Stabilizing Effects of Ethanolic Extract of Mastic Gum on Microtubule Polymers: an In Vitro Study

Authors

  • Ali Dadras University of Tehran
  • Fatemeh Shahrokhi Asl University of Tehran
  • Gholam Hossein Riazi University of Tehran
  • Shahin Ahmadian University of Tehran
  • Tahereh Javdani Khalife University of Tehran

DOI:

https://doi.org/10.30564/jhp.v1i2.1589

Abstract

Terpenoids are novel natural products isolated from mastic gum. Mastic gum was obtained from the Pistacia Lentiscus tree. Scientific investigations have documented medical and pharmacological properties of mastic gum such as memory enhancement, antifungal, and antibacterial activities. It was astonishing to study the possible interaction of mastic gum extract with microtubule proteins which are involved in memory and consciousness since the administration of mastic gum is evidenced in the improvement of brain functions. Since a number of studies have demonstrated the effect of microtubule dynamics on mammals’ memory, in this study, we investigated the effect of Oxygenated Sesquiterpenes (OST) on microtubule polymerization in vitro. OST was purified from the ethanolic extract of mastic gum. The results revealed that OST induces microtubule polymerization; however, microtubule depolymerization was not affected and fluorometric assays showed conformational changes of tubulin in the presence of OST. We interestingly found that colchicine was unable to inhibit MT assembly in the presence of OST and OST was solely more efficient than the combination of OST with paclitaxel for elevating microtubule polymerization rate. We hope that OST could be a promising agent for memory enhancement and the treatment of neurodegenerative diseases as a novel tubulin-binding compound.

Keywords:

Pistacia lentiscus; Mastic gum; Oxygenated Sesquitrepene (OST); Tubulin; Microtubule

References

[1] Castola, V., A. Bighelli, J. Casanova. Intraspecific chemical variability of the essential oil of Pistacia lentiscus L. from Corsica. Biochemical Systematics and Ecology, 2000, 28(1): 79-88.

[2] Fleisher, Z., A. Fleisher. Volatiles of the Mastic Tree—Pistacia lentiscus L. Aromatic Plants of the Holy Land and the Sinai. Part X. Journal of Essential Oil Research, 1992, 4(6): 663-665.

[3] Magiatis, P., et al.. Chemical composition and antimicrobial activity of the essential oils of Pistacia lentiscus var. chia. Planta Med, 1999, 65(8): 749-52.

[4] Miyamoto, T., T. Okimoto, M. Kuwano. Chemical Composition of the Essential Oil of Mastic Gum and their Antibacterial Activity Against Drug-Resistant Helicobacter pylori. Nat Prod Bioprospect, 2014, 4(4): 227-31.

[5] Koutsoudaki, C., M. Krsek, A. Rodger. Chemical composition and antibacterial activity of the essential oil and the gum of Pistacia lentiscus Var. chia. J Agric Food Chem, 2005, 53(20): 7681-5.

[6] Al-Said, M.S., et al.. Evaluation of mastic, a crude drug obtained from Pistacia lentiscus for gastric and duodenal anti-ulcer activity. J Ethnopharmacol, 1986, 15(3): 271-8.

[7] Yaman-Sozbir, S., S. Ayaz-Alkaya, B. Bayrak-Kahraman. Effect of chewing gum on stress, anxiety, depression, self-focused attention, and academic success: A randomized controlled study. Stress Health, 2019. 35(4): 441-446.

[8] Ammari, M., et al.. Pistacia lentiscus oil attenuates memory dysfunction and decreases levels of biomarkers of oxidative stress induced by lipopolysaccharide in rats. Brain Res Bull, 2018, 140: 140-147.

[9] Saidi, S.A., et al.. Liver injury following small intestinal ischemia reperfusion in rats is attenuated by Pistacia lentiscus oil: antioxidant and anti-inflammatory effects. Arch Physiol Biochem, 2017, 123(4): 199-205.

[10] Loizou, S., et al.. Chios mastic gum extract and isolated phytosterol tirucallol exhibit anti-inflammatory activity in human aortic endothelial cells. Exp Biol Med (Maywood), 2009, 234(5): 553-61.

[11] Nelson, R.. Microtubule-stabilising drugs may be therapeutic in AD. Lancet Neurol, 2005, 4(2): 83-4.

[12] Cornet, B., et al.. Refined three-dimensional solution structure of insect defensin A. Structure, 1995. 3(5): 435-48.

[13] Downing, K.H., E. Nogales. Tubulin and microtubule structure. Curr Opin Cell Biol, 1998, 10(1): 16-22.

[14] Nogales, E.. Structural insights into microtubule function. Annu Rev Biochem, 2000, 69: 277-302.

[15] Park, J.H., A. Roll-Mecak. The tubulin code in neuronal polarity. Curr Opin Neurobiol, 2018, 51: 95-102.

[16] Conde, C., A. Caceres. Microtubule assembly, organization and dynamics in axons and dendrites. Nat Rev Neurosci, 2009, 10(5): 319-32.

[17] Downing, K.H.. Structural basis for the interaction of tubulin with proteins and drugs that affect microtubule dynamics. Annu Rev Cell Dev Biol, 2000, 16: 89-111.

[18] Qian, A., P.R. Burton, R.H. Himes, A comparison of microtubule assembly in brain extracts from young and old rats. Brain Res Mol Brain Res, 1993, 18(1-2): 100-6.

[19] Nakayama, T., T. Sawada, Involvement of microtubule integrity in memory impairment caused by colchicine. Pharmacol Biochem Behav, 2002, 71(1-2): 119-38.

[20] Trojanowski, J.Q., et al.. Microtubule-stabilising drugs for therapy of Alzheimer's disease and other neurodegenerative disorders with axonal transport impairments. Expert Opin Pharmacother, 2005, 6(5): 683-6.

[21] Ballatore, C., et al.. Microtubule stabilizing agents as potential treatment for Alzheimer's disease and related neurodegenerative tauopathies. J Med Chem, 2012, 55(21): 8979-96.

[22] Zarei Jaliani, H., et al.. The effect of the crocus sativus L. Carotenoid, crocin, on the polymerization of microtubules, in vitro. Iran J Basic Med Sci, 2013, 16(1): 101-7.

[23] Abidi, A., et al.. Protective Effect of Pistacia lentiscus Oil Against Bleomycin-Induced Lung Fibrosis and Oxidative Stress in Rat. Nutr Cancer, 2017, 69(3): 490-497.

[24] Miller, H.P., L. Wilson, Preparation of microtubule protein and purified tubulin from bovine brain by cycles of assembly and disassembly and phosphocellulose chromatography. Methods Cell Biol, 2010, 95: 3-15.

[25] Weingarten, M.D., et al.. Properties of the depolymerization products of microtubules from mammalian brain. Biochemistry, 1974, 13(27): 5529-37.

[26] Carlsson, N., et al.. Quantification of protein concentration by the Bradford method in the presence of pharmaceutical polymers. Anal Biochem, 2011, 411(1): 116-21.

[27] Scudiero, D.A., et al.. Evaluation of a soluble tetrazolium/formazan assay for cell growth and drug sensitivity in culture using human and other tumor cell lines. Cancer Res, 1988, 48(17): 4827-33.

[28] Solomaha, E., H.C. Palfrey, Conformational changes in dynamin on GTP binding and oligomerization reported by intrinsic and extrinsic fluorescence. Biochem J, 2005, 391(Pt 3): 601-11.

[29] Penazzi, L., L. Bakota, R. Brandt, Microtubule Dynamics in Neuronal Development, Plasticity, and Neurodegeneration. Int Rev Cell Mol Biol, 2016, 321: 89-169.

[30] Brandt, R., L. Bakota, Microtubule dynamics and the neurodegenerative triad of Alzheimer's disease: The hidden connection. J Neurochem, 2017, 143(4): 409-417.

[31] Moeini, R., et al.. Pistacia Genus as a Potential Source of Neuroprotective Natural Products. Planta Med, 2019, 85(17): 1326-1350.

[32] Manka, S.W., C.A. Moores. The role of tubulin-tubulin lattice contacts in the mechanism of microtubule dynamic instability. Nat Struct Mol Biol, 2018, 25(7): 607-615.

[33] Atarod, D., et al.. Microtubule Dynamicity Is More Important than Stability in Memory Formation: an In Vivo Study. J Mol Neurosci, 2015, 56(2): 313-9.

[34] Alves, R.C., et al.. Characteristics, Properties and Analytical Methods of Paclitaxel: A Review. Crit Rev Anal Chem, 2018, 48(2): 110-118.

[35] Dasgeb, B., et al.. Colchicine: an ancient drug with novel applications. Br J Dermatol, 2018, 178(2): 350-356.

[36] Dadras, A., et al.. In vitro study on the alterations of brain tubulin structure and assembly affected by magnetite nanoparticles. J Biol Inorg Chem, 2013, 18(3): 357-69.

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Vol. 1 , Iss. 2 (December 2019)

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