Advertisement

Journal of Natural Medicines

, Volume 67, Issue 4, pp 814–821 | Cite as

The involvement of magnoflorine in the sedative and anxiolytic effects of Sinomeni Caulis et Rhizoma in mice

  • June Bryan I. de la Peña
  • Hye Lim Lee
  • Seo Young Yoon
  • Gun Hee Kim
  • Yong Soo Lee
  • Jae Hoon CheongEmail author
Original Paper

Abstract

The present study seeks to evaluate the sedative and anxiolytic effects of the 70 % ethanol extract of Sinomeni Caulis et Rhizoma (SR). The extract was orally administered to mice at dosages of 25, 50, 100, 200 or 400 mg/kg. The mice were then subjected to an array of behavioral tests to assess the sedative (open-field, rota-rod, and thiopental sodium-induced sleeping test) and anxiolytic (elevated plus maze test) effects of the substance. SR (100, 200 mg/kg) significantly reduced locomotor activity, decreased rota-rod performance, and potentiated thiopental sodium-induced sleeping in mice, all indicative of its sedative effects. SR (50, 100 mg/kg) also produced anxiolytic effects, as shown by an increase in entries and staying time on the open arm of the plus maze. SR’s sedative and anxiolytic effects were comparable to that of the benzodiazepine, diazepam. Moreover, to identify SR’s probable mechanism of action, intracellular Cl ion influx was observed in cultured human neuroblastoma cells. SR dose-dependently increased Cl influx, which was blocked by co-administration of the GABAA receptor competitive antagonist, bicuculline. Among the major constituents of SR, only magnoflorine showed a similar increment in Cl influx, which was also blocked by bicuculline. Altogether, the present results suggest that SR has sedative and anxiolytic effects, probably mediated by magnoflorine through a GABAergic mechanism of action.

Keywords

Sinomeni acutum Sinomeni Magnoflorine Sedative Anxiolytic Benzodiazepine 

Notes

Acknowledgments

The authors are grateful to the Next-Generation BioGreen 21 Project (PJ008192) for financially supporting this study.

References

  1. 1.
    Kim HM, Moon PD, Chae HJ, Kim HR, Chung JG, Kim JJ, Lee EJ (2000) The stem of Sinomenium Acutum inhibits mast cell-mediated anaphylactic reactions and tumor necrosis factor-alpha production from rat peritoneal mast cells. J Ethnopharmacol 70:135–141PubMedCrossRefGoogle Scholar
  2. 2.
    Bao GH, Qin GW, Wang R, Tang XC (2005) Morphinane alkaloids with cell protective effects from Sinomenium Acutum. J Nat Prod 68:1128–1130. doi: 10.1021/np050112+ PubMedCrossRefGoogle Scholar
  3. 3.
    Zhao XX, Peng C, Zhang H, Qin LP (2012) Sinomenium Acutum: a review of chemistry, pharmacology, pharmacokinetics, and clinical use. Pharm Biol 50:1053–1061  10.3109/13880209.2012.656847 Google Scholar
  4. 4.
    Sano T, Matsumura I, Nakamura R, Yamaji H, Hashimoto K, Takeda O, Kiuchi F, Takeda T (2010) Genetic and chemical comparison of Boi (Sinomeni Caulis Et Rhizoma) and Seifuto (Caulis Sinomenii). J Nat Med 64:257–265. doi: 10.1007/s11418-010-0397-6 PubMedCrossRefGoogle Scholar
  5. 5.
    Satoh H (2005) Electropharmacological actions of the constituents of Sinomeni Caulis et Rhizome and Mokuboi-to in Guinea pig heart. Am J Chin Med 33:967–979PubMedCrossRefGoogle Scholar
  6. 6.
    Chen SW, Mi XJ, Wang R, Wang WJ, Kong WX, Zhang YJ, Li YL (2005) Behavioral effects of sinomenine in murine models of anxiety. Life Sci 78:232–238. doi: 10.1016/j.lfs.2005.04.056 PubMedCrossRefGoogle Scholar
  7. 7.
    Yamasaki H (1976) Pharmacology of sinomenine, an anti-rheumatic alkaloid from Sinomenium acutum. Acta Med Okayama 30:1–20PubMedGoogle Scholar
  8. 8.
    Min YD, Choi SU, Lee KR (2006) Aporphine alkaloids and their reversal activity of multidrug resistance (mdr) from the stems and rhizomes of Sinomenium acutum. Arch Pharm Res 29:627–632PubMedCrossRefGoogle Scholar
  9. 9.
    Jin HZ, Wang XL, Wang HB, Wang YB, Lin LP, Ding J, Qin GW (2008) Morphinane alkaloid dimers from Sinomenium acutum. J Nat Prod 71:127–129. doi: 10.1021/np0704654 PubMedCrossRefGoogle Scholar
  10. 10.
    Liu L, Resch K, Kaever V (1994) Inhibition of lymphocyte proliferation by the anti-arthritic drug sinomenine. Int J Immunopharmacol 16:685–691PubMedCrossRefGoogle Scholar
  11. 11.
    Hung TM, Lee JP, Min BS, Choi JS, Na M, Zhang X, Ngoc TM, Lee I, Bae K (2007) Magnoflorine from Coptidis Rhizoma protects high density lipoprotein during oxidant stress. Biol Pharm Bull 30:1157–1160PubMedCrossRefGoogle Scholar
  12. 12.
    Woods JH, Winger G (1995) Current Benzodiazepine Issues. Psychopharmacology (Berl) 118:107–15 (discussion 118, 120–1)Google Scholar
  13. 13.
    Uzun S, Kozumplik O, Jakovljevic M, Sedic B (2010) Side effects of treatment with benzodiazepines. Psychiatr Danub 22:90–93PubMedGoogle Scholar
  14. 14.
    Huh J, Goebert D, Takeshita J, Lu BY, Kang M (2011) Treatment of generalized anxiety disorder: a comprehensive review of the literature for psychopharmacologic alternatives to newer antidepressants and benzodiazepines. Prim Care Companion CNS Disord 13. doi: 10.4088/PCC.08r00709blu
  15. 15.
    N’Gouemo P, Nguemby-Bina C, Baldy-Moulinier M (1994) Some neuropharmacological effects of an ethanolic extract of Maprounea Africana in rodents. J Ethnopharmacol 43:161–166PubMedCrossRefGoogle Scholar
  16. 16.
    Chindo BA, Amos S, Odutola AA, Vongtau HO, Abbah J, Wambebe C, Gamaniel KS (2003) Central nervous system activity of the methanol extract of Ficus Platyphylla stem bark. J Ethnopharmacol 85:131–137PubMedCrossRefGoogle Scholar
  17. 17.
    Yu HS, Lee SY, Jang CG (2007) Involvement of 5-Ht1a and Gabaa receptors in the anxiolytic-like effects of Cinnamomum Cassia in mice. Pharmacol Biochem Behav 87:164–170. doi: 10.1016/j.pbb.2007.04.013 PubMedCrossRefGoogle Scholar
  18. 18.
    Milic M, Divljakovic J, Rallapalli S, van Linn ML, Timic T, Cook JM, Savic MM (2012) The role of alpha1 and alpha5 subunit-containing GABAA receptors in motor impairment induced by benzodiazepines in rats. Behav Pharmacol 23:191–197. doi: 10.1097/FBP.0b013e3283512c85 PubMedCrossRefGoogle Scholar
  19. 19.
    Farkas S, Berzsenyi P, Karpati E, Kocsis P, Tarnawa I (2005) Simple pharmacological test battery to assess efficacy and side effect profile of centrally acting muscle relaxant drugs. J Pharmacol Toxicol Methods 52:264–273. doi: 10.1016/j.vascn.2004.11.005 PubMedCrossRefGoogle Scholar
  20. 20.
    Frye CA, Petralia SM, Rhodes ME (2000) Estrous cycle and sex differences in performance on anxiety tasks coincide with increases in hippocampal progesterone and 3alpha,5alpha-THP. Pharmacol Biochem Behav 67:587–596PubMedCrossRefGoogle Scholar
  21. 21.
    Pellow S, File SE (1986) Anxiolytic and anxiogenic drug effects on exploratory activity in an elevated plus-maze: a novel test of anxiety in the rat. Pharmacol Biochem Behav 24:525–529PubMedCrossRefGoogle Scholar
  22. 22.
    Verkman AS, Sellers MC, Chao AC, Leung T, Ketcham R (1989) Synthesis and characterization of improved chloride-sensitive fluorescent indicators for biological applications. Anal Biochem 178:355–361PubMedCrossRefGoogle Scholar
  23. 23.
    West MR, Molloy CR (1996) A microplate assay measuring chloride ion channel activity. Anal Biochem 241:51–58. doi: 10.1006/abio.1996.0377 PubMedCrossRefGoogle Scholar
  24. 24.
    Shumaker H, Amlal H, Frizzell R, Ulrich CD 2nd, Soleimani M (1999) Cftr drives Na+-Nhco-3 cotransport in pancreatic duct cells: a basis for defective Hco-3 secretion in Cf. Am J Physiol 276:C16–C25PubMedGoogle Scholar
  25. 25.
    Wilson MA, Burghardt PR, Ford KA, Wilkinson MB, Primeaux SD (2004) Anxiolytic effects of diazepam and ethanol in two behavioral models: comparison of males and females. Pharmacol Biochem Behav 78:445–458. doi: 10.1016/j.pbb.2004.04.017 PubMedCrossRefGoogle Scholar
  26. 26.
    Yasar SN, Can OD, Ozturk N, Sagratini G, Ricciutelli M, Vittori S, Maggi F (2012) Central nervous system activities of Hypericum origanifolium extract via gabaergic and opioidergic mechanisms. Phytother Res. doi: 10.1002/ptr.4801 PubMedGoogle Scholar
  27. 27.
    Ding Y, Li J, Lai Q, Rafols JA, Luan X, Clark J, Diaz FG (2004) Motor balance and coordination training enhances functional outcome in rat with transient middle cerebral artery occlusion. Neuroscience 123:667–674PubMedCrossRefGoogle Scholar
  28. 28.
    Griebel G, Sanger DJ, Perrault G (1996) The use of the rat elevated plus-maze to discriminate between non-selective and Bz-1 (Ω 1) selective, benzodiazepine receptor ligands. Psychopharmacology 124:245–254PubMedCrossRefGoogle Scholar
  29. 29.
    Ahmed M, Azmat A, Azeem MA (2004) Dose-response curve of Somina (Herbal Preparation): a study on frog heart. Pak J Pharmacol 21:19–22Google Scholar
  30. 30.
    Rabbani M, Sajjadi S, Mohammadi A (2008) Evaluation of the anxiolytic effect of Nepeta Persica Boiss. In mice. Evidence Based Complementary Altern Med 5:181–186CrossRefGoogle Scholar
  31. 31.
    Akindele A, Adeyemi O (2010) Anxiolytic and sedative effects of Byrsocarpus Coccineus Schum. And Thonn. (Connaraceae) extract. Int J Appl Res Natural Prod 3:28–36Google Scholar
  32. 32.
    Li K, Xu E (2008) The role and the mechanism of gamma-aminobutyric acid during central nervous system development. Neurosci Bull 24:195–200PubMedCrossRefGoogle Scholar
  33. 33.
    Skolnick P (2012) Anxioselective anxiolytics: on a Quest for the Holy Grail. Trends Pharmacol Sci 33:611–620. doi: 10.1016/j.tips.2012.08.003 PubMedCrossRefGoogle Scholar
  34. 34.
    Delaney AJ, Sah P (1999) Gaba receptors inhibited by benzodiazepines mediate fast inhibitory transmission in the Central Amygdala. J Neurosci 19:9698–9704PubMedGoogle Scholar

Copyright information

© The Japanese Society of Pharmacognosy and Springer Japan 2013

Authors and Affiliations

  • June Bryan I. de la Peña
    • 1
  • Hye Lim Lee
    • 1
  • Seo Young Yoon
    • 1
  • Gun Hee Kim
    • 2
  • Yong Soo Lee
    • 3
  • Jae Hoon Cheong
    • 1
    Email author
  1. 1.Uimyung Research Institute for Neuroscience, Department of PharmacySahmyook UniversitySeoulRepublic of Korea
  2. 2.Department of Food and Nutrition, College of Natural ScienceDuksung Women’s UniversitySeoulRepublic of Korea
  3. 3.Department of Pharmacy, College of PharmacyDuksung Women’s UniversitySeoulRepublic of Korea

Personalised recommendations