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Neuroprotective Evaluation of Tilia americana and Annona diversifolia in the Neuronal Damage Induced by Intestinal Ischemia

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Abstract

Tilia americana and Annona diversifolia are plants widely distributed in Mexico and sold in markets for their medicinal properties on the central nervous system (CNS) including possible neuroprotection. Pharmacological studies have corroborated CNS activities due to flavonoid constituents, but evidence of their neuroprotector effects are lacking. This study was conducted to test aqueous and organic extracts of these two plants for neuroprotective effects in a novel experimental model of intestinal ischemia in situ. T. americana and A. diversifolia aqueous and organic extracts were administrated to guinea pigs at an oral dose of 100 and 300 mg/kg for 15 days. Twenty four hours after the last administration, the animals were anesthetized and intestinal ischemia in situ was induced by clamping for 80 min selected branches of the superior mesenteric artery. Ischemic segments placed in an in vitro organ bath were stimulated electrically (0.3 Hz frequency, 3.0 ms duration, 14 V intensity) and chemically (ACh; 1 × 10−9 to 1×10−5 M). Neuroprotection was considered present when the depressed contractile response of the ischemic tissue to electrical stimulation was normalized in the treated animals. Results showed that pretreatment with the T. americana hexane and aqueous extracts, but not with those from A. diversifolia, significantly improved responses of the ischemic tissue. These results suggest that T. americana possesses neuroprotective effects against neuronal damage induced by ischemia, and that flavonoids as well as non-polar constituents are involved. Our study supports the use of this plant in folk medicine and suggests its possible effectiveness for stroke prevention.

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References

  1. Hossmann KA (2006) Pathophysiology and therapy of experimental stroke. Cell Mol Neurobiol 26:1057–1083

    Article  PubMed  Google Scholar 

  2. Sahota P (2011) Investigational therapies for ischemic stroke: neuroprotection and neurorecovery. Neurother 8:434–451

    Article  CAS  Google Scholar 

  3. De Keyser J, Sulter G, Luiten PG (1999) Clinical trials with neuroprotective drugs in acute ischaemic stroke: are we doing the right thing? Trends Neurosci 22:535–540

    Article  PubMed  Google Scholar 

  4. Cheng YD, Al-Khoury L, Zivin JA (2004) Neuroprotection for ischemic stroke: two decades of success and failure. NeuroRx 1:36–45

    Article  PubMed  Google Scholar 

  5. Gomes NG, Campos MG, Órfao JM, Ribeiro CA (2009) Plants with neurobiological activity as potential targets for drug discovery. Prog Neuropsychopharmacol Biol Psychiatry 33:1372–1389

    Article  PubMed  CAS  Google Scholar 

  6. Paganelli RA, Benetoli A, Milani H (2006) Sustained neuroprotection and facilitation of behavioral recovery by the Ginkgo biloba, EGb 761, after transient forebrain ischemia in rats. Behav Brain Res 174:70–77

    Article  PubMed  CAS  Google Scholar 

  7. Abdeen SM, Mathew TC, Path FRS, Dashti HM, Asfar S (2011) Protective effects of green tea on intestinal ischemia-repersufión injury. Nutrition 27:598–603

    Article  PubMed  CAS  Google Scholar 

  8. Elango C, Devaraj SN (2010) Immunomodulatory effect of Hawthorn extract in an experimental stroke model. J Neuroinflammation 30:97

    Article  Google Scholar 

  9. Shri R, Bora KS (2008) Neuroprotective effect of methanolic extracts of Allium cepa on ischemia and reperfusión-induced cerebral injury. Fitoterapia 79:86–96

    Article  PubMed  Google Scholar 

  10. Bora KS, Sharma A (2010) Neuroprotective effect of Artemisia absinthium L. on focal ischemia and reperfusion-induced cerebral injury. J Ethnopharmacol 129:403–409

    Article  PubMed  Google Scholar 

  11. Bora KS, Arora S, Shri R (2011) Role of Ocimum basilicum L. in prevention of ischemia and reperfusión-induced cerebral damage, and motor dysfuntions in mice brain. J Ethnopharmacol 137:1360–1365

    Article  PubMed  Google Scholar 

  12. Nagakannan P, Shivasharan BD, Thippeswamy BS, Veerapur VP, Bansal P (2012) Protective effect of hydroalcoholic extract of Mimusops elengi Linn. flowers against middle cerebral artery occlusion induced brain injury in rats. J Ethnopharmacol 140:247–254

    Article  PubMed  CAS  Google Scholar 

  13. Rabiei Z, Bigdeli MR, Rasoulian B, Ghassempour A, Mirzajani F (2012) The neuroprotection effect of pretreatment with olive leaf extract on brain lipidomics in rat stroke model. Phytomedicine 19:940–946

    Article  PubMed  CAS  Google Scholar 

  14. Kim JY, Jeong HY, Lee HK, Kim S, Hwang BY, Bae K, Seong YH (2012) Neuroprotection of the leaf and stem of Vitis amurensis and their active compounds against ischemic brain damage in rats and excitotoxic in cultured neurons. Phytomedicine 19:150–159

    Article  PubMed  CAS  Google Scholar 

  15. Kim JY, Lee HK, Hwang BY, Kim S, Yoo JK, Seong YH (2012) Neuroprotection of Ilex latifolia and caffeoylquinic acid derivatives against excitotoxic and hypoxic damage of cultured rat cortical neurons. Arch Pharm Res 35:1115–1122

    Article  PubMed  CAS  Google Scholar 

  16. Ruiz SE, Morett A (1997) Las Anonas en el México Prehispánico. Memorias Congreso Internacional de Anonáceas, Chapingo, México

    Google Scholar 

  17. González-Trujano ME, Tapia E, Lopez-Meraz L, Navarrete A, Reyes-Ramirez A, Martínez A (2006) Anticonvulsant effect of Annona diversifolia Saff. and palmitone on penicillin-induced convulsive activity: a behavioral and EEG study in rats. Epilepsia 47:1810–1817

    Article  Google Scholar 

  18. Carballo AI, Martínez AL, González-Trujano ME, Pellicer F, Ventura-Martínez R, Díaz-Reval MI, López-Muñoz FJA (2010) Antinociceptive activity of Annona diversifolia Saff. leaf extracts and palmitone as bioactive compound. Pharmacol Biochem Behav 95:6–12

    Article  PubMed  CAS  Google Scholar 

  19. González-Trujano ME, López-Meraz L, Reyes-Ramírez A, Aguillón M, Martínez A (2009) Effect of repeated administration of Annona diversifolia Saff. (Ilama) extracts and palmitone on rat amygdala kindling. Epilepsy Behav 16:590–595

    Article  PubMed  Google Scholar 

  20. Cano-Europa E, González-Trujano ME, Reyes-Ramírez A, Hernández-García A, Blas-Valdivia V, Ortiz-Butrón R (2010) Palmitone prevents pentylenetetrazole-caused neuronal damage in the CA3 hippocampal region of prepubertal rats. Neurosci Lett 470:111–114

    Article  PubMed  CAS  Google Scholar 

  21. Hardin JW (1990) Variation patterns and recognition of Tilia americana. s, 1. Syst Bot 15:33–48

    Article  Google Scholar 

  22. Martínez M (1979) Catálogo de nombres vulgares y científicos de plantas mexicanas. Fondo de Cultura Económica, México

    Google Scholar 

  23. Coleta M, Campos MG, Cotrim MD, Cunha AP (2001) Comparative evaluation of Melissa officinalis L., Tilia europea L., Passiflora edulis Sims. and Hypericum perforatum L. in the elevated plus maze anxiety test. Pharmacopsychiatry 34:520–521

    Article  Google Scholar 

  24. Pérez-Ortega G, Guevara-Fefer P, Chávez M, Herrera J, Martínez A, Martínez AL, González-Trujano ME (2008) Sedative and anxiolytic efficacy of Tilia americana var. mexicana inflorescences used traditionally by communities of State of Michoacan, Mexico. J Ethnopharmacol 116:461–468

    Article  PubMed  Google Scholar 

  25. Martínez M (1969) Las plantas medicinales de México, 5th edn. Andrés Ediciones Botas, México

    Google Scholar 

  26. Estrada EL (1985) Maximino Martínez (1888–1964). Jardín botánico de plantas medicinales “Maximino Martínez” Universidad Autónoma Chapingo, Chapingo, México

  27. Aguirre-Hernández E, Rosas-Acevedo H, Soto-Hernández M, Martínez AL, Moreno J, González-Trujano ME (2007) Bioactivity-guided isolation of β-Sitosterol and some fatty acids as active compounds in the anxiolytic and sedative effects of Tilia americana var. mexicana. Planta Med 73:1148–1155

    Article  PubMed  Google Scholar 

  28. Aguirre-Hernández E, Martínez AL, Gonzalez-Trujano ME, Moreno J, Vibrans H, Soto-Hernández M (2007) Pharmacological evaluation of the anxiolytic and sedative effects of Tilia americana L. var. mexicana in mice. J Ethnopharmacol 109:140–145

    Article  PubMed  Google Scholar 

  29. Herrera-Ruiz M, Román-Ramos R, Zamilpa A, Tortoriello J, Jiménez-Ferrer JE (2008) Flavonoids from Tilia americana with anxiolytic activity in plus-maze test. J Ethnopharmacol 118:312–317

    Article  PubMed  CAS  Google Scholar 

  30. Martínez AL, González-Trujano ME, Aguirre-Hernández E, Moreno J, Soto-Hernández M, López-Muñoz FJ (2009) Antinociceptive activity of Tilia americana var. mexicana inflorescences and quercetin in the formalin test and in arthritic pain model in rats. Neuropharmacol 56:564–571

    Article  Google Scholar 

  31. Rodriguez R, Ventura-Martínez R, Santiago-Mejia J, Avila-Costa MR, Fortoul TI (2006) Altered responsiveness of the guinea-pig isolated ileum to smooth muscle stimulants and to electrical stimulation after in situ ischemia. Br J Pharmacol 147:371–378

    Article  PubMed  CAS  Google Scholar 

  32. Santiago-Mejia J, Ventura-Martinez R, Gomez C, Parra-Gamez L, Gonzalez-Rios J, Rodriguez R (2007) Polyviewed expression of the altered contractility of the guinea-pig ileum alters ischemia in situ and superfusion in vitro. J Physiol Pharmacol 58:275–285

    PubMed  CAS  Google Scholar 

  33. NOM-062-ZOO-1999 (1999) Secretaría de Salud Norma Oficial Mexicana, México

  34. González-Trujano ME, Navarrete A, Reyes B, Cedillo-Portugal E, Hong E (2001) Anticonvulsant properties and bio-guided isolation of palmitone from leaves of Annona diversifolia. Planta Med 67:136–141

    Article  PubMed  Google Scholar 

  35. Schlie-Guzmán MA, García-Carrancá A, González-Esquinca AR (2009) In vitro and in vivo antiproliferative activity of laherradurin and cherimolin-2 of Annona diversifolia Saff. Phytother Res 23:1128–1133

    Article  PubMed  Google Scholar 

  36. De la Cruz Chacón I, González-Esquinca AR (2012) Liriodenine alkaloid in Annona diversifolia during early development. Nat Prod Res 26:42–49

    Article  Google Scholar 

  37. Aguirre-Hernández E, González-Trujano ME, Martínez AL, Moreno J, Kite G, Terrazas T, Soto-Hernández M (2010) HPLC/MS analysis and anxiolytic-like effects of quercetin and kaempferol flavonoids from Tilia americana var. mexicana. J Ethnopharmacol 127:91–97

    Article  PubMed  Google Scholar 

  38. Ventura-Martínez R, Santiago-Mejia J, Gomez C, Rodriguez R, Fortoul TI (2008) Acute morphological changes in guinea pig ileum myenteric neurons after ischemia in situ with superfusion in vitro. Pathol Res Pract 204:121–127

    Article  PubMed  Google Scholar 

  39. Lees KR, Zivin JA, Ashwood T, Davalos A, Davis SM, Diener HC, Grotta J, Lyden P, Shuaib A, Hårdemark HG, Wasiewski WW (2006) Stroke-acute ischemic NXY treatment (SAINT I) trial investigators NXY-059 for acute ischemic stroke. New Engl J Med 354:588–600

    Article  PubMed  CAS  Google Scholar 

  40. Bornstein JC, Costa M, Grider JR (2004) Enteric motor and interneuronal circuits controlling motility. Neurogastroenterol Motil 16:34–38

    Article  PubMed  Google Scholar 

  41. Gerthoffer W (2005) Signal-transduction pathways that regulate visceral smooth muscle function III. Coupling of muscarinic receptors to signaling kinases and effector proteins in gastrointestinal smooth muscles. Am J Physiol Gastrointest Liver Physiol 288:G849–G853

    Article  PubMed  CAS  Google Scholar 

  42. Reddy H, Watson N, Ford AP, Eglen RM (1995) Characterization of the interaction between muscarinic M2 receptors and β–adrenoceptor subtypes in guinea-pig isolated ileum. Br J Pharmacol 114:49–56

    Article  PubMed  CAS  Google Scholar 

  43. Karaki H, Ozaki H, Hori M, Mitsui-Saito M, Amano KI, Harada KI, Miyamoto S, Nakazawa H, Won KJ, Sato K (1997) Calcium movements, distribution, and functions in smooth muscle. Pharmacol Rev 49:157–215

    PubMed  CAS  Google Scholar 

  44. Hansen TR, Dineen DX, Petrak R (1984) Mechanism of action of barium ion on aortic smooth muscle. Am J Physiol 246:C235–C241

    PubMed  CAS  Google Scholar 

  45. Dajas F, Rivera-Megret F, Blasina F, Arredondo F, Abin-Carriquiry JA, Costa G, Echeverry C, Lafon L, Heizen H, Ferreira M, Morquio A (2003) Neuroprotection by flavonoids. Braz J Med Biol Res 36:1613–1620

    Article  PubMed  CAS  Google Scholar 

  46. Pu F, Mishima K, Irie K, Motohashi K, Tanaka Y, Orito K, Egawa T, Kitamura Y, Egashira N, Iwasaki K, Fujiwara M (2007) Neuroprotective effects of quercetin and rutin on spatial memory impairment in an 8-arm radial task and neuronal death induced by repeat cerebral ischemia in rats. J Pharmacol Sci 104:329–334

    Article  PubMed  CAS  Google Scholar 

  47. Dajas F (2012) Life or death: neuroprotective and anticancer effects of quercetin. J Ethnopharmacol 143:383–396

    Article  PubMed  CAS  Google Scholar 

  48. Akhlaghi M, Bandy B (2009) Mechanisms of flavonoid protection against myocardial ischemia-reperfusion injury. J Mol Cell Cardiol 46:309–317

    Article  PubMed  CAS  Google Scholar 

  49. Jäger AK, Saaby L (2011) Review flavonoids and the CNS. Molecules 16:1471–1485

    Article  PubMed  Google Scholar 

  50. Chen JC, Ho FM, Lee Chao PD, Chen CP, Jeng KC, Hsu HB, Lee ST, Wu WT, Lin WW (2005) Inhibition of iNOS gene expression by quercetin is mediated by the inhibition of lkappaB kinase, nuclear factor-kappa B and STAT1, and depends on heme oxygenase-1 induction in mouse BV-2 microglia. Eur J Pharmacol 521:9–20

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This study was supported by Grants from Program to Support Research Projects and Technological Innovation (PAPIIT, IN201713), National Council of Science and Technology (CONACYT, 80811) and National Institute of Psychiatry (INP-NC093280). PhD. G.E. Angeles-López thankful a fellowship from General Direction of Academic of Personnel Matters of National University of Mexico (DGAPA-UNAM, 070/2012). We are thankful to Mr. Oscar Ramirez for his technical assistance.

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The authors declare that they have no conflict of interest.

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Correspondence to Rosa Ventura-Martínez.

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Angeles-López, G.E., González-Trujano, M.E., Déciga-Campos, M. et al. Neuroprotective Evaluation of Tilia americana and Annona diversifolia in the Neuronal Damage Induced by Intestinal Ischemia. Neurochem Res 38, 1632–1640 (2013). https://doi.org/10.1007/s11064-013-1065-5

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