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Antidepressant-Like Effect of Isorhynchophylline in Mice

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Abstract

Isorhynchophylline (IRN), an oxindole alkaloid, has been identified as the main active ingredient responsible for the biological activities of Uncaria rhynchophylla (Miq) Miq ex Havil. (Rubiaceae). Previous studies in our laboratory have revealed that IRN possesses potent neuroprotective effects in different models of Alzheimer’s disease. However, the antidepressant-like effects of IRN are remained unclear. The present study aims to evaluate the antidepressant-like effects of IRN. The antidepressant-like effects of IRN was determined by using animal models of depression including forced swimming and tail suspension tests. The acting mechanism was explored by determining the effect of IRN on the levels of monoamine neurotransmitters and the activities of monoamine oxidases. Intragastric administration of IRN at 10, 20 and 40 mg/kg for 7 days caused a significant reduction of immobility time in both forced swimming and tail suspension tests, while IRN did not stimulate locomotor activity in the open-field test. In addition, IRN treatment antagonized reserpine-induced ptosis and significantly enhanced the levels of monoamine neurotransmitters including norepinephrine (NE) and 5-hydroxytryptamine (5-HT), and the activity of monoamine oxidase A (MAO-A) in the hippocampus and frontal cortex of mice. These results suggest that the antidepressant-like effects of IRN are mediated, at least in part, by the inhibition of monoamine oxidases.

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References

  1. Kessler RC (2012) The costs of depression. Psychiatr Clin North Am 35:1–14

    Article  PubMed  Google Scholar 

  2. Manji HK, Drevets WC, Charney DS (2010) The cellular neurobiology of depression. Nat Med 7:541–547

    Article  Google Scholar 

  3. Covington HE 3rd, Vialou V, Nestler EJ (2010) From synapse to nucleus: novel targets for treating depression. Neuropharmacology 58:683–693

    Article  CAS  PubMed  Google Scholar 

  4. Laakmann G, Dienel A, KIeser M (1998) Clinical significance of hyperforin for the efficacy of Hypericum extracts on depressive disorders of different severities. Phytomedicine 5:435–442

    Article  CAS  PubMed  Google Scholar 

  5. Jiang ML, Zhang ZX, Li YZ, Wang XH, Yan W, Gong GQ (2015) Antidepressant-like effect of evodiamine on chronic unpredictable mild stress rats. Neurosci Lett 588:154–158

    Article  CAS  PubMed  Google Scholar 

  6. Xu Y, Ku BS, Yao HY et al (2005) The effects of curcumin on depressive-like behaviors in mice. Eur J Pharmacol 518:40–46

    Article  CAS  PubMed  Google Scholar 

  7. Xu Y, Ku BS, Yao HY, Lin YH, Ma X, Zhang YH et al (2005) Antidepressant effects of curcumin in the forced swim test and olfactory bulbectomy models of depression in rats. Pharmacol Biochem Behav 82:200–206

    Article  CAS  PubMed  Google Scholar 

  8. Liu B, Xu C, Wu X, Liu F, Du Y, Sun J et al (2015) Icariin exerts an antidepressant effect in an unpredictable chronic mild stress model of depression in rats and is associated with the regulation of hippocampal neuroinflammation. Neuroscience 294:193–205

    Article  CAS  PubMed  Google Scholar 

  9. Gong MJ, Han B, Wang SM, Liang SW, Zou ZJ (2016) Icariin reverses corticosterone-induced depression-like behavior, decrease in hippocampal brain-derived neurotrophic factor (BDNF) and metabolic network disturbances revealed by NMR-based metabonomics in rats. J Pharm Biomed Anal 123:63–73

    Article  CAS  PubMed  Google Scholar 

  10. Chen J, Lin D, Zhang C (2015) Antidepressant-like effects of ferulic acid: involvement of serotonergic and norepinergic systems. Metab Brain Dis 30:129–136

    Article  CAS  PubMed  Google Scholar 

  11. Kang TH, Murakami Y, Takayama H, Kitajima M, Aimi N, Watanabe H et al (2004) Protective effect of rhynchophylline and isorhynchophylline on in vitro ischemia-induced neuronal damage in the hippocampus: putative neurotransmitter receptors involved in their action. Life Sci 76:331–343

    Article  CAS  PubMed  Google Scholar 

  12. Yuan D, Ma B, Yang JY (2009) Anti-inflammatory effects of rhynchophylline and isorhynchophylline in rat N9 microglial cells and the molecular mechanism. Int Immunopharmacol 9:1549–1554

    Article  CAS  PubMed  Google Scholar 

  13. Shimada Y, Goto H, Itoh T, Sakakibara I, Kubo M, Sasaki H et al (1999) Evaluation of the protective effects of alkaloids isolated from the hooks and stems of Uncaria sinensis on glutamate-induced neuronal death in cultured cerebellar granule cells from rats. J Pharm Pharmacol 51:715–722

    Article  CAS  PubMed  Google Scholar 

  14. Kanatani H, Kohda H, Yamasaki K (1985) The active principle of the branchlets and hook of Uncaria sinensis Oliv. examined with a 5-hydroxytryptamine receptor-binding assay. J Pharm Pharmacol 37:401–404

    Article  CAS  PubMed  Google Scholar 

  15. Matsumoto K, Morishige R, Murakami Y (2005) Suppressive effects of isorhynchophylline on 5-HT2A receptor function in the brain: behavioural and electrophysiological studies. Eur J Pharmacol 517:191–199

    Article  CAS  PubMed  Google Scholar 

  16. Lu JH, Tan JQ, Durairajan SS (2012) Isorhynchophylline, a natural alkaloid, promotes the degradation of alpha-synuclein in neuronal cells via inducing autophagy. Autophagy 8:98–108

    Article  CAS  PubMed  Google Scholar 

  17. Xian YF, Lin ZX, Mao QQ, Ip SP, Su ZR, Lai XP (2012) Protective effect of isorhynchophylline against β-amyloid-induced neurotoxicity in PC12 cells. Cell Mol Neurobiol 32:353–360

    Article  CAS  PubMed  Google Scholar 

  18. Xian YF, Lin ZX, Mao QQ, Zhao M, Hu Z, Ip SP (2012) Bioassay-guided isolation of neuroprotective compounds from Uncaria rhynchophylla against beta-amyloid-induced neurotoxicity in PC12 cells. Evid Based Complement Alternat Med 2012:802625

    PubMed  PubMed Central  Google Scholar 

  19. Xian YF, Mao QQ, Wu JC, Su ZR, Chen JN, Lai XP et al (2014) Isorhynchophylline treatment improves the amyloid-β-induced cognitive impairment in rats via inhibition of neuronal apoptosis and tau protein hyperphosphorylation. J Alzheimers Dis 39:331–346

    CAS  PubMed  Google Scholar 

  20. Huang B, Wu Q, Wen G, Lu Y, Shi J (2001) The distribution of isorhynchophylline in the tissues of the rats and the determination of its plasma half-time. Acta Academiae Medicinae Zunyi 24:119–120

    Google Scholar 

  21. Haginiwa J, Sakai S, Aimi N, Yamanaka E, Shinma N (1973) Studies of plants containing indole alkaloids. 2. On the alkaloids of Uncaria rhynchophylla Miq. Yakugaku Zasshi 93:448–452

    CAS  PubMed  Google Scholar 

  22. Porsolt RD, Pichon MLE, Jalfre M (1977) Behavioral despair in mice: a primary screening test for antidepressant. Arch Int Pharmacodyn Ther 229:327–336

    CAS  PubMed  Google Scholar 

  23. Steru L, Chermat R, Thierry B, Simon P (1985) The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacology (Berl) 85:367–370

    Article  CAS  Google Scholar 

  24. Herrera-Ruiz M, García-Beltrán Y, Mora S (2006) Antidepressant and anxiolytic effects of hydroalcoholic extract from Salvia elegans. J Ethnopharmacol 107:53–58

    Article  PubMed  Google Scholar 

  25. Bourin M, Poncelet M, Chermat R, Simon P (1983) The value of the reserpine test in psychopharmacology. Arzneimittelforschung 33:1173–1176

    CAS  PubMed  Google Scholar 

  26. Sánchez-Mateo CC, Bonkanka CX, Prado B, Rabanal RM (2007) Antidepressant activity of some Hypericum reflexum L. fil. Extracts in the forced swimming test in mice. J Ethnopharmacol 112:115–121

    Article  PubMed  Google Scholar 

  27. Yu ZF, Kong LD, Chen Y (2002) Antidepressant activity of aqueous extracts of Curcuma longa in mice. J Ethnopharmacol 83:161–165

    Article  CAS  PubMed  Google Scholar 

  28. Zhou BH, Li XJ, Yang D (2006) Effect of apocynum venetum on the activity of MAO in mice. China Pharmacist 9:689–692

    Google Scholar 

  29. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with folin phenol reagent. J Biol Chem 193:265–275

    CAS  PubMed  Google Scholar 

  30. Fuchs E, Fliugge G (2006) Experimental animal models for the simulation of depression and anxiety. Dialogues Clin Neurosci 8:323–333

    PubMed  PubMed Central  Google Scholar 

  31. Yin C, Gou L, Liu Y (2011) Antidepressant-like effects of l-theanine in the forced swim and tail suspension tests in mice. Phytother Res 25:1636–1639

    Article  CAS  PubMed  Google Scholar 

  32. Bourin M, Fiocco AJ, Clenet F (2001) How valuable are animal models on defining antidepressant activity? Hum Psychopharmacol 16:9–21

    Article  CAS  PubMed  Google Scholar 

  33. Jans LA, Riedel WJ, Markus CR, Blokland A (2007) Serotonergic vulnerability and depression: assumptions, experimental evidence and implications. Mol Psychiatry 12:522–543

    Article  CAS  PubMed  Google Scholar 

  34. Savegnago L, Jesse CR, Pinto LG, Rocha JB, Nogueira CW, Zeni G (2007) Monoaminergic agents modulate antidepressant-like effect caused by diphenyl diselenide in rats. Prog Neuropsychopharmacol Biol Psychiatry 31:1261–1269

    Article  CAS  PubMed  Google Scholar 

  35. Yi LT, Li YC, Pan Y (2008) Antidepressant-like effects of psoralidin isolated from the seeds of Psoralea corylifolia in the forced swimming test in mice. Prog Neuropsychopharmacol Biol Psychiatry 32:510–519

    Article  CAS  PubMed  Google Scholar 

  36. Dhingra D, Sharma A (2006) Antidepressant-like activity of Glycyrrhiza glabra L. in mouse models of immobility tests. Prog Neuropsychopharmacol Biol Psychiatry 30:449–454

    Article  PubMed  Google Scholar 

  37. Bryant SG, Brown CS (1986) Current concepts in clinical therapeutics: major affective disorders. Part 1. Clin Pharm 5:304–318

    CAS  PubMed  Google Scholar 

  38. Johnston JP (1968) Some observations upon a new inhibitor of monoamine oxidase in brain tissue. Biochem Pharmacol 17:1285–1297

    Article  CAS  PubMed  Google Scholar 

  39. Foley P, Gerlach M, Youdim MB, Riederer P (2000) MAO-B inhibitors: multiple roles in the therapy of neurodegenerative disorders. Parkinsonism Relat Disord 6:25–47

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This study was partially supported by a Seeding Fund from the School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong (Project Number: 2015.1.081).

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Authors and Affiliations

  1. School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, People’s Republic of China

    Yan-Fang Xian, Siu-Po Ip, Qing-Qiu Mao & Zhi-Xiu Lin

  2. Shenzhen Wellsoon Pharmaceutical Company Limited, Shenzhen, Guangdong, China

    Ding Fan

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  1. Yan-Fang Xian
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Correspondence to Zhi-Xiu Lin.

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Xian, YF., Fan, D., Ip, SP. et al. Antidepressant-Like Effect of Isorhynchophylline in Mice. Neurochem Res 42, 678–685 (2017). https://doi.org/10.1007/s11064-016-2124-5

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  • DOI: https://doi.org/10.1007/s11064-016-2124-5

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