Skip to main content

Advertisement

Log in

Potential effects of alpha-pinene, a monoterpene commonly found in essential oils against Toxoplasma gondii infection; an in vitro and in vivo study

  • Original Article
  • Published:
Journal of Parasitic Diseases Aims and scope Submit manuscript

Abstract

This survey designed to assess the in vitro and in vivo activity of α-pinene, a monoterpene commonly originated in essential oils on Toxoplasma gondii. The in vitro effect of various concentration of α-pinene against tachyzoites of T. gondii Rh strain was assessed by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The activity of α-pinene on the stimulation of apoptosis in tachyzoites of T. gondii was also examined using the caspase 3 colorimetric activity assay. In vivo assay, mice were orally received α-pinene at 2 and 4 mg/kg/day for 14 days, then, pre-treated mice were daily tested and the rate of death was recorded. α-pinene meaningfully declined (p < 0.001) the tachyzoites viability with the IC50 value of 23.3 µg/mL. α-pinene induced the apoptosis through increasing the caspase-3 activity by 35.6%. Oral treatment with α-pinene significantly (p < 0.01) improved the survival rate infected mice with by 9th day. α-pinene + atovauone (50 mg/kg) significantly (p < 0.01) improved the survival rate infected mice up to 11 days compared with the control groups. α-pinene especially in combined atovaquone at 50 mg/kg for 2 weeks meaningfully (p < 0.05) declined oxidative stress. We found the promising in vitro anti-Toxoplasma effects of α-pinene on T. gondii RH strain. In addition, we found that α-pinene therapy particularly along with the reference drug declined the mortality rate of infected mice. Although, we just confirmed the stimulation of apoptosis and anti-inflammatory effects as the main anti-Toxoplasma mechanisms of α-pinene; however, more surveys concerning the accurate mechanisms, toxicity, and efficacy on other T. gondii strains are required to confirm these results.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Allenspach M, Steuer C (2021) α-Pinene: a never-ending story. Phytochemistry 1(190):112857

    Article  Google Scholar 

  • Al-Snafi AE (2016) Antiparasitic effects of medicinal plants (part 1): a review. IOSR J Pharm 6(10):51–66

    Google Scholar 

  • Anand U, Jacobo-Herrera NJ, Altemimi AB, Lakhssassi N (2019) A comprehensive review on medicinal plants as antimi-crobial therapeutics: potential avenues of biocompatible drug discovery. Metabolites 9:258. https://doi.org/10.3390/metabo9110258

    Article  CAS  PubMed Central  Google Scholar 

  • Arab-Mazar Z, Kheirandish F, Rajaeian S (2017) Anti-toxoplasmosis activity of herbal medicines: narrative review. Herb Med J pp 43–9

  • Asgari Q, Keshavarz H, Shojaee S, Motazedian MH, Mohebali M, Miri R, Mehrabani D, Rezaeian M (2013) In vitro and in vivo potential of RH strain of Toxoplasma gondii (Type I) in tissue cyst forming. Iran J Parasitol 8(3):367

    PubMed  PubMed Central  Google Scholar 

  • Bauri RK, Tigga MN, Kullu SS (2015) A review on use of medicinal plants to control parasites. Indian J Nat Prod Resour 6(4):268–277

    CAS  Google Scholar 

  • Cheraghipour K, Masoori L, Ezzatkhah F, Salimikia I, Amiri S, Makenali AS, Taherpour F, Mahmoudvand H (2020) Effect of chitosan on Toxoplasma gondii infection: a systematic review. Parasite Epidemiol Control 11:e00189

    Article  PubMed  PubMed Central  Google Scholar 

  • Cheraghipour K, Masoori L, Ezzatpour B, Roozbehani M, Sheikhian A, Malekara V, Niazi M, Mardanshah O, Moradpour K, Mahmoudvand H (2021) The experimental role of medicinal plants in treatment of toxoplasma gondii infection: a systematic review. Acta Parasitol 66(2):303–328

    Article  PubMed  Google Scholar 

  • Cheraghipour K, Zivdari M, Beiranvand M, Shakib P, Kheirandish F, Pour MZ, Ghafarypour M, Marzban A, Alhameedawi AK (2022) Encapsulation of Nepeta cataria essential oils in a chitosan nanocomposite with lethality potential against Toxoplasma gondii. Emergent Mater 14:1–1

    Google Scholar 

  • da Franca Rodrigues KA, Amorim LV, Dias CN, Moraes DF, Carneiro SM, de Amorim Carvalho FA (2015) Syzygium cumini (L.) Skeels essential oil and its major constituent α-pinene exhibit anti-Leishmania activity through immunomodulation in vitro. J Ethnopharmacol 160:32–40

    Article  Google Scholar 

  • Dunay IR, Gajurel K, Dhakal R, Liesenfeld O, Montoya JG (2018) Treatment of toxoplasmosis: historical perspective, animal models, and current clinical practice. Clin Microbiol Rev 31(4):e00057-e117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ezzatkhah F, Khalaf AK, Mahmoudvand H (2021) Copper nanoparticles: Biosynthesis, characterization, and protoscolicidal effects alone and combined with albendazole against hydatid cyst protoscoleces. Biomed Pharmacother 136:111257

    Article  CAS  PubMed  Google Scholar 

  • Fallahi S, Rostami A, Birjandi M, Zebardast N, Kheirandish F, Spotin A (2017) Parkinson’s disease and Toxoplasma gondii infection: sero-molecular assess the possible link among patients. Acta Trop 173:97–101

    Article  PubMed  Google Scholar 

  • Felipe CF, Albuquerque AM, de Pontes JL, de Melo JÍ, Rodrigues TC, de Sousa AM, Monteiro ÁB, Ribeiro AE, Lopes JP, de Menezes IR, de Almeida RN (2019) Comparative study of alpha-and beta-pinene effect on PTZ-induced convulsions in mice. Fundam Clin Pharmacol 33(2):181–190

    Article  CAS  PubMed  Google Scholar 

  • Goldstein EJ, Montoya JG, Remington JS (2008) Management of Toxoplasma gondii infection during pregnancy. Clin Infect Dis 47(4):554–566

    Article  Google Scholar 

  • Hagege D, Nouvelot A, Boucaud J et al (1990) Malondialdehyde titration with thiobarbiturate in plant extracts: avoidance of pigment interference. Phytochem Anal 1(2):86–89

    Article  Google Scholar 

  • Hanifehpour H, Shariat SK, Ghafari MS, Kheirandish F, Saber V, Fallahi S (2019) Serological and molecular diagnosis of Toxoplasma gondii infections in thalassemia patients. Iran J Parasitol 14(1):20

    PubMed  PubMed Central  Google Scholar 

  • Hill DE, Chirukandoth S, Dubey JP (2005) Biology and epidemiology of Toxoplasma gondii in man and animals. Anim Health Res Rev 6(1):41–61

    Article  PubMed  Google Scholar 

  • Hou J, Zhang Y, Zhu Y, Zhou B, Ren C, Liang S, Guo Y (2019) α-Pinene induces apoptotic cell death via caspase activation in human ovarian cancer cells. Med Sci Monitor 25:6631

    Article  CAS  Google Scholar 

  • Innes EA (2010) A brief history and overview of Toxoplasma gondii. Zoonoses Public Health 57(1):1–7

    Article  CAS  PubMed  Google Scholar 

  • Karaman U, Celik T, Kiran TR, Colak C, Daldal NU (2008) Malondialdehyde, glutathione, and nitric oxide levels in Toxoplasma gondii seropositive patients. Korean J Parasitol 46(4):293

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kareshk AT, Keyhani A, Mahmoudvand H, Oliaei RT, Asadi A, Andishmand M, Azzizian H, Babaei Z, Zia-Ali N (2015) Efficacy of the Bunium persicum (Boiss) essential oil against acute toxoplasmosis in mice model. Iran J Parasitol 10(4):625

    Google Scholar 

  • Karthikeyan R, Kanimozhi G, Prasad NR, Agilan B, Ganesan M, Srithar G (2018) Alpha pinene modulates UVA-induced oxidative stress, DNA damage and apoptosis in human skin epidermal keratinocytes. Life Sci 212:150–158

    Article  CAS  PubMed  Google Scholar 

  • Keyhani A, Ziaali N, Shakibaie M, Kareshk AT, Shojaee S, Asadi-Shekaari M, Sepahvand M, Mahmoudvand H (2020) Biogenic selenium nanoparticles target chronic toxoplasmosis with minimal cytotoxicity in a mouse model. J Med Microbiol 69(1):104–110

    Article  CAS  PubMed  Google Scholar 

  • Kheirandish F, Ezatpour B, Fallahi S, Tarahi MJ, Hosseini P, Rouzbahani AK, Tabaei SJ, Akbari S (2019) Toxoplasma serology status and risk of miscarriage, a case-control study among women with a history of spontaneous abortion. Int J Fertility Sterility 13(3):184

    CAS  Google Scholar 

  • Kim DS, Lee HJ, Jeon YD, Han YH, Kee JY, Kim HJ, Shin HJ, Kang J, Lee BS, Kim SH, Kim SJ (2015) Alpha-pinene exhibits anti-inflammatory activity through the suppression of MAPKs and the NF-κB pathway in mouse peritoneal macrophages. Am J Chin Med 43(04):731–742

    Article  CAS  PubMed  Google Scholar 

  • Koziol A, Stryjewska A, Librowski T, Salat K, Gawel M, Moniczewski A, Lochynski S (2014) An overview of the pharmacological properties and potential applications of natural monoterpenes. Mini Rev Med Chem 14(14):1156–1168

    Article  CAS  PubMed  Google Scholar 

  • Li L, Shi C, Yin Z, Jia R, Peng L, Kang S, Li Z (2014) Antibacterial activity of α-terpineol may induce morphostructural alterations in Escherichia coli. Braz J Microbiol 45(4):1409–1413

    Article  CAS  PubMed  Google Scholar 

  • Mahmoudvand H, Kareshk AT, Moradi MN, Fidalgo LM, Mirbadie SR, Niazi M, Khatami M (2020) Efficacy and safety of Zataria multiflora Boiss essential oil against acute toxoplasmosis in mice. Iran J Parasitol 15(1):22

    PubMed  PubMed Central  Google Scholar 

  • Matsuo AL, Figueiredo CR, Arruda DC, Pereira FV, Scutti JA, Massaoka MH, Travassos LR, Sartorelli P, Lago JH (2011) α-Pinene isolated from Schinus terebinthifolius Raddi (Anacardiaceae) induces apoptosis and confers antimetastatic protection in a melanoma model. Biochem Biophys Res Commun 411(2):449–454

    Article  CAS  PubMed  Google Scholar 

  • Melkina OE, Plyuta VA, Khmel IA, Zavilgelsky GB (2021) The mode of action of cyclic monoterpenes (−)-Limoneneand (+)-α-Pinene on bacterial cells. Biomolecules 11(6):806

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miyazawa M, Yamafuji C (2005) Inhibition of acetylcholinesterase activity by bicyclic monoterpenoids. J Agric Food Chem 53(5):1765–1768

    Article  CAS  PubMed  Google Scholar 

  • Nóbrega JR, Silva DD, Andrade Júnior FP, Sousa PM, Figueiredo PT, Cordeiro LV, Lima ED (2021) Antifungal action of α-pinene against Candida spp. isolated from patients with otomycosis and effects of its association with boric acid. Nat Prod Res 35(24):6190–6193

    Article  PubMed  Google Scholar 

  • Rasoulian B, Hajializadeh Z, Esmaeili-Mahani S, Rashidipour M, Fatemi I, Kaeidi A (2019) Neuroprotective and antinociceptive effects of rosemary (Rosmarinus officinalis L.) extract in rats with painful diabetic neuropathy. J Physiol Sci 69(1):57–64

    Article  CAS  PubMed  Google Scholar 

  • Saadatmand M, Al-Awsi GR, Alanazi AD, Sepahvand A, Shakibaie M, Shojaee S, Mohammadi R, Mahmoudvand H (2021) Green synthesis of zinc nanoparticles using Lavandula angustifolia Vera. Extract by microwave method and its prophylactic effects on Toxoplasma gondii infection. Saudi J Biol Sci 28(11):6454–6460

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Saadatnia G, Golkar M (2012) A review on human toxoplasmosis. Scand J Infect Dis 44(11):805–814

    Article  PubMed  Google Scholar 

  • Santos MR, Moreira FV, Fraga BP, Souza DP, Bonjardim LR, Quintans-Junior LJ (2011) Cardiovascular effects of monoterpenes: a review. Rev Bras 21(4):764–771

    CAS  Google Scholar 

  • Silva AC, Lopes PM, Azevedo MM, Costa DC, Alviano CS, Alviano DS (2012) Biological activities of a-pinene and β-pinene enantiomers. Molecules 17(6):6305–6316

    Article  Google Scholar 

  • Smith NC, Goulart C, Hayward JA, Kupz A, Miller CM, van Dooren GG (2021) Control of human toxoplasmosis. Int J Parasitol 51(2–3):95–121

    Article  CAS  PubMed  Google Scholar 

  • Tenter AM, Heckeroth AR, Weiss LM (2000) Toxoplasma gondii: from animals to humans. Int J Parasitol 30(12–13):1217–1258

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tonin AA, Da Silva AS, Thomé GR, Sangoi MB, Oliveira LS, Flores MM, Schetinger MR, Fighera RA, Moresco RN, Camillo G, Vogel FS (2014) Influence of toxoplasmosis on acetylcholinesterase activity, nitric oxide levels and cellular lesion on the brain of mice. Pathol Res Practice 210(8):526–532

    Article  CAS  Google Scholar 

  • Utegenova GA, Pallister KB, Kushnarenko SV, Özek G, Özek T, Abidkulova KT, Kirpotina LN, Schepetkin IA, Quinn MT, Voyich JM (2018) Chemical composition and antibacterial activity of essential oils from Ferula L. species against methicillin-resistant Staphylococcus aureus. Molecules 23(7):1679

    Article  PubMed Central  Google Scholar 

  • Van Zyl RL, Seatlholo ST, Van Vuuren SF, Viljoen AM (2006) The biological activities of 20 nature identical essential oil constituents. J Essent Oil Res 18(sup1):129–133

    Article  Google Scholar 

  • Wang ZD, Liu HH, Ma ZX, Ma HY, Li ZY, Yang ZB, Zhu XQ, Xu B, Wei F, Liu Q (2017) Toxoplasma gondii infection in immunocompromised patients: a systematic review and meta-analysis. Front Microbiol 8:389

    PubMed  PubMed Central  Google Scholar 

  • Wang X, Yu Y, Ge J, Xie B, Zhu S, Cheng X (2019) Effects of α-pinene on the pinewood nematode (Bursaphelenchus xylophilus) and its symbiotic bacteria. PLoS ONE 14(8):e0221099

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Weiss LM, Dubey JP (2009) Toxoplasmosis: a history of clinical observations. Int J Parasitol 39(8):895–901

    Article  PubMed  PubMed Central  Google Scholar 

  • Yang C, Hu DH, Feng Y (2015) Antibacterial activity and mode of action of the Artemisia capillaris essential oil and its constituents against respiratory tract infection-causing pathogens. Mol Med Rep 11(4):2852–2860

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hossein Mahmoudvand.

Ethics declarations

Conflict of interest

The author declares that they have no competing interests.

Additional information

Publisher's Note

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

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kharazmkia, A., Al-Abodi, H.R., Yadegari, J.G. et al. Potential effects of alpha-pinene, a monoterpene commonly found in essential oils against Toxoplasma gondii infection; an in vitro and in vivo study. J Parasit Dis 46, 1055–1061 (2022). https://doi.org/10.1007/s12639-022-01514-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12639-022-01514-1

Keywords

Navigation