The influence of goutweed (aegopodium podagraria l.) Extract and tincture on the behavioural reactions Of mice against the background of caffeine-sodium benzoate


  • O. V. Tovchiga National University of Pharmacy, Ukraine
  • S. J. Shtrygol' National University of Pharmacy, Ukraine
  • A. A. Balia National University of Pharmacy, Ukraine



mice, CNS, goutweed, caffeine, behavioural reactions


Considerable attention has been attracted recently to herbal preparations and dietary components containing hydroxycinnamic acids. High quantity of these compounds is present in the preparations of the aerial part of goutweed (Aegopodium podagraria L.) which exhibit moderate psychotropic and favourable metabolic effects.

Aim. To characterize psychotropic effects of goutweed extract and tincture against the background of caffeine-sodium benzoate in mice.

Materials and methods. The experiments were performed on random-bred mice after the course intragastric administration of goutweed extract (100 mg/kg and 1 g/kg) and goutweed tincture (1 and 5 ml/kg). Against the background of caffeine-sodium benzoate at a dose of 10 mg/kg intraperitoneally, the behavioural reactions were determined in the open-field test. Changes in the levels of anxiety and depression were studied in the elevated plus maze test (EPM) and the tail suspension test, respectively, against the background of a high dose of caffeine-sodium benzoate 120 mg/kg intraperitoneally.

Results. In the open field test, goutweed tincture at a dose of 5 ml/kg eliminated the locomotor-stimulating effect of caffeine in mice, the tincture at a dose of 1 ml/kg and the extract in both doses did not influence on it. Goutweed preparations did not suppress the exploratory behaviour in this test and showed neutrality in relation to the emotional and vegetative manifestations or contributed to their decrease. In the EPM test, the extract in both doses and the tincture at a dose of 5 ml/kg reduced anxiety signs against the background of caffeine, the tincture increased the motor activity. In the tail suspension test, caffeine reduced the duration of immobility of mice, the extract at a dose of 100 mg/kg did not change this effect and eliminated it at a dose of 1 g/kg. The tincture in both doses caused a further decrease in the duration of immobility against the background of caffeine.

Conclusions. Goutweed extract and tincture do not cause a negative influence on the CNS when combined with caffeine, being able to reduce depression and anxiety against the background of this psychostimulant.

Author Biographies

O. V. Tovchiga, National University of Pharmacy

PhD (Pharmacy), associate professor, postdoctorate researcher of the Department of Pharmacology

S. J. Shtrygol', National University of Pharmacy

Prof. Dr. of Medicine, head of the department of pharmacology

A. A. Balia, National University of Pharmacy

student National University of Pharmacy


Nabavi, S. F., Tejada, S., Setzer, W. N., Gortzi, O., Sureda, A., Braidy, N., Nabavi, S. M. (2017). Chlorogenic Acid and Mental Diseases: From Chemistry to Medicine. Current Neuropharmacology, 15 (4), 471–479. doi: 10.2174/1570159x14666160325120625

Poole, R., Kennedy, O. J., Roderick, P., Fallowfield, J. A., Hayes, P. C., Parkes, J. (2017). Coffee consumption and health: umbrella review of meta–analyses of multiple health outcomes. BMJ, j5024. doi: 10.1136/bmj.j5024

Chen, J.–F. (2014). Adenosine Receptor Control of Cognition in Normal and Disease. Adenosine Receptors in Neurology and Psychiatry, 257–307. doi: 10.1016/b978–0–12–801022–8.00012–x

Ohnishi, R., Ito, H., Iguchi, A., Shinomiya, K., Kamei, C., Hatano, T., Yoshida, T. (2006). Effects of Chlorogenic Acid and Its Metabolites on Spontaneous Locomotor Activity in Mice. Bioscience, Biotechnology, and Biochemistry, 70 (10), 2560–2563. doi:10.1271/bbb.60243

Bouayed, J., Rammal, H., Dicko, A., Younos, C., Soulimani, R. (2007). Chlorogenic acid, a polyphenol from Prunus domestica (Mirabelle), with coupled anxiolytic and antioxidant effects. Journal of the Neurological Sciences, 262 (1–2), 77–84. doi:10.1016/j.jns.2007.06.028

Stefanello, N., Schmatz, R., Pereira, L. B., Rubin, M. A., da Rocha, J. B. T., Facco, G., Schetinger, M. R. C. (2013). Effects of chlorogenic acid, caffeine, and coffee on behavioral and biochemical parameters of diabetic rats. Molecular and Cellular Biochemistry, 388 (1–2), 277–286. doi: 10.1007/s11010–013–1919–9

De Paulis, T., Schmidt, D. E., Bruchey, A. K., Kirby, M. T., McDonald, M. P., Commers, P., Martin, P. R. (2002). Dicinnamoylquinides in roasted coffee inhibit the human adenosine transporter. European Journal of Pharmacology, 442 (3), 215–223. doi:10.1016/s0014–2999(02)01540–6

Tovchiga, O. V., Koyro, O. O., Stepanova, S. I., Shtrygol’, S. Yu., Evlash, V. V., Gorban’, V. G. et al. (2017). Goutweed (Aegopodium podagraria L.) biological activity and the possibilities of its use for the correction of the lipid metabolism disorders. J. Food Sci. Technol., 11 (4), 9–20. doi: 10.15673/fst.v11i4.726

Tovchiga, O., Shtrygol’, S. (2015). The influence of Aegopodium podagraria L. extract and tincture on behavioural reactions of random–bred mice. J. Chem. Pharm. Res., 7 (7), 370–384.

Tovchiga, O. V. (2016). Interaction of Aegopodium podagraria L. (goutweed) preparations with central nervous system depressants. Ukraïns’kij Bìofarmacevtičnij Žurnal, 1 (42), 31–36. doi:10.24959/ubphj.16.6

Deiko, R. D., Shtrygol, S. Yu., Kolobov, A. A. et al. (2016). Ukrainskyi zhurnal klinichnoi ta laboratornoi medytsyny, 11 (3), 98–106.

Marin, M. T., Zancheta, R., Paro, A. H., Possi, A. P. M., Cruz, F. C., Planeta, C. S. (2011). Comparison of caffeine–induced locomotor activity between adolescent and adult rats. European Journal of Pharmacology, 660 (2–3), 363–367. doi: 10.1016/j.ejphar.2011.03.052

Ribeiro, J. A., Sebastião, A. M. (2010). Caffeine and Adenosine. Journal of Alzheimer’s Disease, 20 (s1), S3–S15. doi: 10.3233/jad–2010–1379

Jain, N., Kemp, N., Adeyemo, O., Buchanan, P., Stone, T. W. (1995). Anxiolytic activity of adenosine receptor activation in mice. British Journal of Pharmacology, 116 (3), 2127–2133. doi:10.1111/j.1476–5381.1995.tb16421.x

Kulkarni, S. K., Mehta, A. K. (1985). Purine nucleoside ? mediated immobility in mice: Reversal by antidepressants. Psychopharmacology, 85 (4), 460–463. doi: 10.1007/bf00429665

Szopa, A., Poleszak, E., Wyska, E., Serefko, A., Wośko, S., Wlaź, A., Wlaź, P. (2015). Caffeine enhances the antidepressant–like activity of common antidepressant drugs in the forced swim test in mice. Naunyn–Schmiedeberg’s Archives of Pharmacology, 389 (2), 211–221. doi: 10.1007/s00210–015–1189–z

Porsolt, R. D., Anton, G., Blavet, N., Jalfre, M. (1978). Behavioural despair in rats: A new model sensitive to antidepressant treatments. European Journal of Pharmacology, 47 (4), 379–391. doi: 10.1016/0014–2999(78)90118–8

Tovchiga, O. V., Shtrygol’, S. Y. (2016). The effect of medicines with goutweed (Aegopodium podagraria l.) On the physical endurance, cognitive functions and the level of depression in animals. Vìsnik Farmacìï, 1 (85), 71–76. doi: 10.24959/nphj.16.2100

Antoniou, K., Papadopoulou–Daifoti, Z., Hyphantis, T., Papathanasiou, G., Bekris, E., Marselos, M., Ferré, S. (2005). A detailed behavioral analysis of the acute motor effects of caffeine in the rat: involvement of adenosine A1 and A2A receptors. Psychopharmacology, 183 (2), 154–162. doi: 10.1007/s00213–005–0173–6

Alexander, S. P. H. (2006). Flavonoids as antagonists at A1 adenosine receptors. Phytotherapy Research, 20 (11), 1009–1012. doi: 10.1002/ptr.1975

Park, K.–S., Eun, J. S., Kim, H.–C., Moon, D.–C., Hong, J.–T., Oh, K. W. (2010). (–)–Epigallocatethin–3–O–gallate counteracts caffeine–induced hyperactivity: evidence of dopaminergic blockade. Behavioural Pharmacology, 21 (5–6), 572–575. doi:10.1097/fbp.0b013e32833beffb

Wu, J., Chen, H., Li, H., Tang, Y., Yang, L., Cao, S., Qin, D. (2016). Antidepressant Potential of Chlorogenic Acid–Enriched Extract from Eucommia ulmoides Oliver Bark with Neuron Protection and Promotion of Serotonin Release through Enhancing Synapsin I Expression. Molecules, 21 (3), 260. doi: 10.3390/molecules21030260

Zeni, A. L. B., Camargo, A., Dalmagro, A. P. (2017). Ferulic acid reverses depression–like behavior and oxidative stress induced by chronic corticosterone treatment in mice. Steroids, 125, 131–136. doi: 10.1016/j.steroids.2017.07.006

Lenzi, J., Rodrigues, A. F., Rós, A. de S., de Castro, B. B., de Lima, D. D., Magro, D. D. D., Zeni, A. L. B. (2015). Ferulic acid chronic treatment exerts antidepressant–like effect: role of antioxidant defense system. Metabolic Brain Disease, 30 (6), 1453–1463. doi: 10.1007/s11011–015–9725–6

Liu, Y.–M., Hu, C.–Y., Shen, J.–D., Wu, S.–H., Li, Y.–C., Yi, L.–T. (2017). Elevation of synaptic protein is associated with the antidepressant–like effects of ferulic acid in a chronic model of depression. Physiology & Behavior, 169, 184–188. doi: 10.1016/j.physbeh.2016.12.003

Yamada, K., Kobayashi, M., Kanda, T. (2014). Involvement of Adenosine A2A Receptors in Depression and Anxiety. Adenosine Receptors in Neurology and Psychiatry, 373–393. doi:10.1016/b978–0–12–801022–8.00015–5

Chen, J., Lin, D., Zhang, C., Li, G., Zhang, N., Ruan, L., Xu, Y. (2014). Antidepressant–like effects of ferulic acid: involvement of serotonergic and norepinergic systems. Metabolic Brain Disease, 30 (1), 129–136. doi: 10.1007/s11011–014–9635–z

Takeda, H., Tsuji, M., Miyamoto, J., Masuya, J., Iimori, M., Matsumiya, T. (2003). Caffeic acid produces antidepressive– and /or anxiolytic–like effects through indirect modulation of the α1A–adrenoceptor system in mice. NeuroReport, 14 (7), 1067–1070. doi: 10.1097/01.wnr.0000073427.02536.b0

German–Ponciano, L. J., Rosas–Sánchez, G. U., Rivadeneyra Domínguez, E., Rodríguez–Landa, J. F. (2018). Advances in the Preclinical Study of Some Flavonoids as Potential Antidepressant Agents. Scientifica, 2018, 1–14. doi: 10.1155/2018/2963565





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