Protective effect of aqueous and ethanolic extracts of Lippia citriodora Kunth. on acrylamide-induced neurotoxicity

Document Type : Original Research Article

Authors

1 School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

2 Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran. Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

3 Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

Objective: Acrylamide (ACR) neurotoxicity is induced by different mechanisms such as oxidative stress and apoptosis. Scientific researchs have indicated the antioxidative properties of Lippia citriodora. The protective effect of L. citriodora aqueous and ethanolic extracts on ACR-induced neurotoxicity was investigated.
Materials and methods: Male Wistar rats were randomly divided into 13 groups: (1) control, (2) ACR (50 mg/kg, i.p.), (3-6) ACR+aqueous extract (12.5, 25, 50, and 100 mg/kg, i.p.), (7-10) ACR+ethanolic extract (12.5, 25, 50, and 100 mg/kg, i.p.), (11) aqueous extract (100 mg/kg), (12) ethanolic extract (100 mg/kg), and (13) ACR+Vitamin E (200 mg/kg, every other day, i.p.). After 11 days, gait score, MDA, and GSH levels in brain cortical tissue were measured. In the in vitro test, the viability of PC12 cells (using MTT test), the amount of reactive oxygen species (ROS; using DCFH-DA method), and the protein levels of Bax, Bcl2 and caspase 3 (by western blotting) were measured.
Results: In the in vitro study, the IC50 for the treatment of PC 12 cells with ACR after 24 hr was 6 mM.  ACR decreased cell viability, but increased ROS level, Bax/Bcl-2 ratio, and caspase-3 protein level. Pre-treatment by L. citriodora extracts (15-120 µg/ml) ameliorated the toxic effects of ACR on PC12 cells. In the in vivo experiment, ACR-induced movement disorders increased MDA but decreased GSH content. The extracts of L. citriodora improved ACR toxic effects.
Conclusion: Aqueous and ethanolic extracts of L. citriodora were found to reduce ACR-induced neurotoxicity via inhibiting oxidative stress and apoptosis.

Keywords

References

Amin B, Noorani R, Razavi BM,
Hosseinzadeh H. 2018. The effect of
ethanolic extract of lippia citriodora on rats
with chronic constriction injury of
neuropathic pain. Cell J, 19: 528-536.
Bahramsoltani R, Rostamiasrabadi P, Shahpiri
Z, Marques AM, Rahimi R, Farzaei MH.
2018. Aloysia citrodora Paláu (Lemon
verbena): A review of phytochemistry and
pharmacology. J Ethnopharmacol, 222: 34-
51.
Carrera‐Quintanar L, Funes L, Viudes E, Tur
J, Micol V, Roche E, Pons A. 2012.
Antioxidant effect of lemon verbena
extracts in lymphocytes of university
students performing aerobic training
program. Scand J Med Sci Sports, 22: 454-
461.
Chang SK, Zhang Y. 2017. Protein analysis.
In: Suzanne Nielsen S, Food analysis, pp.
315-331, Springer, Cham.
Chen JH, Wu KY, Chiu M, Tsou TC, Chou
CC. 2009. Acrylamide-induced astrogliotic
and apoptotic responses in human
astrocytoma cells. Toxicol In Vitro, 23:
855-861.
Claus A, Carle R, Schieber A. 2008.
Acrylamide in cereal products: A review. J
Cereal Sci, 47: 118-133.
Cushnie TT, Lamb AJ. 2005. Antimicrobial
activity of flavonoids. Int J Antimicrob
Agents, 26: 343-356.
Elmore S. 2007. Apoptosis: a review of
programmed cell death. Toxicol Pathol, 35:
495-516.
Esmaeelpanah E, Razavi BM, Vahdati Hasani
F, Hosseinzadeh H. 2018. Evaluation of
epigallocatechin gallate and epicatechin
gallate effects on acrylamide-induced
neurotoxicity in rats and cytotoxicity in PC
12 cells. Drug Chem Toxicol, 41: 441-448.
Etemad L, Zafari R, Moallem SA, VahdatiMashhadian N, Shirvan ZS, Hosseinzadeh
H. 2016. Teratogenic effect of
verbascoside, main constituent of Lippia
citriodora leaves, in mice. Iran J Pharm
Res, 15: 521-525.
Funes L, Fernández-Arroyo S, Laporta O,
Pons A, Roche E, Segura-Carretero A,
Fernández-Gutiérrez A, Micol V. 2009.
Correlation between plasma antioxidant
capacity and verbascoside levels in rats
after oral administration of lemon verbena
extract. Food Chem, 117: 589-598.
Ghaemi EO, Khorshidi D, Moradi A, Seifi A,
Mazendrani M, Bazouri M, Mansourian
AR. 2007. The efficacy of ethanolic extract
of Lemon verbena on the skin infection due
to Staphylococcus aureus in an animal
model. Pakistan J Biol Sci, 10: 4132-4135.
Effect of Lemon verbena on neurotoxicity
AJP, Vol. 12, No. 3, May-Jun 2022 293
Ghasemzadeh Rahbardar M, Cheraghi Farmed
H, Hosseinzadeh H, Mehri S. 2021.
Protective effects of selenium on
acrylamide-induced neurotoxicity and
hepatotoxicity in rats. Iran J Basic Med Sci,
24:1041-1049.
Ghasemzadeh Rahbardar M, Hemadeh B,
Razavi BM, Eisvand F, Hosseinzadeh H.
2020. Effect of carnosic acid on acrylamide
induced neurotoxicity: in vivo and in vitro
experiments. Drug Chem Toxicol, 1-8.
Herranz-López M, Barrajón-Catalán E,
Segura-Carretero A, Menéndez JA, Joven J,
Micol V. 2015. Lemon verbena (Lippia
citriodora) polyphenols alleviate obesityrelated disturbances in hypertrophic
adipocytes through AMPK-dependent
mechanisms. Phytomedicine, 22: 605-614.
Lee KW, Kim HJ, Lee YS, Park HJ, Choi, JW,
Ha J, Lee KT. 2007. Acteoside inhibits
human promyelocytic HL-60 leukemia cell
proliferation via inducing cell cycle arrest
at G 0/G 1 phase and differentiation into
monocyte. Carcinogenesis, 28: 1928-1936.
Lee KY, Jeong EJ, Lee HS, Kim YC. 2006.
Acteoside of Callicarpa dichotoma
attenuates scopolamine-induced memory
impairments. Biol Pharm bulletin, 29: 71-
74.
Lenoir L, Joubert‐Zakeyh J, Texier O,
Lamaison JL, Vasson MP, Felgines C.
2012. Aloysia triphylla infusion protects
rats against dextran sulfate sodium‐induced
colonic damage. J Sci Food Agric, 92:
1570-1572.
Lenoir L, Rossary A, Joubert-Zakeyh J,
Vergnaud-Gauduchon J, Farges MC,
Fraisse D, Texier O, Lamaison JL, Vasson
MP, Felgines C. 2011. Lemon verbena
infusion consumption attenuates oxidative
stress in dextran sulfate sodium-induced
colitis in the rat. Dig Dis Sci, 56: 3534-
3545.
Li Y, Shi W, Li Y, Zhou Y, Hu X, Song C, Ma
H, Wang C, Li Y. 2008. Neuroprotective
effects of chlorogenic acid against
apoptosis of PC12 cells induced by
methylmercury. Environ Toxicol
Pharmacol, 26: 13-21.
LoPachin RM. 2004. The changing view of
acrylamide neurotoxicity. Neurotoxicology,
25: 617-630.
LoPachin RM. 2005. Acrylamide
neurotoxicity: neurological, morhological
and molecular endpoints in animal model.
In: Friedman M, Mottram D (Eds),
Chemistry and Safety of Acrylamide in
Food. Advances in Experimental Medicine
and Biology, pp. 21-37, Springer, Boston,
MA.
Mehri S, Abnous K, Mousavi SH, Shariaty
VM, Hosseinzadeh H. 2012.
Neuroprotective effect of crocin on
acrylamide-induced cytotoxicity in PC12
cells. Cell Mol Neurobiol, 32: 227-235.
Mehri S, Karami HV, Hassani FV,
Hosseinzadeh H. 2014. Chrysin reduced
acrylamide-induced neurotoxicity in both in
vitro and in vivo assessments. Iran Biomed
J, 18: 101-106.
Moron MS, Depierre JW, Mannervik B. 1979.
Levels of glutathione, glutathione reductase
and glutathione S-transferase activities in
rat lung and liver. Biochim Biophys Acta,
582: 67-78.
Ohkawa H, Ohishi N, Yagi K. 1979. Assay for
lipid peroxides in animal tissues by
thiobarbituric acid reaction. Anal Biochem,
95: 351-358.
Portmann E, Nigro MML, Reides CG, Llesuy
S, Ricco RA, Wagner ML, Gurni AA,
Carballo MA. 2012. Aqueous extracts of
Lippia turbinata and Aloysia citriodora
(Verbenaceae): assessment of antioxidant
capacity and DNA damage. Int J Toxicol,
31: 192-202.
Prasad SN. 2013. Neuroprotective efficacy of
eugenol and isoeugenol in acrylamideinduced neuropathy in rats: behavioral and
biochemical evidence. Neurochem Res, 38:
330-345.
Qiusheng Z, Yuntao Z, Rongliang Z, Dean G,
Changling L. 2005. Effects of verbascoside
and luteolin on oxidative damage in brain
of heroin treated mice. Pharmazie, 60: 539-
543.
Quirantes‐Piné R, Arráez‐Román D, Segura‐
Carretero A, Fernández‐Gutiérrez A. 2010.
Characterization of phenolic and other
polar compounds in a lemon verbena
extract by capillary electrophoresis‐
electrospray ionization‐mass spectrometry.
J Sep Sci, 33: 2818-2827.
Razavi BM, Zargarani N, Hosseinzadeh H.
2017. Anti-anxiety and hypnotic effects of
ethanolic and aqueous extracts of Lippia
citriodora leaves and verbascoside in mice.
Avicenna J Phytomedicine, 7: 353-365.
Rodríguez-Ramiro I, Ramos S, Bravo L, Goya
L, Martín MÁ. 2011. Procyanidin B2 and a
Tandisehpanah et al.
AJP, Vol. 12, No. 3, May-Jun 2022 294
cocoa polyphenolic extract inhibit
acrylamide-induced apoptosis in human
Caco-2 cells by preventing oxidative stress
and activation of JNK pathway. J Nutr
Biochem, 22: 1186-1194.
Sanchez PM, Villarreal ML, Herrera-Ruiz M,
Zamilpa A, Jiménez-Ferrer E, Trejo-Tapia
G. 2013. In vivo anti-inflammatory and
anti-ulcerogenic activities of extracts from
wild growing and in vitro plants of
Castilleja tenuiflora Benth.
(Orobanchaceae). J Ethnopharmacol, 150:
1032-1037.
Satpute R, Hariharakrishnan J, Bhattacharya
R. 2008. Alpha-ketoglutarate and N-acetyl
cysteine protect PC12 cells from cyanideinduced cytotoxicity and altered energy
metabolism. Neurotoxicology, 29: 170-178.
Shahhoseini R, Hosseini N, Ghorbanpour M.
2014. Study of essential oil content and
composition of different parts of lemon
verbena (Lippia citriodora) grown in Iran.
J Essent Oil-Bear Plants, 17: 120-125.
Shipp A, Lawrence G, Gentry R, McDonald T,
Bartow H, Bounds J, Macdonald N,
Clewell H, Allen B, Van Landingham, C,
2006. Acrylamide: review of toxicity data
and dose-response analyses for cancer and
noncancer effects. Crit Rev Toxicol, 36:
481-608.
Sumizawa T, Igisu H. 2007. Apoptosis
induced by acrylamide in SH-SY5Y cells.
Arch Toxicol, 81: 279-282.
Tabeshpour J, Mehri S, Abnous K,
Hosseinzadeh H. 2019. Neuroprotective
effects of thymoquinone in acrylamideinduced peripheral nervous system toxicity
through MAPKinase and apoptosis
pathways in rat. Neurochem Res, 44: 1101-
1112.
Tomassoni D, Martinelli I, Moruzzi M,
Micioni Di Bonaventura MV, Cifani C,
Amenta F, Tayebati SK. 2020. Obesity and
age-related changes in the brain of the
Zucker Lepr fa/fa rats. Nutrients, 12: 1356.
Tyl RW, Friedman MA. 2003. Effects of
acrylamide on rodent reproductive
performance. Reprod Toxicol, 17: 1-13.
Uchiyama M, Mihara M. 1978. Determination
of malonaldehyde precursor in tissues by
thiobarbituric acid test. Anal Biochem, 86:
271-278.
Yoo KM, Lee CH, Lee H, Moon B, Lee CY.
2008. Relative antioxidant and
cytoprotective activities of common herbs.
Food Chem, 106: 929-936.
Avicenna Journal of Phytomedicine
Volume 12, Issue 3
May and June 2022
Pages 281-294

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