actabiomedicaActa Biomedica ScientificaActa Biomedica Scientifica2541-94202587-9596Scientific Centre for Family Health and Human Reproduction Problems10.29413/ABS.2023-8.3.18actabiomedica-4220Research ArticleФАРМАКОЛОГИЯ И ФАРМАЦИЯPHARMACOLOGY AND PHARMACEUTICSПолучение эмульсионных форм фуранокумаринов борщевика Сосновского и оценка их фототоксического действия in vitroObtaining emulsions of furanocoumarins from Sosnowsky’s hogweed and in vitro assessment of their phototoxic effecthttps://orcid.org/0000-0002-5248-0136ШляпкинаВ. И.ShlyapkinaV. I.

Шляпкина Василиса Игоревна – аспирант кафедры фармакологии и клинической фармакологии с курсом фармацевтической технологии

430005, г. Саранск, ул. Большевистская, 68, Россия 

Vasilisa I. Shlyapkina – Postgraduate at the Department of Pharmacology and Clinical Pharmacology with the Course of Pharmaceutical Technology 

Bolshevistskaya str. 68, Saransk 430005, Russian Federation 

shlyapkina.98@mail.ruhttps://orcid.org/0000-0002-0739-3981КуликовО. А.KulikovO. A.

Куликов Олег Александрович – доктор медицинских наук, профессор кафедры фармакологии и клинической фармакологии с курсом фармацевтической технологии

430005, г. Саранск, ул. Большевистская, 68, Россия 

Oleg A. Kulikov – Dr. Sc. (Med.), Professor at the Department of Pharmacology and Clinical Pharmacology with the Course of Pharmaceutical Technology 

Bolshevistskaya str. 68, Saransk 430005, Russian Federation 

oleg-kulikov-84@mail.ruhttps://orcid.org/0009-0000-5145-1029БродовскаяЕ. П.BrodovskayaE. P.

Бродовская Екатерина Павловна – кандидат медицинских наук, доцент кафедры анестезиологии и реаниматологии

430005, г. Саранск, ул. Большевистская, 68, Россия 

Ekaterina P. Brodovskaya – Cand. Sc. (Med.), Associate Professor at the Department of Anesthesiology and Intensive Care Medicine 

Bolshevistskaya str. 68, Saransk 430005, Russian Federation 

ekbrodovskaya@gmail.comhttps://orcid.org/0000-0002-2793-6760Аль-хадж АюбА. М.Al-khadj AioubA. M.

 Аль-хадж Аюб Амина Мухаммед Мадиановна – инженер лаборатории фармакокинетики и таргетной фармакотерапии

430005, г. Саранск, ул. Большевистская, 68, Россия 

Amina M. Al-khadj Aioub – Engineer at the Laboratory of Pharmacokinetics and Targeted Pharmacotherapy 

Bolshevistskaya str. 68, Saransk 430005, Russian Federation 

amina.aioub1@gmail.comhttps://orcid.org/0000-0001-5152-5358АгеевВ. П.AgeevV. P.

 Агеев Валентин Павлович – младший научный сотрудник лаборатории фармакокинетики и таргетной фармакотерапии

430005, г. Саранск, ул. Большевистская, 68, Россия 

Valentin P. Ageev – Junior Research Officer at the Laboratory of Pharmacokinetics and Targeted Pharmacotherapy 

Bolshevistskaya str. 68, Saransk 430005, Russian Federation 

valeageev@yandex.ruhttps://orcid.org/0000-0002-9688-7640ПятаевН. А.PyataevN. A.

Пятаев Николай Анатольевич – доктор медицинских наук, заведующий кафедрой анестезиологии и реаниматологии

430005, г. Саранск, ул. Большевистская, 68, Россия 

Nikolay A. Pyataev – Dr. Sc. (Med.), Head of the Department of Anesthesiology and Intensive Care Medicine 

Bolshevistskaya str. 68, Saransk 430005, Russian Federation 

pyataevna@mail.ruФГБОУ ВО «Национальный исследовательский Мордовский государственный университет им. Н.П. Огарева»РоссияNational Research Ogarev Mordovia State UniversityRussian Federation20231107202383161171Copyright © Шляпкина В.И., Куликов О.А., Бродовская Е.П., Аль-хадж Аюб А.М., Агеев В.П., Пятаев Н.А., 20232023Шляпкина В.И., Куликов О.А., Бродовская Е.П., Аль-хадж Аюб А.М., Агеев В.П., Пятаев Н.А.Shlyapkina V.I., Kulikov O.A., Brodovskaya E.P., Al-khadj Aioub A.M., Ageev V.P., Pyataev N.A.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.actabiomedica.ru/jour/article/view/4220Обоснование

Обоснование. Для фотохимиотерапии различных заболеваний используются средства на основе фуранокумаринов. Доступным источником фуранокумаринов для создания лекарственных препаратов может быть борщевик Сосновского.

Цель исследования

Цель исследования. Получить стабильные эмульсии, содержащие фуранокумарины, из борщевика Сосновского и оценить их фотоцитотоксичность.

Материалы и методы

Материалы и методы. Фуранокумарины для получения эмульсий экстрагировали хлороформом из сока надземной части борщевика Сосновского. Хлороформный экстракт очищали с помощью градиентной колоночной хроматографии на силикагеле. Экстрактивную фракцию, содержащую фуранокумарины, анализировали с помощью высокоэффективной жидкостной хроматографии с ультрафиолетовым (УФ) детектированием. Экстракт с высоким содержанием 8-метоксипсоралена использовали для получения двух видов эмульсий. Экстракт растворяли в персиковом масле и эмульгировали в воде твином-80 (эмульсия № 1) и в водно-глицериновом растворе лецитином (эмульсия № 2). Эмульсии тестировали на темновую и фотоиндуцированную токсичность для фибробластов лёгких человека. Доза УФ-излучения для фотоактивации фуранокумаринов составила 9 Дж/см2. В качестве фотосенсибилизатора сравнения использовали раствор хлорина е6.

Результаты

Результаты. Полученные эмульсии содержали 1 мг/мл 8-метоксипсоралена. Обе эмульсии были гомогенными при макро- и микроскопической визуализации, сохраняли стабильность при хранении в различных температурных условиях в течение 14 дней. Эмульсия № 2 не проявляла темновой токсичности и вызывала статистически значимое угнетение жизнеспособности клеток при УФ-облучении и концентрации 12,5–31,3 мкг/мл. Эмульсия № 1 оказывала токсическое действие на клетки независимо от УФ-облучения из-за содержания в составе твина-80. По данным флуоресцентной микроскопии, фототоксическое действие эмульсии № 2 проявлялось главным образом за счёт апоптоза, в отличие от действия хлорина е6, при котором имелись более выраженные признаки некроза клеток.

Заключение

Заключение. Разработанные экспериментальные эмульсионные формы фуранокумаринов борщевика Сосновского являют собой пример перспективных лекарственных фотосенсибилизаторов растительного происхождения для фототерапии различных заболеваний в сфере дерматологии и онкологии.

Background

Background. Furanocoumarin-based drugs are used for photochemotherapy of various diseases. Sosnovsky’s hogweed can be an available source of furanocoumarins for the development of drugs.

The aim of the study

The aim of the study. To obtain stable emulsions containing furanocoumarins from Sosnowski’s hogweed and to evaluate their photocytotoxicity.

Materials and methods

Materials and methods. To obtain the emulsions, furanocoumarins were extracted with chloroform from the sap of the aerial part of the Sosnowski’s hogweed. The chloroform extract was clarified by silica gel gradient column chromatography. The extractive fraction containing furanocoumarins was analyzed by high performance liquid chromatography with ultraviolet (UV) detection. An extract with a high content of 8-methoxypsoralen was used to prepare two types of emulsions. The extract was dissolved in peach oil and emulsified in water with tween-80 (emulsion No. 1) and in an aqueous glycerin solution with lecithin (emulsion No. 2).

The emulsions were tested for dark and photo-induced toxicity for human lung fibroblasts. The dose of UV radiation for the photoactivation of furanocoumarins was 9 J/cm2. A solution of chlorine e6 was used as a comparison photosensitizer.

Results

Results. The obtained emulsions contained 1 mg/ml 8-methoxypsoralen. Both emulsions were homogeneous at macro- and microscopic visualization, remained stable when stored under various temperature conditions for 14 days. Emulsion No. 2 did not show dark toxicity and caused a statistically significant inhibition of cell viability under UV irradiation at a concentration of 12.5–31.3 µg/mL. Emulsion No. 1 had a toxic effect on cells regardless of UV irradiation due to the content of tween-80. According to fluorescent microscopy, the phototoxic effect of emulsion No. 2 was manifested mainly due to apoptosis, in contrast to the effect of chlorine e6, in which there were more pronounced signs of cell necrosis.

Conclusion

Conclusion. The developed experimental emulsions of furanocoumarins from Sosnovski’s hogweed are an example of promising medicinal photosensitizers of plant origin for phototherapy of various dermatological and oncological diseases.

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The authors declare that there are no conflicts of interest present.