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Combinatorial Chemistry & High Throughput Screening

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ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

Research Article

Solid Lipid Nanoformulation of Berberine Attenuates Doxorubicin Triggered in vitro Inflammation in H9c2 Rat Cardiomyocytes

Author(s): Shalini Rawal, Pooja Gupta*, Priyanka Bhatnagar, Harlokesh Narayan Yadav and Amit Kumar Dinda

Volume 25, Issue 10, 2022

Published on: 27 July, 2022

Page: [1695 - 1706] Pages: 12

DOI: 10.2174/1386207325666220617113744

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Abstract

Aim: The aim of this study was to evaluate the efficacy of solid lipid nanoparticles of berberine against doxorubicin-induced cardiotoxicity.

Background: Berberine (Ber) is cardioprotective, but its oral bioavailability is low, and its effect on chemotherapy-induced cardiotoxicity has not been studied.

Objective: Solid lipid nanoparticles (SLNs) of berberine chloride were prepared, characterized and evaluated in vitro against doxorubicin-induced cardiomyocyte injury.

Methods: Berberine-loaded SLNs (Ber-SLNs) were synthesized using the water-in-oil microemulsion technique with tripalmitin, Tween 80 and poloxamer 407. Ber-SLNs were evaluated for preventive effect against toxicity of doxorubicin in H9c2 cells. The culture was pre-treated (24 h) with Ber (10 μM) and Ber-SLNs (1 and 10 μM), and 1 μM of doxorubicin (Dox) was added for 3 h. The cell viability assay (MTT (3-(4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide) and LDH (Lactate dehydrogenase)), levels of Creatine kinase-MB (CK-MB), Nitrite, MDA (Malondialdehyde), ROS (Reactive oxygen species) generation, and apoptotic DNA (Deoxyribonucleic acid) content were assessed.

Results: Ber-SLNs had a mean particle size of 13.12±1.188 nm, the zeta potential of -1.05 ± 0.08 mV, poly-dispersity index (PDI) of 0.317 ± 0.05 and entrapment efficiency of 50 ± 4.8%. Cell viability was 81 ± 0.17% for Ber-SLNs (10 μM) and 73.22 ± 0.83% for Ber (10 μM) treated cells in the MTT assay. Percentage cytotoxicity calculated from LDH release was 58.91 ± 0.54% after Dox, 40.3 ± 1.3% with Ber (10 μM) and 40.7 ± 1.3% with Ber-SLNs (1 μM) (p<0.001). Inflammation and oxidative stress markers were lower with Ber and Ber-SLNs. Attenuation of ROS generation and apoptosis of cardiomyocytes were noted on fluorescence microscopy.

Conclusion: Ber SLNs effectively prevented doxorubicin-induced inflammation and oxidative stress in rat cardiomyocytes. The results demonstrate that microemulsion is a simple and costeffective technique to prepare Ber-SLNs, and may be considered as a drug delivery vehicle for berberine.

Keywords: Chemotherapy-induced cardiotoxicity, berberine, doxorubicin, H9c2 cells, microemulsion, solid lipid nanoparticles.

Graphical Abstract
[1]
Raggi, P.; Genest, J.; Giles, J.T.; Rayner, K.J.; Dwivedi, G.; Beanlands, R.S.; Gupta, M. Role of inflammation in the pathogenesis of atherosclerosis and therapeutic interventions. Atherosclerosis, 2018, 276, 98-108.
[http://dx.doi.org/10.1016/j.atherosclerosis.2018.07.014] [PMID: 30055326]
[2]
Ramin, C.; Schaeffer, M.L.; Zheng, Z.; Connor, A.E.; Hoffman-Bolton, J.; Lau, B.; Visvanathan, K. All-Cause and cardiovascular disease mortality among breast cancer survivors in clue ii, a long-standing community-based cohort. J. Natl. Cancer Inst., 2021, 113(2), 137-145.
[http://dx.doi.org/10.1093/jnci/djaa096] [PMID: 32634223]
[3]
Henriksen, P.A. Anthracycline cardiotoxicity: An update on mechanisms, monitoring and prevention. Heart, 2018, 104(12), 971-977.
[http://dx.doi.org/10.1136/heartjnl-2017-312103] [PMID: 29217634]
[4]
Stoltzfus, K.C.; Zhang, Y.; Sturgeon, K.; Sinoway, L.I.; Trifiletti, D.M.; Chinchilli, V.M.; Zaorsky, N.G. Fatal heart disease among cancer patients. Nat. Commun., 2020, 11(1), 2011.
[http://dx.doi.org/10.1038/s41467-020-15639-5] [PMID: 32332714]
[5]
Zamorano, J.L.; Lancellotti, P.; Rodriguez Muñoz, D.; Aboyans, V.; Asteggiano, R.; Galderisi, M.; Habib, G.; Lenihan, D.J.; Lip, G.Y.H.; Lyon, A.R.; Lopez Fernandez, T.; Mohty, D.; Piepoli, M.F.; Tamargo, J.; Torbicki, A.; Suter, T.M. 2016 ESC position paper on cancer treatments and cardiovascular toxicity developed under the auspices of the esc committee for practice guidelines: The task force for cancer treatments and cardiovascular toxicity of the european society of cardiology (ESC). Eur. Heart J., 2016, 37(36), 2768-2801.
[http://dx.doi.org/10.1093/eurheartj/ehw211] [PMID: 27567406]
[6]
Deidda, M.; Mercurio, V.; Cuomo, A.; Noto, A.; Mercuro, G.; Cadeddu Dessalvi, C. Metabolomic perspectives in antiblastic cardiotoxicity and cardioprotection. Int. J. Mol. Sci., 2019, 20(19), 4928.
[http://dx.doi.org/10.3390/ijms20194928] [PMID: 31590338]
[7]
Yeddes, W.; Chalghoum, A.; Aidi-Wannes, W.; Ksouri, R.; Saidani Tounsi, M. Effect of bioclimatic area and season on phenolics and antioxidant activities of rosemary (Rosmarinus officinalis L.) leaves. J. Essent. Oil Res., 2019, 31(5), 432-443.
[http://dx.doi.org/10.1080/10412905.2019.1577305]
[8]
Farnad, N.; Heidari, R.; Aslanipour, B. Phenolic composition and comparison of antioxidant activity of alcoholic extracts of Peppermint (Mentha piperita). J. Food Meas. Charact., 2014, 8(2), 113-121.
[http://dx.doi.org/10.1007/s11694-014-9171-x]
[9]
Hosseini, A.; Sahebkar, A. Reversal of doxorubicin-induced cardiotoxicity by using phytotherapy: A review. J. Pharmacopuncture, 2017, 20(4), 243-256.
[PMID: 30151294]
[10]
Yi, X.; Zhu, J.; Zhang, J.; Gao, Y.; Chen, Z.; Lu, S.; Cai, Z.; Hong, Y.; Wu, Y. Investigation of the reverse effect of Danhong injection on doxorubicin-induced cardiotoxicity in H9c2 cells: Insight by LC-MS based non-targeted metabolomic analysis. J. Pharm. Biomed. Anal., 2018, 152, 264-270.
[http://dx.doi.org/10.1016/j.jpba.2018.02.012] [PMID: 29438868]
[11]
Chen, T.; Deng, Z.; Zhao, R.; Shen, H.; Li, W. SYKT alleviates doxorubicin-induced cardiotoxicity via modulating ros-mediated p53 and mapk signal pathways. Evid. Based Complement. Alternat. Med., 2018, 2018, 2581031.
[http://dx.doi.org/10.1155/2018/2581031] [PMID: 30224925]
[12]
Imenshahidi, M.; Hosseinzadeh, H. Berberine and barberry (Berberis vulgaris): A clinical review. Phytother. Res., 2019, 33(3), 504-523.
[http://dx.doi.org/10.1002/ptr.6252] [PMID: 30637820]
[13]
Jin, Y.; Khadka, D.B.; Cho, W.J. Pharmacological effects of berberine and its derivatives: A patent update. Expert Opin. Ther. Pat., 2016, 26(2), 229-243.
[http://dx.doi.org/10.1517/13543776.2016.1118060]
[14]
Sun, Y.; Yuan, X.; Zhang, F.; Han, Y.; Chang, X.; Xu, X.; Li, Y.; Gao, X. Berberine ameliorates fatty acid-induced oxidative stress in human hepatoma cells. Sci. Rep., 2017, 7(1), 11340.
[http://dx.doi.org/10.1038/s41598-017-11860-3] [PMID: 28900305]
[15]
Tang, J.; Feng, Y.; Tsao, S.; Wang, N.; Curtain, R.; Wang, Y. Berberine and Coptidis rhizoma as novel antineoplastic agents: A review of traditional use and biomedical investigations. J. Ethnopharmacol., 2009, 126(1), 5-17.
[http://dx.doi.org/10.1016/j.jep.2009.08.009] [PMID: 19686830]
[16]
Wang, X.; Feng, S.; Ding, N.; He, Y.; Li, C.; Li, M.; Ding, X.; Ding, H.; Li, J.; Wu, J.; Li, Y. Anti-Inflammatory effects of berberine hydrochloride in an LPS-Induced murine model of mastitis. Evid. Based Complement. Alternat. Med., 2018, 2018, 5164314.
[http://dx.doi.org/10.1155/2018/5164314] [PMID: 29849710]
[17]
Lu, Z.; He, B.; Chen, Z.; Yan, M.; Wu, L. Anti-inflammatory activity of berberine in non-alcoholic fatty liver disease via the Angptl2 pathway. BMC Immunol., 2020, 21(1), 28.
[http://dx.doi.org/10.1186/s12865-020-00358-9] [PMID: 32429849]
[18]
Li, C.; Xi, Y.; Li, S.; Zhao, Q.; Cheng, W.; Wang, Z.; Zhong, J.; Niu, X.; Chen, G. Berberine ameliorates TNBS induced colitis by inhibiting inflammatory responses and Th1/Th17 differentiation. Mol. Immunol., 2015, 67(2)(2 Pt B), 444-454.
[http://dx.doi.org/10.1016/j.molimm.2015.07.013] [PMID: 26224047]
[19]
Jiang, D.; Wang, D.; Zhuang, X.; Wang, Z.; Ni, Y.; Chen, S.; Sun, F. Berberine increases adipose triglyceride lipase in 3T3-L1 adipocytes through the AMPK pathway. Lipids Health Dis., 2016, 15(1), 214.
[http://dx.doi.org/10.1186/s12944-016-0383-4] [PMID: 27938388]
[20]
Zou, K.; Li, Z.; Zhang, Y.; Zhang, H.Y.; Li, B.; Zhu, W.L.; Shi, J.Y.; Jia, Q.; Li, Y.M. Advances in the study of berberine and its derivatives: A focus on anti-inflammatory and anti-tumor effects in the digestive system. Acta Pharmacol. Sin., 2017, 38(2), 157-167.
[http://dx.doi.org/10.1038/aps.2016.125] [PMID: 27917872]
[21]
Zhang, L.; Wu, X.; Yang, R.; Chen, F.; Liao, Y.; Zhu, Z.; Wu, Z.; Sun, X.; Wang, L. Effects of berberine on the gastrointestinal microbiota. Front. Cell. Infect. Microbiol., 2021, 10, 588517.
[http://dx.doi.org/10.3389/fcimb.2020.588517] [PMID: 33680978]
[22]
Feng, R.; Zhao, Z.X.; Ma, S.R.; Guo, F.; Wang, Y.; Jiang, J.D. Gut microbiota-regulated pharmacokinetics of berberine and active metabolites in beagle dogs after oral administration. Front. Pharmacol., 2018, 9, 214.
[http://dx.doi.org/10.3389/fphar.2018.00214] [PMID: 29618977]
[23]
Singh, N.; Sharma, B. Toxicological effects of berberine and sanguinarine. Front. Mol. Biosci., 2018, 5, 21.
[http://dx.doi.org/10.3389/fmolb.2018.00021] [PMID: 29616225]
[24]
Sahibzada, M.U.K.; Sadiq, A.; Faidah, H.S.; Khurram, M.; Amin, M.U.; Haseeb, A.; Kakar, M. Berberine nanoparticles with enhanced in vitro bioavailability: Characterization and antimicrobial activity. Drug Des. Devel. Ther., 2018, 12, 303-312.
[http://dx.doi.org/10.2147/DDDT.S156123] [PMID: 29491706]
[25]
Wang, Y.; Zidichouski, J.A. Update on the benefits and mechanisms of action of the bioactive vegetal alkaloid berberine on lipid metabolism and homeostasis. Cholesterol, 2018, 2018, 7173920.
[http://dx.doi.org/10.1155/2018/7173920] [PMID: 30057809]
[26]
Yang, J.; Xu, H.; Wu, S.; Ju, B.; Zhu, D.; Yan, Y.; Wang, M.; Hu, J. Preparation and evaluation of microemulsion-based transdermal delivery of Cistanche tubulosa phenylethanoid glycosides. Mol. Med. Rep., 2017, 15(3), 1109-1116.
[http://dx.doi.org/10.3892/mmr.2017.6147] [PMID: 28138704]
[27]
Chang, W.; Zhang, M.; Li, J.; Meng, Z.; Wei, S.; Du, H.; Chen, L.; Hatch, G.M. Berberine improves insulin resistance in cardiomyocytes via activation of 5′-adenosine monophosphate-activated protein kinase. Metabolism, 2013, 62(8), 1159-1167.
[http://dx.doi.org/10.1016/j.metabol.2013.02.007] [PMID: 23537779]
[28]
Zhang, J.; Cui, L.; Han, X.; Zhang, Y.; Zhang, X.; Chu, X.; Zhang, F.; Zhang, Y.; Chu, L. Protective effects of tannic acid on acute doxorubicin-induced cardiotoxicity: Involvement of suppression in oxidative stress, inflammation, and apoptosis. Biomed. Pharmacother., 2017, 93, 1253-1260.
[http://dx.doi.org/10.1016/j.biopha.2017.07.051] [PMID: 28738542]
[29]
Feelisch, M.; Noack, E. Nitric oxide (NO) formation from nitrovasodilators occurs independently of hemoglobin or non-heme iron. Eur. J. Pharmacol., 1987, 142(3), 465-469.
[http://dx.doi.org/10.1016/0014-2999(87)90090-2] [PMID: 3123257]
[30]
Wallin, B.; Rosengren, B.; Shertzer, H.G.; Camejo, G. Lipoprotein oxidation and measurement of thiobarbituric acid reacting substances formation in a single microtiter plate: Its use for evaluation of antioxidants. Anal. Biochem., 1993, 208(1), 10-15.
[http://dx.doi.org/10.1006/abio.1993.1002] [PMID: 8434778]
[31]
Liu, Y.; Yang, G.; Jin, S.; Xu, L.; Zhao, C-X. Development of high-drug-loading nanoparticles. ChemPlusChem, 2020, 85(9), 2143-2157.
[http://dx.doi.org/10.1002/cplu.202000496] [PMID: 32864902]
[32]
Kogan, A.; Garti, N. Microemulsions as transdermal drug delivery vehicles. Adv. Colloid Interface Sci., 2006, 123-126, 369-385.
[http://dx.doi.org/10.1016/j.cis.2006.05.014] [PMID: 16843424]
[33]
Sharma, A.K.; Garg, T.; Goyal, A.K.; Rath, G. Role of microemuslsions in advanced drug delivery. Artif. Cells Nanomed. Biotechnol., 2016, 44(4), 1177-1185.
[PMID: 25711493]
[34]
Teulon, J.M.; Godon, C.; Chantalat, L.; Moriscot, C.; Cambedouzou, J.; Odorico, M.; Ravaux, J.; Podor, R.; Gerdil, A.; Habert, A.; Herlin-Boime, N.; Chen, S.W.; Pellequer, J.L. On the operational aspects of measuring nanoparticle sizes. Nanomaterials (Basel), 2018, 9(1), 18.
[http://dx.doi.org/10.3390/nano9010018] [PMID: 30583592]
[35]
Gui, S.Y.; Wu, L.; Peng, D.Y.; Liu, Q.Y.; Yin, B.P.; Shen, J.Z. Preparation and evaluation of a microemulsion for oral delivery of berberine. Pharmazie, 2008, 63(7), 516-519.
[PMID: 18717486]
[36]
Hitzman, C.J.; Elmquist, W.F.; Wiedmann, T.S. Development of a respirable, sustained release microcarrier for 5-fluorouracil II: In vitro and in vivo optimization of lipid coated nanoparticles. J. Pharm. Sci., 2006, 95(5), 1127-1143.
[http://dx.doi.org/10.1002/jps.20590] [PMID: 16570303]
[37]
Reddy, L.H.; Vivek, K.; Bakshi, N.; Murthy, R.S. Tamoxifen citrate loaded solid lipid nanoparticles (SLN): Preparation, characterization, in vitro drug release, and pharmacokinetic evaluation. Pharm. Dev. Technol., 2006, 11(2), 167-177.
[http://dx.doi.org/10.1080/10837450600561265] [PMID: 16749527]
[38]
Ucisik, M.H.; Küpcü, S.; Breitwieser, A.; Gelbmann, N.; Schuster, B.; Sleytr, U.B. S-layer fusion protein as a tool functionalizing emulsomes and CurcuEmulsomes for antibody binding and targeting. Colloids Surf. B Biointerfaces, 2015, 128, 132-139.
[http://dx.doi.org/10.1016/j.colsurfb.2015.01.055] [PMID: 25734967]
[39]
Constantinides, P.P.; Welzel, G.; Ellens, H.; Smith, P.L.; Sturgis, S.; Yiv, S.H.; Owen, A.B. Water-in-oil microemulsions containing medium-chain fatty acids/salts: Formulation and intestinal absorption enhancement evaluation. Pharm. Res., 1996, 13(2), 210-215.
[http://dx.doi.org/10.1023/A:1016030812272] [PMID: 8932438]
[40]
Jadhav, K.R.; Shaikh, I.M.; Ambade, K.W.; Kadam, V.J. Applications of microemulsion based drug delivery system. Curr. Drug Deliv., 2006, 3(3), 267-273.
[http://dx.doi.org/10.2174/156720106777731118] [PMID: 16848728]
[41]
Pawar, K.R.; Babu, R.J. Lipid materials for topical and transdermal delivery of nanoemulsions. Crit. Rev. Ther. Drug Carrier Syst., 2014, 31(5), 429-458.
[http://dx.doi.org/10.1615/CritRevTherDrugCarrierSyst.2014010663] [PMID: 25271559]
[42]
Siebel, C.; Lanvers-Kaminsky, C.; Würthwein, G.; Hempel, G.; Boos, J. Bioanalysis of doxorubicin aglycone metabolites in human plasma samples-implications for doxorubicin drug monitoring. Sci. Rep., 2020, 10(1), 18562.
[http://dx.doi.org/10.1038/s41598-020-75662-w] [PMID: 33122763]
[43]
Minotti, G.; Menna, P.; Salvatorelli, E.; Cairo, G.; Gianni, L. Anthracyclines: Molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol. Rev., 2004, 56(2), 185-229.
[http://dx.doi.org/10.1124/pr.56.2.6] [PMID: 15169927]
[44]
Mantawy, E.M.; El-Bakly, W.M.; Esmat, A.; Badr, A.M.; El-Demerdash, E. Chrysin alleviates acute doxorubicin cardiotoxicity in rats via suppression of oxidative stress, inflammation and apoptosis. Eur. J. Pharmacol., 2014, 728, 107-118.
[http://dx.doi.org/10.1016/j.ejphar.2014.01.065] [PMID: 24509133]
[45]
Takemura, G.; Fujiwara, H. Doxorubicin-induced cardiomyopathy from the cardiotoxic mechanisms to management. Prog. Cardiovasc. Dis., 2007, 49(5), 330-352.
[http://dx.doi.org/10.1016/j.pcad.2006.10.002] [PMID: 17329180]
[46]
Förstermann, U.; Xia, N.; Li, H. Roles of vascular oxidative stress and nitric oxide in the pathogenesis of atherosclerosis. Circ. Res., 2017, 120(4), 713-735.
[http://dx.doi.org/10.1161/CIRCRESAHA.116.309326] [PMID: 28209797]
[47]
Wang, J.; Yao, L.; Wu, X.; Guo, Q.; Sun, S.; Li, J.; Shi, G.; Caldwell, R.B.; Caldwell, R.W.; Chen, Y. Protection against doxorubicin-induced cardiotoxicity through modulating iNOS/ARG 2 balance by electroacupuncture at PC6. Oxid. Med. Cell. Longev., 2021, 2021, 6628957.
[http://dx.doi.org/10.1155/2021/6628957] [PMID: 33824696]
[48]
Balli, E.; Mete, U.O.; Tuli, A.; Tap, O.; Kaya, M. Effect of melatonin on the cardiotoxicity of doxorubicin. Histol. Histopathol., 2004, 19(4), 1101-1108.
[PMID: 15375752]
[49]
Simůnek, T.; Stérba, M.; Popelová, O.; Adamcová, M.; Hrdina, R.; Gersl, V. Anthracycline-induced cardiotoxicity: Overview of studies examining the roles of oxidative stress and free cellular iron. Pharmacol. Rep., 2009, 61(1), 154-171.
[http://dx.doi.org/10.1016/S1734-1140(09)70018-0] [PMID: 19307704]
[50]
Shaker, R.A.; Abboud, S.H.; Assad, H.C.; Hadi, N. Enoxaparin attenuates doxorubicin induced cardiotoxicity in rats via interfering with oxidative stress, inflammation and apoptosis. BMC Pharmacol. Toxicol., 2018, 19(1), 3.
[http://dx.doi.org/10.1186/s40360-017-0184-z] [PMID: 29321061]
[51]
Fang, X.; Wang, H.; Han, D.; Xie, E.; Yang, X.; Wei, J.; Gu, S.; Gao, F.; Zhu, N.; Yin, X.; Cheng, Q.; Zhang, P.; Dai, W.; Chen, J.; Yang, F.; Yang, H.T.; Linkermann, A.; Gu, W.; Min, J.; Wang, F. Ferroptosis as a target for protection against cardiomyopathy. Proc. Natl. Acad. Sci. USA, 2019, 116(7), 2672-2680.
[http://dx.doi.org/10.1073/pnas.1821022116] [PMID: 30692261]

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