In Vitro and In Vivo Sucrosomial® Berberine Activity on Insulin Resistance
Abstract
:1. Introduction
2. Materials and Methods
2.1. Reagents
2.2. Cell Cultures
2.3. Cell Viability Assay
2.4. Retrotranscription and Quantitative PCR (RT-qPCR)
2.5. Western Blot Analysis
2.6. Animals and In Vivo Experimental Protocol
2.7. Quantification of Berberine and Its Metabolites in Plasma and Tissues by LC-MS/MS
2.8. Statistical Analysis
3. Results
3.1. Determination of Sucrosomial® Berberine Cytotoxicity in Huh7 Cells
3.2. Effect of Sucrosomial® Berberine on AMPK and GK
3.3. In Vivo Pharmacokinetic Profile of Sucrosomial® Berberine
3.4. In Vivo Efficacy of Sucrosomial® Berberine on Insulin Resistance
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Conflicts of Interest
References
- Dong, H.; Zhao, Y.; Zhao, L.; Lu, F. The effects of berberine on blood lipids: A systemic review and meta-analysis of randomized controlled trials. Planta Med. 2013, 79, 437–446. [Google Scholar] [CrossRef] [PubMed]
- Guo, J.; Chen, H.; Zhang, X.; Lou, W.; Zhang, P.; Qiu, Y.; Zhang, C.; Wang, Y.; Liu, W.J. The Effect of Berberine on Metabolic Profiles in Type 2 Diabetic Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Oxid Med. Cell Longev. 2021, 2021, 2074610. [Google Scholar] [CrossRef] [PubMed]
- Dong, B.; Li, H.; Singh, A.B.; Cao, A.; Liu, J. Inhibition of PCSK9 transcription by berberine involves down-regulation of hepatic HNF1alpha protein expression through the ubiquitin-proteasome degradation pathway. J. Biol. Chem. 2015, 290, 4047–4058. [Google Scholar] [CrossRef]
- Kong, W.; Wei, J.; Abidi, P.; Lin, M.; Inaba, S.; Li, C.; Wang, Y.; Wang, Z.; Si, S.; Pan, H.; et al. Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins. Nat. Med. 2004, 10, 1344–1351. [Google Scholar] [CrossRef]
- Lupo, M.G.; Macchi, C.; Marchiano, S.; Cristofani, R.; Greco, M.F.; Dall’Acqua, S.; Chen, H.; Sirtori, C.R.; Corsini, A.; Ruscica, M.; et al. Differential effects of red yeast rice, Berberis aristata and Morus alba extracts on PCSK9 and LDL uptake. Nutr. Metab. Cardiovasc. Dis. NMCD 2019, 29, 1245–1253. [Google Scholar] [CrossRef]
- Maharjan, B.; Payne, D.T.; Ferrarese, I.; Lupo, M.G.; Shrestha, L.K.; Hill, J.P.; Ariga, K.; Rossi, I.; Shrestha, S.S.; Panighel, G.; et al. Evaluation of the effects of natural isoquinoline alkaloids on low density lipoprotein receptor (LDLR) and proprotein convertase subtilisin/kexin type 9 (PCSK9) in hepatocytes, as new potential hypocholesterolemic agents. Bioorganic Chem. 2022, 121, 105686. [Google Scholar] [CrossRef] [PubMed]
- Adorni, M.P.; Zimetti, F.; Lupo, M.G.; Ruscica, M.; Ferri, N. Naturally Occurring PCSK9 Inhibitors. Nutrients 2020, 12, 1440. [Google Scholar] [CrossRef] [PubMed]
- Brusq, J.M.; Ancellin, N.; Grondin, P.; Guillard, R.; Martin, S.; Saintillan, Y.; Issandou, M. Inhibition of lipid synthesis through activation of AMP kinase: An additional mechanism for the hypolipidemic effects of berberine. J. Lipid Res. 2006, 47, 1281–1288. [Google Scholar] [CrossRef]
- Lee, Y.S.; Kim, W.S.; Kim, K.H.; Yoon, M.J.; Cho, H.J.; Shen, Y.; Ye, J.M.; Lee, C.H.; Oh, W.K.; Kim, C.T.; et al. Berberine, a natural plant product, activates AMP-activated protein kinase with beneficial metabolic effects in diabetic and insulin-resistant states. Diabetes 2006, 55, 2256–2264. [Google Scholar] [CrossRef]
- Yin, J.; Gao, Z.; Liu, D.; Liu, Z.; Ye, J. Berberine improves glucose metabolism through induction of glycolysis. Am. J. Physiol. Endocrinol. Metab. 2008, 294, E148–E156. [Google Scholar] [CrossRef] [Green Version]
- Li, M.; Dang, Y.; Li, Q.; Zhou, W.; Zuo, J.; Yao, Z.; Zhang, L.; Ji, G. Berberine alleviates hyperglycemia by targeting hepatic glucokinase in diabetic db/db mice. Sci. Rep. 2019, 9, 8003. [Google Scholar] [CrossRef] [PubMed]
- Xie, X.; Li, W.; Lan, T.; Liu, W.; Peng, J.; Huang, K.; Huang, J.; Shen, X.; Liu, P.; Huang, H. Berberine ameliorates hyperglycemia in alloxan-induced diabetic C57BL/6 mice through activation of Akt signaling pathway. Endocr. J. 2011, 58, 761–768. [Google Scholar] [CrossRef] [PubMed]
- Liu, C.S.; Zheng, Y.R.; Zhang, Y.F.; Long, X.Y. Research progress on berberine with a special focus on its oral bioavailability. Fitoterapia 2016, 109, 274–282. [Google Scholar] [CrossRef] [PubMed]
- Battu, S.K.; Repka, M.A.; Maddineni, S.; Chittiboyina, A.G.; Avery, M.A.; Majumdar, S. Physicochemical characterization of berberine chloride: A perspective in the development of a solution dosage form for oral delivery. AAPS PharmSciTech 2010, 11, 1466–1475. [Google Scholar] [CrossRef] [PubMed]
- Sut, S.; Faggian, M.; Baldan, V.; Poloniato, G.; Castagliuolo, I.; Grabnar, I.; Perissutti, B.; Brun, P.; Maggi, F.; Voinovich, D.; et al. Natural Deep Eutectic Solvents (NADES) to Enhance Berberine Absorption: An In Vivo Pharmacokinetic Study. Molecules 2017, 22, 11921. [Google Scholar] [CrossRef]
- Gomez-Ramirez, S.; Brilli, E.; Tarantino, G.; Munoz, M. Sucrosomial((R)) Iron: A New Generation Iron for Improving Oral Supplementation. Pharmaceuticals 2018, 11, 97. [Google Scholar] [CrossRef]
- Fabiano, A.; Brilli, E.; Fogli, S.; Beconcini, D.; Carpi, S.; Tarantino, G.; Zambito, Y. Sucrosomial(R) iron absorption studied by in vitro and ex-vivo models. Eur. J. Pharm. Sci. Off. J. Eur. Fed. Pharm. Sci. 2018, 111, 425–431. [Google Scholar] [CrossRef]
- Keepers, Y.P.; Pizao, P.E.; Peters, G.J.; van Ark-Otte, J.; Winograd, B.; Pinedo, H.M. Comparison of the sulforhodamine B protein and tetrazolium (MTT) assays for in vitro chemosensitivity testing. Eur. J. Cancer 1991, 27, 897–900. [Google Scholar] [CrossRef]
- Xia, X.; Yan, J.; Shen, Y.; Tang, K.; Yin, J.; Zhang, Y.; Yang, D.; Liang, H.; Ye, J.; Weng, J. Berberine improves glucose metabolism in diabetic rats by inhibition of hepatic gluconeogenesis. PLoS ONE 2011, 6, e16556. [Google Scholar] [CrossRef]
- Zhang, H.; Wei, J.; Xue, R.; Wu, J.D.; Zhao, W.; Wang, Z.Z.; Wang, S.K.; Zhou, Z.X.; Song, D.Q.; Wang, Y.M.; et al. Berberine lowers blood glucose in type 2 diabetes mellitus patients through increasing insulin receptor expression. Metab. Clin. Exp. 2010, 59, 285–292. [Google Scholar] [CrossRef]
- Ma, J.Y.; Feng, R.; Tan, X.S.; Ma, C.; Shou, J.W.; Fu, J.; Huang, M.; He, C.Y.; Chen, S.N.; Zhao, Z.X.; et al. Excretion of berberine and its metabolites in oral administration in rats. J. Pharm. Sci. 2013, 102, 4181–4192. [Google Scholar] [CrossRef] [PubMed]
- Srai, S.K.S.; Bomford, A.; McArdle, H.J. Iron transport across cell membranes: Molecular understanding of duodenal and placental iron uptake. Best Pr. Res. Cl Ha 2002, 15, 243–259. [Google Scholar] [CrossRef]
- Fabiano, A.; Brilli, E.; Mattii, L.; Testai, L.; Moscato, S.; Citi, V.; Tarantino, G.; Zambito, Y. Ex Vivo and in Vivo Study of Sucrosomial((R)) Iron Intestinal Absorption and Bioavailability. Int. J. Mol. Sci. 2018, 19, 2722. [Google Scholar] [CrossRef] [PubMed]
- Takaishi, N.; Satsu, H.; Shimizu, M. Enhanced daunomycin accumulation in human intestinal Caco-2 cells from non-ionic food emulsifiers unrelated to the p-glycoprotein inhibitory mechanism. Biosci. Biotechnol. Biochem. 2006, 70, 2703–2711. [Google Scholar] [CrossRef]
- Quintanar-Guerrero, D.; Ganem-Quintanar, A.; Allemann, E.; Fessi, H.; Doelker, E. Influence of the stabilizer coating layer on the purification and freeze-drying of poly(D,L-lactic acid) nanoparticles prepared by an emulsion-diffusion technique. J. Microencapsul 1998, 15, 107–119. [Google Scholar] [CrossRef]
- Zuo, F.; Nakamura, N.; Akao, T.; Hattori, M. Pharmacokinetics of berberine and its main metabolites in conventional and pseudo germ-free rats determined by liquid chromatography/ion trap mass spectrometry. Drug Metab. Dispos. Biol. Fate Chem. 2006, 34, 2064–2072. [Google Scholar] [CrossRef]
- Bouw, M.R.; Xie, R.; Tunblad, K.; Hammarlund-Udenaes, M. Blood-brain barrier transport and brain distribution of morphine-6-glucuronide in relation to the antinociceptive effect in rats--pharmacokinetic/pharmacodynamic modelling. Br. J. Pharmacol. 2001, 134, 1796–1804. [Google Scholar] [CrossRef]
- Ouzzine, M.; Gulberti, S.; Ramalanjaona, N.; Magdalou, J.; Fournel-Gigleux, S. The UDP-glucuronosyltransferases of the blood-brain barrier: Their role in drug metabolism and detoxication. Front. Cell Neurosci. 2014, 8, 349. [Google Scholar] [CrossRef]
- Brilli, E.; Khadge, S.; Fabiano, A.; Zambito, Y.; Williams, T.; Tarantino, G. Magnesium bioavailability after administration of sucrosomial(R) magnesium: Results of an ex-vivo study and a comparative, double-blinded, cross-over study in healthy subjects. Eur. Rev. Med. Pharmacol. Sci. 2018, 22, 1843–1851. [Google Scholar] [CrossRef]
- Szuts, A.; Budai-Szucs, M.; Eros, I.; Otomo, N.; Szabo-Revesz, P. Study of gel-forming properties of sucrose esters for thermosensitive drug delivery systems. Int. J. Pharm. 2010, 383, 132–137. [Google Scholar] [CrossRef]
- Kiss, L.; Hellinger, E.; Pilbat, A.M.; Kittel, A.; Torok, Z.; Furedi, A.; Szakacs, G.; Veszelka, S.; Sipos, P.; Ozsvari, B.; et al. Sucrose esters increase drug penetration, but do not inhibit p-glycoprotein in caco-2 intestinal epithelial cells. J. Pharm. Sci. 2014, 103, 3107–3119. [Google Scholar] [CrossRef] [PubMed]
- Zhaojie, M.; Ming, Z.; Shengnan, W.; Xiaojia, B.; Hatch, G.M.; Jingkai, G.; Li, C. Amorphous solid dispersion of berberine with absorption enhancer demonstrates a remarkable hypoglycemic effect via improving its bioavailability. Int. J. Pharm. 2014, 467, 50–59. [Google Scholar] [CrossRef] [PubMed]
- Kohli, K.; Mujtaba, A.; Malik, R.; Amin, S.; Alam, M.S.; Ali, A.; Barkat, M.A.; Ansari, M.J. Development of Natural Polysaccharide-Based Nanoparticles of Berberine to Enhance Oral Bioavailability: Formulation, Optimization, Ex Vivo, and In Vivo Assessment. Polymers 2021, 13, 3833. [Google Scholar] [CrossRef]
- Petrangolini, G.; Corti, F.; Ronchi, M.; Arnoldi, L.; Allegrini, P.; Riva, A. Development of an Innovative Berberine Food-Grade Formulation with an Ameliorated Absorption: In Vitro Evidence Confirmed by Healthy Human Volunteers Pharmacokinetic Study. Evid. Based Complementary Altern. Med. Ecam 2021, 2021, 7563889. [Google Scholar] [CrossRef] [PubMed]
- Guo, H.H.; Feng, C.L.; Zhang, W.X.; Luo, Z.G.; Zhang, H.J.; Zhang, T.T.; Ma, C.; Zhan, Y.; Li, R.; Wu, S.; et al. Liver-target nanotechnology facilitates berberine to ameliorate cardio-metabolic diseases. Nat. Commun. 2019, 10, 1981. [Google Scholar] [CrossRef] [Green Version]
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Lupo, M.G.; Brilli, E.; De Vito, V.; Tarantino, G.; Sut, S.; Ferrarese, I.; Panighel, G.; Gabbia, D.; De Martin, S.; Dall’Acqua, S.; et al. In Vitro and In Vivo Sucrosomial® Berberine Activity on Insulin Resistance. Nutrients 2022, 14, 3595. https://doi.org/10.3390/nu14173595
Lupo MG, Brilli E, De Vito V, Tarantino G, Sut S, Ferrarese I, Panighel G, Gabbia D, De Martin S, Dall’Acqua S, et al. In Vitro and In Vivo Sucrosomial® Berberine Activity on Insulin Resistance. Nutrients. 2022; 14(17):3595. https://doi.org/10.3390/nu14173595
Chicago/Turabian StyleLupo, Maria Giovanna, Elisa Brilli, Virginia De Vito, Germano Tarantino, Stefania Sut, Irene Ferrarese, Giovanni Panighel, Daniela Gabbia, Sara De Martin, Stefano Dall’Acqua, and et al. 2022. "In Vitro and In Vivo Sucrosomial® Berberine Activity on Insulin Resistance" Nutrients 14, no. 17: 3595. https://doi.org/10.3390/nu14173595