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Current Medicinal Chemistry

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ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

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Review Article

Berberine: Pharmacological Features in Health, Disease and Aging

Author(s): Amin Gasmi, Farah Asghar, Saba Zafar, Petro Oliinyk, Oksana Khavrona, Roman Lysiuk, Massimiliano Peana, Salva Piscopo, Halyna Antonyak, Joeri J. Pen, Iryna Lozynska, Sadaf Noor, Larysa Lenchyk, Akram Muhammad, Inna Vladimirova, Natalia Dub, Olha Antoniv, Oksana Tsal, Taras Upyr and Geir Bjørklund*

Volume 31, Issue 10, 2024

Published on: 07 April, 2023

Page: [1214 - 1234] Pages: 21

DOI: 10.2174/0929867330666230207112539

Price: $65

Abstract

Background: Berberine is the main active compound of different herbs and is defined as an isoquinoline quaternary botanical alkaloid found in barks and roots of numerous plants. It exhibits a wide range of pharmacological effects, such as anti-obesity and antidiabetic effects. Berberine has antibacterial activity against a variety of microbiota, including many bacterial species, protozoa, plasmodia, fungi, and trypanosomes.

Objective: This review describes the role of berberine and its metabolic effects. It also discusses how it plays a role in glucose metabolism, fat metabolism, weight loss, how it modulates the gut microbiota, and what are its antimicrobial properties along with its potential side effects with maximal tolerable dosage.

Methods: Representative studies were considered and analyzed from different scientific databases, including PubMed and Web of Science, for the years 1982-2022.

Results: Literature analysis shows that berberine affects many biochemical and pharmacological pathways that theoretically yield a positive effect on health and disease. Berberine exhibits neuroprotective properties in various neurodegenerative and neuropsychological ailments. Despite its low bioavailability after oral administration, berberine is a promising tool for several disorders. A possible hypothesis would be the modulation of the gut microbiome. While the evidence concerning the aging process in humans is more limited, preliminary studies have shown positive effects in several models.

Conclusion: Berberine could serve as a potential candidate for the treatment of several diseases. Previous literature has provided a basis for scientists to establish clinical trials in humans. However, for obesity, the evidence appears to be sufficient for hands-on use.

« Previous Next »
[1]
Quartey, N.K.; Ma, P.H.; Chung, V.C.; Griffiths, S.M. Complementary and alternative medicine education for medical profession: Systematic review. Evid Based Complement Alternat Med, 2012, 2012, 656812.
[2]
WHO monographs on medicinal plants commonly used in the Newly Independent States (NIS); Libros Digitales-World Health Organization (WHO), 2010.
[3]
Lewis, W.H. Pharmaceutical discoveries based on ethnomedicinal plants: 1985 to 2000 and beyond. Econ. Bot., 2003, 57(1), 126-134.
[http://dx.doi.org/10.1663/0013-0001(2003)057[0126:PDBOEP]2.0.CO;2]
[4]
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(1), E148-E156.
[http://dx.doi.org/10.1152/ajpendo.00211.2007] [PMID: 17971514]
[5]
Cordell, G.A.; Quinn-Beattie, M.L.; Farnsworth, N.R. The potential of alkaloids in drug discovery. Phytother. Res., 2001, 15(3), 183-205.
[http://dx.doi.org/10.1002/ptr.890] [PMID: 11351353]
[6]
Kulkarni, S.K.; Dhir, A. Berberine: A plant alkaloid with therapeutic potential for central nervous system disorders. Phytother. Res., 2010, 24(3), 317-324.
[http://dx.doi.org/10.1002/ptr.2968] [PMID: 19998323]
[7]
Vuddanda, P.R.; Chakraborty, S.; Singh, S. Berberine: A potential phytochemical with multispectrum therapeutic activities. Expert Opin. Investig. Drugs, 2010, 19(10), 1297-1307.
[http://dx.doi.org/10.1517/13543784.2010.517745] [PMID: 20836620]
[8]
Ettefagh, K.; Burns, J.; Junio, H.; Kaatz, G.; Cech, N. Goldenseal (Hydrastis canadensis L.) extracts synergistically enhance the antibacterial activity of berberine via efflux pump inhibition. Planta Med., 2011, 77(8), 835-840.
[http://dx.doi.org/10.1055/s-0030-1250606] [PMID: 21157683]
[9]
Chen, W.H.; Pang, J.Y.; Qin, Y.; Peng, Q.; Cai, Z.; Jiang, Z.H. Synthesis of linked berberine dimers and their remarkably enhanced DNA-binding affinities. Bioorg. Med. Chem. Lett., 2005, 15(10), 2689-2692.
[http://dx.doi.org/10.1016/j.bmcl.2004.10.098] [PMID: 15863343]
[10]
Boberek, J.M.; Stach, J.; Good, L. Genetic evidence for inhibition of bacterial division protein FtsZ by berberine. PLoS One, 2010, 5(10), e13745.
[http://dx.doi.org/10.1371/journal.pone.0013745] [PMID: 21060782]
[11]
Bhadra, K.; Kumar, G.S. Therapeutic potential of nucleic acid-binding isoquinoline alkaloids: Binding aspects and implications for drug design. Med. Res. Rev., 2011, 31(6), 821-862.
[http://dx.doi.org/10.1002/med.20202] [PMID: 20077560]
[12]
Chen, Y.; Wang, Y.; Zhang, J.; Sun, C.; Lopez, A. Berberine improves glucose homeostasis in streptozotocin-induced diabetic rats in association with multiple factors of insulin resistance. ISRN Endocrinol, 2011.
[http://dx.doi.org/10.5402/2011/519371]
[13]
Yin, J.; Xing, H.; Ye, J. Efficacy of berberine in patients with type 2 diabetes mellitus. Metabolism, 2008, 57(5), 712-717.
[http://dx.doi.org/10.1016/j.metabol.2008.01.013] [PMID: 18442638]
[14]
Cicero, A.F.G.; Baggioni, A. Berberine and its role in chronic disease. Adv. Exp. Med. Biol., 2016, 928, 27-45.
[http://dx.doi.org/10.1007/978-3-319-41334-1_2] [PMID: 27671811]
[15]
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(6), 1281-1288.
[http://dx.doi.org/10.1194/jlr.M600020-JLR200] [PMID: 16508037]
[16]
Zimetti, F.; Adorni, M.P.; Ronda, N.; Gatti, R.; Bernini, F.; Favari, E. The natural compound berberine positively affects macrophage functions involved in atherogenesis. Nutr. Metab. Cardiovasc. Dis., 2015, 25(2), 195-201.
[http://dx.doi.org/10.1016/j.numecd.2014.08.004] [PMID: 25240689]
[17]
Agnarelli, A.; Natali, M.; Garcia-Gil, M.; Pesi, R.; Tozzi, M.G.; Ippolito, C.; Bernardini, N.; Vignali, R.; Batistoni, R.; Bianucci, A.M.; Marracci, S. Cell-specific pattern of berberine pleiotropic effects on different human cell lines. Sci. Rep., 2018, 8(1), 10599.
[http://dx.doi.org/10.1038/s41598-018-28952-3] [PMID: 30006630]
[18]
Chi, L.; Peng, L.; Pan, N.; Hu, X.; Zhang, Y. The anti-atherogenic effects of berberine on foam cell formation are mediated through the upregulation of sirtuin 1. Int. J. Mol. Med., 2014, 34(4), 1087-1093.
[http://dx.doi.org/10.3892/ijmm.2014.1868] [PMID: 25069720]
[19]
Zielińska, S.; Jezierska-Domaradzka, A.; Wójciak-Kosior, M.; Sowa, I.; Junka, A.; Matkowski, A.M. Greater Celandine’s Ups and Downs−21 Centuries of Medicinal Uses of Chelidonium majus from the viewpoint of today’s pharmacology. Front. Pharmacol., 2018, 9, 299.
[http://dx.doi.org/10.3389/fphar.2018.00299] [PMID: 29713277]
[20]
Poormazaheri, H.; Baghban Kohnerouz, B.; Khosravi Dehaghi, N.; Naghavi, M.; Kalantar, E.; Mohammadkhani, E.; Omidi, M. High-content analysis of chelidonine and berberine from Iranian Chelidonium majus L. ecotypes in different ontogenetical stages using various methods of extraction. J. Agric. Sci. Technol., 2017, 19(6), 1381-1391.
[21]
Zhang, Q.; Xiao, X.; Li, M.; Li, W.; Yu, M.; Zhang, H.; Ping, F.; Wang, Z.; Zheng, J. Berberine moderates glucose metabolism through the GnRH-GLP-1 and MAPK pathways in the intestine. BMC Complement. Altern. Med., 2014, 14(1), 188.
[http://dx.doi.org/10.1186/1472-6882-14-188] [PMID: 24912407]
[22]
Zhou, L.; Yang, Y.; Wang, X.; Liu, S.; Shang, W.; Yuan, G.; Li, F.; Tang, J.; Chen, M.; Chen, J. Berberine stimulates glucose transport through a mechanism distinct from insulin. Metabolism, 2007, 56(3), 405-412.
[http://dx.doi.org/10.1016/j.metabol.2006.10.025] [PMID: 17292731]
[23]
Zhang, B.; Pan, Y.; Xu, L.; Tang, D.; Dorfman, R.G.; Zhou, Q.; Yin, Y.; Li, Y.; Zhou, L.; Zhao, S.; Zou, X.; Wang, L.; Zhang, M. Berberine promotes glucose uptake and inhibits gluconeogenesis by inhibiting deacetylase SIRT3. Endocrine, 2018, 62(3), 576-587.
[http://dx.doi.org/10.1007/s12020-018-1689-y] [PMID: 30117113]
[24]
Gasmi, A.; Peana, M.; Arshad, M.; Butnariu, M.; Menzel, A.; Bjørklund, G. Krebs cycle: Activators, inhibitors and their roles in the modulation of carcinogenesis. Arch. Toxicol., 2021, 95(4), 1161-1178.
[http://dx.doi.org/10.1007/s00204-021-02974-9] [PMID: 33649975]
[25]
Shukla, S.; Sharma, A.; Pandey, V.K.; Raisuddin, S.; Kakkar, P. Concurrent acetylation of FoxO1/3a and p53 due to sirtuins inhibition elicit Bim/PUMA mediated mitochondrial dysfunction and apoptosis in berberine-treated HepG2 cells. Toxicol. Appl. Pharmacol., 2016, 291, 70-83.
[http://dx.doi.org/10.1016/j.taap.2015.12.006] [PMID: 26712469]
[26]
Liu, L.Z.; Cheung, S.C.K.; Lan, L.L.; Ho, S.K.S.; Xu, H.X.; Chan, J.C.N.; Tong, P.C.Y. Berberine modulates insulin signaling transduction in insulin-resistant cells. Mol. Cell. Endocrinol., 2010, 317(1-2), 148-153.
[http://dx.doi.org/10.1016/j.mce.2009.12.027] [PMID: 20036710]
[27]
Petersen, M.C.; Shulman, G.I. Mechanisms of insulin action and insulin resistance. Physiol. Rev., 2018, 98(4), 2133-2223.
[http://dx.doi.org/10.1152/physrev.00063.2017] [PMID: 30067154]
[28]
Kong, W.J.; Zhang, H.; Song, D.Q.; Xue, R.; Zhao, W.; Wei, J.; Wang, Y.M.; Shan, N.; Zhou, Z.X.; Yang, P.; You, X.F.; Li, Z.R.; Si, S.Y.; Zhao, L.X.; Pan, H.N.; Jiang, J.D. Berberine reduces insulin resistance through protein kinase C–dependent up-regulation of insulin receptor expression. Metabolism, 2009, 58(1), 109-119.
[http://dx.doi.org/10.1016/j.metabol.2008.08.013] [PMID: 19059538]
[29]
Xing, L.J.; Zhang, L.; Liu, T.; Hua, Y.Q.; Zheng, P.Y.; Ji, G. Berberine reducing insulin resistance by up-regulating IRS-2 mRNA expression in nonalcoholic fatty liver disease (NAFLD) rat liver. Eur. J. Pharmacol., 2011, 668(3), 467-471.
[http://dx.doi.org/10.1016/j.ejphar.2011.07.036] [PMID: 21839075]
[30]
Pirillo, A.; Catapano, A.L. Berberine, a plant alkaloid with lipid- and glucose-lowering properties: From in vitro evidence to clinical studies. Atherosclerosis, 2015, 243(2), 449-461.
[http://dx.doi.org/10.1016/j.atherosclerosis.2015.09.032] [PMID: 26520899]
[31]
Pilch, P.F.; Bergenhem, N. Pharmacological targeting of adipocytes/fat metabolism for treatment of obesity and diabetes. Mol. Pharmacol., 2006, 70(3), 779-785.
[http://dx.doi.org/10.1124/mol.106.026104] [PMID: 16760360]
[32]
Hu, Y.; Davies, G.E. Berberine inhibits adipogenesis in high-fat diet-induced obesity mice. Fitoterapia, 2010, 81(5), 358-366.
[http://dx.doi.org/10.1016/j.fitote.2009.10.010] [PMID: 19861153]
[33]
Giri, S.; Rattan, R.; Haq, E.; Khan, M.; Yasmin, R.; Won, J.; Key, L.; Singh, A.K.; Singh, I. AICAR inhibits adipocyte differentiation in 3T3L1 and restores metabolic alterations in diet-induced obesity mice model. Nutr. Metab. (Lond.), 2006, 3(1), 31.
[http://dx.doi.org/10.1186/1743-7075-3-31] [PMID: 16901342]
[34]
Pandey, M.K.; Sung, B.; Kunnumakkara, A.B.; Sethi, G.; Chaturvedi, M.M.; Aggarwal, B.B. Berberine modifies cysteine 179 of IkappaBalpha kinase, suppresses nuclear factor-kappaB-regulated antiapoptotic gene products, and potentiates apoptosis. Cancer Res., 2008, 68(13), 5370-5379.
[http://dx.doi.org/10.1158/0008-5472.CAN-08-0511] [PMID: 18593939]
[35]
Leng, S-H.; Lu, F-E.; Xu, L-J. Therapeutic effects of berberine in impaired glucose tolerance rats and its influence on insulin secretion. Acta Pharmacol. Sin., 2004, 25(4), 496-502.
[PMID: 15066220]
[36]
Kim, S.H.; Shin, E.J.; Kim, E.D.; Bayaraa, T.; Frost, S.C.; Hyun, C.K. Berberine activates GLUT1-mediated glucose uptake in 3T3-L1 adipocytes. Biol. Pharm. Bull., 2007, 30(11), 2120-2125.
[http://dx.doi.org/10.1248/bpb.30.2120] [PMID: 17978486]
[37]
Yi, P.; Lu, F-E.; Xu, L-J.; Chen, G.; Dong, H.; Wang, K-F. Berberine reverses free-fatty-acid-induced insulin resistance in 3T3-L1 adipocytes through targeting IKKβ. World J. Gastroenterol., 2008, 14(6), 876-883.
[http://dx.doi.org/10.3748/wjg.14.876] [PMID: 18240344]
[38]
Choi, B.H.; Ahn, I.S.; Kim, Y.H.; Park, J.W.; Lee, S.Y.; Hyun, C.K.; Do, M.S. Berberine reduces the expression of adipogenic enzymes and inflammatory molecules of 3T3-L1 adipocyte. Exp. Mol. Med., 2006, 38(6), 599-605.
[http://dx.doi.org/10.1038/emm.2006.71] [PMID: 17202835]
[39]
Kim, W.S.; Lee, Y.S.; Cha, S.H.; Jeong, H.W.; Choe, S.S.; Lee, M.R.; Oh, G.T.; Park, H.S.; Lee, K.U.; Lane, M.D.; Kim, J.B. Berberine improves lipid dysregulation in obesity by controlling central and peripheral AMPK activity. Am. J. Physiol. Endocrinol. Metab., 2009, 296(4), E812-E819.
[http://dx.doi.org/10.1152/ajpendo.90710.2008] [PMID: 19176354]
[40]
Takasawa, K.; Kubota, N.; Terauchi, Y.; Kadowaki, T. Impact of increased PPARgamma activity in adipocytes in vivo on adiposity, insulin sensitivity and the effects of rosiglitazone treatment. Endocr. J., 2008, 55(4), 767-776.
[http://dx.doi.org/10.1507/endocrj.K08E-018] [PMID: 18506083]
[41]
Tong, Q.; Dalgin, G.; Xu, H.; Ting, C.N.; Leiden, J.M.; Hotamisligil, G.S. Function of GATA transcription factors in preadipocyte-adipocyte transition. Science, 2000, 290(5489), 134-138.
[http://dx.doi.org/10.1126/science.290.5489.134] [PMID: 11021798]
[42]
Kulkarni, S.K.; Dhir, A. On the mechanism of antidepressant-like action of berberine chloride. Eur. J. Pharmacol., 2008, 589(1-3), 163-172.
[http://dx.doi.org/10.1016/j.ejphar.2008.05.043] [PMID: 18585703]
[43]
Zhang, Q.; Xiao, X.; Feng, K.; Wang, T.; Li, W.; Yuan, T.; Sun, X.; Sun, Q.; Xiang, H.; Wang, H. Berberine moderates glucose and lipid metabolism through multipathway mechanism. Evid. Based Complementary Altern. Med., 2010.
[44]
Bandyopadhyay, S.; Patra, P.H.; Mahanti, A.; Mondal, D.K.; Dandapat, P.; Bandyopadhyay, S.; Samanta, I.; Lodh, C.; Bera, A.K.; Bhattacharyya, D.; Sarkar, M.; Baruah, K.K. Potential antibacterial activity of berberine against multi drug resistant enterovirulent Escherichia coli isolated from yaks (Poephagus grunniens) with haemorrhagic diarrhoea. Asian Pac. J. Trop. Med., 2013, 6(4), 315-319.
[http://dx.doi.org/10.1016/S1995-7645(13)60063-2] [PMID: 23608335]
[45]
Čerňáková, M.; Košťálová, D. Antimicrobial activity of berberine—a constituent of Mahonia aquifolium. Folia Microbiol. (Praha), 2002, 47(4), 375-378.
[http://dx.doi.org/10.1007/BF02818693] [PMID: 12422513]
[46]
Singh, B.; Srivastava, J.S.; Khosa, R.L.; Singh, U.P. Individual and combined effects of berberine and santonin on spore germination of some fungi. Folia Microbiol. (Praha), 2001, 46(2), 137-142.
[http://dx.doi.org/10.1007/BF02873592] [PMID: 11501401]
[47]
Yu, H.H.; Kim, K.J.; Cha, J.D.; Kim, H.K.; Lee, Y.E.; Choi, N.Y.; You, Y.O. Antimicrobial activity of berberine alone and in combination with ampicillin or oxacillin against methicillin-resistant Staphylococcus aureus. J. Med. Food, 2005, 8(4), 454-461.
[http://dx.doi.org/10.1089/jmf.2005.8.454] [PMID: 16379555]
[48]
Bäckhed, F.; Ding, H.; Wang, T.; Hooper, L.V.; Koh, G.Y.; Nagy, A.; Semenkovich, C.F.; Gordon, J.I. The gut microbiota as an environmental factor that regulates fat storage. Proc. Natl. Acad. Sci. USA, 2004, 101(44), 15718-15723.
[http://dx.doi.org/10.1073/pnas.0407076101] [PMID: 15505215]
[49]
Tremaroli, V.; Bäckhed, F. Functional interactions between the gut microbiota and host metabolism. Nature, 2012, 489(7415), 242-249.
[http://dx.doi.org/10.1038/nature11552] [PMID: 22972297]
[50]
Larsen, N.; Vogensen, F.K.; van den Berg, F.W.J.; Nielsen, D.S.; Andreasen, A.S.; Pedersen, B.K.; Al-Soud, W.A.; Sørensen, S.J.; Hansen, L.H.; Jakobsen, M. Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults. PLoS One, 2010, 5(2), e9085.
[http://dx.doi.org/10.1371/journal.pone.0009085] [PMID: 20140211]
[51]
Koeth, R.A.; Wang, Z.; Levison, B.S.; Buffa, J.A.; Org, E.; Sheehy, B.T.; Britt, E.B.; Fu, X.; Wu, Y.; Li, L.; Smith, J.D.; DiDonato, J.A.; Chen, J.; Li, H.; Wu, G.D.; Lewis, J.D.; Warrier, M.; Brown, J.M.; Krauss, R.M.; Tang, W.H.W.; Bushman, F.D.; Lusis, A.J.; Hazen, S.L. Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat. Med., 2013, 19(5), 576-585.
[http://dx.doi.org/10.1038/nm.3145] [PMID: 23563705]
[52]
Domadia, P.N.; Bhunia, A.; Sivaraman, J.; Swarup, S.; Dasgupta, D. Berberine targets assembly of Escherichia coli cell division protein FtsZ. Biochemistry, 2008, 47(10), 3225-3234.
[http://dx.doi.org/10.1021/bi7018546] [PMID: 18275156]
[53]
Sun, D.; Courtney, H.S.; Beachey, E.H. Berberine sulfate blocks adherence of Streptococcus pyogenes to epithelial cells, fibronectin, and hexadecane. Antimicrob. Agents Chemother., 1988, 32(9), 1370-1374.
[http://dx.doi.org/10.1128/AAC.32.9.1370] [PMID: 3058020]
[54]
Sack, R.B.; Froehlich, J.L. Berberine inhibits intestinal secretory response of Vibrio cholerae and Escherichia coli enterotoxins. Infect. Immun., 1982, 35(2), 471-475.
[http://dx.doi.org/10.1128/iai.35.2.471-475.1982] [PMID: 7035365]
[55]
Wu, L.T.; Tsou, M.F.; Ho, C.C.; Chuang, J.Y.; Kuo, H.M.; Chung, J.G. Berberine inhibits arylamine N-acetyltransferase activity and gene expression in Salmonella typhi. Curr. Microbiol., 2005, 51(4), 255-261.
[http://dx.doi.org/10.1007/s00284-005-4569-7] [PMID: 16086103]
[56]
Zhang, X.; Zhao, Y.; Xu, J.; Xue, Z.; Zhang, M.; Pang, X.; Zhang, X.; Zhao, L. Modulation of gut microbiota by berberine and metformin during the treatment of high-fat diet-induced obesity in rats. Sci. Rep., 2015, 5(1), 14405.
[http://dx.doi.org/10.1038/srep14405] [PMID: 26396057]
[57]
Zhang, X.; Zhao, Y.; Zhang, M.; Pang, X.; Xu, J.; Kang, C.; Li, M.; Zhang, C.; Zhang, Z.; Zhang, Y.; Li, X.; Ning, G.; Zhao, L. Structural changes of gut microbiota during berberine-mediated prevention of obesity and insulin resistance in high-fat diet-fed rats. PLoS One, 2012, 7(8), e42529.
[http://dx.doi.org/10.1371/journal.pone.0042529] [PMID: 22880019]
[58]
Dao, M.C.; Everard, A.; Aron-Wisnewsky, J.; Sokolovska, N.; Prifti, E.; Verger, E.O.; Kayser, B.D.; Levenez, F.; Chilloux, J.; Hoyles, L.; Dumas, M.E.; Rizkalla, S.W.; Doré, J.; Cani, P.D.; Clément, K. Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology. Gut, 2016, 65(3), 426-436.
[http://dx.doi.org/10.1136/gutjnl-2014-308778] [PMID: 26100928]
[59]
Zhang, C.; Zhang, M.; Wang, S.; Han, R.; Cao, Y.; Hua, W.; Mao, Y.; Zhang, X.; Pang, X.; Wei, C.; Zhao, G.; Chen, Y.; Zhao, L. Interactions between gut microbiota, host genetics and diet relevant to development of metabolic syndromes in mice. ISME J., 2010, 4(2), 232-241.
[http://dx.doi.org/10.1038/ismej.2009.112] [PMID: 19865183]
[60]
Tilg, H.; Kaser, A. Gut microbiome, obesity, and metabolic dysfunction. J. Clin. Invest., 2011, 121(6), 2126-2132.
[http://dx.doi.org/10.1172/JCI58109] [PMID: 21633181]
[61]
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.; He, W.Y.; Wang, Y.; Jiang, J.D. Excretion of berberine and its metabolites in oral administration in rats. J. Pharm. Sci., 2013, 102(11), 4181-4192.
[http://dx.doi.org/10.1002/jps.23718] [PMID: 24006193]
[62]
Wang, Y.; Shou, J.; Jiang, J. Metabolism of Chinese materia medica in gut microbiota and its biological effects. Chin. Herb. Med., 2015, 7(2), 109-115.
[http://dx.doi.org/10.1016/S1674-6384(15)60027-2]
[63]
Chen, W.; Miao, Y.Q.; Fan, D.J.; Yang, S.S.; Lin, X.; Meng, L.K.; Tang, X. Bioavailability study of berberine and the enhancing effects of TPGS on intestinal absorption in rats. AAPS PharmSciTech, 2011, 12(2), 705-711.
[http://dx.doi.org/10.1208/s12249-011-9632-z] [PMID: 21637946]
[64]
Kong, W.; Wei, J.; Abidi, P.; Lin, M.; Inaba, S.; Li, C.; Wang, Y.; Wang, Z.; Si, S.; Pan, H.; Wang, S.; Wu, J.; Wang, Y.; Li, Z.; Liu, J.; Jiang, J.D. Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins. Nat. Med., 2004, 10(12), 1344-1351.
[http://dx.doi.org/10.1038/nm1135] [PMID: 15531889]
[65]
Zhang, C.; Li, S.; Yang, L.; Huang, P.; Li, W.; Wang, S.; Zhao, G.; Zhang, M.; Pang, X.; Yan, Z.; Liu, Y.; Zhao, L. Structural modulation of gut microbiota in life-long calorie-restricted mice. Nat. Commun., 2013, 4(1), 2163.
[http://dx.doi.org/10.1038/ncomms3163] [PMID: 23860099]
[66]
Hunt, K.J.; Hung, S.K.; Ernst, E. Botanical extracts as anti-aging preparations for the skin: A systematic review. Drugs Aging, 2010, 27(12), 973-985.
[http://dx.doi.org/10.2165/11584420-000000000-00000] [PMID: 21087067]
[67]
Gasmi, A.; Chirumbolo, S.; Peana, M.; Mujawdiya, P.K.; Dadar, M.; Menzel, A.; Bjørklund, G. Biomarkers of senescence during aging as possible warnings to use preventive measures. Curr. Med. Chem., 2021, 28(8), 1471-1488.
[http://dx.doi.org/10.2174/0929867327999200917150652] [PMID: 32942969]
[68]
Yu, Y.; Zhao, Y.; Teng, F.; Li, J.; Guan, Y.; Xu, J.; Lv, X.; Guan, F.; Zhang, M.; Chen, L. Berberine improves cognitive deficiency and muscular dysfunction via activation of the AMPK/SIRT1/PGC-1a pathway in skeletal muscle from naturally aging rats. J. Nutr. Health Aging, 2018, 22(6), 710-717.
[http://dx.doi.org/10.1007/s12603-018-1015-7] [PMID: 29806860]
[69]
Nair, K.S. Aging muscle. Am. J. Clin. Nutr., 2005, 81(5), 953-963.
[http://dx.doi.org/10.1093/ajcn/81.5.953] [PMID: 15883415]
[70]
Short, K.R.; Vittone, J.L.; Bigelow, M.L.; Proctor, D.N.; Nair, K.S. Age and aerobic exercise training effects on whole body and muscle protein metabolism. Am. J. Physiol. Endocrinol. Metab., 2004, 286(1), E92-E101.
[http://dx.doi.org/10.1152/ajpendo.00366.2003] [PMID: 14506079]
[71]
Short, K.R.; Vittone, J.L.; Bigelow, M.L.; Proctor, D.N.; Rizza, R.A.; Coenen-Schimke, J.M.; Nair, K.S. Impact of aerobic exercise training on age-related changes in insulin sensitivity and muscle oxidative capacity. Diabetes, 2003, 52(8), 1888-1896.
[http://dx.doi.org/10.2337/diabetes.52.8.1888] [PMID: 12882902]
[72]
Yarasheski, K.E.; Welle, S.; Nair, K.S. Muscle protein synthesis in younger and older men. JAMA, 2002, 287(3), 317-318.
[http://dx.doi.org/10.1001/jama.287.3.317] [PMID: 11790208]
[73]
Chistiakov, D.A.; Sobenin, I.A.; Revin, V.V.; Orekhov, A.N.; Bobryshev, Y.V. Mitochondrial aging and age-related dysfunction of mitochondria. Biomed Res. Int., 2014.
[http://dx.doi.org/10.1155/2014/238463]
[74]
Chirumbolo, S.; Bjørklund, G.; Lysiuk, R.; Vella, A.; Lenchyk, L.; Upyr, T. Targeting cancer with phytochemicals via their fine tuning of the cell survival signaling pathways. Int. J. Mol. Sci., 2018, 19(11), 3568.
[http://dx.doi.org/10.3390/ijms19113568] [PMID: 30424557]
[75]
Wei, Y-H.; Wu, S-B.; Ma, Y-S.; Lee, H-C. Respiratory function decline and DNA mutation in mitochondria, oxidative stress and altered gene expression during aging. Chang Gung Med. J., 2009, 32(2), 113-132.
[PMID: 19403001]
[76]
Hirota, Y.; Kang, D.; Kanki, T. The physiological role of mitophagy: new insights into phosphorylation events. Int. J. Cell Biol., 2012.
[http://dx.doi.org/10.1155/2012/354914]
[77]
Zhao, J.; Brault, J.J.; Schild, A.; Cao, P.; Sandri, M.; Schiaffino, S.; Lecker, S.H.; Goldberg, A.L. FoxO3 coordinately activates protein degradation by the autophagic/lysosomal and proteasomal pathways in atrophying muscle cells. Cell Metab., 2007, 6(6), 472-483.
[http://dx.doi.org/10.1016/j.cmet.2007.11.004] [PMID: 18054316]
[78]
Lee, H-C.; Wei, Y-H. Mitochondria and aging. Adv Exp Med Biol, 2012, 942, 311-327.
[79]
Larsson, N.G. Somatic mitochondrial DNA mutations in mammalian aging. Annu. Rev. Biochem., 2010, 79(1), 683-706.
[http://dx.doi.org/10.1146/annurev-biochem-060408-093701] [PMID: 20350166]
[80]
Onyango, I.G.; Dennis, J.; Khan, S.M. Mitochondrial dysfunction in Alzheimer’s disease and the rationale for bioenergetics based therapies. Aging Dis., 2016, 7(2), 201-214.
[http://dx.doi.org/10.14336/AD.2015.1007] [PMID: 27114851]
[81]
Tower, J. Programmed cell death in aging. Ageing Res. Rev., 2015, 23(Pt A), 90-100.
[http://dx.doi.org/10.1016/j.arr.2015.04.002] [PMID: 25862945]
[82]
Bjørklund, G.; Dadar, M.; Martins, N.; Chirumbolo, S.; Goh, B.H.; Smetanina, K.; Lysiuk, R. Brief challenges on medicinal plants: An eye-opening look at ageing-related disorders. Basic Clin. Pharmacol. Toxicol., 2018, 122(6), 539-558.
[http://dx.doi.org/10.1111/bcpt.12972] [PMID: 29369521]
[83]
McCubrey, J.A.; Lertpiriyapong, K.; Steelman, L.S.; Abrams, S.L.; Yang, L.V.; Murata, R.M.; Rosalen, P.L.; Scalisi, A.; Neri, L.M.; Cocco, L.; Ratti, S.; Martelli, A.M.; Laidler, P.; Dulińska-Litewka, J.; Rakus, D.; Gizak, A.; Lombardi, P.; Nicoletti, F.; Candido, S.; Libra, M.; Montalto, G.; Cervello, M. Effects of resveratrol, curcumin, berberine and other nutraceuticals on aging, cancer development, cancer stem cells and microRNAs. Aging (Albany NY), 2017, 9(6), 1477-1536.
[http://dx.doi.org/10.18632/aging.101250] [PMID: 28611316]
[84]
Ding, A.J.; Zheng, S.Q.; Huang, X.B.; Xing, T.K.; Wu, G.S.; Sun, H.Y.; Qi, S.H.; Luo, H.R. Current perspective in the discovery of anti-aging agents from natural products. Nat. Prod. Bioprospect., 2017, 7(5), 335-404.
[http://dx.doi.org/10.1007/s13659-017-0135-9] [PMID: 28567542]
[85]
Dang, Y.; An, Y.; He, J.; Huang, B.; Zhu, J.; Gao, M.; Zhang, S.; Wang, X.; Yang, B.; Xie, Z. Berberine ameliorates cellular senescence and extends the lifespan of mice via regulating p16 and cyclin protein expression. Aging Cell, 2020, 19(1), e13060.
[http://dx.doi.org/10.1111/acel.13060] [PMID: 31773901]
[86]
Hayflick, L. The limited in vitro lifetime of human diploid cell strains. Exp. Cell Res., 1965, 37(3), 614-636.
[http://dx.doi.org/10.1016/0014-4827(65)90211-9] [PMID: 14315085]
[87]
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] [PMID: 26610159]
[88]
Wang, K.; Feng, X.; Chai, L.; Cao, S.; Qiu, F. The metabolism of berberine and its contribution to the pharmacological effects. Drug Metab. Rev., 2017, 49(2), 139-157.
[http://dx.doi.org/10.1080/03602532.2017.1306544] [PMID: 28290706]
[89]
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.
[http://dx.doi.org/10.1016/j.fitote.2016.02.001] [PMID: 26851175]
[90]
Sefidabi, R.; Mortazavi, P.; Hosseini, S. Antiproliferative effect of berberine on canine mammary gland cancer cell culture. Biomed. Rep., 2017, 6(1), 95-98.
[http://dx.doi.org/10.3892/br.2016.809] [PMID: 28123715]
[91]
Zhao, H.; Halicka, H.D.; Li, J.; Darzynkiewicz, Z. Berberine suppresses gero-conversion from cell cycle arrest to senescence. Aging (Albany NY), 2013, 5(8), 623-636.
[http://dx.doi.org/10.18632/aging.100593] [PMID: 23974852]
[92]
Cicero, A.F.G.; Tartagni, E. Antidiabetic properties of berberine: from cellular pharmacology to clinical effects. Hosp. Pract., 2012, 40(2), 56-63.
[http://dx.doi.org/10.3810/hp.2012.04.970] [PMID: 22615079]
[93]
Zhou, Y.; He, P.; Liu, A.; Zhang, L.; Liu, Y.; Dai, R. Drug-drug interactions between ketoconazole and berberine in rats: pharmacokinetic effects benefit pharmacodynamic synergism. Phytother. Res., 2012, 26(5), 772-777.
[http://dx.doi.org/10.1002/ptr.3621] [PMID: 22114028]
[94]
Zhou, H.; Mineshita, S. The effect of berberine chloride on experimental colitis in rats in vivo and in vitro. J. Pharmacol. Exp. Ther., 2000, 294(3), 822-829.
[PMID: 10945829]
[95]
Wang, Y.; Liu, Q.; Liu, Z.; Li, B.; Sun, Z.; Zhou, H.; Zhang, X.; Gong, Y.; Shao, C. Berberine, a genotoxic alkaloid, induces ATM-Chk1 mediated G2 arrest in prostate cancer cells. Mutat. Res., 2012, 734(1-2), 20-29.
[http://dx.doi.org/10.1016/j.mrfmmm.2012.04.005] [PMID: 22561209]
[96]
Maiti, M.; Kumar, G.S. Polymorphic nucleic acid binding of bioactive isoquinoline alkaloids and their role in cancer. J. Nucleic Acids, 2010.
[http://dx.doi.org/10.4061/2010/593408]
[97]
Xu, N.; Yang, H.; Cui, M.; Song, F.; Liu, Z.; Liu, S. Evaluation of alkaloids binding to the parallel quadruplex structure [d(TGGGGT)]4 by electrospray ionization mass spectrometry. J. Mass Spectrom., 2012, 47(6), 694-700.
[http://dx.doi.org/10.1002/jms.2997] [PMID: 22707161]
[98]
Qin, Y.; Pang, J.Y.; Chen, W.H.; Zhao, Z.Z.; Liu, L.; Jiang, Z.H. Inhibition of DNA topoisomerase I by natural and synthetic mono- and dimeric protoberberine alkaloids. Chem. Biodivers., 2007, 4(3), 481-487.
[http://dx.doi.org/10.1002/cbdv.200790040] [PMID: 17372950]
[99]
Gatto, B.; Sanders, M.M.; Yu, C.; Wu, H-Y.; Makhey, D.; LaVoie, E.J.; Liu, L.F. Identification of topoisomerase I as the cytotoxic target of the protoberberine alkaloid coralyne. Cancer Res., 1996, 56(12), 2795-2800.
[PMID: 8665516]
[100]
Bhowmik, D.; Das, S.; Hossain, M.; Haq, L.; Suresh Kumar, G. Biophysical characterization of the strong stabilization of the RNA triplex poly(U)•poly(A)*poly(U) by 9-O-(ω-amino) alkyl ether berberine analogs. PLoS One, 2012, 7(5), e37939.
[http://dx.doi.org/10.1371/journal.pone.0037939] [PMID: 22666416]
[101]
Xiao, N.; Chen, S.; Ma, Y.; Qiu, J.; Tan, J.H.; Ou, T.M.; Gu, L.Q.; Huang, Z.S.; Li, D. Interaction of Berberine derivative with protein POT1 affect telomere function in cancer cells. Biochem. Biophys. Res. Commun., 2012, 419(3), 567-572.
[http://dx.doi.org/10.1016/j.bbrc.2012.02.063] [PMID: 22369941]
[102]
Wang, Y.; Kheir, M.M.; Chai, Y.; Hu, J.; Xing, D.; Lei, F.; Du, L. Comprehensive study in the inhibitory effect of berberine on gene transcription, including TATA box. PLoS One, 2011, 6(8), e23495.
[http://dx.doi.org/10.1371/journal.pone.0023495] [PMID: 21887260]
[103]
Novikova, D.S.; Garabadzhiu, A.V.; Melino, G.; Barlev, N.A.; Tribulovich, V.G. AMP-activated protein kinase: Structure, function, and role in pathological processes. Biochemistry (Mosc.), 2015, 80(2), 127-144.
[http://dx.doi.org/10.1134/S0006297915020017] [PMID: 25756529]
[104]
Ming, M.; Sinnett-Smith, J.; Wang, J.; Soares, H.P.; Young, S.H.; Eibl, G.; Rozengurt, E. Dose-dependent AMPK-dependent and independent mechanisms of berberine and metformin inhibition of mTORC1, ERK, DNA synthesis and proliferation in pancreatic cancer cells. PLoS One, 2014, 9(12), e114573.
[http://dx.doi.org/10.1371/journal.pone.0114573] [PMID: 25493642]
[105]
Rozengurt, E.; Soares, H.P.; Sinnet-Smith, J. Suppression of feedback loops mediated by PI3K/mTOR induces multiple overactivation of compensatory pathways: An unintended consequence leading to drug resistance. Mol. Cancer Ther., 2014, 13(11), 2477-2488.
[http://dx.doi.org/10.1158/1535-7163.MCT-14-0330] [PMID: 25323681]
[106]
Turner, N.; Li, J.Y.; Gosby, A.; To, S.W.C.; Cheng, Z.; Miyoshi, H.; Taketo, M.M.; Cooney, G.J.; Kraegen, E.W.; James, D.E.; Hu, L.H.; Li, J.; Ye, J.M. Berberine and its more biologically available derivative, dihydroberberine, inhibit mitochondrial respiratory complex I: A mechanism for the action of berberine to activate AMP-activated protein kinase and improve insulin action. Diabetes, 2008, 57(5), 1414-1418.
[http://dx.doi.org/10.2337/db07-1552] [PMID: 18285556]
[107]
Ren, G.; Guo, J.H.; Qian, Y.Z.; Kong, W.J.; Jiang, J.D. Berberine improves glucose and lipid metabolism in HepG2 cells through AMPKα1 activation. Front. Pharmacol., 2020, 11, 647.
[http://dx.doi.org/10.3389/fphar.2020.00647] [PMID: 32457629]
[108]
Kumar, A.; Ekavali; Chopra, K.; Mukherjee, M.; Pottabathini, R.; Dhull, D.K. Current knowledge and pharmacological profile of berberine: An update. Eur. J. Pharmacol., 2015, 761, 288-297.
[http://dx.doi.org/10.1016/j.ejphar.2015.05.068] [PMID: 26092760]
[109]
Yao, J.; Kong, W.; Jiang, J. Learning from berberine: Treating chronic diseases through multiple targets. Sci. China Life Sci., 2015, 58(9), 854-859.
[http://dx.doi.org/10.1007/s11427-013-4568-z] [PMID: 24174332]
[110]
Wang, C.; Jiang, J.-D.; Wu, W.; Kong, W.-J. The compound of mangiferin-berberine salt has potent activities in modulating lipid and glucose metabolisms in HepG2 cells. Biomed Res. Int., 2016.
[http://dx.doi.org/10.1155/2016/8753436]
[111]
Mukhamedyarov, M.; Martinov, A.; Petukhova, E.; Grigoryev, P.; Eshpay, R.; Rizvanov, A.; Zefirov, A. Peripheric dysfunction as one of the mechanisms of pathogenesis of neurodegenerative disesases. Genes Cells, 2015, 10(4), 8-14.
[112]
Skovronsky, D.M.; Lee, V.M.Y.; Trojanowski, J.Q. Neurodegenerative diseases: new concepts of pathogenesis and their therapeutic implications. Annu. Rev. Pathol., 2006, 1(1), 151-170.
[http://dx.doi.org/10.1146/annurev.pathol.1.110304.100113] [PMID: 18039111]
[113]
Kysenius, K.; Huttunen, H.J. Stress-induced upregulation of VLDL receptor alters Wnt-signaling in neurons. Exp. Cell Res., 2016, 340(2), 238-247.
[http://dx.doi.org/10.1016/j.yexcr.2016.01.001] [PMID: 26751967]
[114]
Kim; Cho, K.H.; Shin, M.S.; Lee, J.M.; Cho, H.S.; Kim, C.J.; Shin, D.H.; Yang, H.J. Berberine prevents nigrostriatal dopaminergic neuronal loss and suppresses hippocampal apoptosis in mice with Parkinson’s disease. Int. J. Mol. Med., 2014, 33(4), 870-878.
[http://dx.doi.org/10.3892/ijmm.2014.1656] [PMID: 24535622]
[115]
Jiang, W.; Wei, W.; Gaertig, M.A.; Li, S.; Li, X.J. Therapeutic effect of berberine on Huntington’s disease transgenic mouse model. PLoS One, 2015, 10(7), e0134142.
[http://dx.doi.org/10.1371/journal.pone.0134142] [PMID: 26225560]
[116]
Ahmed, T.; Gilani, A.H.; Abdollahi, M.; Daglia, M.; Nabavi, S.F.; Nabavi, S.M. Berberine and neurodegeneration: A review of literature. Pharmacol. Rep., 2015, 67(5), 970-979.
[http://dx.doi.org/10.1016/j.pharep.2015.03.002] [PMID: 26398393]
[117]
Zhang, J.; Yang, J-Q.; He, B-C.; Zhou, Q-X.; Yu, H-R.; Tang, Y.; Liu, B-Z. Berberine and total base from rhizoma coptis chinensis attenuate brain injury in an aluminum-induced rat model of neurodegenerative disease. Saudi Med. J., 2009, 30(6), 760-766.
[PMID: 19526156]
[118]
Cai, Z.; Wang, C.; Yang, W. Role of berberine in Alzheimer’s disease. Neuropsychiatr. Dis. Treat., 2016, 12, 2509-2520.
[http://dx.doi.org/10.2147/NDT.S114846] [PMID: 27757035]
[119]
Zou, H.; Long, J.; Zhang, Q.; Zhao, H.; Bian, B.; Wang, Y.; Zhang, J.; Zhao, H.; Wang, L. Induced cortical neurogenesis after focal cerebral ischemia – Three active components from Huang-Lian-Jie-Du Decoction. J. Ethnopharmacol., 2016, 178, 115-124.
[http://dx.doi.org/10.1016/j.jep.2015.12.001] [PMID: 26657578]
[120]
Selivanova, A.; Winblad, B.; Dantuma, N.P.; Farmery, M.R. Biogenesis and processing of the amyloid precursor protein in the early secretory pathway. Biochem. Biophys. Res. Commun., 2007, 357(4), 1034-1039.
[http://dx.doi.org/10.1016/j.bbrc.2007.04.062] [PMID: 17466275]
[121]
Beel, A.J.; Sakakura, M.; Barrett, P.J.; Sanders, C.R. Direct binding of cholesterol to the amyloid precursor protein: An important interaction in lipid–Alzheimer’s disease relationships? Biochim. Biophys. Acta Mol. Cell Biol. Lipids, 2010, 1801(8), 975-982.
[http://dx.doi.org/10.1016/j.bbalip.2010.03.008] [PMID: 20304095]
[122]
Ji, H.F.; Shen, L. Berberine: A potential multipotent natural product to combat Alzheimer’s disease. Molecules, 2011, 16(8), 6732-6740.
[http://dx.doi.org/10.3390/molecules16086732] [PMID: 21829148]
[123]
Haghani, M.; Shabani, M.; Tondar, M. The therapeutic potential of berberine against the altered intrinsic properties of the CA1 neurons induced by Aβ neurotoxicity. Eur. J. Pharmacol., 2015, 758, 82-88.
[http://dx.doi.org/10.1016/j.ejphar.2015.03.016] [PMID: 25861937]
[124]
Durairajan, S.S.K.; Liu, L.F.; Lu, J.H.; Chen, L.L.; Yuan, Q.; Chung, S.K.; Huang, L.; Li, X.S.; Huang, J.D.; Li, M. Berberine ameliorates β-amyloid pathology, gliosis, and cognitive impairment in an Alzheimer’s disease transgenic mouse model. Neurobiol. Aging, 2012, 33(12), 2903-2919.
[http://dx.doi.org/10.1016/j.neurobiolaging.2012.02.016] [PMID: 22459600]
[125]
Bjørklund, G.; Dadar, M.; Chirumbolo, S.; Lysiuk, R. Flavonoids as detoxifying and pro-survival agents: What’s new? Food Chem. Toxicol., 2017, 110, 240-250.
[http://dx.doi.org/10.1016/j.fct.2017.10.039] [PMID: 29079495]
[126]
Huang, M.; Chen, S.; Liang, Y.; Guo, Y. The role of berberine in the multi-target treatment of senile dementia. Curr. Top. Med. Chem., 2015, 16(8), 867-873.
[http://dx.doi.org/10.2174/1568026615666150827095433] [PMID: 26311424]
[127]
Zhang, Q.; Qian, Z.; Pan, L.; Li, H.; Zhu, H. Hypoxia-inducible factor 1 mediates the anti-apoptosis of berberine in neurons during hypoxia/ischemia. Acta Physiol. Hung., 2012, 99(3), 311-323.
[http://dx.doi.org/10.1556/APhysiol.99.2012.3.8] [PMID: 22982719]
[128]
Pozza, C.; Isidori, A.M. Imaging in bariatric surgery; Springer, 2018, pp. 1-8.
[http://dx.doi.org/10.1007/978-3-319-49299-5_1]
[129]
Zhang, W.L.; Zhu, L.; Jiang, J.G. Active ingredients from natural botanicals in the treatment of obesity. Obes. Rev., 2014, 15(12), 957-967.
[http://dx.doi.org/10.1111/obr.12228] [PMID: 25417736]
[130]
Chow, Y.L.; Sogame, M.; Sato, F. 13-Methylberberine, a berberine analogue with stronger anti-adipogenic effects on mouse 3T3-L1 cells. Sci. Rep., 2016, 6(1), 38129.
[http://dx.doi.org/10.1038/srep38129] [PMID: 27917887]
[131]
Lau, C.W.; Yao, X.Q.; Chen, Z.Y.; Ko, W.H.; Huang, Y. Cardiovascular actions of berberine. Cardiovasc. Drug Rev., 2001, 19(3), 234-244.
[http://dx.doi.org/10.1111/j.1527-3466.2001.tb00068.x] [PMID: 11607041]
[132]
Ellis, C. In keeping with tradition. Nat. Rev. Drug Discov., 2005, 4(1), 15-15.
[http://dx.doi.org/10.1038/nrd1618]
[133]
Piyanuch, R.; Sukhthankar, M.; Wandee, G.; Baek, S.J. Berberine, a natural isoquinoline alkaloid, induces NAG-1 and ATF3 expression in human colorectal cancer cells. Cancer Lett., 2007, 258(2), 230-240.
[http://dx.doi.org/10.1016/j.canlet.2007.09.007] [PMID: 17964072]
[134]
Holy, E.W.; Akhmedov, A.; Lüscher, T.F.; Tanner, F.C. Berberine, a natural lipid-lowering drug, exerts prothrombotic effects on vascular cells. J. Mol. Cell. Cardiol., 2009, 46(2), 234-240.
[http://dx.doi.org/10.1016/j.yjmcc.2008.10.011] [PMID: 19014947]
[135]
Pan, G.; Wang, G.J.; Liu, X.D.; Fawcett, J.P.; Xie, Y.Y. The involvement of P-glycoprotein in berberine absorption. Pharmacol. Toxicol., 2002, 91(4), 193-197.
[http://dx.doi.org/10.1034/j.1600-0773.2002.t01-1-910403.x] [PMID: 12530470]
[136]
Endicott, J.A.; Ling, V. The biochemistry of P-glycoprotein-mediated multidrug resistance. Annu. Rev. Biochem., 1989, 58(1), 137-171.
[http://dx.doi.org/10.1146/annurev.bi.58.070189.001033] [PMID: 2570548]
[137]
Simon, S.M.; Schindler, M. Cell biological mechanisms of multidrug resistance in tumors. Proc. Natl. Acad. Sci. USA, 1994, 91(9), 3497-3504.
[http://dx.doi.org/10.1073/pnas.91.9.3497] [PMID: 7909602]
[138]
Leu, B.L.; Huang, J. Inhibition of intestinal P-glycoprotein and effects on etoposide absorption. Cancer Chemother. Pharmacol., 1995, 35(5), 432-436.
[http://dx.doi.org/10.1007/s002800050258] [PMID: 7850926]
[139]
Su, S-F.; Huang, J-D. Inhibition of the intestinal digoxin absorption and exsorption by quinidine. Drug Metab. Dispos., 1996, 24(2), 142-147.
[PMID: 8742224]
[140]
Yin, J.; Ye, J.; Jia, W. Effects and mechanisms of berberine in diabetes treatment. Acta Pharm. Sin. B, 2012, 2(4), 327-334.
[http://dx.doi.org/10.1016/j.apsb.2012.06.003]
[141]
Iizuka, N.; Miyamoto, K.; Okita, K.; Tangoku, A.; Hayashi, H.; Yosino, S.; Abe, T.; Morioka, T.; Hazama, S.; Oka, M. Inhibitory effect of Coptidis rhizoma and berberine on the proliferation of human esophageal cancer cell lines. Cancer Lett., 2000, 148(1), 19-25.
[http://dx.doi.org/10.1016/S0304-3835(99)00264-5] [PMID: 10680588]
[142]
Wang, Y.X.; Yao, X.J.; Tan, Y.H. Effects of berberine on delayed afterdepolarizations in ventricular muscles in vitro and in vivo. J. Cardiovasc. Pharmacol., 1994, 23(5), 716-722.
[http://dx.doi.org/10.1097/00005344-199405000-00005] [PMID: 7521453]
[143]
Chang, K.S.S.; Gao, C.; Wang, L-C. Berberine-induced morphologic differentiation and down-regulation of c-Ki-ras2 protooncogene expression in human teratocarcinoma cells. Cancer Lett., 1990, 55(2), 103-108.
[http://dx.doi.org/10.1016/0304-3835(90)90018-S] [PMID: 2265407]
[144]
Li, Y.; Ren, G.; Wang, Y.X.; Kong, W.J.; Yang, P.; Wang, Y.M.; Li, Y.H.; Yi, H.; Li, Z.R.; Song, D.Q.; Jiang, J.D. Bioactivities of berberine metabolites after transformation through CYP450 isoenzymes. J. Transl. Med., 2011, 9(1), 62.
[http://dx.doi.org/10.1186/1479-5876-9-62] [PMID: 21569619]
[145]
Qiu, F.; Zhu, Z.; Kang, N.; Piao, S.; Qin, G.; Yao, X. Isolation and identification of urinary metabolites of berberine in rats and humans. Drug Metab. Dispos., 2008, 36(11), 2159-2165.
[http://dx.doi.org/10.1124/dmd.108.021659] [PMID: 18703644]
[146]
Tsai, P.L.; Tsai, T.H. Hepatobiliary excretion of berberine. Drug Metab. Dispos., 2004, 32(4), 405-412.
[http://dx.doi.org/10.1124/dmd.32.4.405] [PMID: 15039293]
[147]
Yang, Y.; Kang, N.; Xia, H.; Li, J.; Chen, L.; Qiu, F. Metabolites of protoberberine alkaloids in human urine following oral administration of Coptidis rhizoma decoction. Planta Med., 2010, 76(16), 1859-1863.
[http://dx.doi.org/10.1055/s-0030-1250053] [PMID: 20549593]
[148]
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., 2006, 34(12), 2064-2072.
[http://dx.doi.org/10.1124/dmd.106.011361] [PMID: 16956957]
[149]
Li, Z.; Wei, Y.; Chu, T. Radioiodination, biodistribution and pharmacokinetics of berberine in mice. J. Radioanal. Nucl. Chem., 2005, 265(3), 355-359.
[http://dx.doi.org/10.1007/s10967-005-0832-4]
[150]
Ho, J.; KC; Leung, A.; Rabi, D. Hypoglycemic agents in the management of type 2 diabetes mellitus. , 1872-2148.2011
[151]
Shan, Y.Q.; Ren, G.; Wang, Y.X.; Pang, J.; Zhao, Z.Y.; Yao, J.; You, X.F.; Si, S.Y.; Song, D.Q.; Kong, W.J.; Jiang, J.D. Berberine analogue IMB-Y53 improves glucose-lowering efficacy by averting cellular efflux especially P-glycoprotein efflux. Metabolism, 2013, 62(3), 446-456.
[http://dx.doi.org/10.1016/j.metabol.2012.09.009] [PMID: 23079743]
[152]
Di Pierro, F.; Putignano, P.; Montesi, L.; Moscatiello, S.; Marchesini Reggiani, G.; Villanova, N. Preliminary study about the possible glycemic clinical advantage in using a fixed combination of Berberis aristata and Silybum marianum standardized extracts versus only Berberis aristata in patients with type 2 diabetes. Clin. Pharmacol., 2013, 5, 167-174.
[http://dx.doi.org/10.2147/CPAA.S54308] [PMID: 24277991]
[153]
Gu, M.; Xu, J.; Han, C.; Kang, Y.; Liu, T.; He, Y.; Huang, Y.; Liu, C. Effects of berberine on cell cycle, DNA, reactive oxygen species, and apoptosis in L929 murine fibroblast cells. Evid. Based Complement. Alternat. Med., 2015, 2015, 1-13.
[http://dx.doi.org/10.1155/2015/796306] [PMID: 26508985]
[154]
Rad, S.Z.K.; Rameshrad, M.; Hosseinzadeh, H. Toxicology effects of Berberis vulgaris (barberry) and its active constituent, berberine: A review. Iran. J. Basic Med. Sci., 2017, 20(5), 516-529.
[PMID: 28656087]
[155]
Marin - NETO, J.A.; Maciel, B.C.; Secches, A.L.; Gallo, L. Cardiovascular effects of berberine in patients with severe congestive heart failure. Clin. Cardiol., 1988, 11(4), 253-260.
[http://dx.doi.org/10.1002/clc.4960110411] [PMID: 3365876]
[156]
Fang, S.; Guo, S.; Du, S.; Cao, Z.; Yang, Y.; Su, X.; Wei, W. Efficacy and safety of berberine in preventing recurrence of colorectal adenomas: A systematic review and meta-analysis. J. Ethnopharmacol., 2022, 282, 114617.
[http://dx.doi.org/10.1016/j.jep.2021.114617] [PMID: 34509605]
[157]
Huang, J.; Feng, W.; Li, S.; Tang, H.; Qin, S.; Li, W.; Gong, Y.; Fang, Y.; Liu, Y.; Wang, S.; Guo, Y.; Xu, Z.; Shen, Q. Berberine exerts anti-cancer activity by modulating adenosine monophosphate- activated protein kinase (AMPK) and the phosphatidylinositol 3-kinase/ protein kinase B (PI3K/AKT) signaling pathways. Curr. Pharm. Des., 2021, 27(4), 565-574.
[http://dx.doi.org/10.2174/18734286MTEw2Mjg54] [PMID: 32988344]
[158]
Asbaghi, O.; Ghanbari, N.; shekari, M.; Reiner, Ž.; Amirani, E.; Hallajzadeh, J.; Mirsafaei, L.; Asemi, Z. The effect of berberine supplementation on obesity parameters, inflammation and liver function enzymes: A systematic review and meta-analysis of randomized controlled trials. Clin. Nutr. ESPEN, 2020, 38, 43-49.
[http://dx.doi.org/10.1016/j.clnesp.2020.04.010] [PMID: 32690176]
[159]
Xiong, P.; Niu, L.; Talaei, S.; Kord-Varkaneh, H.; Clark, C.C.T.; Găman, M.A.; Rahmani, J.; Dorosti, M.; Mousavi, S.M.; Zarezadeh, M.; Taghizade-Bilondi, H.; Zhang, J. The effect of berberine supplementation on obesity indices: A dose– response meta-analysis and systematic review of randomized controlled trials. Complement. Ther. Clin. Pract., 2020, 39, 101113.
[http://dx.doi.org/10.1016/j.ctcp.2020.101113] [PMID: 32379652]
[160]
Amini, M.R.; Sheikhhossein, F.; Naghshi, S.; Djafari, F.; Askari, M.; Shahinfar, H.; Safabakhsh, M.; Jafari, A.; Shab-Bidar, S. Effects of berberine and barberry on anthropometric measures: A systematic review and meta-analysis of randomized controlled trials. Complement. Ther. Med., 2020, 49, 102337.
[http://dx.doi.org/10.1016/j.ctim.2020.102337] [PMID: 32147051]
[161]
Ilyas, Z.; Perna, S.; Al-thawadi, S.; Alalwan, T.A.; Riva, A.; Petrangolini, G.; Gasparri, C.; Infantino, V.; Peroni, G.; Rondanelli, M. The effect of Berberine on weight loss in order to prevent obesity: A systematic review. Biomed. Pharmacother., 2020, 127, 110137.
[http://dx.doi.org/10.1016/j.biopha.2020.110137] [PMID: 32353823]
[162]
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. 2021.
[http://dx.doi.org/10.1155/2021/2074610]
[163]
Bertuccioli, A.; Moricoli, S.; Amatori, S.; Rocchi, M.B.L.; Vici, G.; Sisti, D. Berberine and dyslipidemia: different applications and biopharmaceutical formulations without statin-like molecules—a meta-analysis. J. Med. Food, 2020, 23(2), 101-113.
[http://dx.doi.org/10.1155/2021/2074610] [PMID: 31441678]
[164]
Shinjyo, N.; Parkinson, J.; Bell, J.; Katsuno, T.; Bligh, A. Berberine for prevention of dementia associated with diabetes and its comorbidities: A systematic review. J. Integr. Med., 2020, 18(2), 125-151.
[http://dx.doi.org/10.1016/j.joim.2020.01.004] [PMID: 32005442]
[165]
Suadoni, M.T.; Atherton, I. Berberine for the treatment of hypertension: A systematic review. Complement. Ther. Clin. Pract., 2021, 42, 101287.
[http://dx.doi.org/10.1016/j.ctcp.2020.101287] [PMID: 33461163]
[166]
Zhao, H.; Xing, C.; Zhang, J.; He, B. Comparative efficacy of oral insulin sensitizers metformin, thiazolidinediones, inositol, and berberine in improving endocrine and metabolic profiles in women with PCOS: A network meta-analysis. Reprod. Health, 2021, 18(1), 171.
[http://dx.doi.org/10.1186/s12978-021-01207-7] [PMID: 34407851]
[167]
Mirzaee, F.; Razmjouei, P.; Shahrahmani, H.; Vafisani, F.; Najaf Najafi, M.; Ghazanfarpour, M. The effect and safety of Berberine on polycystic ovary syndrome: A systematic review. J. Obstet. Gynaecol., 2021, 41(5), 684-689.
[http://dx.doi.org/10.1080/01443615.2020.1787964] [PMID: 32811221]
[168]
Li, H.; Miyahara, T.; Tezuka, Y.; Tran, Q.L.; Seto, H.; Kadota, S. Effect of berberine on bone mineral density in SAMP6 as a senile osteoporosis model. Biol. Pharm. Bull., 2003, 26(1), 110-111.
[http://dx.doi.org/10.1248/bpb.26.110] [PMID: 12520186]
[169]
Zhang, Z.; Li, X.; Li, F.; An, L. Berberine alleviates postoperative cognitive dysfunction by suppressing neuroinflammation in aged mice. Int. Immunopharmacol., 2016, 38, 426-433.
[http://dx.doi.org/10.1016/j.intimp.2016.06.031] [PMID: 27376853]
[170]
El-Horany, H.E.S.; Gaballah, H.H.; Helal, D.S. Berberine ameliorates renal injury in a rat model of D-galactose-induced aging through a PTEN/Akt-dependent mechanism. Arch. Physiol. Biochem., 2020, 126(2), 157-165.
[http://dx.doi.org/10.1080/13813455.2018.1499117] [PMID: 30145915]
[171]
Zhu, X.; Yue, H.; Guo, X.; Yang, J.; Liu, J.; Liu, J.; Wang, R.; Zhu, W. The preconditioning of berberine suppresses hydrogen peroxide-induced premature senescence via Regulation of Sirtuin 1. Oxid. Med. Cell. Longev., 2017, 2017, 1-9.
[http://dx.doi.org/10.1155/2017/2391820] [PMID: 28751929]
[172]
Liu, Q.; Xu, X.; Zhao, M.; Wei, Z.; Li, X.; Zhang, X.; Liu, Z.; Gong, Y.; Shao, C. Berberine induces senescence of human glioblastoma cells by downregulating the EGFR-MEK-ERK signaling pathway. Mol. Cancer Ther., 2015, 14(2), 355-363.
[http://dx.doi.org/10.1158/1535-7163.MCT-14-0634] [PMID: 25504754]
[173]
Pierpaoli, E.; Fiorillo, G.; Lombardi, P.; Salvatore, C.; Geroni, C.; Piacenza, F.; Provinciali, M. Antitumor activity of NAX060: A novel semisynthetic berberine derivative in breast cancer cells. Biofactors, 2018, 44(5), 443-452.
[http://dx.doi.org/10.1002/biof.1440] [PMID: 30178609]
[174]
Ramesh, G.; Das, S.; Bola Sadashiva, S.R. Berberine, a natural alkaloid sensitizes human hepatocarcinoma to ionizing radiation by blocking autophagy and cell cycle arrest resulting in senescence. J. Pharm. Pharmacol., 2020, 72(12), 1893-1908.
[http://dx.doi.org/10.1111/jphp.13354] [PMID: 32815562]
[175]
Li, C.; Jiang, S.; Wang, H.; Wang, Y.; Han, Y.; Jiang, J. Berberine exerts protective effects on cardiac senescence by regulating the Klotho/SIRT1 signaling pathway. Biomed. Pharmacother., 2022, 151, 113097.
[http://dx.doi.org/10.1016/j.biopha.2022.113097] [PMID: 35609366]
[176]
Kumar, R.; Awasthi, M.; Sharma, A.; Padwad, Y.; Sharma, R. Berberine induces dose-dependent quiescence and apoptosis in A549 cancer cells by modulating cell cyclins and inflammation independent of mTOR pathway. Life Sci., 2020, 244, 117346.
[http://dx.doi.org/10.1016/j.lfs.2020.117346] [PMID: 31978448]

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