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Engineering of Crystalline Nano-Suspension of Lycopene for Potential Management of Oxidative Stress–Linked Diabetes in Experimental Animals

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Abstract

Lycopene, a phytonutrient of carotenoid category occurring in tomato and other fruits, has long been recognized for improving the health and in the prevention of chronic diseases such as cancer and metabolic and cardiovascular disorders. However, due to its hydrophobic nature, its bioavailability is low in systemic circulation thus creates difficulty in clinical application. To overcome this restriction, we have prepared lycopene nanoparticles to improve its bioavailability and further subjected them for assessing the antidiabetic activity in experimental animals. Lycopene nanoparticles (LNP) were prepared by nanoprecipitation method and characterized by UV-vis spectroscopy, Fourier-transform infrared (FTIR) spectroscopy, and scanning electron microscopy (SEM). Non-insulin-dependent diabetes mellitus (NIDDM) was induced in Wistar albino rats by intraperitoneal administration of streptozotocin (60 mg/kg). Lycopene (100 mg/kg) and its nanoparticle (LNP 25 mg/kg and 50 mg/kg) were given orally for 21 days as treatment protocol. Blood glucose level measured by a glucometer and various biochemical parameters, viz. cholesterol, triglycerides, LDL, HDL, VLDL, and in vivo antioxidant parameters, were measured by using diagnostic kits. Lycopene nano-suspension exhibited mean particle size and polydispersity index to be 100 ± 4.50 nm and 0.04 respectively, which exhibits uniform nano-formulation. In vivo antidiabetic studies showed a significant decrease (p<0.001) in elevated blood sugar levels and biochemical parameters via oral administration of LNP in a dose-dependent manner with prominent antioxidant effects. The promising results of the study showed that nano-preparation was found to be the most effective for antidiabetic activity due to amelioration of oxidative biomarker.

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References

  1. Kawahito, S., Kitahata, H., & Oshita, S. (2009). Problems associated with glucose toxicity: role of hyperglycemia-induced oxidative stress. World J Gastroenterol, 15, 4137–4142. https://doi.org/10.3748/wjg.15.4137.

    Article  Google Scholar 

  2. Britton, G., Liaaen-Jensen, S., & Pfander, H. (2004). Carotenoids. Basle: Birkhauser.

    Book  Google Scholar 

  3. Gerster, H. (1997). The potential role of lycopene for human health. J Am Coll Nutr, 16, 109–126. https://doi.org/10.1080/07315724.1997.10718661.

    Article  Google Scholar 

  4. Rao, A. V., & Agarwal, S. (1999). Role of lycopene as antioxidant carotenoid in the prevention of chronic diseases: a review. Nutrition Res, 19, 305–323. https://doi.org/10.1016/S0271-5317(98)00193-6.

    Article  Google Scholar 

  5. Zhang, L. X., Cooney, R. V., & Bertram, J. S. (1991). Carotenoids enhance gap junctional communication and inhibit lipid peroxidation in C3H/10T1/2 cells: relationship to their cancer chemopreventive action. Carcinogenesis, 12, 2109–2114. https://doi.org/10.1093/carcin/12.11.2109.

    Article  Google Scholar 

  6. Levy, J., Bosin, E., Feldman, B., Giat, Y., Miinster, A., Danilenko, M., & Sharoni, Y. (1995). Lycopene is a more potent inhibitor of human cancer cell proliferation than either alfa-carotene or beta carotene. Nutr Cancer, 24, 257–266. https://doi.org/10.1080/01635589509514415.

    Article  Google Scholar 

  7. Lingen, C., Ernster, L., & Lindberg, O. (1959). The promoting effect of lycopene on the nonspecific resistance of animals. Exp Cell Res, 16, 384–393. https://doi.org/10.1016/0014-4827(59)90267-8.

    Article  Google Scholar 

  8. Fawzi, W., Herrera, M. G., & Nestel, P. (2000). Tomato intake in relation to mortality and morbidity among Sudanese children. J Nutr, 130, 2537–2542. https://doi.org/10.1093/jn/130.10.2537.

    Article  Google Scholar 

  9. Cumming, R. G., Mitchell, P., & Smith, W. (2000). Diet and cataract: the Blue Mountains Eye studies. Ophthalmology, 107, 450–456. https://doi.org/10.1016/s0161-6420(99)00024-x.

    Article  Google Scholar 

  10. Jiang, W., Guo, M. H., & Hai, X. (2016). Hepatoprotective and antioxidant effects of lycopene on non-alcoholic fatty liver disease in rat. World J Gastroenterol, 22, 10180–10188. https://doi.org/10.3748/wjg.v22.i46.10180.

    Article  Google Scholar 

  11. Biddle, M. J., Lennie, T. A., Bricker, G. V., Kopec, R. E., Schwartz, S. J., & Moser, D. K. (2015). Lycopene dietary intervention: a pilot study in patients with heart failure. J Cardiovasc Nurs, 30, 205–212. https://doi.org/10.1097/JCN.0000000000000108.

    Article  Google Scholar 

  12. Graff, R. E., Pettersson, A., Lis, R. T., et al. (2016). Dietary lycopene intake and risk of prostate cancer defined by ERG protein expression. Am J Clin Nutr, 103, 851–860. https://doi.org/10.3945/ajcn.115.118703.

    Article  Google Scholar 

  13. Wang, L., Liu, S., Pradhan, A. D., Manson, J. E., Buring, J. E., Gaziano, J. M., & Sesso, H. D. (2006). Plasma lycopene, other carotenoids, and the risk of type 2 diabetes in women. Am J Epidemiol, 164, 576–585. https://doi.org/10.1093/aje/kwj240.

    Article  Google Scholar 

  14. Mishra SB, Pandey H, Pandey AC (2013) Nanosuspension of Phyllanthus amarus extract for improving oral bioavailability and prevention of paracetamol induced hepatotoxicity in Sprague–Dawley rats. Adv Nat Sci: Nanosci Nanotechnol, 4, 035007. http://iopscience.iop.org/article/10.1088/2043-6262/4/3/035007. Accessed 02 November 2020

  15. Singh AK, Pandey H, Ramteke PW, Mishra SB (2019) Nano - suspension of ursolic acid for improving oral bioavailability and attenuation of type II diabetes: A histopathological investigation. Biocatalysis and Agricultural Biotechnology 22: 101433. https://doi.org/10.1016/j.bcab.2019.101433. Accessed 02 November 2020

  16. Yen, F. L., Wu, T. H., Lin, L. T., Cham, T. M., & Lin, C. C. (2008). Nanoparticles formulation of Cuscuta chinensis prevents acetaminophen-induced hepatotoxicity in rats. Food Chem Toxicol, 46, 1771–1777. https://doi.org/10.1016/j.fct.2008.01.021.

    Article  Google Scholar 

  17. Michael McClain, R., & Bausch, J. (2003). Summary of safety studies conducted with synthetic lycopene. Regul Toxicol Pharmacol, 37, 274–285. https://doi.org/10.1016/s0273-2300(03)00004-7.

    Article  Google Scholar 

  18. Trumbo, P. R. (2005). Are there adverse effects of lycopene exposure? J Nutr, 135, 2060S–2061S. https://doi.org/10.1093/jn/135.8.2060S.

    Article  Google Scholar 

  19. Mellert, W., Deckardt, K., Gembardt, C., Schulte, S., Van Ravenzwaay, B., & Slesinski, R. (2002). Thirteen-week oral toxicity study of synthetic lycopene products in rats. Food Chem Toxicol, 40, 1581–1588. https://doi.org/10.1016/s0278-6915(02)00113-8.

    Article  Google Scholar 

  20. Mishra, S. B., Verma, A., Mukerjee, A., & Vijayakumar, M. (2012). Amaranthus spinosus L. (Amaranthaceae) leaf extract attenuates streptozotocin-nicotinamide induced diabetes and oxidative stress in albino rats: a histopathological analysis. Asian Pac J Trop Biomed, 2, S1647–S1652. https://doi.org/10.1016/S2221-1691(12)60470-5.

    Article  Google Scholar 

  21. Mishra, S. B., Verma, A., & Vijayakumar, M. (2013). Preclinical evaluation of antihyperglycemic and antioxidant action of Nirmali (Strychnos potatorum) seeds in streptozotocin nicotinamide-induced diabetic Wistar rats: a histopathological investigation. Biomark Genom Med, 5, 157–163. https://doi.org/10.1016/j.bgm.2013.07.010.

    Article  Google Scholar 

  22. Jeon, S. M., Song, S. H., Jang, M. K., Kim, Y. H., Nam, K. T., Jeong, T. S., Park, Y. B., & Choi, M. S. (2002). Comparison of antioxidant effects of naringin and probucol in cholesterol-fed rabbits. Clin Chem Acta, 317, 181–190. https://doi.org/10.1016/s0009-8981(01)00778-1.

    Article  Google Scholar 

  23. Haluzik, M., & Nedvidkova, J. (2000). The role of nitric oxide in the development of streptozotocin-induced diabetes mellitus: experimental and clinical implications. Physiol Res, 49, s37–s42.

    Google Scholar 

  24. Baynes, J. W. (1995). Reactive oxygen in the aetiology and complications of diabetes. In C. Ioannides & P. R. Flatt (Eds.), Drug, diet, and disease vol 2: Mechanistic approach to diabetes (pp. 203–231). Hertfordshire: Ellis Horwood.

    Google Scholar 

  25. Sugiura, M., Nakamura, M., Ikoma, Y., Yano, M., Ogawa, K., Matsumoto, H., Kato, M., Ohshima, M., & Nagao, A. (2005). High serum carotenoids are inversely associated with serum gamma-glutamyltransferase in alcohol drinkers within normal liver function. J Epidemiol, 15, 180–186. https://doi.org/10.2188/jea.15.180.

    Article  Google Scholar 

  26. Coyne, T., Ibiebele, T. I., Baade, P. D., Dobson, A., McClintock, C., Dunn, S., Leonard, D., & Shaw, J. (2005). Diabetes mellitus and serum carotenoids: findings of a population-based study in Queensland, Australia. Am J Clin Nutr, 82, 685–693. https://doi.org/10.1093/ajcn.82.3.685.

    Article  Google Scholar 

  27. Wang, L., Liu, S., Manson, J. E., Gaziano, J. M., Buring, J. E., & Sesso, H. D. (2006). The consumption of lycopene and tomato-based food products is not associated with the risk of type 2 diabetes in women. J Nutr, 136, 620–625. https://doi.org/10.1093/jn/136.3.620.

    Article  Google Scholar 

  28. Patel, G., & Misra, A. (2011). Oral delivery of proteins and peptides: concepts and applications. In A. Misra (Ed.), Challenges in delivery of therapeutic genomics and proteomics (1st ed., pp. 481–529). London: Elsevier.

    Chapter  Google Scholar 

  29. Recharla, N., Riaz, M., Ko, S., & Park, S. (2017). Novel technologies to enhance the solubility of food - derived bioactive compounds: a review. J Funct Foods, 39, 63–73. https://doi.org/10.1016/j.jff.2017.10.001.

    Article  Google Scholar 

  30. Skoog, D. A., Holler, F. J., & Nieman, T. A. (1998). Principles of instrumental analysis. Boston: Thomson.

    Google Scholar 

  31. Takehara, M., Nishimura, M., Kuwa, T., et al. (2014). Characterization and thermal isomerization of (all-E)-lycopene. J Agric Food Chem, 62, 264–269. https://doi.org/10.1021/jf404497k.

    Article  Google Scholar 

  32. Gary, A., & Grundy, S. M. (1990). Management of dyslipidemia in NIDDM. Diab Care, 13, 153–169. https://doi.org/10.2337/diacare.13.2.153.

    Article  Google Scholar 

  33. Cooney, G. J., Thompson, A. L., Furler, S. M., Ye, J., & Kraegen, E. W. (2002). Muscle long chain acyl CoA esters and insulin resistance. Ann N Y Acad Sci, 967, 196–207. https://doi.org/10.1111/j.1749-6632.2002.tb04276.x.

    Article  Google Scholar 

  34. Samuel, V. T., & Shulman, G. I. (2012). Mechanisms for insulin resistance: common threads and missing links. Cell, 148, 852–871. https://doi.org/10.1016/j.cell.2012.02.017.

    Article  Google Scholar 

  35. Britton, G. (1995). Structure and properties of carotenoids in relation to function. FASEB J, 9, 1551–1558. https://doi.org/10.1096/fasebj.9.15.8529834.

    Article  Google Scholar 

  36. DiMascio, P., Kaiser, S., & Sies, H. (1989). Lycopene as the most effective biological carotenoid singlet oxygen quencher. Arch Biochem Biophys, 274, 532–538. https://doi.org/10.1016/0003-9861(89)90467-0.

    Article  Google Scholar 

  37. Stahl, W., & Sies, H. (2003). Antioxidant activity of carotenoids. Mol Aspects Med, 24, 345–351. https://doi.org/10.1016/s0098-2997(03)00030-x.

    Article  Google Scholar 

  38. Wertz, K., Siler, U., & Goralczyk, R. (2004). Lycopene: modes of action to promote prostate health. Arch Biochem Biophys, 430, 127–134. https://doi.org/10.1016/j.abb.2004.04.023.

    Article  Google Scholar 

  39. El-Missiry, M. A., & El-Gindy, A. M. (2000). Amelioration of alloxan induced diabetes mellitus and oxidative stress in rats by oil of Eruca sativa seeds. Ann Nutr Metab, 44, 97–100. https://doi.org/10.1159/000012829.

    Article  Google Scholar 

  40. Fuhrman, B., Elis, A., & Aviram, M. (1997). Hypocholesterolemic effect of lycopene and beta-carotene is related to suppression of cholesterol synthesis and augmentation of LDL receptor activity in macrophages. Biochem Biophys Res Commun, 233, 658–662. https://doi.org/10.1006/bbrc.1997.6520.

    Article  Google Scholar 

  41. Heber, D., & Lu, Q. Y. (2002). Overview of mechanisms of action of lycopene. Exp Biol Med, 227, 920–923. https://doi.org/10.1177/153537020222701013.

    Article  Google Scholar 

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Acknowledgments

The authors are grateful to Prof. Alok Mukerjee, Principal, United Institute of Pharmacy, Prayagraj, for providing an animal house facility to accommodate the animals and carrying out the pharmacological activity. We acknowledge the contribution of Mrs. Shradhanjali Singh, Associate Professor, United Institute of Pharmacy, for serving their practical hands in spectroscopic studies and interpretation of data.

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  1. United Institute of Pharmacy, Prayagraj, Uttar Pradesh, 211010, India

    Shanti Bhushan Mishra & Nidhi Kumari

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Correspondence to Shanti Bhushan Mishra.

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Research Involving Humans and Animals Statement

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted (REG. No: UIP/IAEC/Nov/2019/04).

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Mishra, S.B., Kumari, N. Engineering of Crystalline Nano-Suspension of Lycopene for Potential Management of Oxidative Stress–Linked Diabetes in Experimental Animals. BioNanoSci. 11, 345–354 (2021). https://doi.org/10.1007/s12668-021-00843-4

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