What is tribulus terrestris

Tribulus terrestris is an annual plant of the family Zygophyllaceae, which is commonly known as Tribulus, Hard thorns, and goat head in China ¹. The fruits and roots of tribulus terrestris have been used as a folk medicine for thousands of years in China, India, Sudan, and Pakistan. In folk medicine, tribulus terrestris has been used for generations to energize, vitalize, and improve sexual function and physical performance in men ². Numerous bioactive phytochemicals, such as saponins, flavonoids, glycosides, alkaloids, and tannins ³, have been isolated and identified from tribulus terrestris that are responsible alone or in combination for various pharmacological activities.

Tribulus terrestris is mainly planted in the Mediterranean and in sub-tropical regions such as India, China, South America, Mexico, Spain, Bulgaria, and Pakistan. It is a small, prostrate, 10–60 cm high, hirsute or silky hairy shrub. The leaves are opposite, often unequal, paripinnate, pinnate from 5 to 8 pairs and elliptical or an oblong lanceolate. The fruits from the five mericarps are ax-shaped, 3–6 mm long, and arranged radially and have a diameter of 7–12 mm and a hard texture. The root is slender, fibrous, cylindrical and frequently branched, bears a number of small rootlets and is light brown in color ⁴. The fruits and roots of tribulus terrestris, as a folk medicine, have been used for thousands of years in China. Over the last several years, it has been used for improving sexual function and cardiac protection and providing anti-urolithic, antidiabetic, anti-inflammatory, antitumour and antioxidants effects.

Figure 1. Tribulus terrestris

Tribulus terrestris steroidal saponins

Spirostanol and furostanol saponins are considered the most characteristic chemicals in tribulus terrestris. To date, 108 kinds of steroidal saponins have been isolated from tribulus terrestris (1–108). Among them, there are 58 kinds of spirostane saponins (1–58) and 50 kinds of furostane saponins (59–108). The steroidal saponins, such as protodioscin and protogracillin, are thought to confer tribulus terrestris unique biological activities. Skeletal types of steroidal aglycones in tribulus terrestris are shown in Figure 2. Steroidal saponins (aglycones) in tribulus terrestris are shown in Table 1.

According to literature data, the saponin composition and the saponin content of tribulus terrestris from different geographic regions is different ⁵. Kostova et al.⁵ studied the chemistry and bioactivity of saponins in tribulus terrestris. They reported that furostanol and spirostanol saponins of tigogenin, neotigogenin, gitogenin, neogitogenin, hecogenin, neohecogenin, diosgenin, chlorogenin, ruscogenin, and sarsasapogenin types are frequently found in this plant. In addition, four sulfated saponins of tigogenin and diosgenin type were also isolated. Majorly present are furostanol glycosides including protodioscin and protogracillin, of which protodioscin is the most dominant saponin and spirostanol glycosides are present in small quantities. Wu et al. ⁶ found that the quantity of main flavonoids is about 1.5 times that of main saponins. This indicated that the flavonoid contents in tribulus terrestris should be studied, developed, and further used. Bhutani et al. ⁷ isolated kaempferol, kaempferol-3-glucoside, kaempferol-3-rutinoside, and tribuloside [kaempferol-3-β-d-(6″-p-coumaroyl) glucoside] from leaves as well as fruits and identified them by spectroscopic analysis. Louveaux et al. ⁸ detected 18 flavonoids (caffeoyl derivatives, quercetin glycosides, including rutin and kaempferol glycosides) using high-performance liquid chromatography (HPLC) in four Tribulus species leaf extracts. Yang et al. ⁹ optimized the extraction condition using orthogonal experiment. Matin Yekta et al. ¹⁰ isolated three flavonoid glycosides, viz. quercetin 3-O-glycoside, quercetin 3-O-rutinoside, and kaempferol 3-O-glycoside from the aerial parts of T. terrestris L. var. orientalis (Kerner) G. Beck in the northeast of Iran.

Table 1. Steroidal saponins (aglycones) in tribulus terrestris

No.	Chemicals	Aglycones	R1	R2	R3	R4	R5	R6	25-C
1	Tigogenin	I	OH	H	H	H	H	H	R
2	Neotigogenin	I	OH	H	H	H	H	H	S
3	Tigogenin-3-O-β -d-glc(1 → 4)-β -d-gal (A)	I	Ra	H	H	H	H	H	R
4	Terrestrosin F	I	Rb	H	H	H	H	H	R
5	Desgalactotigonin	I	Rc	H	H	H	H	H	R
6	Gitonin (B)	I	Rd	H	H	H	H	H	R
7	Tigogenin-3-O-β -d-xyl-(1 → 2)-[β -d-xyl-(1 → 3)]-β -d-glc(1 → 4)-[α -l-rha(1 → 2)]-β -d-gal (C)	I	Re	H	H	H	H	H	R
8	Tribulosin	I	Re	H	H	H	H	H	S
9	Terrestrosin A	I	Rf	H	H	H	H	H	R,S
10	Terrestrosin B	I	Rg	H	H	H	H	H	R,S
11	Gitogenin	I	OH	OH	H	H	H	H	R
12	Neogitogenin	I	OH	OH	H	H	H	H	S
13	Gitogenin-3-O-β -d-glc(1 → 4)-β -d-gal	I	Ra	OH	H	H	H	H	R
14	F-gitonin	I	Rd	OH	H	H	H	H	R
15	Desglccolanatigonin	I	Rd	OH	H	H	H	H	R
16	25R,S-5α-spiro-2α,3β-dihydroxyl-3-O-β -d-glc-(1 → 4)-β -d-gal	I	Ra	OH	H	H	H	H	R,S
17	Terrestrosin E	I	Rf	OH	H	H	H	H	R,S
18	Hecogenin	I	OH	H	#NAME?	H	H	H	R
19	Neohecogenin sapogenin	I	OH	H	#NAME?	H	H	H	S
20	Agovoside A	I	Rh	H	#NAME?	H	H	H	R
21	Hecogenin-3-O-β -d-glc-(1 → 4)-β -d-gal (D)	I	Ra	H	#NAME?	H	H	H	R
22	Hecogenin-3-O-β -d-glc-(1 → 2)-β -d-glc(1 → 4)-β -d-gal (E)	I	Ri	H	#NAME?	H	H	H	R
23	Hecogenin-3-O-β -d-xyl-(1 → 3)-β -d-glc(1 → 4)-β -d-gal (F)	I	Rj	H	#NAME?	H	H	H	R
24	Hecogenin-3-O-β -d-glc-(1 → 2)-[3-O-β -d-xyl]-β -d-glc-(1 → 4)-β -d-gal (G)	I	Rd	H	#NAME?	H	H	H	R
25	Terrestrosin D	I	Rk	H	#NAME?	H	H	H	R
26	Hecogenin-3-O-β -d-xyl-(1 → 2)-[β -d-xyl-(1 → 3)]-β -d-glc(1 → 4)-[α -l-rha-(1 → 2)]-β -d-gal (H)	I	Re	H	#NAME?	H	H	H	R
27	Neohecogenin-3-O-β -d-glc	I	Rl	H	#NAME?	H	H	H	S
28	Terreside B	I	Ra	H	#NAME?	H	H	H	S
29	Terreside A	I	Ri	H	#NAME?	H	H	H	R
30	Tettestrosin C	I	Rf	H	#NAME?	H	H	H	R,S
31	25R,S-5α-spiro-12-one-3-O-β -d-xyl-(1 → 2)-[β -d-xyl-(1 → 3)]-β -d-glc(1 → 4)-[α -l-rha(1 → 2)]-β -d-gal	I	Re	H	#NAME?	H	H	H	R,S
32	Hecogenone	I	#NAME?	H	#NAME?	H	H	H	R
33	25R-5α-spiro-3,6,12-triketo	I	#NAME?	H	#NAME?	#NAME?	H	H	R
34	Sarsasaponin	I	OH	H	H	H	H	H	S
35	Isoterrestrosin B(I)	I	Rg	H	H	H	H	H	S
36	Chlorogenin	I	OH	H	H	OH	H	H	R
37	Terrestrinin U	I	H	Rm	H2	H	Rl	H	S
38	Terrestrinin I	I	Ra	H	#NAME?	H	Rl	H	S
39	23S,25S-5α-spiro-24-one-3β,23-diol-3-O-[α -l-rha-(1 → 2)]-O-[β -d-glc-(1 → 4)]-β -d-gal	I	Rn	H	H	H	#NAME?	OH	S
40	24S,25S-5α-spiro-3β,24-diol-3-O-[α -l-rha-(1 → 2)]-O-[β -d-glc-(1 → 4)]-β -d-gal	I	Rn	H	H	H	OH	H	S
41	23S,24R,25R-5α-spiro-3β,23,24-triol-3-O-[α -l-rha-(1 → 2)]-[β -d-glc-(1 → 4)]-β -d-gal	I	Rn	H	H	H	OH	OH	R
42	23S,24R,25S-5α-spiroe-3β,23,24-triol-3-O-[α -l-rha-(1 → 2)-[β -d-glc-(1 → 4)]-β -d-gal	I	Rn	H	H	H	OH	OH	S
43	Diosgenin	II	OH	H					R
44	Yamogenin	II	OH	H					S
45	Trillin	II	Rl	H					R
46	Trillarin	II	Ro	H					R
47	Dioscin	II	Rp	H					R
48	Gracillin	II	Rq	H					R
49	Diosgenin-3-O-α -l-rha-(1 → 3)-β -d-glc	II	Rr	H					R
50	Tribestin	II	Rs	H					R
51	Ruscogenin	II	OH	OH					R
52	Saponin C	II	OH	Rt					R
53	25R-spiro-3,5-diene	III	H						R
54	25R-spiro-3,5-dien-12one	III	#NAME?						R
55	25R-spiro-4-ene-3,12-dione	IV	#NAME?	H	H	H			R
56	25R-spiro-4-ene-3,6,12-trione	IV	#NAME?	H	#NAME?	H			R
57	25R-spiro-24-hydroxy-3,12-dione	IV	#NAME?	H	H	OH			R
58	25R-spiro-2α,3β-hydroxy-4-ene-12one	IV	OH	OH	H	H			R
59	25R-5α-furo-22-methoxy-3β,26-dihydroxy-O-β -d-glc-3-O-β -d-xyl-(1 → 2)-[β-d-xyl-(1 → 3)]-β -d-glc(1 → 4)-[α -l-rha(1 → 2)]-β -d-gal (J)	V	Re	H	H	OCH3	Rl		R
60	Neoprotodioscin	V	Rp	H	H	OH	Rl		R
61	Neoprototribestin	V	Rs	H	H	OH	Rl		R
62	Terrestrinin B	V	Re	H	H	OH	Rl		S
63	Tettestrosin H	V	Rf	H	H	OH	Rl		R,S
64	Terrestroneoside A	V	Re	H	H	OCH3	Rl		Uncertain
65	Terrestrosin F	V	Ra	OH	H	OH	Rl		R
66	25R,S-5α-furo-2α,3β,22α,26-tetrahydroxy-O-β -d-glc-(1 → 4)-β -d-gal	V	Ra	OH	H	OH	Rl		R,S
67	Terrestrosin G	V	Rf	OH	H2	OH	Rl		R,S
68	25R,5α-furo-12-one-3β,22α,26-trihydroxy-O-β -d-glc-3-O-β -d-glc-(1 → 2)-β -d-gal	V	Ru	H	#NAME?	OH	Rl		R
69	25S,5α-furo-12-one-3β,22α,26-trihydroxy-O-β -d-glc-3-O-β -d-glc-(1 → 2)-β -d-gal	V	Ru	H	#NAME?	OH	Rl		S
70	25S,5α-furo-12-one-3β,22α,26-trihydroxy-O-β -d-glc-3-O-β -d-glc-(1 → 4)-[α -l-rha-(1 → 2)]-β -d-gal	V	Rg	H	#NAME?	OH	Rl		S
71	Terrestrosin I	V	Rf	H	#NAME?	OH	Rl		R,S
72	5α-furo-12-one-3β,22,26-trihydroxy-O-β -d-glc-3-O-β -d-xyl-(1 → 3)-[β -d-gal-(1 → 2)]-β -d-glc(1 → 4)-β -d-glc	V	Rv	H	#NAME?	OH	Rl		Uncertain
73	Terrestrinin R	V	H	Rm	#NAME?	OH	Rl		R
74	Terrestrinin S	V	H	Rm	#NAME?	OH	Rl		S
75	Terrestrinin F	V	OH	H	#NAME?	OH	Rl		R
76	26-O-β -d-glc-25R-5α-furo-2α,3β,22α,26-tetraol-3-O-β -d-glc-(1 → 2)-O-β -d-glc-(1 → 4)-β -d-gal	V	Ri	OH	H	CH3	Rl		R
77	Pseudoprotodioscin(K)	VI	Rp	OH	H	Rl			R
78	Methyl pseudo-diosgenin	VI	Rp	OCH3	H	Rl			R
79	Prototribestin	VI	Rs	OH	H	Rl			R
80	Methyprototribestin	VI	Rs	OCH3	H	Rl			R
81	Protogracillin	VI	Rq	OH	H	Rl			R
82	Terrestrosin J	VI	Rf	OH	H	Rl			R,S
83	Tribol	VI	Rp	H	OH	H			R
84	Terrestrinin K	VI	Rm	OH	H	Rl			R
85	Terrestrosin K	VII	Rf	H	#NAME?	H	CH3		R
86	25R,S-5α-furo-12-one-20,22-ene-3β,26-dihydroxy-O-β -d-glc-3-O-β -d-glc-(1 → 4)-β -d-gal	VII	Ra	H	#NAME?	H	CH3	Rl	R,S
87	25R,S-5α-furo-12-one-20,22-ene-3β,26-dihydroxy-O-β -d-gal-(1 → 2)-β -d-glc-(1 → 4)-β -d-gal	VII	Rf	H	#NAME?	H2	CH3	Rl	R,S
88	5α-furo-12-one-20,22-ene-3β,26-dihydroxy-O-β -d-glc-3-O-β -d-xyl-(1 → 3)-[β -d-gal-(1 → 2)]-β -d-glc-(1 → 4)-β -d-glc	VII	Rv	H	#NAME?	H2	CH3	Rl	Uncertain
89	Tribulosaponin A(L)	VII	Rp	H	H	H2	CH3	Rl	S
90	Tribulosaponin B(M)	VII	Rg	H	H	H2	CH3	Rl	S
91	26-O-β -d-glc-25R-5α-furo-20(22)-en-2α,3β,26-triol-3-O-β -d-glc-(1 → 2)-O-β-glc-(1 → 4)-β -d-gal	VII	Rn	H	#NAME?	H	OCH3	Rl	R
92	26-O-β -d-glc-25R-5α-furo-12-one-3β,22α,26-triol-3-O-β -d-glc-(1 → 2)-β -d-glc-(1 → 4)-β -d-gal	VII	Ri	H	#NAME?	H	OH	Rl	R
93	26-O-β -d-glc-25S-5α-furo-22-methoxy-2α,3β, 26-triol-3-O-β -d-glc-(1 → 2)-β -d-glc-(1 → 4)-β -d-gal	VII	Ri	OH	H	H	OCH3	Rl	S
94	Terrestrinin A	VIII	Rl						S
95	Terrestrinin Q	VIII	Rl						R
96	Terrestrinin C	IX	OH	OH	#NAME?	H2	Rl		R
97	Terrestrinin D	IX	#NAME?	H	#NAME?	H2	Rl		R
98	Terrestrinin E	IX	#NAME?	H	#NAME?	#NAME?	Rl		R
99	Terrestrinin G	IX	#NAME?	H	OH	H2	Rl		R
100	Terrestrinin H	IX	#NAME?	H	#NAME?	H2	Rv		R
101	Terrestrinin J	X	Rm	OH	Rl				R
102	Terrestrinin L	XI	Rm	OH	Rl				R
103	Terrestrinin M	XI	Rx	OH	Rl				R
104	Terrestrinin N	XI	Ry	OH	Rl				R
105	Terrestrinin O	XII	Ry	H	Rl				R
106	26-O-β -d-glc-25R-5α-furo-20(22)-en-2α,3β, 26-triol-3-O-β -d-glc-(1 → 2)-O-β -d-glc-(1 → 4)-β -d-gal	XII	Ri	OH	Rl				R
107	Terrestrinin P	XIII	Rm	Rl					R
108	Terrestrinin T	XIV	Rm	Rl					R

[Source ¹¹]

Figure 2. Tribulus terrestris steroidal saponins

[Source ¹¹]

Tribulus terrestris flavonoids

The flavonoids of tribulus terrestris are mainly derivatives of quercetin, kaempferol and isorhamnetin. Quercetin (109), isoquercitrin (110), rutin (111), quercetin-3-O-gent (112), quercetin-3-O-gentr (113), quercetin-3-O-rha-gent (114), quercetin-3-O-gent-7-O-glu (115) are flavonoids with quercetin as the basic parent structure [34–36]. Isorhamnetin (116), isorhamnetin-3-O-glu (117), isorhamnetin-3-O-gent (118), isorhamnetin-3-O-rutinoside (119), isorhamnetin-3-O-gentr (120), isorhamnetin-3,7-di-O-glu (121), isorhamnetin-3-O-p-coumarylglu (122), isorhamnetin-3-O-gent-7-O-glu (123), isorhamnetin-3-O-gentr-7-O-glu (124) are flavonoids with isorhamnetin as the basic parent structure ¹². Kaempferol (125), kaempferol-3-O-glu (126), kaempferol-3-O-gent (127), kaempferol-3-O-rutinoside (128), kaempferol-3-O-gent-7-O-glu (129), tribuloside (130) are flavonoids with kaempferol as the basic parent structure ¹³. Structures of flavonoids in tribulus terrestris are shown in Figure 3.

Figure 3. Tribulus terrestris flavonoids

[Source ¹¹]

Tribulus terrestris alkaloids

Tribulusamide C (131), tribulusterine (132), tribulusin A (133), harmine (134), harman (135), harmmol (136), tribulusimide C (137), terrestriamide (138), N-trans-coumaroyltyramine (139), N-trans-caffeoylyramine (140), terrestribisamide (141) are the main alkaloids isolated from the stems, leaves, and fruits of tribulus terrestris ¹⁴. The nuclear mainly belong to β-carboline alkaloids and amide alkaloids. Structures of the alkaloids in tribulus terrestris are shown in Figure 4.

Figure 4. Tribulus terrestris alkaloids

[Source ¹¹]

Others

Other components of tribulus terrestris include organic acids, amino acids and other substances. Organic acids isolated from tribulus terrestris are benzoic acid ¹⁵, vanillic acid, 2-methyl benzoic acid, ferulic acid ¹⁶, succinic acid, palmitic acid monoglyceride, succinic acid, docosanoic acid ¹⁷, Tribulus acid ¹⁸ and others. The main amino acids are alanine and threonine ¹⁹. In addition, tribulus terrestris also contains 4-ketopinoresinol ²⁰, uracil nucleic acid ¹⁵, coumarin ¹⁷, emodin, and physcion ²¹.

Traditional medicine uses

Tribulus terrestris is used in folk medicines as a tonic, aphrodisiac, palliative, astringent, stomachic, antihypertensive, diuretic, lithotriptic, and urinary disinfectant. The dried fruit of the herb is very effective in most of the genitourinary tract disorders. It is a vital constituent of Gokshuradi Guggul, a potent Ayurvedic medicine used to support proper functioning of the genitourinary tract and to remove the urinary stones ¹. Tribulus terrestris has been used for centuries in Ayurveda to treat impotence, venereal diseases, and sexual debility. In Bulgaria, the plant is used as a folk medicine for treating impotence. In addition to all these applications, the Ayurvedic Pharmacopoeia of India attributes cardiotonic properties to the root and fruit. In traditional Chinese medicine, the fruits were used for treatment of eye trouble, edema, abdominal distension, emission, morbid leukorrhea, and sexual dysfunction. tribulus terrestris is described as a highly valuable drug in the Shern-Nong Pharmacopoeia (the oldest known pharmacological work in China) in restoring the depressed liver, for treatment of fullness in the chest, mastitis, flatulence, acute conjunctivitis, headache, and vitiligo. In Unani medicine, tribulus terrestris is used as diuretic, mild laxative, and general tonic ²².

Improving sexual function

The active extracts and constituents of tribulus terrestris could improve sexual function through activating aphrodisiacs and improving fertility in men. It could also activate sexual desire in postmenopausal women. It is widely believed and insistently advertised that tribulus terrestris possesses aphrodisiac and pro-sexual activities due to its ability to increase testosterone or testosterone precursor levels and this view is outdated ²³.

Aphrodisiac activation

Erectile dysfunction is a sexual disorder characterized by the inability to achieve or maintain a sufficiently rigid erection. Analysis of phytochemical and pharmacological studies in humans and animals revealed an important role for tribulus terrestris in treating erectile dysfunction and sexual desire problems. Rats were fed a standard diet treated with Mucuna pruriens, tribulus terrestris, and Ashwagandha (300 mg kg−1) for 8 weeks. The results indicated that the extract of tribulus terrestris was comparatively more potent than the two others. These herbs are potent enhancers of sexual function and behaviour by increasing the testosterone levels and regulating the NF-κB and Nrf2/HO–1 pathways in male rats ²⁴.

The hormonal effects of tribulus terrestris were evaluated in primates, rabbits and rats to identify its usefulness in the management of erectile dysfunction ²⁵. Blood samples were analysed for testosterone (T), dihydrotestosterone (DHT) and dehydroepiandrosterone sulphate (DHEAS) levels using a radioimmunoassay. tribulus terrestris increased some of the sex hormones, which is possibly due to the presence of protodioscin in the extract. The results indicated that tribulus terrestris may be useful in mild to moderate cases of erectile dysfunction.

The aphrodisiac properties of the furostenol glycoside fraction of tribulus terrestris extract (tribulus terrestris-FG) were previously studied ²⁶. Adult Wister rats were castrated and divided into five groups of six animals each and treated with tribulus terrestris extract (tribulus terrestris-FG) (5, 10, and 25 mg/kg) once daily through subcutaneous injections for 14 days. After the acute (1 day) and subacute (7 and 14 days) treatments with the tribulus terrestris-FG, there was an increase in mounting frequency, intromission frequency, and ejaculation latency and a decrease in mounting latency, intromission latency and post-ejaculation interval and serum testosterone levels in the blood.

There was a randomized, double-blind, placebocontrolled, clinical trial as a piece of evidence for aphrodisiac activation function of tribulus terrestris. 180 males aged between 18 and 65 years with mild or moderate erectile dysfunction and with or without hypoactive sexual desire disorder were randomized in a 1:1 ratio to the two treatments groups (tribulus terrestris or placebo). The tribulus terrestris group received 2 tablets (500 mg) Tribestan orally three times daily after meals for 12 weeks. Each tablet contains the active substance tribulus terrestris herba extractum siccum 250 mg (content of furostanol saponins not less than 112.5 mg). And the placebo group were treated by a identical appearance, colour and taste one. The results showed that there was significant differences of IIEF (International Index of Erectile Function) score between the two groups after 3 months, but no differences in the incidence of adverse effects ²⁷. It can therefore be assumed that tribulus terrestris can improve sexual function.

Improvement in fertility

In the literature, it has been concluded that the ethanol extract of tribulus terrestris (EE tribulus terrestris) influences spermatogenesis, as shown by the evident changes in the tubular compartment of the testes, such as increases in the total tube length, tubular volume and height of the seminiferous epithelium. The hexanic and aqueous soluble fraction in the methanol fractions promoted changes in the intertubular compartment because they increased the nuclear volume, cytoplasmic volume and individual volume of Leydig cells in male Wistar rats ²⁸.

Another animal study describes the protective role of tribulus terrestris against AlCl3-induced adverse effects on male reproductive organs and fertility. High dosages of tribulus terrestris (100 mg kg−1 day−1) in AlCl3-treated mice restored the body weight, sex organ relative weights, sperm count, motility, viability, epididymal sialic acid, seminal vesicular fructose, serum testosterone, antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase-1 (GPx)], mating ability and fertility ²⁹.

Tribulus terrestris was reported to cause reproductive system enhancement and possess antioxidant activity, which may assist in the choice of drugs for longer durations that can be prescribed safely without affecting the fertility potential in males. A high dose of the fruit extract of tribulus terrestris (200 mg/kg per day) restored metronidazole-induced spermatogenic inhibition and reduced the epididymal sperm count. The restoring potential of tribulus terrestris against metronidazole-induced alterations in the spermatogenesis appears to be due to the presence of antioxidative flavonoids rather than steroidal saponins ³⁰.

The in vitro addition of tribulus terrestris extract to human sperm could affect male fertility capacity. The incubation of human semen with 40 and 50 μg/mL of tribulus terrestris extract significantly enhanced the total sperm motility, number of progressive motile spermatozoa, and curvilinear velocity over 60–120 min of holding time. Overall, the sperm viability significantly improved ³¹.

Libido-enhancing activity

Hypoactive sexual desire disorder is defined in Diagnostic and Statistical Manual of Fourth Edition as persistent or recurrent deficiency (or absence) of sexual fantasies/thoughts, and/or desire for or receptivity to sexual activity, which causes personal distress ³². Tribulus terrestris was considered to be a safe alternative for the treatment of hypoactive sexual desire disorder in postmenopausal women because it was effective in reducing symptoms with few side effects through a randomized, double-blinded, placebo-controlled trial (a total of 45 healthy sexually active postmenopausal women who reported a diminished libido were selected to participate in the study and were randomly assigned to receive 750 mg/day of tribulus terrestris or a placebo for 120 days). Its probable mechanism of action involves an increase in the serum levels of free and bioavailable testosterone ³³.

Other clinical research established that regarding the treatment in the domains of desire and sexual interest of 74 postmenopausal women with sexual dysfunction, the tribulus terrestris treatment (250 mg, orally three times a day for 90 days) was considered to be effective in treating sexual problems among menopausal women ³⁴.

Antiurolithic activity

The fruits of tribulus terrestris have long been used in traditional systems of medicine for the treatment of various urinary diseases including urolithiasis. Calcium oxalate is a major type of crystal found in kidney stones. Calcium oxalate is classified into two types: calcium oxalate monohydrate stones and calcium oxalate dihydrate. Many medicinal plants have been used for centuries for the treatment of urinary stones in spite of the lack of rationale behind their use. The aqueous extract of tribulus terrestris fruits and its fractions were studied to evaluate its antiurolithiatic potential using different models. The inhibitory potency of the plant was tested on the nucleation and growth of the most commonly occurring kidney stones and calcium oxalate monohydrate stones. The results showed that the bioactive n-butanol fraction, due to higher contents of quercetin, diosgenin and tannic acid, has a protective capacity rather than a curative property against urolithiasis ³⁵.

A protein (60 kDa) purified from tribulus terrestris showed the highest similarity with carotenoid cleavage dioxygenase 7 (CCD7) of Arabidopsis thaliana after matching peptide mass fingerprints with the MASCOT search engine. CCD7 belong to a family of dioxygenases, which possess five characteristic conserved histidines spread throughout their primary protein sequence. Histidine is said to induce the conversion of oxalate to formic acid and carbon dioxide (CO2). The purified protein decreased cell injury induced by oxalate in a concentration dependent manner and showed the ability to inhibit calcium oxalate (CaOx) crystallization in vitro ³⁶.

Human clinical data indicated that tribulus terrestris extract may be useful in the treatment of kidney stone. After oral administration of the extract, the levels of mean citrate, oxalate, proteins and glycosaminoglycan in patients’ 24 h urine samples decreased significantly. Urine volume and phosphate level in the serum were not altered significantly in the urolithic patients ³⁷. It was concluded that tribulus terrestris extract was useful in the treatment of urolithiasis.

Antidiabetic activity

Diabetes mellitus is a metabolic disorder with chronic hyperglycaemia, which results from a defect in insulin secretion, insulin action, or both. The gross saponins of tribulus terrestris (GS tribulus terrestris) showed inhibitory activity against α-glucosidase. In addition, it showed the inhibition activities of a postprandial increase in blood glucose and improvement in insulin dependent diabetes symptoms ³⁸. Animal experiments indicated that GS tribulus terrestris significantly reduced the postprandial blood glucose levels by intragastric administration of sucrose in normal rats and type 2 diabetic rats but did not affect the postprandial blood glucose levels of the rats with intragastric administration of glucose ³⁹. Clinical trials proved that the water extract of tribulus terrestris (WE tribulus terrestris) has an antidiabetic activity. The fasting blood glucose, 2-h postprandial glucose, glycosylated haemoglobin and lipid profile of diabetic women treated with tribulus terrestris extract (1000 mg/day) for three months were lowered compared to those of the placebo group ⁴⁰.

Prevention and treatment of cardiovascular diseases

Presently, the clinical treatments are thrombolysis and nerve protection. Thrombolysis has a significant effect. However, it is limited by a narrow therapeutic time window. Therefore, the development of neuroprotective agents is of great significance. Studies have shown that gross saponins of tribulus terrestris has a neuroprotective effect on cerebral ischaemia injury, and these saponins have been commercially available as active compounds in traditional Chinese medicine formulations, such as “Xin-nao-shutong”, which has been used for the treatment of cardiovascular disease ⁴¹. Meanwhile, tribulus terrestris plays an important role in the treatment of cardiovascular disease with anti-myocardial ischaemia and myocardial ischaemia–reperfusion injury. Gross saponins of tribulus terrestris has a protective effect on myocardial ischaemia–reperfusion injury. Gross saponins of tribulus terrestris reduced the levels of lactate dehydrogenase (LDH), methane dicarboxylic aldehyde (MDA), tumor necrosis factor (TNF)-α and interleukin (IL)-6, increased SOD and the rate of apoptosis, and improved the structure of cardiomyocytes in rats ⁴². Moreover, GStribulus terrestris could improve coronary flow and heart function and increase adenosine triphosphate (ATP) activity in myocardial ischaemia–reperfusion injury ⁴³. The methanol extract of tribulus terrestris (ME tribulus terrestris) fruits, which mainly contains ferulic acid, phloridzin and diosgenin, had an effect on mitochondrial dysfunction in a cell-based (H9c2) myocardial ischaemia model. The extract guards the mitochondria via its antioxidant potential ⁴⁴. The cellular and molecular mechanisms of the prevention activity against arthrosclerosis occurs when gross saponins of tribulus terrestris significantly suppresses the increase in cell proliferation induced by angiotensin II, significantly suppresses the increase in the intracellular production of hydrogen peroxide (H2O2) induced by angiotensin II, significantly inhibits the increase in intracellular free Ca2+ induced by H2O2, significantly inhibits the increase in phospho-ERK1/2 induced by angiotensin II, and significantly inhibits the increase in the mRNA expressions of c-fos, c-jun and pkc-α induced by angiotensin II ⁴⁵.

Tribulus terrestris significantly suppressed the proliferation of ox-LDL-induced human umbilical vein endothelial cells (HUVECs) and the apoptosis rate. It also prolonged the HUVEC survival time and postponed the cells’ decaying stage (from the 69 h to over 100 h). tribulus terrestris normalized the increased mRNA expressions of PI3Kα and Socs3. It also decreased the mRNA expressions of Akt1, AMPKα1, JAK2, LepR and STAT3 induced by ox-LDL. The most notable changes were for JAK2, LepR, PI3Kα, Socs3 and STAT3. It is thought that the JAK2/STAT3 and/or PI3K/AKT pathway might be a very important pathway that is involved in the mechanism of tribulus terrestris as a vascular protective agent ⁴⁶.

In addition, tribulus terrestris functions as a protector of the myocardium. It supported cardioprotective properties against myocardial ischaemia, protected myocardial cells and reduced the apoptosis rate induced by oxidative stress damage ⁴⁷. Inhibition of cardiac muscle cell apoptosis occurs when gross saponins of tribulus terrestris reduces cell apoptosis through regulating protein expression of Bcl-2 and Bax ⁴⁸.

Protective activity in neuronal cells

tribulus terrestris has a protective effect for neuron injury mainly via its anti-inflammatory and antioxidant effects. Gross saponins of tribulus terrestris has a neuroprotective effect on cerebral ischaemia–reperfusion injury in rats by suppressing NF-κB, TNF-α and IL-1β. It plays a neuroprotective role in rat cerebral ischaemia reperfusion injury by inhibiting the inflammatory response and PPARγ protein expression ⁴⁹. Gross saponins of tribulus terrestris decreased the damage to PC12 cells induced by H2O2. The membrane potential of mitochondria and Bcl-2 protein expression in PC12 cells of the gross saponins of tribulus terrestris group was significantly increased in a dosage-dependent manner ⁵⁰. After cerebral haemorrhaging, brain tissue generates many free radicals that causes lipid peroxidation. Gross saponins of tribulus terrestris significantly increased the SOD content and decreased the MDA and NO levels in plasma and brain tissue to attenuate neuron injury ⁵¹.

The apoptosis of retinal ganglion cells (RGCs) is an important cause of glaucoma. tribulus terrestris can block the optic nerve injury pathway and enhance the survival of the optic nerve to protect the optic nerve ⁵². It was reported that tribulus terrestris could reduce the degeneration of RGCs and the retinal nerve fibre layer in hyper-intraocular pressure rabbits by intravenous administration with tribulus terrestris sterilization powder ⁵³.

Improvement of athletic ability activity

Athletic fatigue is generally measured by the levels of testosterone and corticosterone (cortisol), and the testosterone and cortisol (T/C) ratio. Herbs and herbal combinations have been used to improve athletic ability through several ways that mimic epinephrine effects, mimic testosterone effects, and increase the productions of corticotropin and cortisol. tribulus terrestris contains gitonin, protodioscin, and tribulosaponins A and B, which are believed to mimic testosterone-like effects in humans because of the similarities of their chemical structures ⁵⁴. The main effect is an increase of testosterone anabolic and androgenic action via the activation of endogenous testosterone production ⁵⁵.

The administration of gross saponins of tribulus terrestris (120 mg/kg) can prolong the time to exhaustion and increase body mass, relative mass, and protein levels of gastrocnemius in overtrained rats. The level of testosterone can directly affect the motor ability of the body and its restoration. Corticosterone can accelerate the decomposition of proteins in the body ⁵⁶. Treatment of rats with gross saponins of tribulus terrestris during overtraining dramatically increased the serum level of testosterone and led to a significant decrease in the serum level of corticosterone. The testosterone and cortisol (T/C) ratio with GS tribulus terrestris was much higher than that with the blank control.

In addition, the cognate receptor of testosterone is AR. IGF-1 is closely related to muscle mass, conservation of the musculoskeletal system, the metabolic rate, and muscle strength. Gross saponins of tribulus terrestris resulted in a significant increase in AR in gastrocnemius and significantly suppressed the overtraining-induced increase in IGF-1R in the liver. It was concluded that gross saponins of tribulus terrestris significantly improves exercise performance due to changes in the androgen–AR axis and IGF-1R signalling ⁵⁷.

Antitumour activity

Gross saponins of tribulus terrestris is likely to affect the processes of apoptosis and metastasis of cancer cells. The overexpression of CXCR4 has been associated with the formation of metastases and poor prognosis of patients with breast and other types of cancer. CCR7 is reportedly correlated with lymphatic metastasis and poor prognosis in breast cancers. The product of the BCL2 gene is a mitochondrial membrane protein that blocks apoptosis. After implying a cell-specificity for gross saponins of tribulus terrestris , CXCR4 expression was reduced in both cell lines, and CCR7 and BCL2 levels decreased only in tumourigenic MCF-7 cells ⁵⁸.

The anticancer mechanism of terrestrosin D was detected by observing in vitro Caspase-3 activity and vascular endothelial growth factor secretion and the in vivo anticancer effect of the PC-3 xenograft mouse model. It was concluded that terrestrosin D inhibited tumour growth through the inhibition of tumour angiogenesis. In addition, gross saponins of tribulus terrestris has a preventive efficacy against UVB-induced carcinogenesis. The photo protective effect of gross saponins of tribulus terrestris is tightly correlated with the enhancement of NER gene expression and the blocking of UVB-mediated NF-κB activation ⁵⁹.

Antibacterial activity

The antibacterial activity of tribulus terrestris had been widely studied. A total of 50% of H. pylori strains were sensitive to a concentration of 1000 mg mL−1 of total extract of tribulus terrestris by the in vitro cup plate method ⁶⁰. Gross saponins of tribulus terrestris inhibited the Candida albicans ACS1, ACS2, ERG1, ERG2, ERG6, ERG7, ERG11, ERG25, ERG26 and ERG27 genes, which are directly involved in the ergosterol synthesis pathway. An anti-fungi agent, GStribulus terrestris may function through direct binding to sterol on the cell membrane and may inhibit ERG gene expression in C. Albicans ⁶¹. tribulus terrestris was extracted with different solvents (methanol, petroleum ether, chloroform, and ethanol). The results showed that methanol extract has the highest inhibition zone for Bacillus cereus, Escherichia coli and Staphylococcus aureus. For Staphylococcus aureus and Pseudomonas aeruginosa, water extract tribulus terrestris also had a certain inhibitory effect ⁶². The ethanol extract of tribulus terrestris exhibited good antibacterial activity against Streptococcus mutans, Streptococcus sanguis, Actinomyces viscosus, Enterococcus faecalis, Staphylococcus aureus, and Escherichia coli. Complexes of T. terrestris, Capsella bursa-pastoris, and Glycyrrhiza glabra had synergistic effects compared with those of any of the herbs alone ⁶³.

Antioxidant activity

Tribulus terrestris exhibited effective antioxidant activity in a concentration-dependent manner by 2,2-di-(4-tert-octylphenol)-1-picrylhydrazyl (DPPH), H2O2, and superoxide scavenging activity, as well as the FRAP (Ferric reducing antioxidant power) assay ⁶⁴. The experiment proved that the antioxidant effect of gross saponins of tribulus terrestris is excellent and that it could improve SOD activity and MDA content for chronically high intraocular pressure in rabbits ⁶⁵. Compared with the ethanolic extraction, the butanol extract (1 mg ml−1) was rich in saponin and had notable quenching of nitric oxide (90.30%), hydroxyl radicals (90.02%), and hydrogen peroxide radicals (89%) ⁶⁶. Diosgenin from the callus of T. terrestris was found to have great antioxidant activity ⁶⁷.

Anti-inflammatory activity

The ethanol extract of tribulus terrestris and N-trans-ρ-caffeoyl tyramine isolated from tribulus terrestris had marked anti-inflammatory activities ⁶⁸. Eethanol extract of tribulus terrestris and N-trans-ρ-caffeoyl tyramine inhibited the productions of nitric oxide (NO), TNF-α, IL-6 and IL-10 in lipopolysaccharide (LPS) stimulated RAW264.7 cells in a dose dependent manner. In addition, N-trans-ρ-caffeoyl tyramine markedly suppressed the expression of cycloxygense (COX)-2 and the production of prostaglandinE2 (PGE2) through decreasing p-JNK expression.

Methanol extract of tribulus terrestris (200 and 400 mg kg−1) showed a dose-dependent inhibition of rat paw volume in a carrageenan-induced rat paw edema model. The tribulus terrestris extract and diclofenac sodium (a COX-inhibitor) were injected 30 min prior to carrageenan. The results showed that both drugs can reduce the paw volume 1–4 h after injection of carrageenan by inhibiting the releases of histamine, serotonin and kinins in the early phase. Furthermore, the anti-inflammatory effect of 400 mg kg−1 of tribulus terrestris extract is equivalent to that of 20 mg kg−1 of Diclofenac sodium ⁶⁹.

Hepatoprotective activity

Gross saponins of tribulus terrestris can ameliorate injured liver cells and have a protective effect on acute hepatic injury in mice induced by tripterygium glycosides. Gross saponins of tribulus terrestris can significantly increase the levels of SOD and GPx, decrease the level of MDA in serum, supress Caspase-3 expression and improve the ultrastructure of liver tissue in a mouse model. Caspase-3 is a class of hydrolytic protease, and its activation plays an important role in hepatocyte apoptosis. Gross saponins of tribulus terrestris can interrupt the cascade in the process of apoptosis by reducing the expression of Caspase-3. The mechanism of its hepatoprotective activity may be related to the antioxidant activity, the influence on metabolism regulation and the repression of apoptosis of liver cells, which effectively reduces the level of Caspase-3 in liver tissue ⁷⁰.

Anthelmintic and larvicidal activity

Methanol extract of tribulus terrestris resulted in wormicidal activity by inhibiting spontaneous motility (paralysis) and causing death with lower doses. The effects were comparable with that of Albendazole ⁷⁰. In addition, tribulus terrestris exhibited high larvicidal activity. Anopheles stephensi, Aedes aegypti and Culex quinque-fasciatus have been identified as the primary vectors of malaria, dengue fever and lymphatic filariasis, respectively, in this part of the desert. The larvicidal potential of tribulus terrestris was evaluated by calculating the mortality percent of A. stephensi, A. aegypti and C. quinque-fasciatus. The results showed that the fruits were a more potent form regarding larvicidal activity than the leaves ⁷¹.

Anticarious activity

Tribulus terrestris was certified to have an anticarious effect. Streptococcus mutans is an important oral pathogen that causes dental caries. The anticarious effect of tribulus terrestris was evaluated for inhibiting S. mutans bacteria. In vitro studies showed that the extract exhibited antibacterial activity for inhibiting S. mutans growth in a dose dependent manner. Meanwhile, tribulus terrestris extract suppressed the adherence of S. mutans to saliva-coated hydroxyapatite (S-HA), which simulated teeth, and inhibited the formation of water-insoluble glucans ⁷².

Antiaging and memory improvement activity

Gross saponins of tribulus terrestris can effectively increase SOD activity, decrease MDA and hydroxyproline (Hyp) in the skin and increase the activities of CAT and GPx in the whole blood of d-galactose-induced senile mice. Compared with the ageing model group, the gross saponins of tribulus terrestris group showed a thicker dermis and more compactly arranged fibre content. The skin morphology of the gross saponins of tribulus terrestris group was close to that of the normal group ⁷³.

Ageing is accompanied by a decline in memory, but gross saponins of tribulus terrestris can improve memory impairment. A study showed that gross saponins of tribulus terrestris significantly improved obtained memory disorder, consolidated memory disorder and recovered memory disorder ⁷⁴. The effect of the water extract of tribulus terrestris fruits on learning and memory ability in rodents was evaluated by recording the time of reaching the reward chamber (TRC) in the Hebb William Maze and the transfer latency (TL) in the T-zema. The results showed that the water extract of tribulus terrestris fruits significantly reduced the time of arrival at the maze in a dose-dependent manner ⁷⁵.

Absorption enhancer

Tribulus terrestris promotes absorption. The biopharmaceutics classification system (BCS) is a scientific classification method based on solubility in vitro and permeability of drugs in the intestine. Metformin hydrochloride (HCl) is a BCS class III drug with a high solubility and poor absorption characteristics. Therefore, it is necessary to increase the intestinal permeability of drugs to improve their bioavailability. The experiment indicated that tribulus terrestris can enhance the absorption of Metformin HCl in a goat intestine ⁷⁶. The absorption enhancement effect of tribulus terrestris was concluded by the presence of saponin.

Tribulus terrestris does it work

Tribulus terrestris is a commonly available weed with significant value in the traditional systems of medicine, viz. Ayurveda, Chinese, Siddha, and Unani. Despite some positive test tube and laboratory animal studies, we cannot say whether tribulus terrestris work or not. The only unbiased and scientific proof for herbs or supplements efficacy is to do human clinical trials. And without well conducted double blind and placebo controlled human trial results we cannot say whether tribulus terrestris supplement work. More clinical research is needed.

Tribulus terrestris side effects

An animal study investigated the acute toxicity of methanol extract of tribulus terrestris (2 g/kg, given orally to 5 mice for 14 days). The methanol extracts mainly consisted of flavonoids, anthraquinones, phenols/tannins, and steroids/triterpenes. As a result, there were no toxic symptoms or mortality observed in any animals and no obvious differences between the treated and control animals regarding behavioural changes and toxicological signs (general behaviour, motor activities, aggressiveness, reaction to noise, reaction to pinch, state of the tail and state of excrement) ⁷².

The genotoxic potential of tribulus terrestris extracts, as assessed by a Comet assay in a rat kidney cell line and by an Ames assay in Salmonella typhimurium strains, was evaluated ⁷⁷. The methanol extract of tribulus terrestris had relatively higher genotoxic activities (2400 mg/mL methanol extract of tribulus terrestris, tDNA%: 11.43) and cytotoxic activities (IC50 = 160 mg/mL) than water extract tribulus terrestris and the chloroform extracts of tribulus terrestris but did not damage the deoxyribonucleic acid (DNA), whereas the 300 mg/mL water extract tribulus terrestris might induce frame shift mutations when metabolically activated. Water extract tribulus terrestris showed oestrogenic activity at concentrations higher than 27 mg/mL (2.6-fold), and none of the extracts had androgenic activity.

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