Evaluation of anxiolytic, sedative, and antioxidant activities of Vitex peduncularis Wall. leaves and investigation of possible lead compounds through molecular docking study


Vitex peduncularis, belongs to the Verbenaceae family, locally known as ‘Boruna’, ‘Horina’, ‘Ashmul gaas’, is commonly used for treating various chronic diseases in the folk medicine such as malarial fevers, jaundice, diabetes, chest pain, joint ache, abnormality in eyes & face, and urethritis, etc. In the present study, we investigated the anxiolytic, sedative, and antioxidant activities of ethanol extract of V. peduncularis leaves (EEVP) in both in vivo and in vitro models. Then, a molecular docking analysis was carried out to determine the possible lead compounds of EEVP for the biological properties described above. The anxiolytic and sedative activity of EEVP was determined using hole board and hole cross tests, respectively. Antioxidant activity was measured using DPPH and FRPA assays, whereas docking was done by using the Schrödinger suite (Maestro v10.1). Our result demonstrated that EEVP has significant and dose-dependent anxiolytic and sedative activity at the doses of 200 and 400 mg/kg (b.w.) in both models. This study also exhibited that EEVP has significant antioxidant activity compared to reference standard ascorbic acid. The molecular docking study revealed that 3,4-dihydroxybenzoic acid, 4-hydroxybenzoic acid, and vitexilactone have the best binding affinities against the target receptors (potassium channel receptor, human gamma-aminobutyric acid receptor, and human peroxiredoxin 5) for anxiolytic, sedative, and antioxidant activities. The present study confirmed that EEVP has anxiolytic, sedative, and antioxidant properties, which could be because of the occurrence of various phytochemicals and three bioactive phytocompounds which found potential during molecular docking analysis.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3
Fig. 4:
Fig. 5:
Fig. 6:



Ethanol extract of Vitex peduncularis leaves


Central nervous system


Protein Data Bank


Root-mean-square deviation


Optimized potentials for liquid simulations


Statistical package for the social sciences


Analysis of variance


Standard error mean


Room temperature


Relative humidity


Body weight


Ferric reducing power activity


1,1 Diphenyl-1-picrylhydrazyl


  1. Adnan M, Nazim Uddin Chy M, Rudra S et al (2018) Evaluation of Bonamia semidigyna (Roxb.) for antioxidant, antibacterial, anthelmintic and cytotoxic properties with the involvement of polyphenols. Orient Pharm Exp Med 1:3. https://doi.org/10.1007/s13596-018-0334-x

    CAS  Article  Google Scholar 

  2. Adnan M, Azad MOK, Ju HS et al (2019a) Development of biopolymer-mediated nanocomposites using hot-melt extrusion to enhance the bio-accessibility and antioxidant capacity of kenaf seed flour. Appl Nanosci 8:1–13

    Google Scholar 

  3. Adnan M, Chy MNU, Kamal ATMM et al (2019b) Investigation of the biological activities and characterization of bioactive constituents of Ophiorrhiza rugosa var. prostrata (D.Don) & mondal leaves through in vivo, in vitro, and in silico approaches. Molecules 24:1367. https://doi.org/10.3390/MOLECULES24071367

    Article  PubMed Central  Google Scholar 

  4. Adnan M, Chy M, Uddin N et al (2020a) Comparative study of Piper sylvaticum Roxb. leaves and stems for anxiolytic and antioxidant properties through in vivo, in vitro, and in silico approaches. Biomedicines 8:68

    PubMed Central  Google Scholar 

  5. Adnan M, Chy MNU, Kamal ATMM et al (2020b) Intervention in neuropsychiatric disorders by suppressing inflammatory and oxidative stress signal and exploration of in silico studies for potential lead compounds from Holigarna caustica (Dennst.) Oken leaves. Biomolecules 10:561. https://doi.org/10.3390/biom10040561

    CAS  Article  PubMed Central  Google Scholar 

  6. Ancoli-Israel S, Roth T (1999) Characteristics of insomnia in the United States: results of the 1991 National Sleep Foundation Survey. I. Sleep 22:S347

    PubMed  Google Scholar 

  7. Asolkar LV, Kakkar KK, Chakre OJ, et al (1992) Second supplement to Glossary of Indian medicinal plants with active principles: part-1 (A-K). Publications and information directorate, New-Dehli

    Google Scholar 

  8. Auniq R, Chy M, Adnan M et al (2019) Assessment of anti-nociceptive and anthelmintic activities of Vitex peduncularis Wall. leaves and in silico molecular docking, ADME/T, and PASS prediction studies of its isolated compounds. J Complement Med Res 10:170. https://doi.org/10.5455/jcmr.20190805024523

    Article  Google Scholar 

  9. Barua CC, Roy JD, Buragohain B et al (2009) Anxiolytic effect of hydroethanolic extract of Drymaria cordata L Willd. Indian J Exp Biol 47(12):969–973

    PubMed  Google Scholar 

  10. Berman HM, Battistuz T, Bhat TN et al (2002) The protein data bank. Acta Crystallogr Sect D Biol Crystallogr 58:899–907

    Google Scholar 

  11. Braca A, De Tommasi N, Di Bari L et al (2001) Antioxidant principles from Bauhinia tarapotensis. J Nat Prod 64:892–895

    CAS  PubMed  Google Scholar 

  12. Cryan JF, Sweeney FF (2011) The age of anxiety: role of animal models of anxiolytic action in drug discovery. Br J Pharmacol 164:1129–1161

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Declercq J-P, Evrard C, Clippe A et al (2001) Crystal structure of human peroxiredoxin 5, a novel type of mammalian peroxiredoxin at 1.5 Å resolution. J Mol Biol 311:751–759

    CAS  PubMed  Google Scholar 

  14. Deniz GY, Laloglu E, Altun S et al (2020) Antioxidant and anti-apoptotic effects of vitexilactone on cisplatin-induced nephrotoxicity in rats. Biotech Histochem 22:1–8

    Google Scholar 

  15. Ebert B, Wafford KA, Deacon S (2006) Treating insomnia: current and investigational pharmacological approaches. Pharmacol Ther 112:612–629

    CAS  PubMed  Google Scholar 

  16. Fernández S, Wasowski C, Paladini AC, Marder M (2004) Sedative and sleep-enhancing properties of linarin, a flavonoid-isolated from Valeriana officinalis. Pharmacol Biochem Behav 77:399–404

    PubMed  Google Scholar 

  17. Friesner RA, Banks JL, Murphy RB et al (2004) Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy. J Med Chem 47:1739–1749

    CAS  PubMed  Google Scholar 

  18. Friesner RA, Murphy RB, Repasky MP et al (2006) Extra precision glide: docking and scoring incorporating a model of hydrophobic enclosure for protein–ligand complexes. J Med Chem 49:6177–6196

    CAS  PubMed  Google Scholar 

  19. Gopalakrishnan A, Ji LL, Cirelli C (2004) Sleep deprivation and cellular responses to oxidative stress. Sleep 27:27–35

    PubMed  Google Scholar 

  20. Griffin CE, Kaye AM, Bueno FR, Kaye AD (2013) Benzodiazepine pharmacology and central nervous system–mediated effects. Ochsner J 13:214–223

    PubMed  PubMed Central  Google Scholar 

  21. Haque ME, Rani M, Jahan A et al (2018) An overview study on chemical constituents and biological activities of Vitex peduncularis wall. Moj Bioorg Org Chem 2:6–9

    Google Scholar 

  22. Hasanat A, Chowdhury AT, Kabir SM et al (2017) Antinociceptive activity of Macaranga denticulata Muell. Arg. (Family: Euphorbiaceae): in vivo and in silico studies. Medicines. https://doi.org/10.3390/medicines4040088

    Article  PubMed  PubMed Central  Google Scholar 

  23. Hatano T, Edamatsu R, Hiramatsu M et al (1989) Effects of the interaction of tannins with co-existing substances. VI.: effects of tannins and related polyphenols on superoxide anion radical, and on 1, 1-diphenyl-2-picrylhydrazyl radical. Chem Pharm Bull 37:2016–2021

    CAS  Google Scholar 

  24. Hoffman DL, Dukes EM, Wittchen H (2008) Human and economic burden of generalized anxiety disorder. Depress Anxiety 25:72–90

    PubMed  Google Scholar 

  25. Islam NU, Khan I, Rauf A et al (2015) Antinociceptive, muscle relaxant and sedative activities of gold nanoparticles generated by methanolic extract of Euphorbia milii. BMC Complement Altern Med 15:1–11

    Google Scholar 

  26. Jung JW, Yoon BH, Oh HR et al (2006) Anxiolytic-like effects of Gastrodia elata and its phenolic constituents in mice. Biol Pharm Bull 29:261–265

    CAS  PubMed  Google Scholar 

  27. Kähkönen MP, Hopia AI, Vuorela HJ et al (1999) Antioxidant activity of plant extracts containing phenolic compounds. J Agric Food Chem 47:3954–3962

    PubMed  Google Scholar 

  28. Kannathasan K, Senthilkumar A, Venkatesalu V (2015) Crystal structure and antibacterial evaluation of epifriedelinol isolated from Vitex peduncularis Wall. ex Schauer. Arab J Chem 12:2289–2292

    Google Scholar 

  29. Kessler RC, Berglund P, Demler O et al (2005) Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 62:593–602

    PubMed  Google Scholar 

  30. Khan SA, Chatterjee SS, Kumar V (2015) Potential anti-stress, anxiolytic and antidepressant like activities of mono-hydroxybenzoic acids and aspirin in rodents: a comparative study. Austin J Pharmacol Ther 3:1073

    Google Scholar 

  31. Kimiskidis VK, Triantafyllou NI, Kararizou E et al (2007) Depression and anxiety in epilepsy: the association with demographic and seizure-related variables. Ann Gen Psychiatry 6:28

    PubMed  PubMed Central  Google Scholar 

  32. Lee J, Koo N, Min DB (2004) Reactive oxygen species, aging, and antioxidative nutraceuticals. Compr Rev Food Sci Food Saf 3:21–33

    CAS  Google Scholar 

  33. Lenaeus MJ, Burdette D, Wagner T et al (2014) Structures of KcsA in complex with symmetrical quaternary ammonium compounds reveal a hydrophobic binding site. Biochemistry 53:5365–5373

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Makhmoor T, Choudhary MI (2010) Radical scavenging potential of compounds isolated from Vitex agnus-castus. Turk J Chem 34:119–126

    Google Scholar 

  35. Marandi RR, Britto SJ, George M, Minj E (2016) Pharmacognostic, fluorescent, antibacterial and phytochemical analysis of tuber of Dioscorea bulbifera L. from Jharkhand. J Pharmacogn Phytochem 5:8

    CAS  Google Scholar 

  36. Meng X-Y, Zhang H-X, Mezei M, Cui M (2011) Molecular docking: a powerful approach for structure-based drug discovery. Curr Comput Aided Drug Des 7:146–157

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Miller PS, Aricescu AR (2014) Crystal structure of a human GABA A receptor. Nature 512:270–275

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Oyaizu M (1986) Studies on products of browning reaction. Jpn J Nutr Diet 44:307–315

    CAS  Google Scholar 

  39. Panda SS, Sahoo K, Parida S et al (2012) In-vitro antimicrobial screening of leaf and stem extracts of Vitex peduncularis Wall. ex schauer. Int J Pharm Pharm Sci 4:177–180

    Google Scholar 

  40. Rajput MA, Khan RA (2017) Phytochemical screening, acute toxicity, anxiolytic and antidepressant activities of the Nelumbo nucifera fruit. Metab Brain Dis 32:743–749

    CAS  PubMed  Google Scholar 

  41. Rao Ch B, Venkateswarlu V (1956) Vitexin from Vitex peduncularis Wall. J Biosci 8:328–329

    Google Scholar 

  42. Roth T (2007) Insomnia: definition, prevalence, etiology, and consequences. J Clin Sleep Med JCSM 3:S7

    PubMed  Google Scholar 

  43. Rudrapaul P, Gruner M, Knoelker H-J, Dinda B (2015) Flavones and triterpenes from the leaves of Vitex peduncularis. Indian J Chem 54B:279–282

    CAS  Google Scholar 

  44. Sahu NP, Roy SK, Mahato SB (1984) Triterpenoids and flavonoids of Vitex peduncularis. Planta Med 50:527

    CAS  PubMed  Google Scholar 

  45. Shafaghi B, Naderi N, Tahmasb L, Kamalinejad M (2010) Anxiolytic effect of Echium amoenum L. in mice. Iran J Pharm Res 1:37–41

    Google Scholar 

  46. Shoibe M, Chy MNU, Alam M et al (2017) In vitro and in vivo biological activities of Cissus adnata (Roxb.). Biomedicines. https://doi.org/10.3390/biomedicines5040063

    Article  PubMed  PubMed Central  Google Scholar 

  47. Suksamrarn A, Kumpun S, Kirtikara K et al (2002) Iridoids with anti-inflammatory activity from Vitex peduncularis. Planta Med 68:72–73

    CAS  PubMed  Google Scholar 

  48. Takagi K, Watanabe M, Saito H (1971) Studies of the spontaneous movement of animals by the hole cross test; effect of 2-dimethyl-aminoethanol and its acyl esters on the central nervous system. Jpn J Pharmacol 21:797–810

    CAS  PubMed  Google Scholar 

  49. Takahashi RN, de Lima TCM, Morato GS (1986) Pharmacological actions of tannic acid; II. Evaluation of CNS activity in animals. Planta Med 52:272–275

    Google Scholar 

  50. Takeda H, Tsuji M, Matsumiya T (1998) Changes in head-dipping behavior in the hole-board test reflect the anxiogenic and/or anxiolytic state in mice. Eur J Pharmacol 350:21–29

    CAS  PubMed  Google Scholar 

  51. Tsaluchidu S, Cocchi M, Tonello L, Puri BK (2008) Fatty acids and oxidative stress in psychiatric disorders. BMC Psychiatry 8(Suppl 1):S5. https://doi.org/10.1186/1471-244X-8-S1-S5

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  52. Tung Y-T, Wu J-H, Kuo Y-H, Chang S-T (2007) Antioxidant activities of natural phenolic compounds from Acacia confusa bark. Bioresour Technol 98:1120–1123

    CAS  PubMed  Google Scholar 

  53. Tye KM, Prakash R, Kim S-Y et al (2011) Amygdala circuitry mediating reversible and bidirectional control of anxiety. Nature 471:358–362

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Wing YK (2001) Herbal treatment of insomnia. Hong Kong Med J 7:392–402

    CAS  PubMed  Google Scholar 

  55. Yang Y-R, Cho J-Y, Park Y-K (2012) Isolation and identification of antioxidative compounds 3, 4-dihydroxybenzoic acid from black onion. Korean J Food Preserv 19:229–234

    Google Scholar 

  56. You J-S, Peng M, Shi J-L et al (2012) Evaluation of anxiolytic activity of compound Valeriana jatamansi Jones in mice. BMC Complement Altern Med 12:223

    PubMed  PubMed Central  Google Scholar 

  57. Zhang X-M, Zhu J-L, Sun Y et al (2018) Anxiolytic potency of iridoid fraction extracted from Valeriana jatamansi Jones and its mechanism: a preliminary study. Nat Prod Res 32:2071–2075

    CAS  PubMed  Google Scholar 

Download references


The authors are grateful to the Department of Pharmacy, International Islamic University Chittagong, Bangladesh, and also thankful to GUSTO A Research Group for their kind help. We are also thankful to Dr. Shaikh Bokhtear Uddin for his kind co-operation in the identification of this plant.


This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author information




RBJA, MNUC, and MA conceived and designed the experiments. RBJA, MNUC, MA, AP, MRC, IJ, MRT, MS, NC, and SH carried out experimental works, collected data, and wrote the original draft. RBJA, MNUC, and MA analyzed and interpreted experimental results and wrote the final draft. MNUC, MRC, AP, TD, SSI, and MIHS performed the molecular docking and wrote the relevant potions. MNUC and MA furnished the designing of the work, checked the experimental results, and drafted the final manuscript. This work was carried out in collaboration between all authors. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Md. Adnan.

Ethics declarations

Ethical statement

This study was performed based on the internationally accepted principle for the proper use of laboratory animals’ viz. International Council for Laboratory Animal Science (ICLAS) and National Institutes of Health (NIH). This study protocol (Pharm-P&D-61/08’16-129) was approved by the “P&D committee” of the Department of Pharmacy, International Islamic University Chittagong, Chittagong 4318, Bangladesh.

Conflict of interest

Reedwan Bin Jafar Auniq has no conflict of interest. Md. Nazim Uddin Chy has no conflict of interest. Md. Adnan has no conflict of interest. Md. Riad Chowdhury has no conflict of interest. Trishala Dutta has no conflict of interest. Sadab Sipar Ibban has no conflict of interest. Israt Jahan has no conflict of interest. Marzia Rahman Tona has no conflict of interest. Mutakabrun Shima has no conflict of interest. Md. Imtiajul Habib Sawon has no conflict of interest. Nishan Chakrabarty has no conflict of interest. Shakawat Hossain has no conflict of interest. Arkajyoti Paul has no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Auniq, R.B.J., Chy, M.N.U., Adnan, M. et al. Evaluation of anxiolytic, sedative, and antioxidant activities of Vitex peduncularis Wall. leaves and investigation of possible lead compounds through molecular docking study. ADV TRADIT MED (ADTM) (2020). https://doi.org/10.1007/s13596-020-00461-7

Download citation


  • Vitex peduncularis
  • Anxiolytic
  • Sedative
  • Antioxidant activity
  • Molecular docking