INVESTIGATION OF ACUTE TOXICITY AND NEUROTROPIC PROPERTIES OF THE FLOWERS' DENSE EXTRACTS OF TAWNY DAYLILY (HEMEROCALLIS FULVA L.) AND HYBRID DAYLILY (HEMEROCALLIS HYBRIDA VAR. «STELLA DE ORO»)

Анотація

INVESTIGATION OF ACUTE TOXICITY AND NEUROTROPIC PROPERTIES OF THE FLOWERS' DENSE EXTRACTS OF TAWNY DAYLILY (HEMEROCALLIS FULVA L.) AND HYBRID DAYLILY (HEMEROCALLIS HYBRIDA VAR. «STELLA DE ORO»)

S. M. Marchyshyn¹, O. V. Zarichanska², S. Yu. Cholach¹

I. Horbachevsky Ternopil State Medical University¹

Vinnytsia National Memorial Medical University by M. I. Pyrohov²

Introduction.  In modern conditions almost no one person is able to avoid stressful situations that lead to manifestations of functional disorders of the central nervous system - neuroses. Anxiety, depression, sleep disturbances and disorder of emotional sphere due to the prevalence among the population gain significant measures. In accordance with the urgency of the problem, the search for safety and effective remedies for correction of mild neurosis’ manifestations among the preparations of plant origin is promising. From the literature sources, it is known that preparations from flowers of Daylily genus plants (Hemerocallis L.) show effects on the nervous system and are used in traditional medicine in China, Japan and North America for the treatment of depression, insomnia and other psycho-emotional disorders. Previously we performed a comprehensive phytochemical study of plant raw materials of two species of daylilies – tawny daylily (Hemerocallis fulva L.) and hybrid daylily (Hemerocallis hybrida var. “Stella De Oro”). Analysis of quantitative composition and qualitative content of biologically active substances of two investigated daylilies’ species demonstrates the appropriateness of the creation of phytosubstances on their base and investigation of phytosubstances’ pharmacological properties. The purpose of these studies was to determine the safety of thick extracts from flowers of tawny daylily and hybrid daylily, to establish the influence of extracts on behavioral responses and emotional state, depressive behavior and physical endurance of laboratory mice.

Investigation methods. The investigation was conducted on 48 male white nonlinear mice weighing 18-25 grams, which were divided into 8 groups (n = 6): Group 1 – intact control; 2-5 groups – animals, injected with thick extracts from flowers of tawny daylily and hybrid daylily variety “Stella De Oro” in the form of aqueous solutions intragastric at doses 100 and 250 mg / kg. 6-7 comparison groups received medication according to the behavioral model: imipramine (solution for injection “Melipramine”, Egis, Hungary) 25 mg / kg (for Porsolt’s test of antidepressant activity); 2-etyltiobenzimidazole hydrobromide – the active component of actoprotective drugs “Bemityl” and “Metaprot” at dose 50 mg / kg (for test of actoprotective effect). To determine the effect of daylilies flowers’ extracts on behavioral responses and emotional state of intact animals common open field test was used without medicinal preparation’s control.

Results and discussions. Investigation of acute toxicity has shown safety of both extracts samples – at dose 5000 mg / kg these substances did not cause any symptoms of poisoning. In open field behavioral test extract from tawny daylily’s flowers in dose 100 mg / kg shown pronounce stimulating effect; extract from hybrid daylily’s flowers in dose 250 mg / kg elucidated sedative activity. In behavioral despair’s test with immobilization the extract of hybrid daylily’s flowers in dose of 250 mg / kg shown distinct antidepressant properties, which are close to the level of activity of tricyclic antidepressant imipramine.

Tawny daylily and hybrid daylily flowers’ extracts at both investigated doses had no effect on physical endurance of mice in the forced swim test with a load, whereas reference-medication shown expressive actoprotective effect.

Conclusions. The acute toxicity of the dense extracts from flowers of tawny daylily and hybrid daylily of “Stella De Oro” variant has been determined for the first time; the investigated substances were assigned to the 5^th classof substances’ toxicity according to the classification of Hodge and Sterner (practically non-toxic substances – LD₅₀ > 5000 mg/kg). The effect of investigated extracts on behavioral reactions and emotional condition, depressive behavior and physical endurance of laboratory mice has been defined using behavioral tests. Diverse and expressive influence of investigated thick extracts on central nervous system and physical endurance of laboratory mice has been elucidated.

References

1. Azymova Yu. E. Depresiya i yiyi somatychni proyavy / Yu. E. Azymova, G. R. Tabyeyeva // Lechashhyj vrach. – 2009. – [Elektronyj resurs]. – Rezhym dostupu: http://www.lvrach.ru/2009/09/10637387/
2. Akimova M. S. Eksperymentalne doslidzhennya stresprotektornyx vlastyvostej kriopodribnenogo poroshku aroniyi chornoplidnoyi pry gipokinetychnomu stresi: avtoref. dys. na zdobuttya nauk. stupenya kand. farm. nauk : specz. 14.03.05 «Farmakologiya» / M. S. Akimova; Nacionalnyj farmacevtychnyj universytet. – Kharkiv, 2014. – 20 s.
3. Eksperymentalne vyvchennya novyh adaptogennyh zasobiv: metod. rekomendaciyi / L. V. Yakovlyeva, O. Ya. Mishhenko, Yu. B. Laryanovska, O. Yu. Koshova ta in. – K.: DFCz, 2009. – 38 s.
4. Konovalova O. Yu. Analiz rynku antydepresyvnyh preparativ na osnovi zviroboyu zvychajnogo, yaki zareyestrovani v Ukrayini / O. Yu. Konovalova, T. K. Shurayeva, T. V. Dzhan, T. A. Groshovyj, N. P. Darzuli // Farmacevtychnyj chasopys. – 2010. – № 2. – S. 52-57.
5. Kurkin V. A. Izuchenie nejrotropnoj aktyvnosty novyh lekarstvennyh preparatov iz travy zveroboya / V. A. Kurkyn, A. V. Dubyshhev, O. E. Pravdyvceva, L. N. Zymyna // Medycynskyj almanah. – 2009. – № 4 (9). – S. 33-36.
6. Marchyshyn S. M. Vmist aminokyslot u pidzemnyh i nadzemnyh organax lilijnyka buro-zhovtogo (Hemerocallis fulva L.) ta lilijnyka gibrydnogo (Hemerocallis hybrida var. “Stella De Oro”) / S. M. Marchyshyn, O. V. Zarichanska //  Farmacevtychnyj chasopys. – 2015. – № 1 (33). – S. 11-14.
7. Marchyshyn S. M. Vmist karbonovyx kyslot u pidzemnyh i nadzemnyh organah lilijny` buro-zhovtogo (Hemerocallis fulva L.) ta lilijnyka gibrydnogo (Hemerocallis hybrida var. “Stella De Oro”)  / S. M. Marchyshyn, S. S. Kozachok, O. V. Zarichanska // Farmacevtychnyj zhurnal. – 2015. – № 2. – S. 53-57.
8. Marchyshyn S. M. Doslidzhennya flavonoyidiv nadzemnyx organiv lilijnyka buro-zhovtogo (Hemerocallis fulva L.) ta lilijnyka gibrydnogo (Hemerocallis hybrida var. “Stella De Oro”) / S. M. Marchyshyn, O. V. Zarichanska, M. S. Garnyk // Fitoterapiya. Chasopys. – 2015. – № 3. – S. 52-55.
9.  Rukovodstvo po provedenyyu doklynycheskyh issledovanyj lekarstvennyh sredstv / Pod red. dokt. med. nauk A. N. Myronova. – Chast pervaya. – M.: Gryf i K, 2012. – 944 s.
10.  Czokalo I. Ye. Eksperymentalne vyvchennya stresprotektornoyi j aktoprotektornoyi diyi kompozyciyi exinaceyi ta burshtynovoyi kysloty / I. Ye. Czokalo, O. I. Zajcev, K. G. Shhokina // Farmakom. – 2010. – № 4. – S. 72-75.
11. Deacon R. M. Housing, husbandry and handling of rodents for behavioral experiments / R. M. Deacon // Nature Protocols. – 2006. – V. 1. – № 2. – P. 936–946.
12. Eico Uezu. Effects of Hemerocallis on sleep in mice / College of Education, University of the Ryukyus, Okinawa, Japan. Psychiatry and Clinical Neurosciences, –1998 Apr.; 52(2). – P. 136-137.
13. Handbook of medicinal herbs / James A. Duke, Mary Jo Bogenschutz-Godwin, Judi duCellier, Peggy-Ann K. Duke. – 2nd ed. – CRC Press LLC, 2002. – P. 246.
14. Hodge Н.С. Tabulation of toxicity classes / Н.С. Hodge, L.H. Sterner // Am. Industr. Hyg. Ass. Quart. – 1943. – Vol. 10. – № 4. – P. 93.
15. Porsolt R.D. Behavioral models of depression / R.D. Porsolt, A. Lenegre, J.M. Elliot [et al.] // Experimental Approaches to Anxiety and Depression. – Chichester New York, 1992. – P. 73-85.
16. Zarichanska Olena. Investigation of the volatile oil in modified roots, flowers and leaves of Hemerocallis species / Olena Zarichanska, Svitlana Marchyshyn, Myroslava Garnyk // 46th International Symposium on Essential Oils 2015 Abstracts. Natural Volatiles and Essential Oils – 2015. – №2(3) – Lublin (Poland), September 13-16, 2015. – PP-099. 
17. Zarichanska O. V. Qualitative composition and quantitative content of macro- and microelements in plant raw materials of plants of Hemerocallis L. genus / O. V. Zarichanska // Topical issues of new drugs development. International Scientific And Practical Conference Of Young Scientists And Student, NUPh – April 23, 2015. – P.111-112.