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Antidepressant-like effect and toxicological parameters of extract and withanolides isolated from aerial parts of Solanum capsicoides All. (Solanaceae)

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Abstract

The present work describes the evaluation of the antidepressant-like activity of the extract, fractions, and compounds obtained from the aerial parts of Solanum capsicoides. The methanolic extract (MESC) obtained by conventional maceration was partitioned with solvents of increasing polarities yielding the respective fractions of hexane (HE), dichloromethane (DCM), and ethyl acetate (EA). The dichloromethane and ethyl acetate fractions were submitted to chromatographic and spectroscopic techniques, leading to the isolation and identification of cilistadiol (1), astragalin (2), and cilistol A (3). In relation to the antidepressant activity, the extract was active against the forced swimming test (FST) at a concentration of 300 mg/kg an ED50 (deffective dose that reduces 50% of immobility time) of 120.3 (117.3–123.4) mg/kg. Similar values were observed when evaluated in the tail suspension test (TST). In addition, the results showed no influence on motor behavior when evaluated in the open field test (OFT). Based on the observed profile of the MESC, dichloromethane fraction presenting the best profile, in both FST and TST test. Likewise, the fraction also did not present motor impairment when evaluated by the OFT test. Considering that the dichloromethane fraction was more effective, the isolated compounds cilistadiol and cilistol A were evaluated in the same experimental models. In FST, both compounds had a significant antidepressant-like effect, with ED50 values of 0.22 (0.16–0.28) and 1.03 (0.89–1.18) μmol/kg, respectively. When evaluated in the TST, showed ED50 values of 0.30 (0.18–0.52) and 1.49 (1.27–1.73) μmol/kg, respectively. The isolated compounds also did not present significant differences in the motor behavior when evaluated on OFT test in comparison with the control group. No toxicological parameters were observed until the highest dose of MESC (2000 mg/kg), demonstrating safety in the use of this plant.

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References

  • Abbas AK, Lichtman AHH, Pillai S (2015) Imunologia Celular e Molecular, 8a edn. Elsevier, Rio de Janeiro

    Google Scholar 

  • Adeoluwa OA, Aderibigbe AO, Bakre AG (2015) Evaluation of antidepressant-like effect of Olax subscorpioidea Oliv. (Olacaceae) extract in mice. Drug Res 65:306–311

    CAS  Google Scholar 

  • Akula SJ, Compr Phar (2014) Evaluation of antidepressant activity of ethanoic and aqueous extract of. Solanum tuberosum peel 5: 164–167

  • Alexander RC, Preskorn S (2014) Clinical pharmacology in the development of new antidepressants: the challenges. Curr Opin Pharmacol 14:6–10

    Article  CAS  PubMed  Google Scholar 

  • American Psychiatric Association (2013) Diagnostic and statistical manual of mental disorders, 5th edn. APA, Washington

    Book  Google Scholar 

  • Aswar U, Gurav M, More G, Rashed K, Aswar M (2014) Effect of aqueous extract of Solanum xanthocarpum Schrad. & Wendl. on postmenopausal syndrome in ovariectomized rats. J Integr Med 12:439–446

    Article  PubMed  Google Scholar 

  • Atanasov CG, Waltenberger B, Pferschy-Wenzig E, Linder T, Wawrosch C, Uhrin P, Temml V, Wang L, Schwaiger S, Heiss EH, Rollinger JM, Schuster D, Breuss JM, Bochkov V, Mihovilovic MD, Kopp B, Bauer R, Dirsch VM, Stuppner H (2015) Discovery and resupply of pharmacologically active plant-derived natural products: a review. Biotechnol Adv 33:1582–1614

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Attari M, Jamaloo F, Shadvar S, Fakhraei N, Dehpour AR (2016) Effect of Withania somnifera dunal root extract on behavioral despair model in mice: a possible role for nitric oxide. Acta Med Iran 54:165–172

    PubMed  Google Scholar 

  • Bharathi P, Seshayamma V, Jagannadharao GH, Sivakumar N (2015) Evaluation of antidepressant activity of aqueous extract of Withania somnifera [Aswagandha] roots in albino mice. IOSR J Pharm Biol Sci 10:27–29

    Google Scholar 

  • Bhattacharya SK, Bhattacharya A, Sairam K, Ghosal S (2000) Anxiolytic-antidepressant activity of Withania somnifera glycowithanolides: an experimental study. Phytomedicine 7:463–469

    Article  CAS  PubMed  Google Scholar 

  • Bogdanova OV, Kanekar S, D’Ancid KE, Renshaw PF (2013) Factors influencing behavior in the forced swim test. Physiol Behav 118:227–239

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bongiorno P, LoGiudice P (2010) Hypericum for depression. Nat Med 2:1–9

    Google Scholar 

  • Borsini F (1995) Role of the serotonergic system in the forced swimming test. Neurosci Biobehav Rev 19:377–395

    Article  CAS  PubMed  Google Scholar 

  • Brusotti G, Cesari I, Dentamaro A, Caccialanza G, Massolini G (2014) Isolation and characterization of bioactive compounds from plant resources: the role of analysis in the ethnopharmacological approach. J Pharm Biomed Anal 87:218–228

    Article  CAS  PubMed  Google Scholar 

  • Chen B, Chen Y, Lin Y, Huang C, Uvarani C, Hwang T, Chiang M, Liu H, Sheu J (2015) Capsisteroids A–F, withanolides from the leaves of Solanum capsicoides. RSC Adv 5:88841–88847

    Article  CAS  Google Scholar 

  • Costa JP, Lourenço NV, Santos CCMP, Tomé AR, Sousa GF, Sousa DP, Almeida RN, Freitas R (2012) Avaliação da toxicidade aguda e das alterações histopatológicas em camundongos tratados com fitol. Rev Cienc Farm Básica 33:421–428

    CAS  Google Scholar 

  • Cryan JF, Mombereau C, Vassout A (2005) The tail suspension test as a model for assessing antidepressant activity: review of pharmacological and genetic studies in mice. Neurosci Biobehav Rev 29:571–625

    Article  CAS  PubMed  Google Scholar 

  • De Souza GR, De-Oliveira ACAX, Soares V, Chagas LF, Barbi NS, Paumgartten FJR, da Silva AJR (2018) Chemical profile, liver protective effects and analgesic properties of a Solanum paniculatum leaf extract. Biomed Pharmacother 110:129–138

    Article  CAS  PubMed  Google Scholar 

  • Deng S, Deng Z, Fan Y, Peng Y, Li J, Xiong D, Liu R (2009) Isolation and purification of three flavonoid glycosides from the leaves of Nelumbo nucifera (Lotus) by high-speed counter-current chromatography. J Chromatogr B 877:2487–2492

    Article  CAS  Google Scholar 

  • Dereli FTG, Ilhan M, Akkol EK (2018) New drug discovery from medicinal plants and phytoconstituents for depressive disorders. CNS Neurol Disord Drug Targets 18:92–102. https://doi.org/10.2174/1871527317666181114141129

    Article  CAS  Google Scholar 

  • Detke M, Rickels M, Lucki I (1995) Active behaviors in the rat forced swimming test differentially activated by serotonergic and noradrenergic antidepressants. Psychopharmacol 121:66–72

    Article  CAS  Google Scholar 

  • Devaraj VC (2011) Hepatoprotective activity of Hepaxa polyherbal formulation. Asian Pac J Trop Biomed 1:142–146

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ferreira RA, Cristiane KL, Lucinda-Silva RM, Branco JO (2013) Leaf morphoanatomy of Solanum capsicoides All. (Solanaceae) from resting area. Lat Am J Pharm 32:287–291

    Google Scholar 

  • Ferreira MF, Castanheira L, Sebastião AM, Telles-Correia D (2018) Depression assessment in clinical trials and pre-clinical tests: a critical review. Curr Top Med Chem 18:1677–1703

    Article  CAS  PubMed  Google Scholar 

  • Guan L, Liu B (2016) Antidepressant-like effects and mechanisms of flavonoids and related analogues. Eur J Med Chem 12:47–57

    Article  CAS  Google Scholar 

  • Holzmann I, Cechinel Filho V, Cáceres A, Martinês JV, Cruz SM, De Souza MM (2016) Antidepressant-like effect of hydroalcoholic extract of Valeriana prionophylla Standl. from Guatemala: evidence for the involvement of the monoaminergic systems. Intern J Phytopharm 6:14–26

    Google Scholar 

  • Kandhare AD, Bodhankar SL, Mohan V, Thakurdesai PA (2015) Acute and repeated doses (28 days) oral toxicity study of glycosides based standardized fenugreek seed extract in laboratory mice. Regul Toxicol Pharmacol 72:323–334

    Article  CAS  PubMed  Google Scholar 

  • Karaa NZ, Stukalin Y, Einat H (2018) Revisiting the validity of the mouse forced swim test: systematic review and meta-analysis of the effects of prototypic antidepressants. Neurosci Biobehav Rev 84:1–11

    Article  CAS  Google Scholar 

  • Keerthi V, Sriramoju M, Alumdri DB, Akula S (2014) Evaluation of antidepressant activity of ethanoic and aqueous extract of. Solanum tuberosum peel. J Compr Phar 5:164–167

    Google Scholar 

  • Kulkarni SK, Dhir A (2008) Effect of various classes of antidepressants in behavioral paradigms of despair. Prog Neuro-Psychopharmacol Biol Psychiatry 31:1248–1254

    Article  CAS  Google Scholar 

  • LAB Test Online. (2018)Ureia. Accessible in: www.labtestsonline.org.br/understanding/analytes/bun/tab/test/ Assessed 28 November 2018

  • Martins J, Brijesh S (2018) Phytochemistry and pharmacology of anti-depressant medicinal plants: a review. Biomed Pharmacother 104:343–365

    Article  CAS  PubMed  Google Scholar 

  • Matos LC, Martins B (2005) Hepatites tóxicas: revisão da literatura. Med Int 12:239–258

    Google Scholar 

  • Mohan M, Attarde D, Momin R, Kasture S (2013) Antidepressant, anxiolytic and adaptogenic activity of torvanol A: an isoflavonoid from seeds of Solanum torvum. Nat Prod Res 27:2140–2143

    Article  CAS  PubMed  Google Scholar 

  • Momin R, Mohan M (2012) Involvement of central noradrenaline, serotonin and dopamine system in the antidepressant activity of fruits of Solanum torvum (Solanaceae). Nat Prod Res 26:416–422

    Article  CAS  PubMed  Google Scholar 

  • Niero R, Silva IT, Tonial GC, Camacho BS, Gacs-Baitz E, Delle Monache G, Delle Monache F (2006) Cilistepoxide and cilistadiol, two new withanolides from Solanum sisymbiifolium. Nat Prod Res 20:1164–1168

    Article  CAS  PubMed  Google Scholar 

  • OECD Guideline for testing of chemicals (2001) Acute oral toxicity-fixed dose procedure test. 401:1–14

  • Olson H, Betton G, Robinson D, Thomas K, Monro A, Kolaja G, Lilly P, Sanders J, Sipes G, Bracken W, Dorato M, Van Deun K, Smith P, Berger B, Heller A (2000) Concordance of toxicity of pharmaceuticals in humans and in animals. Regul Toxicol Pharmacol 32:56–67

    Article  CAS  PubMed  Google Scholar 

  • Perviz S, Khan H, Pervaiz A (2016) Plant alkaloids as an emerging therapeutic alternative for the treatment of depression. Front Pharmacol 7:1–7

    Article  CAS  Google Scholar 

  • Pletsch F, Rotta LN (2010) Cistatina C: um novo marcador de função renal. Newslab 103:118–132

    Google Scholar 

  • Porsolt RD, Pichon M, Jalfre M (1977) Depression: a new animal model sensitive to antidepressant treatments. Nature 266:730–732

    Article  CAS  PubMed  Google Scholar 

  • Saki K, Bahmani M, Rafieian-Kopaei M, Hassanzadazar H, Dehghan K, Bahmani F, Asadzadeh J (2014) The most common native medicinal plants used for psychiatric and neurological disorders in Urmia city, northwest of Iran. Asian Pac J Trop Dis 4:895–901

    Article  Google Scholar 

  • Sarris J, Panossian A, Schweitzer I, Stough C, Scholey A (2011) Herbal medicine for depression, anxiety and insomnia: a review of psychopharmacology and clinical evidence. Eur Neuropsychopharmacol 21:841–860

    Article  CAS  PubMed  Google Scholar 

  • Shan PC, Trivedi NA, Bhatt JD, Hemavathi KG (2006) Effect of Withania somnifera on forced swimming test induced immobility in mice and its interaction with various drugs. Indian J Physiol Pharmacol 50:409–415

    Google Scholar 

  • Silva TM, Batista MM, Camara CA, Agra MF (2005) Molluscicidal activity of some Brazilian Solanum spp. (Solanaceae) against Biomphalaria glabrata. Ann Trop Med Parasitol 99:419–425

    Article  CAS  PubMed  Google Scholar 

  • Silva TM, Nascimento RJB, Batista MM, Agra MF, Camara CA (2007a) Brine shrimp bioassay of some species of Solanum from Northestern Brazil. Rev Bras 17:35–38

    Google Scholar 

  • Silva MIG, Aquino-Neto MR, Teixeira-Neto PF, Moura BA, Amaral JF, Sousa DP, Vasconcelos SMM, Sousa FCF (2007b) Central nervous system activity of acute administration of isopulegol in mice. Pharmacol Biochem Behav 88:141–147

    Article  CAS  PubMed  Google Scholar 

  • Simões LO, Conceição-Filho G, Ribeiro TS, Jesus AM, Fregoneze JB, Silva AQG, Petreanu M, Cechinel-Filho V, Niero R, Niero H, Tamanaha MS, Silva DF (2016) Evidences of antihypertensive potential of extract from Solanum capsicoides All. in spontaneously hypertensive rats. Phytomedicine 23:498–508

    Article  CAS  PubMed  Google Scholar 

  • Teste JF, Pelsy-Johann I, Decelle T, Boulu RG (1993) Anti-immobility activity of different antidepressant drugs using the tail suspension test in normal or reserpinized mice. Fundam Clin Pharmacol 7:219–226

    Article  CAS  PubMed  Google Scholar 

  • Thaakur S, Pendyala V (2016) Phytochemical and pharmacological evaluation of Solanum surattense for antidepressant activity in albino mice. Int J Toxic Pharmacol Research 8:368–371

    Google Scholar 

  • Valvassori SS, Budni J, Varela RB, Quevedo J (2013) Contributions of animal models to the study of mood disorders. Rev Bras Psiquiatr 2:121–131

    Article  Google Scholar 

  • Willner P, Scheel-Krüger P, Belzung C (2013) The neurobiology of depression and antidepressant action. Neurosci Biobehav Rev 37:2331–2371

    Article  CAS  PubMed  Google Scholar 

  • Wong DT, Perry KW, Bymaster FP (2005) Case history: the discovery of fluoxetine hydrochloride (Prozac). Nat Rev Drug Discov 4:764–774

    Article  PubMed  Google Scholar 

  • World Health Organization (2018) http://www.who.int/mediacentre/factsheets/fs369/en/. Accessed 28 November 2018

  • Zhang P, Wang P, Yan L, Liu L (2018) Synthesis of gold nanoparticles with Solanum xanthocarpum extract and their in vitro anticancer potential on nasopharyngeal carcinoma cells. Int J Nanomedicine 13:7047–7059

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Funding

This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brazil (CAPES) - Finance Code 001. This study was financially supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo à Pesquisa e Inovação do Estado de Santa Catarina (FAPESC), and Universidade do Vale do Itajaí (UNIVALI).

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MMS and MP designed and performed the experiments, analyzed the data, and wrote the manuscript. PM, JLRP, LCL, and FDM performed the experiments, analyzed the data, edited, and approved the manuscript. ALPS and GSA contributed to the drafting of the manuscript. VCF and RN edited and approved the manuscript.

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Correspondence to Rivaldo Niero.

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Petreanu, M., Maia, P., da Rocha Pittarello, J.L. et al. Antidepressant-like effect and toxicological parameters of extract and withanolides isolated from aerial parts of Solanum capsicoides All. (Solanaceae). Naunyn-Schmiedeberg's Arch Pharmacol 392, 979–990 (2019). https://doi.org/10.1007/s00210-019-01648-9

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