The effects of cinnamaldehyde and eugenol on human adipose-derived mesenchymal stem cells viability, growth and differentiation: a cheminformatics and in vitro study

Document Type: Original Research Article

Authors

1 Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

2 Department of Anatomical Sciences, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

3 Shefa Neuroscience Research Center, Khatam Alanbia Hospital, Tehran, Iran.

Abstract


Objective: The aim of this study was to estimate the cheminformatics and qualitative structure-activity relationship (QSAR) of cinnamaldehyde and eugenol. The effects of cinnamaldehyde and eugenol on the viability, doubling time and adipogenic or osteogenic differentiations of human adipose-derived mesenchymal stem cells (hASCs) were also investigated. 

Materials and Methods: QSAR and toxicity indices of cinnamaldehyde and eugenol were evaluated using cheminformatics tools including Toxtree and Toxicity Estimation Software Tool (T.E.S.T) and molinspiration server. Besides, their effects on the hASCs viability, doubling time and differentiation to adipogenic or osteogenic lineages were evaluated.

Results: Cinnamaldehyde is predicted to be more lipophilic and less toxic than eugenol. Both phytochemicals may be developmental toxicants. They probably undergo hydroxylation and epoxidation reactions by cytochrome-P450. The 2.5 µM/ml cinnamaldehyde and 0.1 µg/ml eugenol did not influence hASCs viability following 72 hr of treatment. But higher concentrations of these phytochemicals insignificantly increased hASCs doubling time till 96 hr, except 1 µg/ml eugenol for which the increase was significant. Only low concentrations of both phytochemicals were tested for their effects on the hASCs differentiation. The 2.5 µM/ml cinnamaldehyde and 0.1 µg/ml eugenol enhanced the osteogenesis and decreased the adipogenesis of hASCs meaningfully.

Conclusion: According to the cheminformatics analysis and in vitro study, cinnamaldehyde and eugenol are biocompatible and low toxic for hASCs. Both phytochemicals may be suitable for regenerative medicine and tissue engineering when used at low concentrations, but maybe useful for neoplastic growth inhibition when used at high concentrations.

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Aggarwal S, Ichikawa H, Takada Y, Sandur SK, Shishodia S, Aggarwal BB. 2006. Curcumin (diferuloylmethane) down-regulates expression of cell proliferation and antiapoptotic and metastatic gene products through suppression of IκBα kinase and Akt activation. Mol Pharmacol,  69:  195-206.

Alarcón de la Lastra C, Villegas I. 2005. Resveratrol as an anti‐inflammatory and anti‐aging agent: Mechanisms and clinical implications. Mol Nutr Food Res,  49:  405-430.

Auddy B, Ferreira M, Blasina F, Lafon L, Arredondo F, Dajas F, Tripathi PC, Seal T, Mukherjee B. 2003. Screening of antioxidant activity of three Indian medicinal plants, traditionally used for the management of neurodegenerative diseases. J Ethnopharmacol,  84:  131-138.

Bunnell BA, Estes BT, Guilak F, Gimble JM, 2008. Differentiation of adipose stem cells, Adipose Tissue Protocols. Springer, pp. 155-171.

Cai Y, Luo Q, Sun M, Corke H. 2004. Antioxidant activity and phenolic compounds of 112 traditional Chinese medicinal plants associated with anticancer. Life Sci,  74:  2157-2184.

Chen R, Chen J, Cheng S, Qin J, Li W, Zhang L, Jiao H, Yu X, Zhang X, Lahn BT, Xiang AP. 2010. Assessment of embryotoxicity of compounds in cosmetics by the embryonic stem cell test. Toxicol Mech Methods,  20:  112-118.

de Villiers JA, Houreld N, Abrahamse H. 2009. Adipose derived stem cells and smooth muscle cells: implications for regenerative medicine. Stem Cell Rev,  5:  256-265.

Gimble JM, Katz AJ, Bunnell BA. 2007. Adipose-derived stem cells for regenerative medicine.        Circ Res,  100:  1249-1260.

Gimble JM, Nuttall ME. 2011. Adipose-derived stromal/stem cells (ASC) in regenerative medicine: pharmaceutical applications. Curr Pharm Des,  17:  332-339.

Ho YS, So KF, Chang RCC. 2010. Anti-aging herbal medicine—How and why can they be used in aging-associated neurodegenerative diseases? Ageing Res Rev,  9:  354-362.

Irwin JJ, Shoichet BK. 2005. ZINC-a free database of commercially available compounds for virtual screening. J Chem Inf Model,  45:  177-182.

Izadpanah R, Trygg C, Patel B, Kriedt C, Dufour J, Gimble JM, Bunnell BA. 2006. Biologic properties of mesenchymal stem cells derived from bone marrow and adipose tissue. J Cell Biochem,  99:  1285-1297.

Jaganathan SK, Mazumdar A, Mondhe D, Mandal M. 2011. Apoptotic effect of eugenol in human colon cancer cell lines. Cell Biol Int,  35:  607-615.

Ka H, Park HJ, Jung HJ, Choi JW, Cho KS, Ha J, Lee KT. 2003. Cinnamaldehyde induces apoptosis by ROS-mediated mitochondrial permeability transition in human promyelocytic leukemia HL-60 cells. Cancer Lett,  196:  143-152.

King AA, Shaughnessy DT, Mure K, Leszczynska J, Ward WO, Umbach DM, Xu Z, Ducharme D, Taylor JA, Demarini DM, Klein CB. 2007. Antimutagenicity of cinnamaldehyde and vanillin in human cells: Global gene expression and possible role of DNA damage and repair. Mutat Res,  616:  60-69.

Kuzuhara T, Suganuma M, Fujiki H. 2008. Green tea catechin as a chemical chaperone in cancer prevention. Cancer Lett,  261:  12-20.

Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. 2012. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Delivery Rev,  64:  4-17.

Promega, 2012. CellTiter 96® AQueous Non-Radioactive Cell Proliferation Assay, in: Bulletin, T. (Ed.).

Thompson D, Constantin-Teodosiu D, Egestad B, Mickos H, Moldéus P. 1990. Formation of glutathione conjugates during oxidation of eugenol by microsomal fractions of rat liver and lung. Biochem Pharmacol,  39:  1587-1595.

Thompson DC, Thompson JA, Sugumaran M, Moldéus P. 1993. Biological and toxicological consequences of quinone methide formation. Chem -Biol Interact,  86:  129-162.

Veber DF, Johnson SR, Cheng H-Y, Smith BR, Ward KW, Kopple KD. 2002. Molecular properties that influence the oral bioavailability of drug candidates.      J Med Chem,  45:  2615-2623.

Wong C-C, Li H-B, Cheng K-W, Chen F. 2006. A systematic survey of antioxidant activity of 30 Chinese medicinal plants using the ferric reducing antioxidant power assay. Food Chem,  97:  705-711.