RU2524799C1 - Method for endothelial protection with api-phytocomposition - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: method involves simulating endothelial dysfunction in Wistar male rats by daily intraperitoneal introduction of L-nitro-arginine-methyl ester 25 mg/kg/day for 7 days. Endothelial dysfunction is corrected by intragastric introduction of an api-phytocomposition in the form of an aqueous suspension of honey, royal jelly, bee bread, Resveratrol in the ratio of 10:1:1:2. The composition is introduced in a dose of 200 mg/kg of an animal's body weight once a day for 7 days.

EFFECT: method provides synergetic endothelioprotective effects with no side effects observed when treating with synthetic preparations.

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Description

The invention relates to medicine, in particular to experimental pharmacology.

According to well-known literature, resveratrol, along with hypolipidemic, antioxidant, estrogenic, antiaggregatory activity, also has endotheliotropic activity in vitro experiments. The endotheliotropic activity of resveratrol is due to activation of the eNOS enzyme (Leikert JF, Rathel TR, Wohlfart P, Cheynier V, Vollmar AM, Dirsch VM. Red wine polyphenols enhance endothelial nitric oxide synthase expression and subsequent nitric oxide release from endothelial cells. Circulation. 2002 Sep 24; 106 (13): 1614-7.). Perga and royal jelly are used in the complex therapy of cardiovascular diseases (hypertension, atherosclerosis, etc.)

A known method for the correction of endothelial dysfunction with a combination of enalapril and resveratrol in L-NAME-induced nitric oxide deficiency (RU 2301670 publ. 06/27/2007), which is characterized by the fact that dysfunction is simulated by daily intraperitoneal administration of L-nitro-arginine-methyl ether Wistar rats at a dose of 25 mg / kg. Against the background of modeling dysfunction, it is corrected by the simultaneous administration of enalapril intragastrically at a dose of 0.5 mg / kg and resveratrol intraperitoneally at a dose of 2 mg / kg once a day. In this case, the degree of development of dysfunction and the activation of its correction with the help of these means is evaluated by the ratio of endothelium-independent (ENZV) and endothelium-dependent vasodilation (ESV). The method provides the opportunity to study the endothelioprotective effects of resveratrol and the activation of endothelial NO synthase at the stage of modeling endothelial dysfunction and their assessment using the above ratio of ENZV and ESV. 2 tab.

The main disadvantage of this method is that enalapril is not indicated for impaired renal function, renal artery stenosis, hyperkalemia, pregnancy, children, etc. The use of enalapril can cause a number of side effects: convulsions, insomnia, impaired renal and liver function, increased liver transaminases and concentration bilirubin in the blood, etc.

Closest to the claimed solution is a method of correcting endothelial dysfunction with a combination of losartan and resveratrol in L-NAME-induced nitric oxide deficiency (RU 2306924 publ. 09/27/2007), which is characterized by the fact that endothelial dysfunction is simulated by daily intraperitoneal administration to rats L arginine methyl ester at a dose of 25 mg / kg. Then, on the 7th day from the start of the experiment, losartan is intragastrically administered at a dose of 6 mg / kg and resveratrol is administered intraperitoneally at a dose of 2 mg / kg once a day. The method provides effective correction of endothelial dysfunction in specific experimental conditions. 2 tab.

The main disadvantage of this method is that losartan - a synthetic drug - has a large number of side effects, precautions.

The objective of the invention is a method of endothelioprotection api-phytocomposite containing honey, royal jelly, bee bread, resveratrol, devoid of the disadvantages of the known solutions.

The task is achieved by the fact that against the background of the reproduction of endothelial dysfunction in male Wistar rats by daily, for 7 days, intraperitoneal administration of a blocker of the synthesis of NO L-nitro-arginine methyl ether (L-NAME) at a dose of 25 mg / kg / day and carrying out its correction, and the correction of endothelial dysfunction is carried out by intragastric (through a probe) administration of api-phytocomposition in the form of an aqueous suspension of honey, royal jelly, perga, resveratrol in a mass ratio of 10: 1: 2: 1, at a dose of 200 mg / kg of animal body weight , once a day, for 7 days to.

The combination in the api-phytocomposition of resveratrol, royal jelly and bee bread leads to a synergy of endothelioprotective effects.

The main advantage of the proposed method is the absence of side effects observed when taking the synthetic drug losartan, as well as the natural origin of all components of the api-phytocomposition.

The method is as follows

The experiments were carried out on white rats male Wistar line weighing 250-300 g. N-HHTpo-L-arginine methyl ether (L-NAME) was administered intraperitoneally at a dose of 25 mg / kg / day. On the 8th day from the beginning of the experiment, under anesthesia (chloral hydrate 300 mg / kg), a catheter is inserted into the right carotid artery to record blood pressure (BP), bolus administration of pharmacological agents is carried out in the right femoral vein. Vascular tests are carried out for endothelium-dependent vasodilation (ESV) - intravenous administration of acetylcholine (AH) at a dose of 40 μg / kg, and endothelium-dependent vasodilation (ENZV) - intravenous administration of sodium nitroprusside (NP) at a dose of 30 μg / kg disfunction coefficient (QED):

$$\mathrm{TO}ED=\frac{S_{\mathrm{BUT}D}{}_{\text{NP}}}{{\text{S}}_{\text{HELL}}{}_{\text{OH}}},$$

where QED is the coefficient of endothelial dysfunction; S _{AD BP} - the area of the triangle above the recovery curve of blood pressure during a functional test with the introduction of sodium nitroprusside, S _{AD AX} - the area of the triangle above the recovery curve of blood pressure during a functional test with the introduction of acetylcholine at a dose of 40 μg / kg (Patent No. 2301015 dated 06/20/2007 g. (Bull. No. 17).

In statistical data processing, the average value of the standard deviation is calculated. Differences are considered significant at p <0.05.

Concrete example

The blockade of NO synthase caused by the 7-day administration of L-NAME to male laboratory rats led to disruption of the relationship between vasodilating and vasoconstrictor mechanisms for regulating vascular tone, as evidenced by the results of vascular tests for endothelium-dependent (acetylcholine) and endothelium-independent sodium (nitroprotic) an increase in QED from 1.28 ± 0.23 in intact animals to 3.52 ± 0.32 (p <0.05). Daily, for 7 days, intragastric administration of api-phytocomposition against the background of endothelial dysfunction led to a significant decrease in QED to 1.73 ± 0.09, which is significantly less than in the group of animals with L-NAME (p <0.05) . Blood pressure in intact animals was: systolic (SBP) - 125.0 ± 5.3 mm Hg, diastolic (DBP) - 89.0 ± 5.8 mm Hg. With the introduction of L-NAME there was an increase blood pressure up to 183.1 ± 9.4 mmHg and 141.7 ± 7.4 mm Hg respectively. The introduction of the studied api-phytocomposite against the background of L-NAME lowered blood pressure to 143.5 ± 2.35 mm Hg. and 108.7 ± 4.9 mmHg respectively (p <0.05).

Thus, the obtained results indicate a pronounced correction of endothelial dysfunction under conditions of L-NAME-induced deficiency of nitric oxide in rats with api-phytocomposite, including honey, royal jelly, bee bread, resveratrol.

Claims (1)

An endothelioprotection method with api-phytocomposite, comprising reproducing endothelial dysfunction in male Wistar rats daily, for 7 days, by intraperitoneal administration of an NO synthesis blocker of L-nitro-arginine-methyl ether (L-NAME) at a dose of 25 mg / kg / day and carrying out its correction, characterized in that the correction of endothelial dysfunction is carried out by intragastric administration of api-phytocomposition in the form of an aqueous suspension of honey, royal jelly, perga, resveratrol in a ratio of 10: 1: 2: 1, at a dose of 200 mg / kg of animal body weight, once per day , For 7 days.