BABIN ZUB – BUGARSKI Tribulus terrestris Bulgaricum (Zygophyllaceae)

BABIN ZUB – BUGARSKI Tribulus terrestris Bulgaricum (Zygophyllaceae)

Tribulus terrestris (Zygophyllaceae)

Tribulus terrestris (family Zygophyllaceae), commonly known as Gokshur or Gokharu or puncture vine, has been used for a long time in both the Indian and Chinese systems of medicine for treatment of various kinds of diseases.
Its various parts contain a variety of chemical constituents which are medicinally important, such as flavonoids, flavonol glycosides, steroidal saponins, and alkaloids.
It has diuretic, aphrodisiac, antiurolithic, immunomodulatory, antidiabetic, absorption enhancing, hypolipidemic, cardiotonic, central nervous system, hepatoprotective, anti-inflammatory, analgesic, antispasmodic, anticancer, antibacterial, anthelmintic, larvicidal, and anticariogenic activities.

Tribulus terrestris (Zygophyllaceae)

Common name: Puncture-vine

How used: Medicinal

Activities: 380 Chemicals w/Activities: 27l Chemicals: 50






































Tribulus terrestris (Zygophyllaceae)

CRC Handbook of Medicinal Herbs and/or CRC Handbook of Proximate Analyses

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Tribulus terrestris (Zygophyllaceae)

Common name(s): Puncture-vine

How used: Medicinal

Activities: 380 Chemicals w/Activities: 27 Chemicals: 50



Antiinflammatory Hypocholesterolemic Pesticide Cancer-Preventive Antioxidant Antiviral Vasodilator

Hypotensive Antitumor Aldose-Reductase-Inhibitor Antispasmodic

Hepatoprotective Antihypertensive Antimutagenic Antihistaminic Diuretic Antibacterial

Antiprostatitic Antiallergic Estrogenic Antileukemic Apoptotic Antiulcer Antidiabetic Antiarthritic Propecic

Antiaggregant Cytotoxic Antiradicular Antiseptic Antiherpetic Hypoglycemic 5-Alpha-Reductase-Inhibitor Anxiolytic Antiatherosclerotic Antidepressant Antiandrogenic Antihepatotoxic Lipoxygenase-Inhibitor Antialopecic Antistress Immunostimulant Antiobesity Mutagenic Antimalarial Cardioprotective cAMP-Phosphodiesterase-Inhibitor Antifatigue Antitumor-Promoter Flavor Antitrypanosomic MAO-Inhibitor  Topoisomerase-II-Inhibitor Immunomodulator Antiedemic Antiosteoporotic Antitumor (Lung) Antinociceptive Carcinogenic Anticataract Topoisomerase-I-Inhibitor Antifeedant Angiotensin-Receptor-Blocker fungicide Antimenopausal Hepatomagenic 11B-HSD-Inhibitor Capillariprotective Antiproliferant Antileukotriene-D4 Diaphoretic? Tranquilizer Antifibrinolytic Beta-Blocker Insectifuge Artemicide Nematicide Antimetastatic Antidementia Antitumor (Breast) …


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The preliminary phytochemical study of TT revealed the presence of saponins, flavonoids, glycosides, alkaloids, and tannins. According to literature data, the saponin composition and the saponin content of TT from different geographic regions is different. Kostova et al. studied the chemistry and bioactivity of saponins in TT. 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. found that the quantity of main flavonoids is about 1.5 times that of main saponins. This indicated that the flavonoid contents in TT should be studied, developed, and further used.[9] Bhutani et al. 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. 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. optimized the extraction condition using orthogonal experiment. Matin Yekta et al. 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.

Raja and Venkataraman identified flavonoids from the petroleum ether and chloroform extracts of fresh fruits of TT from India using ethyl acetate: benzene (1:9) solvent system. These flavonoids were not detected in the fruit extracts of other variety, namely T. alatus. Hence, presence of such pharmacognostic constituents can be used as a diagnostic tool in the identification of the species and study of contamination/adulteration. Tian Shung et al. isolated and characterized three new compounds, terrestribisamide, 25R-spirost-4-en-3, 12-dione, and tribulusterine, together with 10 known compounds, N-p-coumaroyltyramine, terrestriamide, hecogenin, aurantiamide acetate, xanthosine, fatty acid ester, ferulic acid, vanillin, p-hydroxybenzoic acid, and β-sitosterol, from the dried fruits of TT. The alkaloids present are harmane and norharmane. The β-carboline alkaloid, tribulusterine, is present in minor quantities in fruits. Gas chromatography-mass spectrometry analysis of methanolic extract of the whole plant of TT revealed the presence of α-Amyrin as the major constituent and seven minor constituents, which are 3,7,11,15-tetramethyl-2-hexadecen-1-ol, n-hexadecadienoic acid, hexadecadienoic acid ethyl ester, phytol, 9,12-octadecadienoic acid, 9,12,15-octadecatrienoic acid, and 1,2-benzenedicarboxylic acid disoctyl ester. Sterols such as β-sitosterols and stigmasterols were also found to be present.

TT 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. TT 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. TT 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, TT is used as diuretic, mild laxative, and general tonic.

Diuretic activity

The diuretic properties of TT are due to large quantities of nitrates and essential oil present in its fruits and seeds. The diuretic activity can also be attributed to the presence of potassium salts in high concentration. Ali et al. tested the aqueous extract of TT prepared from its fruit and leaves in rat diuretic model and strips of isolated Guinea pig ileum were used for the contractility test. The aqueous extract of TT, in oral dose of 5 g/kg, elicited a positive diuresis, which was slightly more than that of furosemide. Sodium and chloride concentrations in the urine were increased. The increased tonicity of the smooth muscles, which was produced by TT extract, together with its diuretic activity helped in the propulsion of stones along the urinary tract.Saurabh et al. evaluated the different extracts of TT fruits, viz. aqueous, methanolic, Kwatha-high strength, Kwatha-low strength, and Ghana powder, for diuretic activity in rats. Kwatha-high strength showed diuretic effect comparable to that of the reference standard frusemide and also exhibited additional advantage of potassium-sparing effect. The diuretic action of TT makes it useful as an anti-hypertensive agent.

Aphrodisiac activity
Adaikan et al. reported that the TT extract exhibited a pro-erectile effect on rabbit corpus cavernosum smooth muscle ex vivo after oral treatment at doses of 2.5, 5, and 10 mg/kg body weight for 8 weeks. A significant relaxation of 24% was observed with nitroglycerine in the corpus cavernosum smooth muscle tissue. Similarly, 10% relaxation was observed with both acetylcholine and electrical field stimulation, respectively, following the above treatment with TT in rabbits. The enhanced relaxant effect observed is due to increase in the release of nitric oxide from the endothelium and nitrergic nerve endings, which may account for its claims as an aphrodisiac. Singh et al. evaluated the acute and repeated dose administration of lyophilized aqueous extract of the dried fruits of TT (LAET) at doses of 50 and 100 mg/kg of body weight as a sexual enhancer in the management of sexual dysfunction in male rat. A dose-dependent improvement in sexual behavior was observed with the LAET treatment, which was more prominent on chronic administration of LAET. A significant increase in serum testosterone levels too was observed. These findings confirm the traditional use of TT as a sexual enhancer in the management of sexual dysfunction in males. Ethanolic extract of TT exhibited protective effect against cadmium-induced testicular damage. The protective effect appears to be mediated directly either through inhibition of testicular tissue peroxidation by antioxidant and metal chelating activity or by stimulating the testosterone production from Leydig cells. TT extract (100-300 mg/l) treatment to a fish colony was found to be effective in increasing the proportion of males in the population. It was found that testes of fish treated with TT extract showed all stages of spermatogenesis with improved growth performance in Poeciliata reticulata fish species. The two main components of the saponin fraction from TT, namely protodioscin and protogracillin, are responsible for the observed biological aphrodisiac activity. It is suggested that protodioscin works by increasing the conversion of testosterone into the potent dehydrotestosterone, which stimulates not only increase in the sex drive but also the production of red cells from bone marrow along with muscular developments contributing to improvement of blood circulation and the oxygen transport systems, leading to optimal health.

Antiurolithic activity
An ethanolic extract of TT fruits was tested in urolithiasis induced by glass bead implantation in albino rats by Anand et al. It exhibited significant dose-dependent protection against deposition of calculogenic material around the glass bead, leukocytosis, and elevation in serum urea levels. Subsequent fractionation of the ethanol extract led to decrease in activity. Various other biochemical parameters in urine, serum, and the histopathology of urinary bladder were restored in a dose-dependent manner. A novel antilithic protein having cytoprotective potency and of molecular weight ~ 60 kDa was purified from TT.Aggarwal tested the activity of TT on the nucleation and growth of calcium oxalate (CaOx) crystals as well as on oxalate-induced cell injury of NRK 52E renal epithelial cells. The experiments revealed that TT extract not only has a potential to inhibit nucleation and growth of the CaOx crystals but also has a cytoprotective role. TT was found to inhibit stone formation in various models of urolithiasis using sodium glycolate and ethylene glycol.[29]

Glycolate oxidase (GOX) is one of the principal enzymes involved in the pathway of oxalate synthesis converting glycolate to glyoxylate by oxidation and finally to oxalate. The antiurolithic activity of TT is attributed to its GOX inhibition. Quercetin and kaempherol, the active components of TT, were found to be non-competitive and competitive inhibitors of GOX, respectively.

Immunomodulatory activity
Saponins isolated from the fruits of TT demonstrated dose-dependent increase in phagocytosis, indicating stimulation of nonspecific immune response. An alcoholic extract of the whole plant of TT exhibited a significant dose-dependent increase in humoral antibody titre and delayed type hypersensitivity response, indicating increased specific immune response.

Antidiabetic activity
Saponin from TT possesses hypoglycemic properties.TT significantly reduced the level of serum glucose, serum triglyceride, and serum cholesterol, while serum superoxide dismutase (SOD) activity was found to be increased in alloxan-induced diabetic mice. The decoction of TT showed inhibition of gluconeogenesis in mice. TT ethanolic extract at 2 g/kg body weight produced protective effect in streptozotocin-induced diabetic rats by inhibiting oxidative stress. Ethanolic extract of TT exhibited 70% inhibition of α-glucosidase at 500 μg/ml using maltose as the substrate and 100% inhibition of aldose reductase at a dose of 30 μg/ml using dl-glyceraldehyde as the substrate.[35] A significant decrease in the postprandial blood glucose level of rats was found after administration of saponin from TT. TT produced dilation of coronary artery and improved the coronary circulation. It is therefore recommended in Ayurveda for the treatment of angina pectoris and other cardiac complications of diabetes. Thus, TT could be beneficial in the treatment of diabetes by lowering blood glucose, lipid levels, and by its antioxidant mechanism.

Absorption enhancer
Ethanolic extract of TT enhanced the absorption of metformin hydrochloride, a Biopharmaceutics Classification System (BCS) class III drug, in everted sac technique using goat intestine, due to the presence of saponins in the extract.

Hypolipidemic activity
The aqueous extract of the fruits of TT was evaluated for their hypolipidemic activity in Wistar albino rats. A dose of 580 mg/kg of the extract was found to decrease cholesterol-induced hyperlipidemia, with a decrease in cholesterol, triglycerides, low density lipoprotein (LDL), very low density lipoprotein (VLDL), and atherogenic index (AI), and an increase in high density lipoprotein (HDL) levels in the blood. Hypolipidemic activity may be due to the presence of phenolic compounds leading to increased lipoprotein lipases in the muscles and decreased activity in the adipose tissues, thus indicating that plasma triglycerides are utilized for energy production by the muscle and not for energy storage by the adipose tissue. The pleotropic effect of TT at 5 mg/kg/day dose for 8 weeks on the lipid profile and vascular endothelium of the abdominal aorta in New Zealand rabbits fed on a cholesterol-rich diet was studied. It was found that dietary intake of the herb significantly lowered the serum lipid profile, decreased endothelial cellular surface damage as well as ruptures, and partially repaired the endothelial dysfunction resulting from hyperlipidemia.

Saponins from TT were studied on diet-induced hyperlipidemia in mice for its preventive and therapeutic effect. The preventive effect was demonstrated by decrease in the levels of serum total cholesterol (TC) and LDL-cholesterol. It also reduced the liver TC and triglycerides and increased the activity of SOD in the liver. It showed therapeutic effect by significantly reducing the serum TC and liver TC.

Activity in cardiac disorders
TT showed significant effect in the treatment of various cardiac diseases including coronary disease, myocardial infarction, cerebral arteriosclerosis, and the sequelae of cerebral thrombosis. Zhang et al. evaluated the protective effect of tribulosin from TT against cardiac ischemia/reperfusion injury to study the underlying mechanism in rats. Tribulosin protected myocardium against ischemia/reperfusion injury through protein kinase C epsilon activation.[40] Tribulosin treatment resulted in a significant reduction of malondialdehyde, aspartate transaminases, creatine kinase, lactate dehydrogenase activity, and myocardial apoptosis rate. It increased the activity of SOD. Crude saponin fraction of this plant has shown significant effects in the treatment of various cardiac diseases including hypertension, coronary heart disease, myocardial infarction, cerebral arteriosclerosis, and thrombosis. It also has been shown that the aqueous extract of TT fruits has significant acetylcholinesterase (ACE) inhibitory effects in vitro. Methanolic and aqueous extracts of TT are shown to possess significant antihypertensive activity by direct arterial smooth muscle relaxation and membrane hyperpolarization in spontaneously hypertensive rats. TT also appears to protect the heart cells and may even improve the heart function following a heart attack.

Central nervous system (CNS) activity
Swiss Albino mice demonstrated antidepressant and anxiolytic activity on administration of 260 mg/kg dose of Rasayana Ghana tablet comprising three potent well-established rejuvenator herbs, viz. Tinospora cordifolia (stem), Emblica officinalis (fruit), and TT (fruit and root), present in equal quantities in the tablet. It was suggested that harmine, a β-carboline alkaloid present in TT, is one of the main active constituents that contributes to the above-mentioned activities. Harmine is an inhibitor of monoamine oxidase which helps to increase level of dopamine in the brain.

Hepatoprotective activity
The TT extract (250 mg/kg) showed a remarkable hepatoprotective activity against acetaminophen-induced hepatotoxicity in Oreochromis mossambicus fish. The elevated biochemical parameters and decreased level of reduced glutathione enzymes were normalized by treatment with TT extract (250 mg/kg) for acetaminophen-induced toxicity in freshwater fish.

Antiinflammatory activity
The ethanolic extract of TT inhibited the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in lipopolysaccharide-stimulated RAW264.7 cells. It also suppressed the expression of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-4 in macrophage cell line. Thus, the ethanolic extract of TT inhibits the expression of mediators related to inflammation and expression of inflammatory cytokines, which has a beneficial effect on various inflammatory conditions.[45] The methanolic extract of TT showed a dose-dependent inhibition of rat paw volume in carrageenan-induced inflammation in rats.

Analgesic activity
Analgesic activities of TT were studied in male mice using formalin and tail flick test. The study indicated that the methanolic extract of TT at a dose of 100 mg/kg produced analgesic effect. This analgesic effect of the TT extract may be mediated centrally and/or peripherally. Effect of the extract was lower than morphine and higher than acetylsalicylic acid (aspirin) in both tests. Pretreatment of animals with opioid receptor antagonist, naloxone, did not change the analgesic effect of the extract in both tests; therefore, the involvement of opioid receptors in the analgesic effect of TT is excluded. However, the other mechanisms responsible for the analgesic effect of TT remain to be investigated. The results of ulcerogenic studies indicate that the gastric ulcerogenecity of TT is lower than indomethacin in the rat’s stomach.

Antispasmodic activity
The lyophilized saponin mixture of the plant exhibited a significant decrease in peristaltic movements of rabbit jejunum preparation in a dose-dependent manner. These results showed that the saponin mixture may be useful for smooth muscle spasms or colic pains.

Anticancer activity
Chemopreventive potential of the aqueous extract of the root and fruit of TT at 800 mg/kg on 7,12-dimethylbenz (a) anthracene (DMBA) and croton oil induced papillomagenesis in Swiss albino male mice depicted significant reduction in tumor incidence, tumor burden, and cumulative number of papillomas, along with a significant increase in the average latent period in mice treated orally with TT suspension continuously at pre-, peri-, and post-initiation stages of papillomagenesis, as compared to the control group treated with DMBA and croton oil alone. The root extract of TT exhibited better chemopreventive potential than the fruit extract at the same concentration (800 mg/kg body weight) in skin papillomagenesis in mice. The aqueous extract of TT blocked proliferation in HepG2 cells and could also induce apoptosis through the inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ĸB) signaling. Thus, TT has clinical therapeutic effects against liver cancer cells. The aqueous root extract of TT produced significant radioprotection when given orally (800 mg/kg) for seven consecutive days prior to gamma irradiation. TT extract pretreatment protected against radiation damage by inhibiting radiation-induced glutathione depletion and decreasing lipoperoxidation level in the liver of mice. Saponins isolated from the aerial parts of TT were studied for their cytostatic/cytototoxic activity on human fibroblasts. The effects were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) analysis and3H thymidine incorporation to assess cell viability and proliferation, respectively. Saponins showed a dose-dependent decrease in3H thymidine incorporation into the DNA, indicating decreased proliferation. Similarly, they were found to be less toxic for normal human skin fibroblasts. The mechanism of action involves up- and down regulation of polyamines’ homeostasis, suppression of proliferation, and induction of apoptosis.

Antibacterial activity
All parts (fruits, stems, leaves, and roots) of Turkish and Iranian TT showed antibacterial activity against Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, in contrast to the aerial parts of Yemeni TT which had no detectable antibacterial activity against these bacteria, while only the fruits and leaves of Indian TT were active exclusively against E. coli and S. aureus. These different results relating to the antibacterial activity of TT may be due to using different geographic sources of the plant, types of strains, and assay methods. The methanolic extract of fruits of TT was found to be most active against gram-positive and gram-negative bacteria, while moderate activity was observed in its petroleum ether extract and chloroform extract.

Anthelmintic activity
The methanolic extract of TT was found to be more effective than the petroleum ether, chloroform, and water extracts for in vitro anthelmintic activity on the nematode Caenorhabditis elegans. Further bioactivity-guided fractionation confirmed tribulosin and β-sitosterol-d-glucoside to be the active components with ED50 of 76.25 and 82.50 μg/ml, respectively.

Larvicidal activity
The petroleum ether extract of the leaves of TT exhibited better larvicidal activity against the third instar larvae and adults of the mosquito, Aedes aegypti, which is the vector of dengue fever, with LC50 of 64.6 ppm as compared to the crude ethanol and acetone extracts.

Anticariogenic activity
The ethanolic extract of fruits of TT (0.1-0.5 mg/ml) possesses significant anticariogenic activity against Streptococcus mutans, the pathogen responsible for dental caries. The growth, acid production, adhesion, and water-insoluble glucan synthesis of S. mutans were significantly inhibited in the presence of the ethanol extract of TT. Further studies are necessary to elucidate the active constituents of TT responsible for such activities.

Recommended dose of TT in Ayurveda
Fruit: 3-6 g of the drug in powder form; 20-30 g of the drug for decoction

Root: 20-30 g of the drug for decoction.
TT, a commonly available weed, is of significant value in the traditional systems of medicine, viz. Ayurveda, Chinese, Siddha, and Unani. TT is also a reputed herb in the folk medicine of many countries for a number of diseases. The whole plant of TT has been explored exhaustively for its phytochemical and pharmacological activities such as diuretic, aphrodisiac, antiurolithic, immunomodulatory, antihypertensive, antihyperlipidemic, antidiabetic, hepatoprotective, anticancer, anthelmintic, antibacterial, analgesic, and anti-inflammatory. Considering the available literature on TT, the plant could have a potential as a herbal medicine for effective blood pressure control due to its diuretic activity (potassium sparing), antihyperlipidemic activity, and cardioprotective activity. Though TT has been used extensively over the centuries and currently scientific evidence with respect to its pharmacological activities is also being generated, more studies at the molecular level are needed to further understand the mechanism by which it modifies the disease condition. The pharmacological experiments performed on the plant must be extended to the next level of clinical trials to generate novel drugs. This will help TT in achieving a status of medicine or to be prescribed as a dietary supplement in various disease conditions.

Pakovanje mL/ g:
 10 20 30 50 100 250 500 1000

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