INTRODUCTION:

In the pharmaceutical industry, in most cases, plant raw materials are used inefficiently since mainly one drug is obtained from one plant. However, it is known that after the main extraction of medicinal plant raw materials, the meal, which is disposed of as production waste, contains other biologically active compounds. Rational processing of these wastes will make it possible to obtain biologically active substances as the basis for new pharmaceutical preparations from the same plant raw materials^1,2,3.

One such plant is Tribulus terrestris L. which is one of the sources of raw materials that are widely processed in the pharmaceutical industry.

Tribulus terrestris L. from the family Zygophyllaceae is an annual creeping herbaceous plant. In the world, Tribulus terrestris L. is distributed in warm regions of Europe, America, Africa, Australia, India^4,5,6,7, and Uzbekistan, it is found in Tashkent, Namangan, Andijan, Fergana, Samarkand, Bukhara, Kashkadarya, and Surkhandarya regions⁸.

The aerial part of Tribulus terrestris contains steroidal saponins (trillin, dioscin, diosgenin, tigogenin, neotigogenin, gracillin, protodioscinin, gitogenin, neogitogenin, chlorogenin, ruscogenin, sarsasapogenin), flavonoids (kaempferol, quercetin, rhamnetin, azaleatin, isorhamnetin, tamarack tin), alkaloids, tannins, vitamin C. The composition of the aerial part of Tribulus terrestris includes macro elements such as potassium, sodium, calcium, and magnesium; trace elements: manganese, copper, iron, zinc, cobalt, molybdenum, chromium, aluminum, barium, vanadium, selenium, nickel, strontium, cadmium, boron, lead^9-16.

Various pharmacological properties of Tribulus terrestris are known, including tonic, immunomodulatory, antidiabetic, vasodilator, hypotensive, hypolipidemic, antitumor, anti-inflammatory, analgesic, antioxidant, antimicrobial, hepatoprotective and cardiotonic effects. A hypocholesterolemic drug has been created based on the sum of steroid glycosides from the Tribulus terrestris, which helps reduce blood clotting, increases the tone of the small intestine, and has anabolic activity^13,17-24. Based on protodioscin, which is a steroidal glycoside of the furostanol type, drugs (Tribestan, Tribusponin, etc.) have been developed and introduced to increase strength and muscle mass of the body, for rapid recovery after difficult working conditions, intense training, and after taking anabolic steroids²⁵.

At the Institute Chemistry of Plant Substances, a technology has been developed for the production and serial production of the substance “Dry extract Tribulus” with a content of furostanol saponins of at least 45% in terms of protodioscin from the aerial part of Tribulus terrestris has been launched. “Dry extractTribulus” is produced at the “Scientific and Technology Center according to GMP requirements” of the Institute Chemistry of Plant Substances according to the requirements of FA 42 Uz-3283-2021. The “Dry Tribulus Extract” technology is as follows: the aerial part of Tribulus terrestris is extracted six times with 70% ethyl alcohol at room temperature and infused for 8 hours each. The combined and filtered extract is concentrated to a dry mass content of 25% in the bottom residue. The bottom residue is treated three times with chloroform, and then twice with ethyl acetate. From a purified aqueous solution, furostanol saponins are extracted four times with butanol. The butanol extract is concentrated, dissolved in water, and dried in a spray dryer^26,27.

As can be seen from the review, Tribulus terrestris has various pharmacological actions due to its rich chemical composition. However, the introduced drugs are mainly based on saponins. To rationally use plant raw materials, research was carried out on developing a new pharmaceutical substance (as a dry extract) from processing waste of aerial part Tribulus terrestris, namely, from the meal formed after extraction with 70% ethanol.

Among the large number of various diseases found in humans, kidney disease occupies one of the important places. In renal failure, impaired renal function leads to a decrease in the excretion of substances excreted in the urine, and the most important is a violation of the excretion of nitrogen metabolism products, which in turn leads to the development of azotemia. Rapid correction of azotemia can lead to restoration of renal function. Treatment may include drugs to increase cardiac output and blood pressure, as well as treating the underlying cause of azotemia. Effective herbal preparations for the treatment of acute and chronic deficiency with symptoms of azotemia have now been introduced such drugs as lespefril, lepeflan, сynaroside, etc.^28,29. At the same time, it should be noted that the arsenal of drugs used in the treatment of renal failure, especially accompanied by azotemia, is very small. Therefore, the search among natural compounds for pharmacological agents that increase the functional activity of the kidneys and normalize nitrogen metabolism in acute and chronic failure is an urgent task.

The study aimed to study the hypoazotemic action of dry extracts obtained from Tribulus terrestris meal.

MATERIALS AND METHODS:

Plant Material and Extract Preparation:

To obtain dry extracts, the raw materials were prepared from Tribulus terrestris meal, obtained at the “Scientific and Technological Center for GMP Requirements” of the Institute Chemistry of Plant Substances, which is discarded as waste from the production of the substance “Dry extract Tribulus” containing furostanol saponins of at least 45% in terms of protodioscin. The meal remains in production after the regeneration of ethanol, extracted from the aerial part of Tribulus terrestris with 70% ethanol. The analysis showed that the meal contained up to 30% moisture, including ethanol. Therefore, the meal was dried in a drying apparatus with forced air ventilation under the following conditions: the thickness of the layer of plant material on the dryer salver is 20 mm; air speed flow – 15 m/s; process temperature – no more than 70℃; the duration of the process is at least 5 hours.

After drying, the moisture content in the meal was 6.0% (further in the text raw materials), which was used as a raw material to obtain various samples of dry extracts. Samples were extracted from the dry extracts as follows:

Method I:

12.0 kg of raw material was loaded into the extractor using an installed pump to circulate the extractant, 72.0 liters of water (water ratio 1:6) were poured in, and the extraction was carried out by circulating the extractant at a speed of 120 l/hour at a temperature of 80 ℃. The extractant was circulated by drawing the extract from the bottom of the extractor, feeding it from above in the form of a shower. The first extraction was carried out for 5 hours, then the extract was poured out in an amount of 48.0 liters (hydraulic ratio 1:4). A new portion of purified water (48.0 liters) was poured into the extractor, and extraction was carried out under conditions similar to the first extraction. The second extract was drained and a third extraction was carried out similarly to the second extraction. The resulting extracts were cooled, combined, and filtered on a suction filter (vacuum -0.06-0.08 MPa) filled with belting. The filtered extract was concentrated (vacuum -0.06-0.08 Mpa, temperature 60 ℃), and the thick mass was dried and analyzed. We obtained 264 g of dry extract (sample 1). The yield was 4.4% by weight of the raw material.

Method II:

The second portion of the concentrate obtained in method I was concentrated (vacuum -0.8...-0.6 kgf/cm2, temperature 60°C) to a content of 60% dry mass. The resulting concentrate was poured into a container and, with vigorous stirring, 96% ethanol was added in a concentrate-alcohol volume ratio of 1:5. Then the lid of the container was closed and left for 6 hours. The precipitate that formed was separated by filtration on a suction filter (vacuum -0.06-0.08 MPa). The precipitate was dried and analyzed. We obtained 168 g of dry extract (sample 2). The yield was 2.8% by weight of the raw material.

Method III:

The filtrate from method II was concentrated, and the thick mass was dried and analyzed. We obtained 93 g of dry extract (sample 3). The yield was 1.55% by weight of the raw material.

Method IV:

10.0 kg of raw material was loaded into the extractor and 60 liters of 40% ethanol, preheated to a temperature of 60 °C, was poured in and infused for 3 hours. The extract was poured in an amount of 38.0 liters and 40.0 liters of a new portion of hot 40% ethyl alcohol was poured into the extractor and extracted for 3 hours. The third and fourth extractions were carried out similarly to the second extraction. The extracts were combined, filtered, and concentrated, and the thick mass was dried and analyzed. We obtained 565 g of dry extract (sample 4). The yield was 5.65% by weight of the raw material.

Method V:

Dry extract samples were obtained similarly to method IV, extracting with 40% ethanol at room temperature. We obtained 310 g of dry extract (sample 5). The yield was 3.1% by weight of the raw material.

Pharmacological studies:

Experiments were carried out on white mongrel male rats weighing 200-250g. The studied dry extract obtained from the Tribulus terrestris meal was administered orally (through a special probe into the stomach) at a dose of 100 mg/kg. The hypoazotemic activity of the studied extract of the Tribulus terrestris was compared with the effect of the preparation of Cynaroside approved for use in clinical practice. Cynaroside was administered orally at a dose of 50 mg/kg. The preparations were ground using apricot gum. The control group animals were orally injected with an appropriate volume of apricot gum emulsion. The content of urea and creatinine in the blood serum of animals was determined two hours after administration of the preparations.

During the experiments, urea (enzymatic-colorimetric test-Berthelot, Cypress Diagnostics, Belgium) and creatinine (colorimetric-Jaffe, Cypress Diagnostics, Belgium) were determined in the blood using a standard set of reagents. To do this, blood was taken from the tail vein and after decapitation of rats.

The glycerol model of acute renal failure:

Acute pathology was caused by intramuscular administration of 50% aqueous glycerin solution at a dose of 10 ml/kg to rats. Following the introduction of glycerin, the rats developed symptoms of acute renal failure, which was manifested by an increase in the concentration of urea and creatinine in the blood serum. These indicators reached their maximum values on the third day after the end of the administration of a 50% aqueous glycerin solution^30,31. Blood was taken on the third day, and the content of urea and creatinine was determined.

Acute renal pathology caused by iodine tincture:

Acute kidney pathology, accompanied by hyperazotemia, was caused as follows: In rats weighing 200–250 g under ether anesthesia, both kidneys were carefully removed through a lumbar incision, they were lubricated with 10.0% alcohol tincture of iodine³², placed in the renal bed and the wound was sewn up. These animals usually develop severe azotemia on the first day after surgery.

Statistical Analysis:

The statistical significance of differences was evaluated by the Student’s t‐test. The level of significance was defined as p < 0.05. Results are expressed as means ± standard deviation.

Reference drug:

The substance Cynaroside, which is obtained from the aerial part of Ferula varia Trautv., family Apiaceae, was used as a reference drug. Cynaroside contains at least 95.0% luteolin-7-O-β-D-glucopyranoside or 7-O-β-D-glucopyranoside-5,3′,4′- trioxyflavone (C₂₁H₂₀O₄) in terms of dry matter. Cynaroside reduces the content of urea and residual nitrogen in the blood and also helps restore the excretion of creatinine and urea. The drug is approved for use in medicine as a hypoazotemic agent^28,33.

Method for quantitative analysis of polysaccharides:

About 2.0 g (exactly weighed) of the analytical sample was placed in a 100 ml volumetric flask, 30 ml of water was added and placed in an ultrasonic bath until completely dissolved. The volume of the solution was brought to the mark and mixed. The resulting solution was filtered (solution A). 25 ml of solution A was placed in a centrifuge tube, and 75 ml of 95% alcohol was added, mixed, and heated in a water bath to 30 ℃ for 5 minutes. After an hour, the contents were centrifuged at 5000 rpm for 30 minutes. The supernatant liquid was filtered under vacuum at a residual pressure of 13-16 kPa through a POR 16 glass filter with a diameter of 40 mm, dried to constant weight at a temperature of 100-105 ℃. The precipitate was quantitatively transferred to a filter and washed successively with 15 ml of a solution of 95% alcohol in water (3:1), 10 ml of acetone, and 10 ml of ethyl acetate³⁴. The filter with the sediment was dried first in air, then at a temperature of 100-105 °C to constant weight. The percentage of polysaccharides (X) was calculated using the formula:

(m₂ – m₁) + 100 +100

X = ----------------------------

m+25

Where: m₁ - is filter mass in grams; m₂- is the mass of the filter with sediment in grams; m- is the mass of the sample in grams.

Quantitative determination of the total phenolic compounds.

Place about 1.0 g (exactly weighed) of the substance into a 100 ml volumetric flask, add 50 ml of 40% ethyl alcohol, and stir until the substance is completely dissolved. The volume of the contents of the flasks was mixed, brought to the mark with the same solvent, and mixed (Solution A). 1 ml of solution A was placed in a 100 ml volumetric flask, 1.0 ml of Folin-Ciocalteu reagent and 10 ml of 20% sodium carbonate solution were added, the volume was adjusted to the mark with distilled water, everything was thoroughly mixed and kept in a dark place. After 15 minutes, the optical density of the resulting solution was measured on a Shimadzu-1800 spectrophotometer at a wavelength of 720 nm in a cuvette with a layer thickness of 10 mm. The reference solution is a similar solution without the addition of test solution A^35,36. The content of the total phenolic compounds in percent (X) in terms of gallic acid in the substance was calculated using the formula:

DV₁V₂ 100

X = ---------------------------------

V₃m(100-W) E^1%_1cm

where: D – optical density of the test solution; V₁– extract volume, ml (100 ml); V₂ – volume of solution for spectrophotometry, ml (100 ml); V₃ – volume of extract taken for determination, ml (1 ml); E^1%_1cm – specific absorption index of gallic acid in complex with the Folin-Ciocalto reagent at a wavelength of 720 nm, equal to 90; m – mass of the substance in grams; W – weight loss when drying the substance as a percentage.

RESULT AND DISCUSSION:

The method of obtaining a dry extract from Tribulus terrestris meal with a hypoazotemic effect was chosen based on pharmacological studies. To do this, the effect of the studied extracts on the content of urea and creatinine in the blood serum of intact rats was studied.

In this study, we have tested the effects of five samples from Tribulus terrеstris meal on the content of urea and creatinine in the blood of intact rats and compared them to the effects of the known substance Сynaroside. In Table 1, two hours after administration, all five samples (100 mg/kg) have decreased urea and creatinine concentrations in the blood, with Sample 4 being the most effective (28.1% reduction in urea and 23.8% reduction in creatinine). The reference substance Cynaroside (50 mg/kg) also peaked two hours after administration and reduced the content of urea and creatinine by 24.5 and 16.7%, respectively.

Thus, in experiments on intact rats, it was found that with a single injection, all the studied samples from Tribulus terrеstris meal at a dose of 100 mg/kg had a hypoazotemic effect. Sample 4 showed a more pronounced hypoazotemic effect. In terms of the degree of decrease in the content of urea and creatinine in the blood, sample 4 from Tribulus terrеstris meal even surpassed the reference drug Cynaroside. In addition, from the examples given in the experimental part, it can be seen that the yield of sample 4 (Triburenal) is greater than the rest of the samples. Based on this, method 4 was chosen to obtain a dry extract from Tribulus terrestris meal with a hypoazothemic effect.

The study continued to study the effect of the substance Triburenal on the content of urea and creatinine in the blood serum of rats with acute renal pathology caused by glycerin. These indicators reached their maximum values on the third day after the end of the administration of a 50% aqueous solution of glycerin (in the control groups, the increase in urea and creatinine was 204.0% and 172.0%) (table 2). In animals injected with sample 4, the content of urea and creatinine in the blood serum was also higher than the initial, but not as significant as in the control. If we express the increase in urea as a percentage relative to the baseline level, then the urea content in the blood serum of rats receiving the substance Triburenal on the third day was 152.0% higher (the difference with the control was 52.0%). Similar changes were noted in the serum creatinine content. Table 2 shows that this indicator was 123.0% higher than the baseline level (in the control group rats, this increase was 172.0%, i.e. the difference with the control was 49.0%).

Under similar experimental conditions, the substance Cynaroside, like the substance Triburenal, prevented an increase in urea and creatinine in the blood serum of rats with advanced pathology, but to a lesser extent. When it was used on the third day, the studied indicators increased by 163.0 and 141.0% relative to the baseline level (the difference with the control was 41.0 and 31.0%, respectively).

Тable 2. The effect of the substance Triburenal and Cynaroside on the urea content in the blood serum of rats after administration of an aqueous solution of glycerin (M±m, n=6)

Experimental conditions	Urea, mmol/l		Creatinine, mmol/l
Experimental conditions	Initial	After 72 hours	Initial	After 72 hours
Control	5.6±0.24	17.0±0.76	71.2±2.6	193.8±3.4
Triburenal	5.9±0.24	14.9±0.66*	68.4±2.4	152.4±2.7*
Cynaroside	5.7±0.19	15.0±0.62*	72.2±2.7	174.2±3.3*

Note. *-reliable in relation to the corresponding control indicators (p<0.05).

Thus, in male rats with an experimental model of acute renal failure caused by the administration of a 50% aqueous solution of glycerin, it was found that the substance Triburenal exhibits a significant hypoazotemic effect. It prevents a sharp increase in the final products of nitrogen metabolism in the blood serum of animals and reduces these indicators on the 3^rd day of administration. In terms of its effectiveness under these conditions, the substance Triburenal is significantly superior to Cynaroside. Such a pronounced hypoazotemic effect of the substance Triburenal in the conditions of this pathology could be due to its normalizing effect on kidney function.

The acute renal pathology is caused by iodine tincture. The results of this series of experiments are presented in Table 3, from which it can be seen that in the group of control animals, already one day after the operation, the content of urea and creatinine in the blood serum increased by 189.0% and 124.0%, respectively. And for the next five days, they remained at a high level. The decrease in the final products of nitrogen metabolism in the blood serum occurred gradually and returned to the initial level after fifteen days.

Table 3. The effect of the substance Triburenal and Cynaroside on the content of urea and creatinine in the blood serum of rats with experimental renal pathology caused by lubrication of the kidneys with 10% iodine tincture (M±m, n=6)

The studied parameters	Observation days	Experimental conditions
The studied parameters	Observation days	Control	Triburenal	Cynaroside
Initial	-	5.7±0.18	5.6±0.46	5.5±0.25
Urea content in rat blood serum, mmol/l	1 3 5 10 15	16.5±0.61* 13.1±0.65* 10.1±0.64* 10.6±0.31* 8.8±0.21	12.1±0.38* 8.4±0.30* 6.1±0.24* 5.7±0.39 6.4±0.32*	13.2±0.53* 8.8±0.53* 7.2±0.51* 6.4±0.32* 6.1±0.28
Initial	-	61.7±1.8	64.6±4.6	63.6±2.5
Creatinine content in rat blood serum, mmol/l	1 3 5 10 15	138.4±6.5* 110.7±6.5* 93.2±6.4* 72.1±3.5* 68.6±2.6	120.2±5.8* 90.2±3.6* 68.9±2.9 65.2±4.2 64.7±3.8	128.2±5.2* 105.8±6.2* 71.4±6.0* 67.4±6.0 65.1±3.2

Note: *-reliable in relation to the corresponding indicators of the initial level (p<0.05).

Group 2 rats injected with the substance Triburenal developed moderate azotemia. So, a day after the operation and the introduction of the substance Triburenal, the content of urea in the blood serum increased by 116%, and creatinine by 86.0%. With further administration of the drug, the effect was even more significant. On the third day, the increase in urea was only 50.0% and creatinine by 39.6%, and on the fifth day, the content of urea and creatinine in the blood serum of these animals did not differ significantly from the baseline level (the increase was 8.9 and 6.6%, respectively). In the control at this time, the urea content was 77.0%, and creatinine was 51.0% higher than the baseline level with a high degree of confidence.

In the third group of animals, which were injected with Cynaroside after causing renal pathology, the increase in urea and creatinine was lower compared to the control, but higher than the corresponding indicators of the group of rats receiving sample 4, and besides, their normalization occurred only on the 10^th day of observation (table 3).

Thus, in experimental acute renal failure, the substance Triburenal showed a hypoazotemic effect, which had a positive effect on kidney function and prevented the development of oliguria, and in this case, it was superior to the reference of the substance Cynaroside.

Based on the results of the analysis, it was revealed that in the substance Triburenal, the content of polysaccharides is 22%, and 31.3% of the total phenolic compounds (Table 4).

Table 4. Organoleptic and physicochemical properties of the substance Triburenal.

Indicators	Results
Appearance	Yellow powder
Solubility	Soluble in 40% ethanol and 40% methanol, poorly soluble in water, insoluble in chloroform
рН	6.37±0.12
Weight loss on drying, %	4.28±0.09
Sulfate ash, %	0.032±0.01
Heavy metals, %	0.0001± 3·10^-6
Polysaccharide content, %	22.14±0.43
the total phenolic compounds content, %	31.3±0.07

CONCLUSION:

It has been established that Triburenal substance, containing 22% polysaccharides and 51.3% total phenolic compounds, exhibits a hypoazotemic effect, which has a positive effect on kidney function. The meal of Tribulus terrestris was first proposed to the pharmaceutical industry as a raw material for producing a hypoazotemic substance. As a result of the study, a new Triburenal substance with hypoazotemic action was developed from processing waste of Tribulus terrestris, allowing for this plant's rational use.

CONFLICT OF INTEREST:

The authors have no conflicts of interest regarding this research.

ACKNOWLEDGMENTS:

The authors are grateful to the Innovative Development Agency for providing a special grant PZ-2020102917 on the theme “Development of a technology for obtaining the substance of a new drug with hypoazotemic action based on the Tribulus terrestris”.

REFERENCES:

1. Mamatkhanov AU, Khalilov RM, Mamatkhanova MA. Complex processing of Rhaponticum carthamoides rhizomes with roots to produce ecdisten substance, total flavonoids, and lipid concentrate. Pharmaceutical Chemistry Journal. 2021; 54(10): 1040-1044. doi.org/10.1007/s11094-021-02325-z

2. Mamatkhanov AU, Khajibaev TA, Khalilov RM. Technology of obtaining the sum of iridoids from the waste processing the aerial part of Ajuga turkestanica. Khimiya Rastitel'nogo Syr'ya. 2023; 3: 293–302. doi.org/10.14258/jcprm.20230311829.

3. Khalilov RM, et al. Component composition of lipid-containing waste from processing aerial parts of Ferula tenuisecta and Ferula kuhistanica and development of an oil composition with wound-healing action. Pharmaceutical Chemistry Journal. 2023; 57(5): 683-687. doi.org/10.1007/s11094-023-02938-6

4. Grigorova S, et al. Effect of Tribulus terrestris extract on semen quality and serum total cholesterol content in white Plymouth rock-mini cocks. Biotechnology in Animal Husbandry. 2008; 24(3-4): 139-146. doi.org/10.2298/BAH0804139G

5. Mamdouh NS, et al. Pharmacognostical Studies on Stem of Tribulus terrestris L. Research J. Pharmacognosy and Phytochemistry. 2013; 5(4): 171-177.

6. Mamdouh NS, et al. Pharmacognostical Studies on Leaf of Tribulus terrestris L. Research J. Pharmacognosy and Phytochemistry 2012; 4(6): 303-309.

7. Mamdouh NS, et al. Tribulin, a New Steroidal Saponin from the Aerial parts of Tribulus terrestris. Research J. Pharmacognosy and Phytochemistry. 2012; 4(5): 237-239.

8. Toyjonov K, Nigmatullaev BA, Sagdullaev ShSh. Etymological dictionary of Latin names of medicinal plants of Uzbekistan. Tashkent. 2016.

9. Zhurba OV, Dmitriev MYa. Medicinal, Poisonous and Harmful Plants. Moscow. 2008.

10. Burda NYe, et al. The element composition study of thick extract from Tribulus terrestris L. Herb. Research Journal of Pharmaceutical, Biological and Chemical Sciences. 2016; 7(6): 2200-2202.

11. Xu Y, et al. A new furostanol glycoside from Tribulus terrestris. Molecules. 2010; 15(2): 613-618. doi.org/10.3390/molecules15020613

12. Khudenko PE, et al. Flavonoids in the grass of Tribulus terrestris L. Pharmacy and Pharmacology. 2015; 2(9): 18-23. doi.org/10.19163/2307-9266-2015-3-2(9)-18-23

13. Hammoda HM, et al. Chemical constituents from Tribulus terrestris and screening of their antioxidant activity. Phytochemistry. 2013; 92: 153-159. doi.org/10.1016/j.phytochem.2013.04.005

14. Noori M, Dehshiri MM, Zolfaghari MR. Tribulus Terrestris L. (Zygophyllaceae) Flavonoid Compounds. International Journal of Modern Botany. 2012; 2(3): 35-39. doi.org/10.5923/j.ijmb.20120203.01

15. Madhavi T, et al. A Phytochemical Review on Tribulus terrestris Linn. Research J. Pharmacology and Pharmacodynamics. 2011; 3(5): 218-222.

16. Madhavi T, et al. Isolation of Tiliroside from Tribulus terrestris. Research J. Pharmacognosy and Phytochemistry. 2011; 3(6): 281-285.

17. Sharifi AM, Darabi R, Akbarloo N. Study of antihypertensive mechanism of Tribulus terrestris in 2K1C hypertensive rats: role of tissue ACE activity. Life Sciences 2003; 73(23): 2963-2971. doi.org/10.1016/j.lfs.2003.04.002

18. Chhatre S, et al. Phytopharmacological overview of Tribulus terrestris. Pharmacognosy Reviews. 2014; 8(15): 45-51. doi.org/10.4103/0973-7847.125530

19. Heidari MR, et al. The Analgesic Effect of Tribulus terrestris Extract and Comparison of Gastric Ulcerogenicity of the Extract with Indomethacine in Animal Experiments. Annals of the New York Academy of Sciences. 2007; 1095(1): 418-427. doi.org/10.1196/annals.1397.045

20. Ojha SK, et al. Chronic Administration of Tribulus terrestris Linn. extracts improve cardiac function and Attenuates Myocardial Infarction in Rats. International Journal of Pharmacology. 2008; 4(1): 1-10. doi.org/10.3923 / ijp.2008.1.10

21. Sudhanshu KM, et al. Experimental studies on the Renal Protective effect of Gokshura (Tribulus terrestris Linn) and Varuna (Crataeva nurvala Buch-Ham). Research J. Pharmacology and Pharmacodynamics. 2016; 8(2): 75-82. doi: 10.5958/2321-5836.2016.00014.8

22. Latifa NA, et al. Evaluation of Antibacterial and Antioxidant activities of Tribulus terrestris L. Fruits. Research Journal of Pharmacy and Technology. 2021; 14(1): 331-336. doi: 10.5958/0974-360X.2021.00061.5

23. Dileep SB, et al. Formulation, Evaluation and Assessment of In Vitro Potential of Gokshur Ghan Tablet against Urolithiasis (Mutrakrichra). Research Journal of Pharmacy and Technology. 2021; 14(4): 1945-2. doi: 10.52711/0974-360X.2021.00344

24. Latifa NA, et al. Evaluation of Anticancer Activity of Withania somnifera L. and Tribulus terrestris L. on Human Breast Cancer Cells In vitro. Research Journal of Pharmacy and Technology 2023; 16(7): 3079-2. doi: 10.52711/0974-360X.2023.00506

25. Khristich TN, et al. Tribestan helps athletes going in for power sports. Bukovinian Medical Herald. 2011; 15(2-58) 126-129.

26. Khajibaev TA, Khalilov RM. The process optimization of furostanol saponins extraction from the aerial part of Tribulus Terrestris. International Journal of Scientific Research in Chemical Sciences. 2023; 10(6): 1-7.

27. Hajibaev TA, Ibragimov TF, Khalilov RM. Optimal conditions for cleaning and drying furostanol saponins from Tribulus terrestris. Khimiya Rastitel'nogo Syr'ya. 2023; 2: 327–333. doi.org/10.14258/jcprm.20230211444

28. Mamatkhanova MA, et al. Technology for cynaroside production from the aerial part of Ferula varia and evaluation of its hypoazotemic activity. Pharmaceutical Chemistry Journal, 2009; 43(3): 160-162. doi.org/10.1007/s11094-009-0262-7

29. Guliaev VG, Ivanov I.I, Guliaeva SF. The hypoazotemic and diuretic action of lespeflan in acute kidney failure. Urol Nefrol (Mosk). 1993; 4: 32-34.

30. Borisova IV, Shtrygol SYu. Renal and neuroprotective effects of perftoran on a model of toxic kidney damage in rats. Russian Biomedical Journal. 2004; 5(36): 136-139.

31. Valdivielso JM, et al. Role of glomerular nitric oxide in glycerol-induced acute renal failure. Canadian Journal of Physiology and Pharmacology. 2000; 78(6): 476-482. doi.org/10.1139/y00-012

32. Sokolova VE. On the hypoazotemic effect of flavonoids. Pharmacology and toxicology. Republican interdepartmental collection. 1975; 10:62-66.

33. Kotenko LD, et al. Standardization of the herb Ferula varia. Khimiya Rastitel'nogo Syr'ya. 2009; 4: 151–154.

34. Kakhramanova SD, Bokov DO, Samylina IA. Quantification of polysaccharides in medicinal plant raw materials. Farmatsiya, 2020; 69(8): 5–12. doi.org/10/29296/25419218-2020-08-01.

35. Nikolaeva TN, Lapshin PV, Zagoskina NV. Method for determining the total content of phenolic compounds in plant extracts with folindenis reagent and folin-chocalteu reagent: modification and comparison. Khimija rastitel'nogo syr'ja. 2021; 2:291–299. doi.org/10.14258/jcprm.2021028250

36. Sonia, Singh Sumitra. Tribulus terrestris L. fruits: An extensive Pharmacognostical and Phytochemical Quality Assesment using UV-spectrophotometer. Research Journal of Pharmacy and Technology. 2022; 15(12): 5431-5. doi.org/10.52711/0974-360X.2022.00915

Received on 10.02.2024 Modified on 08.05.2024

Research J. Pharm. and Tech 2024; 17(10):4826-4832.

DOI: 10.52711/0974-360X.2024.00742

Experimental conditions	Urea, mmol/l			Creatinine, mmol/l
Experimental conditions	The initial level	2 hours after administration of the drug	Effect, %	The initial level	2 hours after administration of the drug	Effect, %
Control	5.4±0.24	5.6±0.18		70.4±2.6	68.8±2.2
Simple 1	5.3±0,19	4.4±0.15	16.9	74.4±2.3	62.7±2.2^*	15.7
Simple 2	5.5±0.26	4.6±0.19^*	16.3	69.5±3.2	60.2±2.8	13.4
Simple 3	5.8±0.26	4.5±0.15^*	22.0	71.2±3.1	58.3±1.8^*	18.1
Simple 4	5.7±0.24	4.1±0.12^*	28.1	70.4±2.4	53.6±1.4^*	23.8
Simple 5	5.4±0.26	4.5±0.19^*	16.7	72.6±2.5	62.5±2.8	13.9
Сynaroside	5.3±0.19	4.0±0.13^*	24.5	68.8±1.8	57.3±2.0*	16.7