EVALUATION OF ETHOSOMAL EPIGALLOCATECHIN-3-GALLATE GEL FORMULATIONS AS AN ANTIOXIDANT AND THERMOGENIC AGENT

Authors

  • WALAA M. SARHAN Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt
  • OMNIA SARHAN Department of Pharmaceutics, Faculty of Pharmacy, Badr University in Cairo, Egypt

DOI:

https://doi.org/10.22159/ijpps.2020v12i11.39276

Keywords:

Bioavailability, Lecithin, Green tea extract, Transdermal, Ethosome, Uncoupling proteins (UCPs) and Real-Time Polymerase Chain Reaction (RT-PCR)

Abstract

Objective: The aim of this study was to investigate in vitro and in vivo behavior of the prepared ethosomal formulations of green tea extract, which in turn would result in enhancing their therapeutic efficacy as antioxidants and thermogenic agents in obese mice.

Methods: Fat Wistar rats were acclimated for at least 7 d in environmentally controlled cages, then they were divided into five groups: 1st received only distilled water, 2nd received an oral dose of green tea extract, in 3rd group green tea extract loaded gel base was applied on the previously shaven dorsal side of rats and in the other 2 groups selected green tea extract loaded Ethosomal gel base were applied on the previously shaven dorsal side of rats. Total antioxidant capacity by ferric reducing ability of plasma (FRAP) method, catalase enzyme activity, malondialdehyde (MDA) and thiobarbituric acid reactive substance (TBARs) levels, and real-time qPCR of UCP2 and 3 were then determined.

Results: Formulation of green tea extract as ethosomal preparations exhibited a controlled release rate due to the reservoir action of ethosomes. The levels of TBARs and MDA were lower in groups supplemented with green tea extracts compared to control group and in groups (3-5) received it transdermal (P<0.0001 in all 3 groups) was lower than group received it orally with P = 0.0081. The messenger RNA levels of UCPs 2 and 3 in BAT were increased in those 3 groups.

Conclusion: The results support the efficiency of ethosomal gel in penetrating the lipid rich biological membrane. The in vivo study confirms the antioxidant and thermogenic behavior of transdermal applied green tea extract.

Downloads

Download data is not yet available.

References

Fabricant DS, Farnsworth NR. The value of plants used in traditional medicine for drug discovery. Environ Health Persp 2001;109(Suppl 1):69-75.

Namita P, Mukesh R, Vijay KJ. Camellia sinensis (green tea): a review. Glob J Pharmacol 2012;6:52-9.

Anand J, Upadhyaya B, Rawat P, Rai N. Biochemical characterization and pharmacognostic evaluation of purified catechins in green tea (Camellia sinensis) cultivars of India. 3 Biotech 2015;5:285-94.

Sharangi AB. Medicinal and therapeutic potentialities of tea (Camellia sinensis L.)–a review. Food Res Int 2009;42:529-35.

Legeay S, Rodier M, Fillon L, Faure S, Clere N. Epigallocatechin gallate: a review of its beneficial properties to prevent metabolic syndrome. Nutrients 2015;7:5443-68.

Mereles D, Hunstein W. Epigallocatechin-3-gallate (EGCG) for clinical trials: more pitfalls than promises? Int J Mol Sci 2011;12:5592-603.

Anwar EF, Utami TD, Ramadon DE. Transfersomal gel containing green tea (Camellia sinensis L. Kuntze) leaves extract: increasing in vitro penetration. Asian J Pharm Clin Res 2017;10:294-8.

Ramadon D, Goldie AW, Anwar E. Novel transdermal ethosomal gel containing green tea (Camellia sinensis L. Kuntze) leaves extract: formulation and in vitro penetration study. J Young Pharm 2017;9:336.

Patel A, Velikov K. Non-covalent interactions of green tea polyphenol: source of novel colloidal structures. In green tea: varieties, production and health benefits. Nova Biomedical; 2013. p. 151-66.

Tanwar H, Sachdeva R. Transdermal drug delivery system: a review. Int J Pharm Sci Res 2016;7:2274.

Touitou E, Dayan N, Bergelson L, Godin B, Eliaz M. Ethosomes-novel vesicular carriers for enhanced delivery: characterization and skin penetration properties. J Controlled Release 2000;65:403-18.

Mishra D, Dubey V, Asthana A, Saraf DK, Jain NK. Elastic liposomes mediated transcutaneous immunization against Hepatitis B. Vaccine 2006;24:4847-55.

Ricquier D, Casteilla L, Bouillaud F. Molecular studies of the uncoupling protein. FASEB J 1991;5:2237-42.

Avadhani KS, Amirthalingam M, Reddy MS, Udupa N, Mutalik S. Development and validation of RP-HPLC method for estimation of Epigallocatechin-3-gallate (EGCG) in lipid-based nanoformulations. Res J Pharm Tech 2016;9:725-30.

Roman MC, Hildreth J, Bannister S. Determination of catechins and caffeine in camillia sinensis raw materials, extracts, and dietary supplements by HPLC-uv: single-laboratory validation. J AOAC Int 2013;96:933-41.

Malakar J, Sen SO, Nayak AK, Sen KK. Formulation, optimization and evaluation of transferosomal gel for transdermal insulin delivery. Saudi Pharm J 2012;20:355-63.

Duangjit S, Opanasopit P, Rojanarata T, Ngawhirunpat T. Evaluation of meloxicam-loaded cationic transfersomes as transdermal drug delivery carriers. AAPS PharmSciTech 2013;14:133-40.

Mitkari BV, Korde SA, Mahadik KR, Kokare CR. Formulation and evaluation of topical liposomal gel for fluconazole. Indian J Pharm Educ Res 2010;44:324-33.

Setyawati DR, Surini S, Mardliyati E. Optimization of luteolin-loaded transfersome using response surface methodology. Int J Appl Pharm 2017;9:107-11.

Fasinu P, Choonara YE, Kumar P, Du Toit LC, Bijukumar D, Khan RA, et al. Enhancement of the oral bioavailability of felodipine employing 8-arm-poly (ethylene glycol): in vivo, in vitro and in silico evaluation. AAPS PharmSciTech 2017;18:617-28.

Abdelrahman AA, Salem HF, Khallaf RA, Ali AM. Modeling, optimization, and in vitro corneal permeation of chitosan-lomefloxacin HCl nanosuspension intended for ophthalmic delivery. J Pharm Innov 2015;10:254-68.

El-Mahrouk GM, El-Gazayerly ON, Aboelwafa AA, Taha MS. Chitosan lactate wafer as a platform for the buccal delivery of tizanidine HCl: in vitro and in vivo performance. Int J Pharm 2014;467:100-12.

Shaji JE, Lal MA. Nanocarriers for targeting in inflammation. Asian J Pharm Clin Res 2013;6:3-12.

Fahmy UA. Nanoethosomal transdermal delivery of vardenafil for treatment of erectile dysfunction: optimization, characterization, and in vivo evaluation. Drug Des Dev Ther 2015;9:6129.

Lambert JD, Kim DH, Zheng R, Yang CS. Transdermal delivery of (‐)‐epigallocatechin‐3‐gallate, a green tea polyphenol, in mice. J Pharm Pharmacol 2006;58:599-604.

Ibrahim KE, Al-Mutary MG, Bakhiet AO, Khan HA. Histopathology of the liver, kidney, and spleen of mice exposed to gold nanoparticles. Molecules 2018;23:1848.

Benzie IF, Strain JJ. The ferric reducing ability of plasma (FRAP) as a measure of" antioxidant power": the FRAP assay. Anal Biochem 1996;15:1.

Pari L, Latha M. Protective role of scoparia dulcis plant extract on brain antioxidant status and lipid peroxidation in STZ diabetic male wistar rats. BMC Complementary Altern Med 2004;4:16.

Draper HH, Hadley M. Oxygen radicals in biological systems part b: oxygen radicals and antioxidants. Vol. 186. Meth Enzymol; 1990. p. 421-31.

Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2− ΔΔCT method. Methods 2001;25:402-8.

Huo Q, Hao J, Shi R. Determination of catechin by high-performance liquid chromatography and ultraviolet spectrophotometer. Asian J Chem 2013;25:8940-2.

Dayan N, Touitou E. Carriers for skin delivery of trihexyphenidyl HCl: ethosomes vs. liposomes. Biomaterials 2000;21:1879-85.

Elsayed MM, Abdallah OY, Naggar VF, Khalafallah NM. Lipid vesicles for skin delivery of drugs: reviewing three decades of research. Int J Pharm 2007;332:1-6.

Paolino D, Lucania G, Mardente D, Alhaique F, Fresta M. Ethosomes for skin delivery of ammonium glycyrrhizinate: in vitro percutaneous permeation through human skin and in vivo anti-inflammatory activity on human volunteers. J Controlled Release 2005;106:99-110.

Agro AS, Garner ET, Wright III JW, de Escobar IC, Villeda B, Seidlin M. Clinical trial of ototopical ofloxacin for treatment of chronic suppurative otitis media. Clin Ther 1998;20:744-59.

Okonogi S, Oguchi T, Yonemochi E, Puttipipatkhachorn S, Yamamoto K. Improved dissolution of ofloxacin via solid dispersion. Int J Pharm 1997;156:175-80.

Mokhtar M, Sammour OA, Hammad MA, Megrab NA. Effect of some formulation parameters on flurbiprofen encapsulation and release rates of niosomes prepared from proniosomes. Int J Pharm 2008;361(1 Suppl 2):104-11.

Nounou M, El-Khordagui LK, Khalafallah NA, Khalil SA. In vitro drug release of hydrophilic and hydrophobic drug entities from liposomal dispersions and gels. Acta Pharmaceutica 2006;56:311-24.

Panwar P, Pandey B, Lakhera PC, Singh KP. Preparation, characterization, and in vitro release study of albendazole-encapsulated nanosize liposomes. Int J Nanomed 2010;5:101.

Tanwar H, Sachdeva R. Transdermal drug delivery system: a review. Int J Pharm Sci Res 2016;7:2274.

El Zaafarany GM, Awad GA, Holayel SM, Mortada ND. Role of edge activators and surface charge in developing ultra deformable vesicles with enhanced skin delivery. Int J Pharm 2010;397(1 Suppl 2):164-72.

Fang JY, Yu SY, Wu PC, Huang YB, Tsai YH. In vitro skin permeation of estradiol from various proniosome formulations. Int J Pharm 2001;215(1 Suppl 2):91-9.

Wu PS, Li YS, Kuo YC, Tsai SJ, Lin CC. Preparation and evaluation of novel transfersomes combined with the natural antioxidant resveratrol. Molecules 2019;24:600.

Forester SC, Lambert JD. The role of antioxidant versus pro‐oxidant effects of green tea polyphenols in cancer prevention. Mol Nutr Food Res 2011;55:844-54.

Chacko SM, Thambi PT, Kuttan R, Nishigaki I. Beneficial effects of green tea: a literature review. Chinese Med 2010;5:1-9.

Li YM, Chan HY, Huang Y, Chen ZY. Green tea catechins upregulate superoxide dismutase and catalase in fruit flies. Mol Nutr Food Res 2007;51:546-54.

Nelson SK, Bose SK, Grunwald GK, Myhill P, McCord JM. The induction of human superoxide dismutase and catalase in vivo: a fundamentally new approach to antioxidant therapy. Free Radical Biol Med 2006;40:341-7.

Pal S, Dey SK, Saha C. Inhibition of catalase by tea catechins in free and cellular state: a biophysical approach. PLoS One 2014;9:e102460.

Britton C, Helmut S, Alberto B. Hydroperoxide metabolism in mammalian organ. Physiol Rev 1979;59:527-605.

Mohamadin AM, El-Beshbishy HA, El-Mahdy MA. Green tea extract attenuates cyclosporine a-induced oxidative stress in rats. Pharmacol Res 2005;51:51-7.

Awoniyi DO, Aboua YG, Marnewick J, Brooks N. The effects of rooibos (Aspalathus linearis), green tea (Camellia sinensis) and commercial rooibos and green tea supplements on epididymal sperm in oxidative stress‐induced rats. Phytother Res 2012;26:1231-9.

Messarah M, Saoudi M, Boumendjel A, Kadeche L, Boulakoud MS, Feki AE. Green tea extract alleviates arsenic-induced biochemical toxicity and lipid peroxidation in rats. Toxicol Ind Health 2013;29:349-59.

Prabakar J, John T, Arumugham M, Kumar P. Go natural, say no to chemicals-a systematic review on effectiveness of green tea extract containing formulations on dental caries. Asian J Pharm Clin Res 2019;12:63-9.

Basu A, Sanchez K, Leyva MJ, Wu M, Betts NM, Aston CE, et al. Green tea supplementation affects body weight, lipids, and lipid peroxidation in obese subjects with metabolic syndrome. J Am Coll Nutr 2010;29:31-40.

Bornhoeft J, Castaneda D, Nemoseck T, Wang P, Henning SM, Hong MY. The protective effects of green tea polyphenols: lipid profile, inflammation, and antioxidant capacity in rats fed an atherogenic diet and dextran sodium sulfate. J Med Food 2012;15:726-32.

Cunha CA, Lira FS, Rosa Neto JC, Pimentel GD, Souza GI, da Silva CM, et al. Green tea extract supplementation induces the lipolytic pathway, attenuates obesity, and reduces low-grade inflammation in mice fed a high-fat diet. Mediators Inflamm 2013. DOI:10.1155/2013/635470

Hassan AF, Kahtan M, Al-Shawi NN, Numan IT, Bahader GA. The cytoprotective activity of aqueous green tea extract against metronidazole and tinidazole genotoxic effect. Asian J Pharm Clin Res 2019;12:428-31.

Princen HM, van Duyvenvoorde W, Buytenhek R, Blonk C, Tijburg LB, Langius JA, et al. No effect of consumption of green and black tea on plasma lipid and antioxidant levels and on LDL oxidation in smokers. Arterioscler Thromb Vasc Biol 1998;18:833-41.

Erba D, Riso P, Bordoni A, Foti P, Biagi PL, Testolin G. Effectiveness of moderate green tea consumption on antioxidative status and plasma lipid profile in humans. J Nutr Biochem 2005;16:144-9.

Fukino Y, Ikeda A, Maruyama K, Aoki N, Okubo T, Iso H. Randomized controlled trial for an effect of green tea-extract powder supplementation on glucose abnormalities. Eur J Clin Nutr 2008;62:953-60.

Dulloo AG, Duret C, Rohrer D, Girardier L, Mensi N, Fathi MM, et al. Efficacy of a green tea extract rich in catechin polyphenols and caffeine in increasing 24-h energy expenditure and fat oxidation in humans. Am J Clin Nutr 1999;70:1040-5.

Dulloo AG, Seydoux J, Girardier L, Chantre P, Vandermander J. Green tea and thermogenesis: interactions between catechin-polyphenols, caffeine and sympathetic activity. Int J Obes 2000;24:252-8.

Choo JJ. Green tea reduces body fat accretion caused by high-fat diet in rats through β-adrenoceptor activation of thermogenesis in brown adipose tissue. J Nutr Biochem 2003;14:671-6.

Lee MS, Kim CT, Kim Y. Green tea (–)-epigallocatechin-3-gallate reduces body weight with the regulation of multiple genes expression in adipose tissue of diet-induced obese mice. Ann Nutr Metab 2009;54:151-7.

Kim SJ, Bang CY, Guo YR, Choung SY. Anti-obesity effects of aster spathulifolius extract in high-fat diet-induced obese rats. J Med Food 2016;19:353-64.

Published

01-11-2020

How to Cite

SARHAN, W. M., and O. SARHAN. “EVALUATION OF ETHOSOMAL EPIGALLOCATECHIN-3-GALLATE GEL FORMULATIONS AS AN ANTIOXIDANT AND THERMOGENIC AGENT”. International Journal of Pharmacy and Pharmaceutical Sciences, vol. 12, no. 11, Nov. 2020, pp. 122-30, doi:10.22159/ijpps.2020v12i11.39276.

Issue

Section

Original Article(s)