<i>In silico</i> and <i>in vivo</i> anti-stress potential of <i>Stachytarpheta cayennensis</i> (Verbenaceae) in mice

Authors

  • ItunuOluwa M. Akanmu Department of Pharmacology and Toxicology, College of Pharmacy, Igbinedion University, Okada, Edo State, Nigeria.
  • Lateef A. Akinpelu Department of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of Ilorin, Ilorin, Kwara State, Nigeria.
  • A. Aliyu Department of Pharmaceutical Microbiology & Biotechnology, Faculty of Pharmaceutical Sciences, University of Ilorin, Ilorin, Kwara State, Nigeria.
  • Moses A. Akanmu Department of Pharmacology, Faculty of Pharmacy, Obafemi Awolowo University, Ile Ife, Osun State, Nigeria.

DOI:

https://doi.org/10.51412/psnnjp.2024.34

Keywords:

Stachytarpheta cayennensis, betulinic acid, in vivo studies, in silico studies, antistress potential
         Abtract Views | PDF Download: 84 / 28

Abstract

Background: Stachytarpheta cayennensis is locally used as an antistress agent but no scientific rationale for its use. Hence, this study evaluated the antistress potential of ethanol leaf extract of Stachytarpheta cayennensis (ELSC) in mice.

Methods: The stress induced anxiety was assessed using elevated plus maze following acute restraint stress in mice. The in silico studies of previously reported compounds from Stachytarpheta cayennensis (S. cayennensis) were also carried out.

Results and discussion: There was significant (p<0.001) increase in anxiety status of stressed control mice compared to the unstressed control suggesting stress induction. However, ELSC stressed at 125 and 250 mg/kg and diazepam stressed control significantly (p<0.001) reduced the anxiety indices of mice compared to the stressed control group suggesting the reversal of stress-induced anxiety in mice. The results of in silico studies revealed betulinic acid was the most favourable compound in terms of pharmacokinetics, toxicity profile and binding affinity. The post docking analysis showed that betulinic acid and the positive antistress drug (diazepam) interacted with amino acid residues of the target receptor protein active pockets. Moreso, betulinic acid has a stronger binding affinity (-7.8
Kcal/Mol) compared to diazepam (-6.9 Kcal/Mol), suggesting that betulinic acid may be a more effective antistress agent than diazepam.

Conclusion: This study therefore, concluded that betulinic acid may at least in part be responsible for the observed antistress effect of Stachytarpheta cayennensis. However, further studies may be carried out on the antistress potential of betulinic acid. 

References

Yaribeygi H, Panahi Y, Sahraei H, Johnston TP, Sahebkar A (2017) The impact of stress on body function: A review. EXCLI Journal. 16:1057-1072. doi: 10.17179/excli2017-480

Nicolaides NC, Chrousos GP (2013). Impact of stress on health in childhood and adolescence. Hormone Research in Paediatrics 96(1): 5–7. https://doi.org/10.1159/000528065

Baum A, Polsusnzy D (1999) Health Psychology: Mapping Biobehavioral Contributions to Health and Illness. Annual Review of Psychology 50:137-163. https://doi.org/10.1146/annurev.psych.50.1.137.

Khan S, Khan RA (2017). Chronic stress leads to anxiety and depression. Annals of Psychiatry and Mental Health 5(1): 1091.

Al-Shargie F, Taresh SM, Al-Ezzi A (2024) Mental stress and cognitive deficits management. Brain Sciences 14(4): 316. https://doi.org/10.3390/brainsci14040316

Shields GS, Sazma MA, McCullough AM, Yonelinas AP (2017) The effects of acute stress on episodic memory: A meta-analysis and integrative review. Psychological Bulletin 143(6): 636–675. doi: 10.1037/bul0000100

Dimsdale JE (2008) Psychological Stress and Cardiovascular Disease. Journal of the American College of Cardiology 51: 1237–1246. doi:10.1007/s11936-019-0724-5

Mondelli V (2014) From stress to psychosis: whom, how, when and why? Epidemiology and Psychiatric Sciences 23(3): 215-8. doi: 10.1017/S204579601400033X

Lisman J, Buzsáki G, Eichenbaum H, Nadel L, Ranganath C, Redish AD (2017) Viewpoints: how the hippocampus contributes to memory, navigation and cognition. Nature Neuroscience 20 (11): 1434-1447. doi: 10.1038/nn.4661

Hammen C (2005) Stress and depression. Annual Review in Clinical Psychology 1:293-319. https://doi.org/10.1146/annurev.clinpsy.1.102803.143938

Greenberg N, Carr JA, Summers CH (2002) Causes and consequences of stress. Integrative and Comparative Biology 42(3): 508-516. doi:10.1093/icb/42.3.508

Glaeske G, Hoffmann F (2011). Medikamente– psychotrope und andere Arzneimittel mit Missbrauchsund Abhängigkeitspotenzial. Jahrbuch Sucht. pp73-96.

Husain I, Zameer S, Madaan T, Minhaj A, Ahmad W, Iqubaal A, Ali A, Najmi AK (2019) Exploring the multifaceted neuroprotective actions of Emblica officinalis (Amla): A review. Metabolic Brain Diseases. 34: 957-65. doi: 10.1007/s11011-019-00400-9.

Habbu PV, Mahadevan KM, Kulkarni PV, Daulatsingh C, Veerapur VP and Shastry RA (2010) Adoptogenic and in vitro antioxidant activity of flavanoids and other fractions of Argyreia speciosa (Burm. F) Boj. in acute and chronic stress paradigms in rodents. Indian Journal Experimental Biology 48:53-60.

Chaachouay N, Zidane L (2024). Plant-derived natural products: A source for drug discovery and development. Drugs Drug Candidates 3:184-207. https://doi.org/10.3390/ddc3010011

Akinpelu LA, Aiyelero OM and Olayiwola G (2019). Ethanol leaf extract of Milicia excelsa mitigates anxiety and depressive-like behaviours induced by acute restraint stress in mice. GSC Biological and Pharmaceutical Sciences 6(2): 30-39. doi: 10.30574/gscbps.2019.6.2.0012

Aiyelero OM, Adeyemi IA., Akinpelu LA, Akanmu MA (2023) Anxiolytic and antistress potentials of ethanol stem-bark extract ofMilicia excelsa (Moraceae) in mice. Iranian Journal of Pharmaceutical Sciences 19(1):68-78. https://doi.org/10.22037/ijps.v19i1.43269

Adedeji O (2010) Palynology of the genus Stachytarpheta Vahl. (Verbenaceae). Notulae Scientia Biologicae 2:27-33.

Yadav P D, ModiKP, Shah M B (2021) Phytochemistry, pharmacology, and botanical aspects of Stachytarpheta species –A review. International Journal of Green Pharmacy 15 (2): 114. https://doi.org/10.22377/ijgp.v15i2.3078

Alvarenga N, Olmedo DA, González-Maldonado P, Soto-Rifo R, Valiente-Echeverría F, Langjahr P, Sotelo PH (2024) Unraveling the antiviral activity of Stachytarpheta cayennensis against SARS-CoV-2 variants using in vitro and molecular docking analysis. South African Journal of Botany 69: 567-575. https://doi.org/10.1016/j.sajb.2024.04.041

Onofre SB, Santos ZMQ, Kagimura FY, Mattiello SP (2015) Antioxidant activity, total phenolic and flavonoids contents in Stachytarpheta cayennensis, (Rich.) Vahl. (Verbenaceae). Journal of Medicinal Plant Research 9(17):569- 575.

Burkill, HM (1996). Stachytarpheta cayennensis. The Useful Plants of West Africa. Royal Botanical Keids 5: 268-9.

Hammer MLA, Johns EA (1993) Tapping and Amazonian plethora: four medicinal plants of Marajó Island, Pará-Brazil. Journal of Ethnopharmacology 40:53-75. https://doi.org/10.1016/0378-8741(93)90089-N

Schapoval EES, Winter DE, Vargas MR, Chaves CG, Raquel BJA, Zuanazzi ATH (1998) Anti- inflammatory and antinoceptive activities of extracts and isolated compounds from Stachytarpheta cayennensis. Journal of Ethnopharmacology 60(1):53-59. https://doi.org/10.1016/S0378-741(97)00136-0

Vela MS, Souccar C, Lima-Landman MT, Lapa AJ (2004) Pharmacological study of Stachytarpheta cayennensis Vahl in rodents. Phytomedicine 11:616-624. doi: 10.1016/j.phymed.2003.05.001.

Taylor L (2012) Raintree, tropical plant database. Milam County, Texas, USA. Alice CB, Vargas VMF, Silva GAAB, De Siqueira NCS, Schapoval EES, Gleve J, Henriques JAP, Henriques AT (1991) Screening of plants used in South Brazilian folk medicine. Journal of Ethnopharmacology 35(2):165-171. https://doi.org/10.1016/0378-8741(91)90069-P

Vela NS, Souccar C, Lima-Landman (1997) Inhibition of gastric acid secretion by three aqueous extracts and purified extracts of Stachytarpheta cayennensis. Planta Medica 63(1): 36-9.doi: 10.1055/s-2006-957599.

Penido C, Costa KA, Futuro DO, Paiva SR, Kaplan WA, Figueiredo MR, Henriques MG (2006) Anti-inflammatory and antiulcerogenic properties of Stachytarpheta cayennensis (L.C. Rich) Vahl. Journal of Ethnopharmacology 104:225-33. doi: 10.1016/j.jep.2005.09.006

Almeida CE, Kamikowski MG, Foleto R, Baldisserotto B (1995) Analysis of the antidiarrhoeic effects of plants used in popular medicine. Revista de Saude Publica 29: 428-33. doi: 10.1590/s0034-89101995000600002.

Adebajo AC, Olawode EO, Omobuwajo OR, Adesanya SA, Begrow F, Elkhawad A, Akanmu MA, Edrada R, Proksch P, Schmidt TJ, Klaes M, Verspohl EJ (2007) Hypoglycaemic constituents of Stachytarpheta cayennensis leaf. Planta Medica 73(3): 241-50. doi:10.1055/s-2007-967125

Okokon JE, Ettebong E, Antia BS (2008) In vivo antimalarial activity of ethanolic leaf extract of Stachytarpheta cayennensis. Indian Journal of Pharmacology 40: 111-113. doi: 10.4103/0253-7613.42303

Kvist LP., Christensen SB., Rasmusen HB., Mejia K. Gonzalez A (2006) Identification and evaluation of Peruvian plants used to treat malaria and leishmaniasis. Journal of Ethnopharmacology106: 390-402. doi: 10.1016/j.jep.2006.01.020.

Akanmu MA, Olayiwola G, Ukponmwan OE, Honda K (2005) Acute toxicity and sleep-wake EEG analysis of Stachytarpheta cayennensis (Verbenaceae) in rodents. African Journal of Traditional Complementary and Alternative Medicine 2: 222-232.

Olayiwola G, Ukponmwan O, Olawode D (2013) Sedative and anxiolytic effects of the extracts of the leaves of Stachytarpheta cayennensis in mice African Journal of Traditional Complementary and Alternative Medicine 10(6):568-579. doi: 10.4314/ajtcam.v10i6.32.

Okoye TC, Akah PA, Okoli CO, Ezike AC, Mbaoji FN (2010) Antimicrobial and antispasmodic activity of leaf extract and fractions of Stachytarpheta cayennensis. Asian Pacific Journal of Tropical Medicine 3: 189-192. https://doi.org/10.1016/S1995-7645(10)60006-5

Hazarika I, Geetha KM, Sundrai PS, Madhu D (2019) Acute oral toxicity evaluation of extracts of Hydrocotyle sibthorpiodes in wistar albino rats as per OECD 425 TG. Toxicological Report 6: 321-328. doi: 10.1016/j.toxrep.2019.04.001

Mechan AO, Moran PM, Elliot M, Young AJ, Joseph MH, Green RA (2022) Comparison between Dark Agouti and Sprague-Dawley rats in their behavior on the elevated plus-maze, open field apparatus and activity meters and their response to diazepam. Psychopharmacology 159:188-195. doi: 10.1007/s002130100902.

Sturman O, Germain PL, Bohacek J (2018) Exploratory rearing: a context- and stress- sensitive behavior recorded in the open-field test. Stress 21(5):443–452. doi: 10.1080/10253890.2018.1438405.

Adebayo MA, Akinpelu LA, Okwuofu EO, Ibia DE, Lawson-Jack AF, Igbe I (2020) Anxiolytic, antiamnesic and anticonvulsant activities of methanol leaf extract of Bambusa vulgaris (Poaceae) in mice. Journal of African Association of Physiological Science 8(2):149-157.

Akinpelu LA, Adebayo MA, Fajana A, Adeniyi- Akee MA, Ubogu SE, Aminu NS (2019). Phytochemical analyses, anxiolytic and anti- amnesic effect of methanol stem bark extract of Vitex doniana (Sweet) in mice. Nigerian Journal of Natural Product and Medicine 23:104-111.

Souza PAD, Silva CG, Machado BRP, de Lucas NM, Leitão GG, Eleutherio ECA, Ortiz GMD, Benchetrit LC. Evaluation of antimicrobial, antioxidant and phototoxic activities of extracts and isolated compounds from Stachytarpheta cayennensis (Rich.) Vahl, Verbenaceae. Brazilian Journal of Pharmacognosy 20(6):922-928. doi: 10.1590/S0102-695X2010005000042.

Ganapathy S, Shruthi SD, Lakshmikantha RY (2017). Antibacterial and molecular docking studies of bioactive component from leaves of Stachytarpheta cayennensis (Rich.) Vahl. Research Journal of Phytochemistry 11(1):28-34. doi: 10.3923/rjphyto.2016

Iwu IC, Onu UL, Ukaoma AA, Oze RN (2019). Phytochemical, antimicrobial and GC/MS analysis of the root of Stachytarpheta cayennensis (Vahl) grown in Eastern Nigeria. International Research Journal of Nat Science 7(2):20-32.

Otom OP, Okwute SK (2020). Chemical and biological screening of the leaves of Stachytarpheta cayennensis (Vahl). International Journal of Research and Scientific Innovation 6(12):61-67.

Yadav PD, Modi KP, Shah MB (2021). Phytochemistry, pharmacology, a n d botanical aspects of Stachytarpheta species - doi: 10.1016/j.crtox.2023.100118

Banerjee P, Eckert AO, Schrey AK, Preissner R (2018) ProTox-II: a webserver for the prediction of toxicity of chemicals. Nucleic Acids Research 46:257–63. doi: 10.1093/nar/gky318

Drwa MN, Banerjee P, Dunkel M, Wettig MR, Preissner R (2014) ProTox: a web server for the in silico prediction of rodent oral toxicity. Nucleic Acids Research 42(1):53–8. doi: 10.1093/nar/gku401

Aliyu A, Ibrahim YKE , Tytler BA, Olowo-Okere A (2022) Antimicrobial peptide design, molecular docking and ADMET studies against the methicillin-resistant Staphylococcus aureus and carbapenem resistant and carbapenemase- producing Pseudomonas aeruginosa. Trends Peptide Protein Science 7:9. https://doi.org/10.22037/tpps.v7i.39110

Hazarika I, Geetha KM, Sundrai PS, Madhu D (2019) Acute oral toxicity evaluation of extracts of Hydrocotyle sibthorpiodes in wistar albino rats as per OECD 425 TG. Toxicological Reports 6: 321-328. https://doi.org/10.22037/tpps.v7i.39110

Winder C, Azzi R, Wagner D (2005) The development of the globally harmonized system (GHS) of classifcation and labelling of hazardous chemicals. Journal of Hazardous Materials 125(1–3):29–44. doi: 10.1016/j.jhazmat.2005.05.035.

Oyemitan IA, Bello OA, Akinpelu LA. (2015) Neuropharmacological evaluation of ethanolic leaf extract of Alternanthera brasiliana (L.) Kuntze (Amaranthaceae) in mice. International Journal of Pharmaceutical Science and Research 6(9):3796-06. doi: 10.13040/IJPSR.0975-8232.6(9).3796-08

Duraisimi R, Mohite VA, Kasbe AJ (2010) Anti- stress, adaptogenic activity of standardized dried fruit extract of Aegle marmelos against diverse stressors. Asian Journal of Pharmaceutical and Clinical Research 2010;3(4): 1-3.

Raghu RA, Harsha SNS, Kumar DY, Neelima KSSN (2013) Effect of Trichopus zeyylanicus leaf extract on acute stress induced anxiety in mice. International Journal of Pharmaceutical Chemistry and Analysis 1(7):445-449.

Sulakhiya K, Patel VK, Saxena R, Dashore J, Srivastava AK, Rathore M (2016) Effect of Beta vulgaris Linn. Leaves extract on anxiety- and depressive-like behavior and oxidative stress in mice after acute restraint stress. Pharmacolognosy Research 8(1):1-7. doi: 10.4103/0974-8490.171100

Oliveira TAS, Silva JBA, Barco JG, Groppo M, de Souza SL, Martins, CHG (2023) Chemical composition and antibacterial activity of the essential oil from Stachytarpheta cayennensis leaves grown in Brazil Southeast. Journal of Essential Oil & Plant Composition 1(2):32-38. doi:10.58985/jeopc.2023.v01i02.06

Negi A, Singh P, Taneja N, Mani S (2018) Molecular-docking study of anti-stress natural compounds against GABAA Receptor portends the novel approach to stress treatment. Journal of Applied Pharmaceutical Sciences 8(12):038- 043. doi: 10.7324/JAPS.2018.81205

Dallakyan S, Olson AJ (2015) Small-molecule library screening by docking with PyRx. Methods in Molecular in Biology 1263:243 250. doi: 10.1007/978-1-4939-2269-7_19.

Olubodun-Obadun TG, Ishola IO, Akinwande AS, Adeyemi OO (2023). Cajanus cajan (L) Millsp. seed extract ameliorates scopolamine- induced amnesia through increase in antioxidant defense mechanisms and cholinergic neurotransmission. Nigerian Journal of Physiological Science 38:91–99. doi: 10.54548/njps.v38i1.13.

Daina A, Michielin O, Zoete V (2017) SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Scientific Reports. 7: 1–13. doi: 10.1038/srep42717.

Lipinski CA, Lombardo F, Dominy BW, Feeney PJ (2001) Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Advance Drug Delivery Review. 46(1–3): 3–26. doi: 10.1016/s0169- 409x(00)00129-0.

Rai M, Singh AV, Paudel N, Kanase A, Falletta E, Kerkar P, Heyda J, Barghash RF, Pratap SS, Soos M (2023). Herbal concoction unveiled: a computational analysis of phytochemicals' pharmacokinetic and toxicological profiles using novel approach methodologies (NAMs). Current Research in Toxicology 5: 100118.

Srivastava AK, Rathore M (2016) Effect of Beta vulgaris Linn. Leaves extract on anxiety- and depressive-like behavior and oxidative stress in mice after acute restraint stress. Pharmacolognosy Research 8(1):1-7. doi: 10.4103/0974-8490.171100

Anuradha H, Srikumar BN, Rao BSS, Lakshmana M (2008). Euphorbia hirta reverses chronic stress-induced anxiety and mediates its action through the GABAA receptor benzodiazepine recptor-Cl2 channel complex. Journal of Neural Transmission 115: 3542. doi: 10.1007/s00702-007-0821-6.

Pagadala NS, Syed K, Tuszynski J (2017) Software for molecular docking: A review. Biophysical Reviews 9: 91-102.

Utami JP, Diana S, Arifin R. (2022) In silico study of Stachytarpheta jamaicensis active compounds as antibacterial material. Dentino Jurnal Kedokteran Gigi. 7(1): 62-67.

Pisha E, Chai H, Lee IS, Chagwedera TE, Farnsworth NR, Cordell GA, Beecher CWW, Fong HHS, Kinghorn AD, Brown DM, Wani MC, Wall ME, Hieken TJ, Das Gupta TK, Pezzuto JM (1995) Discovery of betulinic acid as a selective inhibitor of human melanoma that functions by induction of apoptosis. Nature Medicine 1:1046- 1051. doi: 10.1038/nm1095-1046.

Udeani GO, Zhao GM, Geun Shin Y, Cooke BP, Graham J, Beecher CW, Kinghorn AD, Pezzuto JM (1999) Pharmacokinetics and tissue distribution of betulinic acid in CD-1 mice. Biopharm Drug Dispos. 20(8):379-83. doi: 10.1002/1099-081x(199911)20:8<379::aid bdd198>3.0.co;2-c.

Laskowski RA, Swindells MB (2011) LigPlot+: multiple ligand-protein interaction diagrams for drug discovery. Journal of Chemical Information and Modeling 51: 2778-2786. https://doi.org/10.1021/ci200227u

Moghaddam MG, Ahmad JBH, Samzadeh- Kermani A (2012) Biological activity of betulinic acid: A review. Phamacology and Pharmacy 3:119–123. doi: 10.4236/pp.2012.32018.

Ríos JL, Máñez S (2018) New pharmacological opportunities for betulinic acid. Planta Medica 84: 8–19. doi: 10.1055/s-0043-123472

Muceniece R, Saleniece K, Rumaks J, Krigere L, Dzirkale Z, Mezhapuke R, Zharkova O, Klusa V (2008) Betulin binds to gamma-aminobutyric acid receptors and exerts anticonvulsant action in mice. Pharmacology Biochemistry and Behaviour. 90:712-716. doi:10.1016/j.pbb.2008.05.015.

Puniani E, CayerC, Kent P,Mullally M, SánchezVindas P, Álvarez LP, Cal V, Merali Z, Arnason JT, Durst T (2015) Ethnopharmacology of Souroubea sympetala and Souroubea gilgii (Marcgraviaceae) and identification of betulinic acid as an anxiolytic principle. Phytochemistry 113:73-78. doi: 10.1016/j.phytochem.2014.02.017.

Li B, Yang Y, Song Z, Tang Z (2024) Comparative analysis of the sedative and hypnotic effects among various parts of Zizyphus spinosus Hu and their chemical analysis. Pharmaceuticals (Basel). 17(4):413. https://doi.org/10.3390/ph17040413

Osunsanmi FO, Zharare GE, Mosa RA, Ikhile MI , Shode FO, Opoku AR (2019) Anti-oxidant, anti- inflammatory and antiacetylcholinesterase activity of betulinic acid and 3β- acetoxybetulinic acid from Melaleuca bracteata 'Revolution Gold'. Tropical Journal of Pharmaceutical Research 18(2):303-309. doi: 10.4314/tjpr.v18i2.12

Oliveira-Costa JF, Meira CS, Neves MVGd, Dos Reis BPZC Soares MBP (2022). Anti- inflammatory activities of betulinic acid: A review. Frontiers in Pharmacology 13:883857. doi: 10.3389/fphar.2022.883857

Khan MF, Nahar N, Rashid RB, Chowdhury A, Rashid MA (2018). Computational investigations of physicochemical, pharmacokinetic, toxicological properties and molecular docking of betulinic acid, a constituent of Corypha taliera (Roxb.) with Phospholipase A2 (PLA2). BMC Complementary and Alternative Medicine 18:48. doi: 10.1186/s12906-018-2116-x.

Okoye TC, Aguwa CN, Okoli CO, Akah PA, Nworu CS (2008) Anticonvulsant and sedative effects of leaf extracts of Stachytarpheta cayennensis. Journal of Tropical Medicinal Plants 9(1):17-22.

Downloads

Published

2024-11-04

How to Cite

Akanmu, I. M., Akinpelu, L. A., Aliyu, A., & Akanmu, M. A. (2024). <i>In silico</i> and <i>in vivo</i> anti-stress potential of <i>Stachytarpheta cayennensis</i> (Verbenaceae) in mice. The Nigerian Journal of Pharmacy, 58(2), 370–385. https://doi.org/10.51412/psnnjp.2024.34