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The Natural Products Journal

Editor-in-Chief

ISSN (Print): 2210-3155
ISSN (Online): 2210-3163

Research Article

Cuminum cyminum Prevents Lipotoxicity and Apoptosis but Cuminaldehyde Fails to Do So: A Study on Mouse Macrophage (RAW 264.7) Cells

Author(s): Ranjitsinh Devkar*, Jaymesh Thadani, Shridhar Sanghvi, Kiran Lagu and Kavita Shirsath

Volume 10, Issue 3, 2020

Page: [333 - 339] Pages: 7

DOI: 10.2174/2210315509666190624130123

Price: $65

Abstract

Aim: The present study aims to compare the cytoprotective effect of Cuminum cyminum L. (CC) extract and cuminaldehyde (CA) against lipotoxicity induced by oxidized low density lipoprotein (Ox-LDL) in mouse macrophage (RAW 264.7) cells.

Objectives:

i) To assess comparative Cytoprotective potential of CC and CA against Ox-LDL induced cytotoxicity.

ii) To study efficacy of CC and CA in preventing Ox-LDL induced apoptosis.

Methods: Protective effect of CC extract and CA aganist Ox-LDL induced cytotoxicity in RAW 264.7 cells was assessed by MTT assay. DCFDA stain was used to check the generation of ROS followed by analysis of apoptotic genes by quantitative RT-PCR.

Results: CC extract was found to be non-toxic up to 300 μg/ml but CA showed significant toxicity from 50 to 300 μg/ml. Cells treated with Ox-LDL recorded 80 % decrement in cell viability as compared to the control cells. But Ox-LDL+CC treated group accounted for improved cell viability (88 %) which was comparable to that of control. However, Ox-LDL+CA treated cells did not record any improvement in cell viability (19 %). DCF-DA staining revealed that the presence of CC could minimize intracellular oxidative stress but similarly this was persistent in CA supplemented group. Furthermore, mRNA expression of apoptotic genes revealed that Ox-LDL induced upregulation of Bax and downregulation of Bcl-2 genes were not recorded in Ox-LDL+CC treated group.

Conclusion: It can be concluded that CC extract efficiently prevented Ox-LDL induced lipotoxicity and apoptosis and has an anti-atherosclerotic potential. The failure of CA emphasizes the importance of naturally occurring polyherbal formulations over pure compounds in imparting bioactivity and for therapeutic applications.

Keywords: Cuminum cyminum L., Cuminaldehyde, LDL oxidation, macrophage, apoptosis, oxidative stress.

Graphical Abstract
[1]
Young, I.; McEneny, J. Lipoprotein oxidation and atherosclerosis; Portland Press Limited: London, 2001.
[2]
Melnick, J.L.; Adam, E.; Debakey, M.E.; Cytomegalovirus and atherosclerosis. Eur. Heart J., 1993, 14(Suppl. K), 30-38.
[3]
Watson, C.; Alp, N.J. Role of Chlamydia pneumoniae in atherosclerosis. Clin. Sci. (Lond.), 2008, 114(8), 509-531.
[4]
Bai, N.; Kido, T.; Suzuki, H.; Yang, G.; Kavanagh, T.J.; Kaufman, J.D.; Rosenfeld, M.E.; van Breemen, C.; Eeden, S.F. Changes in atherosclerotic plaques induced by inhalation of diesel exhaust. Atherosclerosis, 2011, 216(2), 299-306.
[5]
Yin, F.; Lawal, A.; Ricks, J.; Fox, J.R.; Larson, T.; Navab, M.; Fogelman, A.M.; Rosenfeld, M.E.; Araujo, J.A. Diesel exhaust induces systemic lipid peroxidation and development of dysfunctional pro-oxidant and pro-inflammatory high-density lipoprotein. Arterioscler. Thromb. Vasc. Biol., 2013, 33(6), 1153-1161.
[6]
Libby, P.; Ridker, P.M.; Maseri, A. Inflammation and atherosclerosis. Circulation, 2002, 105(9), 1135-43.
[7]
Thounaojam, M.C.; Jadeja, R.N.; Devkar, R.V.; Ramachandran, A., In vitro evidence for the protective role of Sida rhomboidea. Roxb extract against LDL oxidation and oxidized LDL-induced apoptosis in human monocyte-derived macrophages. Cardiovas. Toxicol., 2011, 11(2), 168-179.
[8]
Jadeja, R.N.; Thounaojam, M.C.; Devkar, R.V.; Ramachandran, A.V. Clerodendron glandulosum.Coleb extract prevents in vitro human LDL oxidation and oxidized LDL induced apoptosis in human monocyte derived macrophages. Food Chem. Toxicol., 2011, 49(6), 1195-202.
[9]
Patel, D.; Desai, S.; Gajaria, T.; Devkar, R.; Ramachandran, A. Coriandrum sativum L. seed extract mitigates lipotoxicity in raw 264.7 cells and prevents atherogenic changes in rats. EXCLI, 2013, 12, 313.
[10]
Gajaria, T.K.; Patel, D.K.; Devkar, R.V.; Ramachandran, A. Flavonoid rich extract of Murraya Koenigii alleviates in-vitro LDL oxidation and oxidized LDL induced apoptosis in raw 264.7 Murine macrophage cells. J. Food Sci. Technol., 2015, 52(6), 3367-3375.
[11]
Nadkarni, K.M. Indian materia medica: with Ayurvedic, Unani-Tibbi, Siddha, allopathic, homeopathic, naturopathic & home remedies, appendices & indexes. 1; Popular Prakashan: Mumbai, India, 1996, 1.
[12]
Mnif, S.; Aifa, S. Cumin (Cuminum cyminum L.) from traditional uses to potential biomedical applications. Chem. Biodivers., 2015, 12(5), 733-742.
[13]
Bettaieb, I.; Bourgou, S.; Wannes, W.A.; Hamrouni, I.; Limam, F.; Marzouk, B. Essential oils, phenolics, and antioxidant activities of different parts of cumin (Cuminum cyminum L.). J. Agric. Food Chem., 2010, 58(19), 10410-8.
[14]
Hajlaoui, H.; Mighri, H.; Noumi, E.; Snoussi, M.; Trabelsi, N.; Ksouri, R.; Bakhrouf, A. Chemical composition and biological activities of Tunisian Cuminum cyminum L. essential oil: A high effectiveness against Vibrio spp. strains. Food Chem. Toxicol., 2010, 48(8-9), 2186-92.
[15]
Dhandapani, S.; Subramanian, V.R.; Rajagopal, S.; Namasivayam, N. Hypolipidemic effect of Cuminum cyminum L. on alloxaninduced diabetic rats. Pharmacol. Res., 2002, 46(3), 251-255.
[16]
Wieland, H.; Seidel, D. A simple specific method for precipitation of low density lipoproteins. J. Lipid Res., 1983, 24(7), 904-909.
[17]
Lowry, O.H.; Rosebrough, N.J.; Farr, A.L.; Randall, R.J. Protein measurement with the Folin phenol reagent. J. Biol. Chem, 1951, 193(1), 265-275.
[18]
Buege, J.A.; Aust, S.D. Microsomal lipid peroxidation. Methods Enzymol., 1978, 52, 302-310.
[19]
Esterbauer, H.; Striegl, G.; Puhl, H.; Rotheneder, M. Continuous monitoring of in vitro oxidation of human low density lipoprotein. Free Rad. Res. Comm., 1989, 6(1), 67-75.
[20]
Degli Esposti, M.; McLennan, H. Mitochondria and cells produce reactive oxygen species in virtual anaerobiosis: Relevance to ceramide-induced apoptosis. FEBS Lett., 1998, 430(3), 338-342.
[21]
Prieur, X.; Rőszer, T.; Ricote, M. Lipotoxicity in macrophages: Evidence from diseases associated with the metabolic syndrome. Biochim. Biophys. Acta (BBA)-Mol. Cell Biol. Lipids, 2010, 1801(3), 327-337.
[22]
Rudijanto, A. The role of vascular smooth muscle cells on the pathogenesis of atherosclerosis. Acta Med. Indones., 2007, 39(2), 86-93.
[23]
Ferrari, M.; Fornasiero, M.C.; Isetta, A.M. MTT colorimetric assay for testing macrophage cytotoxic activity in vitro. J. Immunol. Methods, 1990, 131(2), 165-72.
[24]
Glass, C.K.; Witztum, J.L. Atherosclerosis: The road ahead. Cell, 2001, 104(4), 503-516.
[25]
Einafshar, S.; Poorazrang, H.; Farhoosh, R.; Seiedi, S.M. Antioxidant activity of the essential oil and methanolic extract of cumin seed (Cuminum cyminum). Eur. J. Lipid Sci. Technol., 2012, 114(2), 168-174.
[26]
Giovannini, C.; Varì, R.; Scazzocchio, B.; Sanchez, M.; Santangelo, C.; Filesi, C.; D’Archivio, M.; Masella, R. OxLDL induced p53-dependent apoptosis by activating p38MAPK and PKCδ signaling pathways in J774A.1 macrophage cells. J. Mol. Cell Biol., 2011, 3(5), 316-318.
[27]
Chen, T.G.; Chen, T.L.; Chang, H.C.; Tai, Y.T.; Cherng, Y.G.; Chang, Y.T.; Chen, R.M. Oxidized low-density lipoprotein induces apoptotic insults to mouse cerebral endothelial cells via a Bax-mitochondria-caspase protease pathway. Toxicol. Appl. Pharmacol., 2007, 219(1), 42-53.
[28]
Devkar, R.; Lagu, K.; Thadani, J.; Shirsath, K. Cuminum cyminum methanolic extract prevents oxidative modification of low density lipoproteins: Preliminary evidence on its anti-atherosclerotic potential. J. Phytopharmacol., 2018, 7(1), 79-83.
[29]
Parasuraman, S.; Thing, G.S.; Dhanaraj, S.A. Polyherbal formulation: Concept of ayurveda. Pharmacogn. Reviews, 2014, 8(16), 73.

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