Фармакологічне дослідження фітозасобів з хости ланцетолистої (Hosta lancifolia Engl.)

Abstract

Дисертаційна робота присвячена фармакологічному дослідженню настойки та сухого екстракту з листя хости ланцетолистої. Доведено, що настойка належить до VI класу токсичності (ЛД50>15000 мг/кг) – відносно нешкідливі речовини, екстракт належить до V класу токсичності (ЛД50>5000 мг/кг) – практично нетоксичні речовини. Встановлена умовно-терапевтична доза – 0,15 мл/кг маси тіла для настойки та 100 мг/кг маси тіла для сухого екстракту з листя хости ланцетолистої. Виявлено, що настойка з листя хости ланцетолистої проявляє гепатопротекторні властивості, сухий екстракт – гепатопротекторні та кардіопротекторні властивості. Механізм реалізації фармакологічних ефектів настойки та сухого екстракту з листя хости ланцетолистої насамперед пов'язаний із його антиоксидантними властивостями, що підтверджується пригніченням процесів перекисного окиснення ліпідів та окисної модифікації протеїнів, зменшенням проникності плазматичних мембран гепатоцитів та кардіоцитів, зменшенням ендогенної інтоксикації та відновленням показників системи антиоксидантного захисту. Проведені дослідження підтверджують перспективність подальшого дослідження лікарських форм з листя хости ланцетолистої як антиоксидантних засобів з метою створення на їх основі нових рослинних гепатопротекторних та кардіопротекторних препаратів.

Диссертационная работа посвящена фармакологическому исследованию настойки и сухого экстракта из листьев хосты ланцетолистной. Доказано, что настойка относится к VІ классу токсичности (ЛД50>15000 мг/кг) – относительно безвредные вещества, экстракт относится к V классу токсичности (ЛД50>5000 мг/кг)– практически нетоксичные вещества. Установлена условно-терапевтическая доза - 0,15 мл/кг массы тела для настойки и 100 мг/кг массы тела для сухого экстракта из листьев хосты ланцетолистной. Выявлено, что настойка из листьев хосты ланцетолистой проявляет гепатопротекторные свойства, сухой экстракт - гепатопротекторные и кардиопротекторными свойства. Механизм реализации фармакологических эффектов настойки и сухого экстракта из листьев хосты ланцетолистной прежде всего связан с его антиоксидантными свойствами, что подтверждается угнетением процессов перекисного окисления липидов и окислительной модификации протеинов, уменьшением проницаемости плазматических мембран гепатоцитов и кардиоцитов, уменьшением эндогенной интоксикации и восстановлением показателей системы антиоксидантной защиты. Проведенные исследования подтверждают перспективность дальнейшего исследования лекарственных форм из листьев хосты ланцетолистой как антиоксидантных средств с целью создания на их основе новых растительных гепатопротекторных и кардиопротекторных препаратов.

The thesis is devoted to the pharmacological research of the tincture and dry extract made from the leaves of hosta lancifolia. It is proved that tincture belongs to the VI class toxicity (LD50>15000 mg/kg) that are relatively harmless substances, extract belongs to the V class toxicity (LD50>5000 mg/kg that are practically nontoxic substances. The prescribed therapeutic dose is defined as 0.15 ml/kg body weight for tincture and 100 mg/kg body weight for dry extract from the leaves of hosta lancifolia. It was found that the corrective effect of the investigated factors on the development of inflammation was less noticed than in diclofenac sodium as a result of the study of anti-inflammatory activity of the THL and DEHL. While studying the effects of the THL and DEHL on the condition of the mucous membrane of the stomach, it was found out that both pharmacological drugs do not show ulcerogenic effect. The study of local irritating properties of the THL and DEHL has shown that the studied dosage forms do not show an irritative effect while it has been in contact with the mucous membrane of the eye of rabbits. Hepatoprotective properties of the tincture and a dry extract from the leaves of hosta lancifolia were studied on the model of tetra chloromethane effect of rats’ liver. The THL and DEHL have a positive effect on the processes of POL in the organism of affected animals. The decrease of the TBA-AP content by 13.1%, DEHL - by 38.7% relative to the level of affected animals was noticed in the blood serum due to the use of THL on the 4th day of the research. The use of the THL and DEHL was stated by the normalization of 2, 4-DNFH (370 nm) neutral and 2, 4 -DNFH (430 nm) of a basic nature in the blood serum. The THL and DEHL have a positive effect on the antioxidant system. It was found that THL had the most positive effect on the 14th day of the experiment in the study of SOD activity in liver homogenate. After taking DEHL SOD the activity has increased by 23.3% on the 4th day, by 18.8% on the 7th year, by 27.5% on the 14th relative to the level of SOD in animals with controlled pathology. The CT activity in the blood serum and liver homogenate of the rats affected by tetra chloromethane was studied. Infusion of it into the infected organism has led to a possible increase of this indicator in serum only on the 14th day of the experiment. The use of DEHL was effective on the 7th and 14th day of the experiment (catalase activity in serum increased by 1.6 and 1.3 times, respectively, in comparison with control pathology). It is noted that rats’ liver damaged by tetrachloromethane leads to the development of destructive processes in the body, which is indicated by an increase activity of the aminotransferase in the blood serum. After taking of THL on the 4th day of the experiment, the activity of ALAT in the blood serum of the affected rats decreased by 3.6 times, on the 7th day of the experiment - by 3.8 times. The probable decrease (p≤0.05) of ALAT activity in serum was observed in the last term of the study (14 days of the experiment). Similar changes were noted in the study of the activity of ASAT. The DEHL from our study led to a decreased activity of aminotransferase after affection. The bile duct and its biliary functions were examined on the model of tetrachloromethane lesion of the liver. There was a decrease in the volume of bile and the rate of its secretion in the body of rats with controlled pathology. After taking the THL and DEHL the maximum increase in bile volume was observed on the 14th day of the experiment - 1.2 times the level of animals with control pathology, the probable increase in the rate of bile secretion was observed on the 4th, 7th and 14th days of the experiment. The activity of the neutralizing function of the liver was studied on the model of tetrachloromethane lesion. On the 4th day after the last leading of tetrachloromethane, the time of biotransformation of hexenal in the liver (sleep duration) was 23 minutes longer compared to the control group. In animals with pathology receiving tincture, the duration of sleep decreased, but no probable changes were noted. The use of DEHL led to a probable (p <0.05) decrease in the duration of hexenal sleep. Morphological studies of the structure of the liver have been done. According to the morphological data, the most positive hepatoprotective effect was shown by silymarin. The use of the extract was less effective, although it also has influenced the regeneration of the structural components of the affected liver. The least positive corrective effect was observed while taking the tincture. The cardioprotective properties of DEHL have been studied in the conditions of adrenal myocardial dystrophy. It was established that the activation of lipid peroxidation was observed on the background of the adrenaline infusion in a dose of 0.5 mg / kg body weight in the myocardium and blood serum of rats. The use of DEHL has led to the decrease in the activity of lipoperoxidation processes, reduced the TBA-AP content in the myocardium homogenate by 82%, which confirmed the anticipated antioxidant properties of the given pharmacological procedure. DEHL has shown an effective influence on the content of OMP decreasing it by the end of the experiment as compared to the control group. ECG confirmed the development of myocardial dystrophy in the rats which received a toxic dose of adrenaline. The introduction of dry extract from the leaves of the host in the development of adrenaline myocardial dystrophy contributes to the growth of ventricular depolarization and increase in the contractile capacity of the heart. Cardioprotective properties of DEHL are confirmed by histological studies of myocardial infarction.