-stimulated RAW264.7 macrophages. Mol. Med. Rep. 2017, 16, 4421–4428. [Google Scholar] [CrossRef]
  49. Zhang, X.; Wei, N.; Huang, K.; Tan, Y.; Jin, D. A new feruloyl amide derivative from the fruits of Tribulus terrestris, Nat. Prod. Res. 2012, 26, 1922–1925. [Google Scholar] [CrossRef]
  50. Javaid, A.; Anjum, F.; Akhtar, N. Molecular Characterization of Pyricularia oryzae and its Management by Stem Extract of Tribulus terrestris. Int. J. Agric. Biol. 2019, 1256–1262. [Google Scholar]
  51. Vadakkan, K.; Vijayanand, S.; Hemapriya, J.; Gunasekaran, R. Quorum sensing inimical activity of Tribulus terrestris against gram negative bacterial pathogens by signalling interference. 3 Biotech 2019, 9, 1–6. [Google Scholar] [CrossRef] [PubMed]
  52. Zhang, X.; Guo, Z.; Li, J.; Ito, Y.; Sun, W.; Heart, N. A new quantitation method of protodioscin by HPLC–ESI-MS/MS in rat plasma and its application to the pharmacokinetic study. Steroids 2016, 106, 62–69. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  53. Zhang, X.; Li, J.; Ito, Y.; Sun, W. Simultaneous quantification of five steroid saponins from Dioscorea zingiberensis C.H.Wright in rat plasma by HPLC- MS/MS and its application to the pharmacokinetic studies. Steroids 2015, 1, 16–24. [Google Scholar]
  54. Tang, Y.N.; Pang, Y.X.; He, X.C.; Zhang, Y.Z.; Zhang, J.Y.; Zhao, Z.Z.; Yi, T.; Chen, H.B. UPLC-QTOF-MS identification of metabolites in rat biosamples after oral administration of Dioscorea saponins: A comparative study. J. Ethnopharmacol. 2015, 165, 127–140. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  55. Bors, W.; Heller, W.; Michel, C.; Saran, M. Flavonoids as antioxidants: Determination of radical-scavenging efficiencies. Methods Enzymol. 1990, 186, 343–355. [Google Scholar] [PubMed]
  56. Aboul-Enein, H.; Kruk, I.; Kladna, A.; Lichszteld, K.; Michalska, T. Scavenging effects of phenolic sompounds on reactive oxygen species. Biopolymers 2007, 86, 222–230. [Google Scholar] [CrossRef]
  57. Durgawale, P.P.; Datkhile, K.D. Study of Polyphenol Content and Anti- Oxidative Potential of Tribulus terrestris Dry Fruit Extract. Int. J. Pharmacogn. Phytochem. Res. 2017, 9, 716–721. [Google Scholar]
  58. Zheleva-Dimitrova, D.; Obreshkova, D.; Nedialkov, P. Antioxidant activity of Tribulus terrestris - a natural product in infertility therapy. Int. J. Pharm. Pharm. Sci. 2012, 4, 508–511. [Google Scholar]
  59. Dutt-Roy, R.; Kayalvizhi, E.; Chandrasekhar, M. Evaluation of the antidepressant activity of Tribulus terrestris in diabetic depression in rat model. Int. J. Pharm. Sci. Res. 2017, 8, 5392–5399. [Google Scholar]
  60. Pamela C., C.; Harvey, R.A.; Ferrier, D.R. Lippincott Biochimie Ilustrată; Ediția a 4; București: Editura Medicală Callisto: București, Romania, 2010. [Google Scholar]
  61. Marnett, L.J. Lipid peroxidation - DNA damage by malondialdehyde. Mutat. Res. 1999, 424, 83–95. [Google Scholar] [CrossRef]
  62. Amin, A.; Lotfy, M.; Shafiullah, M.; Adeghate, E. The protective effect of Tribulus terrestris in diabetes. Ann. N. Y. Acad. Sci. 2006, 1084, 391–401. [Google Scholar] [CrossRef] [PubMed]
  63. Khaleghi, S.; Bakhtiari, M.; Asadmobini, A.; Esmaeili, F. Tribulus terrestris Extract Improves Human Sperm Parameters In Vitro. J. Evidence-Based Complement. Altern. Med. 2017, 22, 407–412. [Google Scholar] [CrossRef] [PubMed]
  64. Kam, S.C.; Do, J.M.; Choi, J.H.; Jeon, B.T.; Roh, G.S.; Hyun, J.S. 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, 2544–2551. [Google Scholar] [CrossRef] [PubMed]
  65. Pavin, N.F.; Izaguirry, A.P.; Soares, M.B.; Spiazzi, C.C.; Mendez, A.S.L.; Leivas, F.G.; dos Santos Brum, D.; Cibin, F.W.S. Tribulus terrestris Protects against Male Reproductive Damage Induced by Cyclophosphamide in Mice. Oxid. Med. Cell. Longev. 2018, 2018, 1–9. [Google Scholar] [CrossRef] [Green Version]
  66. Yin, L.; Wang, Q.; Wang, X.; Song, L.-N. Effects of Tribulus terrestris saponins on exercise performance in overtraining rats and the underlying mechanisms. Can. J. Physiol. Pharmacol. 2016, 94, 1193–1201. [Google Scholar] [CrossRef]
  67. Ghanbari, A.; Moradi, M.; Raoofi, A.; Falahi, M.; Seydi, S. Tribulus terrestris Hydroalcoholic Extract Administration Effects on Reproductive Parameters and Serum Level of Glucose in Diabetic Male Rats. Int. J. Mophol. 2016, 34, 796–803. [Google Scholar] [CrossRef] [Green Version]
  68. Haghmorad, D.; Mahmoudi, M.B.; Haghighi, P.; Alidadiani, P.; Shahvazian, E.; Tavasolian, P.; Hosseini, M.; Mahmoudi, M. Improvement of fertility parameters with Tribulus Terrestris and Anacyclus Pyrethrum treatment in male rats. Int. Braz. J. Urol. 2019, 45, 1043–1054. [Google Scholar] [CrossRef]
  69. Oliveira, N.N.P.M.; Félix, M.A.R.; Pereira, T.C.S.; Rocha, L.G.P.; Miranda, J.R.; Zangeronimo, M.G.; Pinto, J.E.B.P.; Bertolucci, S.K.V.; Sousa, R.V.D. Sperm quality and testicular histomorphometry of wistar rats supplemented with extract and fractions of fruit of Tribulus terrestris L. Brazilian Arch. Biol. Technol. 2015, 58, 891–897. [Google Scholar] [CrossRef] [Green Version]
  70. Gauthaman, K.; Adaikan, P.G.; Prasad, R.N.V. Aphrodisiac properties of Tribulus Terrestris extract (Protodioscin) in normal and castrated rats. Life Sci. 2002, 71, 1385–1396. [Google Scholar] [CrossRef]
  71. Kamenov, Z.; Fileva, S.; Kalinov, K.; Jannini, E.A. Evaluation of the efficacy and safety of Tribulus terrestris in male sexual dysfunction—A prospective, randomized, double-blind, placebo-controlled clinical trial. Maturitas 2017, 99, 20–26. [Google Scholar] [CrossRef]
  72. Santos, C.A.; Reis, L.O.; 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, 244–248. [Google Scholar] [CrossRef] [PubMed]
  73. Milasius, K.; Dadeliene, R.; Skernevicius, J. The influence of the Tribulus terrestris extract on the parameters of the functional preparedness and athletes’ organism homeostasis. Fiziol. Zh. 2009, 55, 89–96. [Google Scholar] [PubMed]
  74. Iacono, F.; Prezioso, D.; Illiano, E.; Romeo, G.; Ruffo, A.; Amato, B. Sexual asthenia: Tradamixina versus Tadalafil 5 mg daily. BMC Surg. 2012, 12, S23. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  75. Aguirre, G.A.; Ita, J.R.; Garza, R.G.; Castilla-Cortazar, I. Insulin-like growth factor-1 deficiency and metabolic syndrome. J. Transl. Med. 2016, 14, 1–23. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  76. Neychev, V.K.; Mitev, V.I. The aphrodisiac herb Tribulus terrestris does not influence the androgen production in young men. J. Ethnopharmacol. 2005, 101, 319–323. [Google Scholar] [CrossRef] [PubMed]
  77. Rogerson, S.; Riches, C.J.; Jennings, C.; Weatherby, R.P.; Meir, R.A.; Marshall-Gradisnik, S.M. The effect of five weeks of Tribulus terrestris supplementation on muscle strength and body composition during preseason training in elite rugby league players. J. Strength Cond. Res. 2007, 21, 348–353. [Google Scholar]
  78. Banihani, S.A. Testosterone in males as enhanced by onion (Allium cepa l.). Biomolecules 2019, 9, 75. [Google Scholar] [CrossRef] [Green Version]
  79. Phillips, O.A.; Mathew, K.T.; Oriowo, M.A. Antihypertensive and vasodilator effects of methanolic and aqueous extracts of Tribulus terrestris in rats. J. Ethnopharmacol. 2006, 104, 351–355. [Google Scholar] [CrossRef]
  80. Malavige, L.; Levy, J. Erectile dysfunction and diabetes mellitus. J. Sex. Med. 2009, 6, 1232–1247. [Google Scholar] [CrossRef]
  81. Vale, F.B.C.; Zanolla Dias de Souza, K.; Rezende, C.R.; Geber, S. Efficacy of Tribulus Terrestris for the treatment of premenopausal women with hypoactive sexual desire disorder: A randomized double-blinded, placebo-controlled trial. Gynecol. Endocrinol. 2018, 34, 442–445. [Google Scholar] [CrossRef]
  82. Fatima, L.; Sultana, A. Efficacy of Tribulus terrestris L. (fruits) in menopausal transition symptoms: A randomized placebo controlled study. Adv. Integr. Med. 2017, 4, 56–65. [Google Scholar] [CrossRef]
  83. Akhtari, E.; Raisi, F.; Keshavarz, M.; Hosseini, H.; Sohrabvand, F.; Bioos, S.; Kamalinejad, M.; Ghobadi, A. Tribulus terrestris for treatment of sexual dysfunction in women: Randomized double-blind placebo—Controlled study. Daru 2014, 22, 40. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  84. World Anti-Doping Agency (WADA). Endogenous Anabolic Androgenic Steroids Measurement and Reporting. WADA Tech. Doc. – TD2016EAAS 2016, 1–16. [Google Scholar]
  85. Tag, H.; Abdelazek, H.; Mahoud, Y.; El-Shenawy, N. Efficay of Tribulus terrestris extract and metformin on fertility indices and oxidative stress of testicular tissue in streptozotocin-induced diabetic male rats. African J. Pharm. Pharmacol. 2015, 9, 861–874. [Google Scholar]
  86. Zhang, H.; Tong, W.T.; Zhang, C.R.; Li, J.L.; Meng, H.; Yang, H.G.; Chen, M. 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. Targets Ther. 2019, 12, 1705–1716. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  87. Mohammed, M.J. Biological Activity of Saponins Isolated from Tribulus terrestris ( Fruit ) on Growth of Some Bacteria. Tikrit J. Pure Sci. 2008, 13, 3. [Google Scholar]
  88. Jindal, A.; Kumar, P.; Gautam, K. Evaluation of antibiotic potential of alkaloids of Tribulus terrestris L. against some pathogenic microorganisms. Int. J. Green Pharm. 2013, 7, 102–105. [Google Scholar] [CrossRef]
  89. Soleimanpour, S.; Sedighinia, F.S.; Safipour Afshar, A.; Zarif, R.; Ghazvini, K. Antibacterial activity of Tribulus terrestris and its synergistic effect with Capsella bursa-pastoris and Glycyrrhiza glabra against oral pathogens: An in-vitro study. Avicenna J. phytomedicine 2015, 5, 210–217. [Google Scholar]
  90. Batoei, S.; Mahboubi, M.; Yari, R. Antibacterial activity of Tribulus terrestris methanol extract against clinical isolates of Escherichia coli. Herba Pol. 2016, 62, 57–66. [Google Scholar] [CrossRef] [Green Version]
  91. Recio, M.C.; Rios, J.L.; Villar, A. Antimicrobial activity of selected plants employed in the Spanish Mediterranean area. Part II. Phyther. Res. 1989, 3, 77–80. [Google Scholar] [CrossRef]
  92. Kianbakht, S.; Jahaniani, F. Evaluation of Antibacterial Activity of Tribulus terrestris L. Growing in Iran. Iran. J. Pharmacol. Ther. 2003, 2, 22–24. [Google Scholar]
  93. Böttger, S.; Hofmann, K.; Melzig, M.F. Saponins can perturb biologic membranes and reduce the surface tension of aqueous solutions: A correlation? Bioorganic Med. Chem. 2012, 20, 2822–2828. [Google Scholar] [CrossRef] [PubMed]
  94. Bangham, A.; Horne, R. Action of saponin on biological cell membranes. Nature 1962, 4858, 952–953. [Google Scholar] [CrossRef] [PubMed]
  95. Ercan, P.; El, S.N. Inhibitory effects of chickpea and Tribulus terrestris on lipase, alpha-amylase and alpha-glucosidase. Food Chem. 2016, 205, 163–169. [Google Scholar] [CrossRef] [PubMed]
  96. Ponnusamy, S.; Ravindran, R.; Zinjarde, S.; Bhargava, S.; Ravi Kumar, A. Evaluation of traditional Indian antidiabetic medicinal plants for human pancreatic amylase inhibitory effect in vitro. Evidence-based Complement. Altern. Med. 2011, 2011, 1–10. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  97. Zhang, S.; Qu, W.; Zhong, S. Inhibitory effects of saponins from Tribulus terrestris on alpha-glucosidase in small intestines of rats. Zhongguo Zhong Yao Za Zhi 2006, 31, 910–913. [Google Scholar]
  98. El-Tantawy, W.H.; Hassanin, L.A. Hypoglycemic and hypolipidemic effects of alcoholic extract of Tribulus alatus in streptozotocin-induced diabetic rats: A comparative study with T. terrestris (Caltrop). Indian J. Exp. Biol. 2007, 45, 785–790. [Google Scholar]
  99. Lamba, H.S.; Bhargava, C.S.; Thakur, M.; Bhargava, S. α-glucosidase and aldose reductase inhibitory activity in vitro and antidiabetic activity in vivo of Tribulus terrestris L. (dunal). Int. J. Pharm. Pharm. Sci. 2011, 3, 270–272. [Google Scholar]
  100. El-Shaibany, A.; Al-Habori, M.; Al-Tahami, B.; Al-Massarani, S. Anti-hyperglycaemic activity of Tribulus terrestris L aerial part extract in glucose-loaded normal rabbits. Trop. J. Pharm. Res. 2015, 14, 2263–2268. [Google Scholar] [CrossRef]
  101. Kalailingam, P.; Kannaian, B.; Tamilmani, E.; Kaliaperumal, R. Efficacy of natural diosgenin on cardiovascular risk, insulin secretion, and beta cells in streptozotocin (STZ)-induced diabetic rats. Phytomedicine 2014, 21, 1154–1161. [Google Scholar] [CrossRef]
  102. Tharaheswari, M.; Jayachandra Reddy, N.; Kumar, R.; Varshney, K.C.; Kannan, M.; Sudha Rani, S. Trigonelline and diosgenin attenuate ER stress, oxidative stress-mediated damage in pancreas and enhance adipose tissue PPARγ activity in type 2 diabetic rats. Mol. Cell. Biochem. 2014, 396, 161–174. [Google Scholar] [CrossRef] [PubMed]
  103. Soldatov, V.O.; Shmykova, E.A.; Pershina, M.A.; Ksenofontov, A.O.; Zamitsky, Y.M. Imidazoline receptors agonists: Possible mechanisms of endothelioprotection. Res. Results Pharmacol. 2018, 4, 11–19. [Google Scholar] [CrossRef]
  104. Samani, N.B.; Jokar, A.; Soveid, M.; Heydari, M.; Mosavat, S.H. Efficacy of the Hydroalcoholic Extract of Tribulus terrestris on the Serum Glucose and Lipid Profile of Women With Diabetes Mellitus: A Double-Blind Randomized Placebo-Controlled Clinical Trial. J. Evidence-Based Complement. Altern. Med. 2016, 21, NP91–NP97. [Google Scholar] [CrossRef] [PubMed]
  105. Ramteke, R.; Thakar, A.; Trivedi, A.; Patil, P. Clinical efficacy of Gokshura-Punarnava Basti in the management of microalbuminuria in diabetes mellitus. AYU (An Int. Q. J. Res. Ayurveda) 2012, 33, 537–541. [Google Scholar] [CrossRef]
  106. Karakas, M.; Schäfer, S.; Appelbaum, S.; Ojeda, F.; Kuulasmaa, K.; Brückmann, B.; Berisha, F.; Schulte-Steinberg, B.; Jousilahti, P.; Blankenberg, S.; et al. Testosterone levels and type 2 diabetes—No correlation with age, differential predictive value in men and women. Biomolecules 2018, 8, 76. [Google Scholar] [CrossRef] [Green Version]
  107. Navarro, G.; Allard, C.; Xu, W.; Mauvais-Jarvis, F. The role of androgens in metabolism, obesity, and diabetes in males and females. Obesity 2015, 23, 713–719. [Google Scholar] [CrossRef] [Green Version]
  108. Kim, H.J.; Kim, J.C.; Min, J.S.; Kim, M.J.; Kim, J.A.; Kor, M.H.; Yoo, H.S.; Ahn, J.K. Aqueous extract of Tribulus terrestris Linn induces cell growth arrest and apoptosis by down-regulating NF-κB signaling in liver cancer cells. J. Ethnopharmacol. 2011, 136, 197–203. [Google Scholar] [CrossRef]
  109. Hong, C.H.; Hur, S.K.; Oh, O.J.; Kim, S.S.; Nam, K.A.; Lee, S.K. Evaluation of natural products on inhibition of inducible cyclooxygenase (COX-2) and nitric oxide synthase (iNOS) in cultured mouse macrophage cells J. Ethnopharmacol. 2002, 83, 153–159. [Google Scholar] [CrossRef]
  110. Ghareeb, D.A.; ElAhwany, A.M.D.; El-Mallawany, S.M.; Saif, A.A. In vitro screening for anti-acetylcholiesterase, Anti-oxidant, Anti-glucosidase, Anti-inflammatory and anti-bacterial effect of three traditional medicinal plants. Biotechnol. Biotechnol. Equip. 2014, 28, 1155–1164. [Google Scholar] [CrossRef] [Green Version]
  111. Mohammed, M.S.; Alajmi, M.F.; Alam, P.; Khalid, H.S.; Mahmoud, A.M.; Ahmed, W.J. Chromatographic finger print analysis of anti-inflammatory active extract fractions of aerial parts of Tribulus terrestris by HPTLC technique. Asian Pac. J. Trop. Biomed. 2014, 4, 203–208. [Google Scholar] [CrossRef] [Green Version]
  112. Qiu, M.; An, M.; Bian, M.; Yu, S.; Liu, C.; Liu, Q. Terrestrosin D from Tribulus terrestris attenuates bleomycin-induced inflammation and suppresses fibrotic changes in the lungs of mice. Pharm. Biol. 2019, 57, 694–700. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  113. Bourke, C.A. Staggers in sheep associated with the ingestion of Tribulus terrestris. Aust. Vet. J. 1984, 61, 360–363. [Google Scholar] [CrossRef] [PubMed]
  114. Chauhdary, Z.; Saleem, U.; Ahmad, B.; Shah, S.; Shah, M.A. Neuroprotective evaluation of Tribulus terrestris L. In aluminum chloride induced Alzheimer’s disease. Pak. J. Pharm. Sci. 2019, 32, 805–816. [Google Scholar] [PubMed]
  115. Song, S.; Fajol, A.; Chen, Y.; Ren, B.; Shi, S. Anticonvulsive effects of protodioscin against pilocarpine-induced epilepsy. Eur. J. Pharmacol. 2018, 833, 237–246. [Google Scholar] [CrossRef]
  116. Abudayyak, M.; Jannuzzi, A.T.; Özhan, G.; Alpertunga, B. Investigation on the toxic potential of Tribulus terrestris in vitro. Pharm. Biol. 2015, 53, 469–476. [Google Scholar] [CrossRef] [Green Version]
  117. Aslani, M.; Movassaghi, A.; Mohri, M.; Pedram, M.; Abavisani, A. Experimental Tribulus terrestris poisoning in sheep: Clinical, laboratory and pathological findings. Vet. Res. Commun. 2003, 27, 53–62. [Google Scholar] [CrossRef]
  118. Gandhi, S.; Srinivasan, B.P.; Akarte, A.S. Potential nephrotoxic effects produced by steroidal saponins from hydro alcoholic extract of Tribulus terrestris in STZ-induced diabetic rats. Toxicol. Mech. Methods 2013, 23, 548–557. [Google Scholar] [CrossRef]
  119. Bourke, C.A. A novel nigrostriatal dopaminergic disorder in sheep affected by Tribulus terrestris staggers. Res. Vet. Sci. 1987, 43, 347–350. [Google Scholar] [CrossRef]
  120. Hemalatha, S.; Hari, R. Acute and subacute toxicity studies of the saponin rich butanol extracts of Tribulus terrestris fruits in wistar rats. Int. J. Pharm. Sci. Rev. Res. 2014, 27, 307–313. [Google Scholar]
  121. Talasaz, A.H.; Abbasi, M.R.; Abkhiz, S.; Dashti-Khavidaki, S. Tribulus terrestris-induced severe nephrotoxicity in a young healthy male. Nephrol. Dial. Transplant. 2010, 25, 3792–3793. [Google Scholar] [CrossRef]
  122. Campanelli, M.; De Thomasis, R.; Tenaglia, R.L. Priapism caused by “Tribulus terrestris”. Int. J. Impot. Res. 2015, 28, 39–40. [Google Scholar] [CrossRef] [PubMed]
  123. Ryan, M.; Lazar, I.; Nadasdy, G.M.; Nadasdy, T.; Satoskar, A.A. Acute kidney injury and hyperbilirubinemia in a young male after ingestion of Tribulus terrestris. Clin. Nephrol. 2015, 83, 177–183. [Google Scholar] [CrossRef] [PubMed]
  124. Selvaraju, R.; Thiruppathi, G.; Raman, R.G.; Dhakshanamoorthy, D. Estimation of Essential and Trace Elements in the Medicinal Plant Tribulus Terrestris By Icp-Oes and Flame Photometric Techniques. Rom. J. Biol. Plant Biol. 2015, 56, 65–75. [Google Scholar]
  125. Hassa, L.; Umar, K.; Umar, Z. Antinutritive factors in Tribulus terrestris (Linn.) leaves and predicted calcium and zinc bioavailability. J. Trop. Biosci. 2007, 7, 33–36. [Google Scholar]
  126. U.S. National Library of Medicine. Available online: (accessed on 23 April 2020).
Figure 1. Spirostanol (left) and furostanol (right) saponins.
Figure 1. Spirostanol (left) and furostanol (right) saponins.
Biomolecules 10 00752 g001
Figure 2. The most common compounds found in TT extracts.
Figure 2. The most common compounds found in TT extracts.
Biomolecules 10 00752 g002aBiomolecules 10 00752 g002b
Figure 3. The presumed mechanisms of action responsible for the effects of TT extracts in sexual disorders. GnRH, gonadotropin-releasing hormone; FSH, follicle-stimulating hormone; LH, luteinizing hormone; ITT, intratesticular testosterone; eNOS, endothelial nitric oxide synthase; NO, nitric oxide; sGC, soluble guanylate cyclase; and cGMP, cyclic guanosine monophosphate.
Figure 3. The presumed mechanisms of action responsible for the effects of TT extracts in sexual disorders. GnRH, gonadotropin-releasing hormone; FSH, follicle-stimulating hormone; LH, luteinizing hormone; ITT, intratesticular testosterone; eNOS, endothelial nitric oxide synthase; NO, nitric oxide; sGC, soluble guanylate cyclase; and cGMP, cyclic guanosine monophosphate.
Biomolecules 10 00752 g003
Figure 4. The presumed mechanism of diosgenin stimulation of PPARγ receptors. PPARγ, peroxisome proliferator-activated receptor gamma; DNA, deoxyribonucleic acid; mRNA, messenger ribonucleic acid; FFA, free fatty acids; GLUT-4, glucose transporter 4; and CD36, cluster of differentiation 36 (fatty acid translocase).
Figure 4. The presumed mechanism of diosgenin stimulation of PPARγ receptors. PPARγ, peroxisome proliferator-activated receptor gamma; DNA, deoxyribonucleic acid; mRNA, messenger ribonucleic acid; FFA, free fatty acids; GLUT-4, glucose transporter 4; and CD36, cluster of differentiation 36 (fatty acid translocase).
Biomolecules 10 00752 g004
Table 1. Previous reviews.
Table 1. Previous reviews.
Year of the ReviewMain TopicYears SurveyedLimitationsReference
2005Phytochemistry and pharmacology<2004 [6]
2014TT supplementsNS [1]
2014Phytochemistry and pharmacology short review[7]
2014Phytochemistry and pharmacologyNSshort review[8]
2016Analysis of human and animal evidence1968–2015 [2]
2016PhytochemistryNSOnly the composition of fruits was discussed[9]
2016Phytochemistry and pharmacologyNS [10]
2017Phytochemistry and pharmacologyNS [11]
2018Male infertility short review[5]
2019Phytochemistry and ethnomedicineNSbrief presentation of constituents[12]
2019Male infertilityNS [13]
2019Phytochemistry and pharmacology1965–2017 [14]
2020Phytochemistry and pharmacologyNSthe review is based mostly on Ayurvedic preparation
The pharmacological effects are briefly presented
NS, not specified.
Table 2. Chemical compounds identified in Tribulus terrestris (TT).
Table 2. Chemical compounds identified in Tribulus terrestris (TT).
CompoundChemical FormulaPlant PartConc. mg/100 gPlant OriginReferences
Furostanol Saponins
ProtodioscinC51H84O22aerial parts109–1530Bulgaria[3,4,16,17]
aerial parts340–1000Turkey[3]
aerial parts220–790Greece[3]
aerial parts420–990Macedonia[3]
aerial parts200Serbia[3]
aerial parts560Georgia[3]
aerial parts3Vietnam[3]
aerial parts190Russia[18]
NeoprotodioscinC51H86O22aerial partsNSBulgaria[16]
PrototribestinC45H73NaO20Saerial parts130–2200Bulgaria[3,4,16,19]
aerial parts,310–1000Turkey[3]
aerial parts220–790Greece[3]
aerial parts420–990Macedonia[3]
aerial parts170Serbia[3]
aerial parts240Georgia[3]
NeoprototribestinC45H75NaO20Saerial partsNSBulgaria[16]
Terestrinin AC33H48O9fruitsNSChina[20]
Terestrinin BC60H95O30rootNSGeorgia[21]
Terrestrinin DC33H50O10fruits5.6China[22,23]
Terestrinin J-T whole plantNSChina[24]
Terestroside A rootNSGeorgia[21]
Terrestrosin KC51H82O24fruits1.27China[22]
Terrestrosin IC51H84O25whole plantNSChina[23,24]
Tribufuroside DC45H74O21fruitsNSChina[23,25]
Tribufuroside EC45H74O21fruitsNSChina[23,25]
Tribulosaponin AC51H84O21fruitsNSChina[26]
Polianthoside DC56H92O29rootNSGeorgia[21]
Spirostanol Saponins
DioscinC45H72O16aerial partsNSEgypt[27]
aerial parts60Russia[18]
fruits, leaves, stem10–43Bulgaria[3,4,28]
aerial parts6–13Turkey[3]
aerial parts26–31Greece[3]
aerial parts13–15Macedonia[3]
aerial parts87Serbia[3]
aerial parts8Georgia[3]
TribestinC39H61NaO14Saerial parts2–220Bulgaria[3,28]
aerial parts6.8–28Turkey[3]
aerial parts24Greece[3]
aerial parts7.3–10Macedonia[3]
aerial parts210Serbia[3]
aerial parts6Georgia[3]
TribulosinC55H90O25aerial parts0.1–7.7Bulgaria[3]
aerial parts0.03–1.7Turkey[3]
aerial parts1.3–2.4Greece[3]
aerial parts0.68Macedonia[3]
aerial parts2.24Serbia[3]
aerial parts0.56Georgia[3]
aerial parts22Vietnam[3]
whole plantNSIndia[32]
Terestrinin U whole plantNSChina[24]
Agovoside A fruitsNSChina[20]
Prosapogenin B aerial partsNSEgypt[27]
Cinnamic Acid Amides
Ferulic acid fruitsNSTaiwan[34]
Quinic Acid Derivatives
5-p-cis-coumaroylquinic acidC16H18O8aerial partsNSEgypt[27]
5-p-trans-coumaroylquinic acid aerial partsNSEgypt[27]
4,5-Di-p-trans-coumaroylquinic acid aerial partsNSEgypt[27]
4,5-Di-p-cis-coumaroylquinic acid aerial partsNSEgypt[27]
TribulosideC30H26O13leaves, fruitsNSIndia[38]
KaempferolC15H10O6leaves, fruits18India[31,38]
Astragalin (kaempferol 3-glucoside) C21H20O11leaves, fruitsNSIndia[38]
Kaempferol 3-rutinosideC27H30O15leaves, fruitsNSIndia[38]
Kaempferol-3- gentiobiosideC27H30O16fruits leavesNSChina[39,40]
fruits, leavesNSIndia
fruits, leaves70–250Bulgaria
QuercetinC15H10O7fruits, leavesNSIndia[42]
Quercetin-3-O-arabinosyl galactoside Isorhamnetin-3-glucosideC26H28O16fruits leavesNSChina[39,40]
Quercetin-3- gentiobiosideC27H30O17fruits, leavesNSChina[39,40]
Quercetin 3,7-diglucosideC27H30O17fruits, leavesNSChina[39,40]
IsoquercitrinC21H20O12fruits, leavesNSChina[39,40]
Luteolin-7-O-β-D- glucosideC30H18O11leavesNSChina[39]
Apiotribosides A-D rootsNSGeorgia[21]
fruits, stem, leaves, rootsNSTurkey[44]
HarmaneC12H10N2fruits, stem, leaves, rootsNSTurkey[44]
aerial partsNSAustralia[45]
HarmalolC12H12N2Ofruits, stem, leaves, rootsNSTurkey[44]
HarmalineC13H14N2Ostem, leaves, rootsNSTurkey[44]
NorharmaneC11H8N2aerial partsNSAustralia[45]
not specifiedNSIndia[46]
n-Caffeoyltyramine fruitsNSKorea[36,47]
fruits China
PerlolyrineC16H12N2O2not specifiedNSIndia[46]
Amides and Lignanamides
TerrestribisamideC13 H18NO5fruitsNSTaiwan[34]
Tribulusamide AC36H36N2O8fruitsNSChina[37]
Tribulusamide BC36H34N2O9fruitsNSChina[37]
Tribulusamide DC17H15NO5fruitsNSKorea[48]
Tribulusamide CC18H15NO6fruitsNSChina[49]
Fatty Acids and Fatty Acid Esters
Oleic acidC18H34O2stemNSPakistan[50]
Palmitic acidC16H32O2stemNSPakistan[50]
6,9,12,15-Docosatetraenoic acid, methyl esterC23H38O2stemNSPakistan[50]
Pentadecanoic acid, 14-methyl-, methyl esterC17H34O2stemNSPakistan[50]
9,12-Octadecadienoic acid, methyl ester (E,E)-C19H34O2stemNSPakistan[50]
β-sistosterol-D-glucosideC35H60O6whole plantNSIndia[32]
Other Compounds
ß-1, 5-O-dibenzoyl ribofuranoseC19H18O7rootsNSIndia[51]
1,3-Benzenedicarboxylic acid, bis(2-ethylhexyl) esterC24H38O4stemNSPakistan[50]
Concentration is expressed in mg/100 g DW (dry weight). NS, not specified or the concentration could not be calculated using the given data in research paper.
Table 3. In vitro and in vivo studies regarding the efficacy of TT extracts in sexual disorders and their design evaluation.
Table 3. In vitro and in vivo studies regarding the efficacy of TT extracts in sexual disorders and their design evaluation.
Herbal Drug and SubjectsAssay/ParametersOutcome of Treated GroupStudy Design EvaluationReference
In Vitro Studies
Organ bath study of the corpus cavernosum fromRelaxation levelConcentration-dependent relaxation responsePart of the plant: NOKam et al. (2012)
male rabbitsOrigin: NO[64]
Phytochemical analysis: NO
Control group: NO
Appropriate Statistical analysis: YES
Human sperm from 40 healthy volunteersMotility analysisMotility ↑ * after 60 minutes of incubationPart of the plant: NOKhaleghi et al. (2017)
TT extractSperm viability analysisViability ↑ * in a dose-dependent manner after 120 minutes of incubationOrigin: YES[63]
Determination of DNA fragmentationNo 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 normalSexual behavior studies: MF, IF, ML, IL, EL, PEITreatment of castrated rats (with testosterone or TT extract) showed increase in prostate weight and ICP that were statistically significantPart of the plant: NCSGauthaman et al. (2002)
TT extractICPMild to moderate improvement of sexual behavior parametersOrigin: YES[70]
Phytochemical analysis: NCS
Control group: YES
Positive control group: YES
Appropriate statistical analysis: YES
Male Sprague Dawley ratsICPICP concentration-dependent increase in TT treated group*Part of the plant: NCSKam et al. (2012)
TT extract, Cornus officinalis extract and a mixture of bothcAMP, cGMP in corpus cavernosumcAMP ↑* in the group treated with the mixtureOrigin: YES[64]
cGMP no significant difference as compared with the controlPhytochemical analysis: NO
Control group: YES
Positive control group: NO
Appropriate statistical analysis: YES
-Male ratsMorphometric analysisTesticular weight ↑*Origin: YESOliveira et al. (2015)
TT fruit extract and fractionsGonadosomatic indexGonadosomatic index increased in the group supplemented with ethanolic extractPart of the plant: YES[69]
Sperm quality analysis: motility,-Nuclear, cytoplasmic, and individual volume of Leydig cells increased in supplementation with hexanic and aqueous fractionsPhytochemical analysis: NO
sperm count,The extract influenced the spermatogenesisControl group: YES
morphology, viability Positive control group: NO
Appropriate statistical analysis: YES
Male Wistar rats with STZ-induced diabetes (55 mg/kg)Sperm characteristics, morphologyTT restored antioxidant enzyme activity in testisPart of the plant: YESTag et al. (2015)
TT fruit extractBody and genital organ weightImproved lipid profile content in serumOrigin: YES[85]
Serum testosterone, FSH, LPO level in testicular homogenateTT 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)TestosteroneSperm motility, sperm count, percentage of sperms with normal morphology ↑*Part of the plant: YESGhanbari et al. (2016)
TT seed extractSperm analysis: morphology, count and motilityTestosterone ↑*Origin: NO[67]
Phytochemical analysis: NO
Control group: YES
Positive control group: NO
Appropriate statistical analysis: YES
Male Sprague Dawley ratsTime to exhaustion of over trained ratsPerformance (time to exhaustion) ↑*Origin: YESYin et al. (2016)
TT fruit extract (saponins >70%)Serum testosterone, corticosterone, AR, IGF-1R in liver, gastrocnemius, and soleusIncrease in body weights, relative weights, and protein levels of gastrocnemiusPart 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 miceSOD, CAT, GPx,SOD, CAT, GST ↓#Part of the plant: YESPavin et al. (2018)
TT fruit extractGR, GST, GSH, 17β-HSDGPx ↑#Origin: YES[65]
Plasma testosterone17β-HSD activity in treated group was not statistically significant different as compared with the control groupPhytochemical analysis: YES (UHPLC-Q-TOF/MS)
Semen analysis:Testosterone ↑Control group: YES
motility, vigor, membrane integrityMotility ↑#Positive control group: YES
Histology of testesNo significant modifications in testicular architectureAppropriate statistical analysis: YES
Male Wistar ratsSperm analysis: sperm count, viability, motilityTestosterone, LH ↑*Part of the plant: YESHaghmorad
TT flower extract andSerum testosterone, LH, FSH levelsAll the treatment groups had higher number of Leydig, spermatogonia and spermatid cellsOrigin: YES et al. (2019)
Anacyclus Pyrethrum dried root extractHistological 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, MAPICP, ICP/MAP ↑ *Part of the plant: NCSZhang et al. (2019)
Gross saponins of TT (GSTT)eNOS expression levelNitric oxide ↑*Origin: YES[86]
Nitric oxide levelROS ↓*Phytochemical analysis: NCS
cAMP expression levelNo significant difference between the GSTT group and the sildenafil group in increasing cGMP levelsControl group: YES
ROS levels Positive control group: YES
Appropriate statistical analysis: YES
Clinical Studies
20–36-Year-old menTestosterone, 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 LHPart of the plant: YESNeychev and Mitev (2005)
TT extractOrigin: YES[76]
Phytochemical analysis or standardization: YES
Placebo group: YES
Randomization: YES
Double-blind: NCS
Appropriate statistical analysis: YES
Australian elite male rugby league playersStrength, fat free massNo significant changesPart of the plant: NCSRogerson et al. (2007)
Urinary T/E ratioNo changes in urinary T/E ratioOrigin: YES[77]
Phytochemical analysis or standardization: YES
Placebo group: YES
Randomization: YES
Double-blind: YES
Appropriate statistical analysis: YES
20–22-Year-old athletesCK, testosteroneCK ↑*Part of the plant: NCSMilasius et al. (2009)
TT capsulesAnaerobic alactic muscular powerTestosterone ↑* during the first half (10 days) of the experimentOrigin: NCS[73]
Anaerobic alactic glycolytic powerAnaerobic 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 trialIIEF, SQolM,IIEF ↑*Part of the plant: NCSIacono et al. (2012)
Male patients > sixty years withTestosterone levels after 60 days of treatment,SQolM ↑*Origin: NCS[74]
reduced libido, with or without erectile dysfunction (ED)Side effectsTT level increasedPhytochemical 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 studyIIEF and serum testosterone were obtained before randomization and after 30 days of studyNo effects as compared with the placeboPart of the plant: NOSantos et al. (2014)
Healthy men, spontaneously complaining of ED, ≥40 years of ageOrigin: NO[72]
TT extractPhytochemical analysis or standardization: NO
Placebo group: YES Randomization: YES
Double-blind: YES
Appropriate statistical analysis: YES
Randomized, double-blind, placebo controlled clinical trial studyFSFI scoreFSFI ↑*Part of the plant: YESAkhtari et al. (2014)[83]
Women with hypoactive sexual desire disorderOrigin: YES
TT leaves extractPhytochemical analysis or standardization: NCS
Placebo group: YES
Randomization: YES
Double-blind: YES
Appropriate statistical analysis: YES
Prospective, randomized, double-blind, placebo controlled clinical trialIIEF scoreIIEF score ↑*Part of the plant: YESKamenov et al. (2017)
Male with mild to moderate EDGEQ responsesGEQ 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 studyMRSSeverity of menopausal transition sympt. ↓*Part of the plant: YESFatima and Sultana (2017)
Perimenopausal womenSeverity of menopausal transition symptomsMRS ↓*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 scoreFSFI ↑*Part of the plant: NCSVale et al. (2018)
Premenopausal women with diminished libidoQS-F scoreQS-F ↑*Origin: YES[81]
TT extractSerum testosteroneSerum 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.
Table 4. In vitro and in vivo pharmacological studies and the study design evaluation.
Table 4. In vitro and in vivo pharmacological studies and the study design evaluation.
Herbal Drug and SubjectsAssay/ParametersOutcome of Treated GroupStudy Design EvaluationReference
In Vitro Studies
TT fruit extractα-GlucosidaseActivity inhibition on all tested enzymesPart of the plant: YESLamba et al. (2011)
Aldose reductaseOrigin: YES[99]
Phytochemical analysis: NCS
Control group: YES
Positive control group: YES
Appropriate statistical analysis: YES
TT seedsα-AmylaseConcentration- inhibition of enzyme activityPart of the plant: YESPonnusamy et al. (2011)
Kinetic studies.Origin: YES[96]
Phytochemical analysis: YES (identification reactions, GC/MS)
Positive control: YES
Appropriate statistical analysis: YES
TT leavesLipaseActivity inhibition on all tested enzymesPart of the plant: YESErcan and El (2016)
α-AmylaseOrigin: YES[95]
α-GlucosidasePhytochemical analysis: YES (spectrophotometric)
Positive control: YES
Appropriate statistical analysis: YES
In Vivo Animal Studies
Male Swiss albino rats with STZ-induced diabetes (55 mg/kg)BW, BG, Hb, HbA1c, TG, TC, HDL, LDL-cBW ↑*Part of the plant: YESEl-Tantawy and Hassanin (2007)
TT aerial part extractHistopathological analysis of the pancreasBG ↓* after 2,4, and 6 hOrigin: YES[98]
HbA1c returned to the normal valuesPhytochemical analysis: NO
HDL ↑*Control group: YES
TG, TC, LDL-c ↓*Positive control group: YES
Histological structure was less affected as compared with the control groupAppropriate statistical analysis: YES
Wistar rats with STZ-induced diabetes (50 mg/kg)BG, BW, HbA1c, INS, GLGBG ↓*Part of the plant: YESLamba et al. (2011)
TT fruit extractUrinary albumin levelsBW ↑*Origin: YES[99]
HbA1c, GLG ↑Phytochemical analysis: NCS
Control group: YES
Positive control group: YES
Appropriate statistical analysis: YES
Male Wistar rats with STZ-induced diabetes (40 mg/kg)BGBG, PT, APTT, TC, TG, LDL, ALT, AST, ALP, glucose-6-phosphatas, fructose-1, 6-bisphosphatase, LPO ↓ *Control group: YESKalailingam et al (2014)
DiosgeninHbA1cHDL, SOD, CAT, GSH ↑ *Positive control group: NO[101]
TC, TG, HDL, LDL, AST, ALP Appropriate statistical analysis: YES
Hepatic glucose-6-phosphatase, fructose-1, 6-bisphosphatase SOD, CAT, GSH, LPO
Male Sprague Dawley rats with type 2 diabetes induced with high-fat diet (HFD) + STZ (35 mg/kg)BG, INS, BWBG ↓ *, INS ↑ *, BW ↑ *Control group: YESTharaheswari et al. (2014)
DiosgeninFFA, TNF-α, IL-6, leptinFFA, TNF-α, IL-6, leptin ↓ *Positive control group: NO[102]
HOMA-IR, HOMA-B, QUICKIHOMA-IR, HOMA-B, QUICKI – improved valuesAppropriate statistical analysis: YES
In tissue homogenate were determined: LPO, GSH, SOD, CAT, GPxIncreased adipose tissue mass
Histopathological analysis of pancreasEnhanced PPARc expression
Quantification of adipose PPAR γGood interaction of diosgenin with PPAR γ
Glucose-loaded normal rabbits,FBG at 30 min, 1, 2, 3 h after dosingFBG ↓* at 2 hoursPart of the plant: YESEl-Shaibany et al. (2015)
TT aerial parts extractAcute toxicity studyNo toxicityOrigin: YES[100]
Phytochemical analysis: YES (TLC)
Control group: YES
Positive control group: YES
Appropriate Statistical analysis: YES
Male Wistar rats with STZ-induced diabetes (55 mg/kg)BGBG ↓*Part of the plant: YESTag et al. (2015)
TT fruit extractINSINS ↑*Origin: YES[85]
Phytochemical analysis: YES (identification reactions)
Control group: YES
Positiv control group: YES
Appropriate Statistical analysis: YES
Sprague Dawley rats with type 2 diabetes induced with high-fat and high-sugar feeding and STZ (30 mg/kg)BGBG ↓Part of the plant: NOZhang et al. (2019)
Gross saponins of TTBWNo significant differences in BWOrigin: YES[86]
Phytochemical analysis: NCS
Control group: YES
Positive control group: YES
Appropriate statistical analysis: YES
Clinical Studies
100 Patients suffering from DM with microalbuminuriaBGBG ↓ *Part of the plant: NCSRamteke et al. (2012)
Ayurvedic preparation with TTBPBP ↓ *Origin: NCS[105]
Urine albuminUrine albumin ↓*Phtochemical analysis or standardization: NO
Placebo group: NO
Randomization: YES
Double-blind: NCS
Appropriate statistical analysis: YES
Double-blind randomized placebo controlled clinical trialFBG, BG 2-hour postprandial HbA1cBG ↓*Part of the plant: NCSSamani et al. (2016)[104]
Ninety-eight women with diabetes mellitus type 2TG, TC, LDL, HDLTC, LDL ↓*Origin: YES
TT extract HbA1c, TG, HDL - no significant differences as compared with the placeboPhtochemical analysis or standardization: YES
Placebo group: YES
Randomization: YES
Double-blind: YES
Appropriate statistical analysis: YES
NCS, not clearly specified; GC/MS, gas chromatography-mass spectrometry; TLC, thin layer chromatography; STZ, streptozotocin; BW, bodyweight; BG, blood glucose; Hb, hemoglobin; HbA1c, glycosylated hemoglobin; TG, serum triglycerides; TC, total cholesterol; HDL, high density lipoprotein; LDL-c, low density lipoprotein cholesterol; INS, insulin; GLG, glycogen; FBG, fasting blood glucose; AST, aspartate aminotransferase; ALP, alkaline phosphatase; PT, prothrombin time; APTT, activated partial thromboplastin time; SOD, superoxide dismutase; CAT, catalase; GSH, glutathione; LPO, lipid peroxidase; FFA, serum free fatty acids; TNF-α, tumor necrosis factor-α; IL-6, interleukin-6; HOMA-IR, homeostasis model assessment of insulin resistance; HOMA-B, homeostasis model assessment of β-cell function; QUICKI, quantitative insulin sensitivity check index, PPARγ, peroxisome proliferator-activated receptor gamma; GPx, glutathione peroxidase; BP, blood pressure; *, significant difference as compared with the control group and the placebo group.
Table 5. Toxicological information of some compounds from the U.S. National Library of Medicine [126].
Table 5. Toxicological information of some compounds from the U.S. National Library of Medicine [126].
CompoundToxicological Information
DiosgeninOral LD50 (rat) > 8 g/kg
Intraperitoneal LD50 (rat) 4872 mg/kg
Oral LD50 (mouse) > 8 g/kg
Intraperitoneal LD50 (mouse) 3564 mg/kg
DioscinSubcutaneous LD50 (mouse) >300 mg/kg
Oral TDLo (rat) 1050 mg/kg/1W (intermittent)
Oral TDLo (mouse):400 mg/kg/10D (intermittent)
TigogeninIntraperitoneal LDLo (rat):10 mg/kg
Harmine Intramuscular TDLo (man):3 mg/kg
Intravenous LDLo (cat) 10 mg/kg
Subcutaneous LDLo (frog) 300 mg/kg
Subcutaneous LD50 (mouse) 243 mg/kg
Intravenous LDLo (mouse) 50 mg/kg
Subcutaneous LD50 (rat) 200 mg/kg
HarmaneIntraperitoneal LD50 (mouse) 50 mg/kg
Interperitoneal TDLo (rat) 1 mg/kg
Intraperitoneal LD50 (rabbit) 200 mg/kg
HarmalineSubcutaneous LD50 (rat) 120 mg/kg
Subcutaneous LD50 (mouse) 120 mg/kg
Intraperitoneal TDLo (rat) 4 mg/kg
NorharmaneOral TDLo (rat) 1050 mg/kg/6W (continuous)
LD50, median lethal dose; TDLo, lowest published toxic dose; LDLo, lowest lethal dose.

Share and Cite

MDPI and ACS Style

Ștefănescu, R.; Tero-Vescan, A.; Negroiu, A.; Aurică, E.; Vari, C.-E. A Comprehensive Review of the Phytochemical, Pharmacological, and Toxicological Properties of Tribulus terrestris L. Biomolecules 2020, 10, 752.

AMA Style

Ștefănescu R, Tero-Vescan A, Negroiu A, Aurică E, Vari C-E. A Comprehensive Review of the Phytochemical, Pharmacological, and Toxicological Properties of Tribulus terrestris L. Biomolecules. 2020; 10(5):752.

Chicago/Turabian Style

Ștefănescu, Ruxandra, Amelia Tero-Vescan, Ancuța Negroiu, Elena Aurică, and Camil-Eugen Vari. 2020. "A Comprehensive Review of the Phytochemical, Pharmacological, and Toxicological Properties of Tribulus terrestris L." Biomolecules 10, no. 5: 752.

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop