Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins
Abstract
We identify berberine (BBR), a compound isolated from a Chinese herb, as a new cholesterol-lowering drug. Oral administration of BBR in 32 hypercholesterolemic patients for 3 months reduced serum cholesterol by 29%, triglycerides by 35% and LDL-cholesterol by 25%. Treatment of hyperlipidemic hamsters with BBR reduced serum cholesterol by 40% and LDL-cholesterol by 42%, with a 3.5-fold increase in hepatic LDLR mRNA and a 2.6-fold increase in hepatic LDLR protein. Using human hepatoma cells, we show that BBR upregulates LDLR expression independent of sterol regulatory element binding proteins, but dependent on ERK activation. BBR elevates LDLR expression through a post-transcriptional mechanism that stabilizes the mRNA. Using a heterologous system with luciferase as a reporter, we further identify the 5' proximal section of the LDLR mRNA 3' untranslated region responsible for the regulatory effect of BBR. These findings show BBR as a new hypolipidemic drug with a mechanism of action different from that of statin drugs.
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Grundy, S. M., Bilheimer, D. W., Chait, A., Clark, L. T., Denke, M. A., Havel, R. J., Hazzard, W. R., Hulley, S. B., Hunninghake, D. B., Kreisberg, R. A., et al. (1993) · JAMA · doi:10.1001/jama.269.23.3015 · Cited by 27,944 · see citing works
Expert Panel on Detection, E. (2001) · JAMA: The Journal of the American Medical Association · doi:10.1001/jama.285.19.2486 · Cited by 26,011 · see citing works
A Receptor-Mediated Pathway for Cholesterol Homeostasis
Brown, M. S., & Goldstein, J. L. (1986) · Science · doi:10.1126/science.3513311 · Cited by 5,703 · see citing works
Regulation of the mevalonate pathway
Goldstein, J. L., & Brown, M. S. (1990) · Nature · doi:10.1038/343425a0 · Cited by 5,394 · see citing works
The human LDL receptor: A cysteine-rich protein with multiple Alu sequences in its mRNA
Yamamoto, T., Davis, C. G., Brown, M. S., Schneider, W. J., Casey, M. L., Goldstein, J. L., & Russell, D. W. (1984) · Cell · doi:10.1016/0092-8674(84)90188-0 · Cited by 1,382 · see citing works
A proteolytic pathway that controls the cholesterol content of membranes, cells, and blood
Brown, M. S., & Goldstein, J. L. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.20.11041 · Cited by 1,327 · see citing works
Effect of Statins on Risk of Coronary Disease: A Meta-analysis of Randomized Controlled Trials
LaRosa, J. C., He, J., & Vupputuri, S. (1999) · JAMA · doi:10.1001/jama.282.24.2340 · Cited by 1,246 · see citing works
National Cholesterol Education Program
Lenfant, C. (1991) · Archives of Internal Medicine · doi:10.1001/archinte.1991.00400060019005 · Cited by 1,184 · see citing works
SREBP-1, a membrane-bound transcription factor released by sterol-regulated proteolysis
Wang, X., Sato, R., Brown, M. S., Hua, X., & Goldstein, J. L. (1994) · Cell · doi:10.1016/0092-8674(94)90234-8 · Cited by 1,003 · see citing works
Yokoyama, C., Wang, X., Briggs, M. R., Admon, A., Wu, J., Hua, X., Goldstein, J. L., & Brown, M. S. (1993) · Cell · doi:10.1016/s0092-8674(05)80095-9 · Cited by 968 · see citing works
Self-citationBriggs, M. R., Yokoyama, C., Wang, X., Brown, M. S., & Goldstein, J. L. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)85265-1 · Cited by 401 · see citing works
Post-transcriptional Control of Cyclooxygenase-2 Gene Expression
Dixon, D. A., Kaplan, C. D., McIntyre, T. M., Zimmerman, G. A., & Prescott, S. M. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.16.11750 · Cited by 348 · see citing works
Regulated Step in Cholesterol Feedback Localized to Budding of SCAP from ER Membranes
Nohturfft, A., Yabe, D., Goldstein, J. L., Brown, M. S., & Espenshade, P. J. (2000) · Cell · doi:10.1016/s0092-8674(00)00037-4 · Cited by 347 · see citing works
Wang, X., Briggs, M. R., Hua, X., Yokoyama, C., Goldstein, J. L., & Brown, M. S. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)85266-3 · Cited by 299 · see citing works
Cardiovascular actions of berberine
Lau, C., Yao, X., Chen, Z., Ko, W., & Huang, Y. (2001) · Cardiovascular Drug Reviews · doi:10.1111/j.1527-3466.2001.tb00068.x · Cited by 281 · see citing works
Goldstein, J. L., Rawson, R. B., & Brown, M. S. (2002) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.2001.2615 · Cited by 250 · see citing works
Nohturfft, A., DeBose‐Boyd, R. A., Scheek, S., Goldstein, J. L., & Brown, M. S. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.20.11235 · Cited by 244 · see citing works
Smith, J. R., Osborne, T. F., Goldstein, J. L., & Brown, M. S. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)39976-4 · Cited by 236 · see citing works
Statin Trials and Goals of Cholesterol-Lowering Therapy
Grundy, S. M. (1998) · Circulation · doi:10.1161/01.cir.97.15.1436 · Cited by 197 · see citing works
Effect of Statins on Risk of Coronary Disease: A Meta-analysis of Randomized Controlled Trials
LaRosa, J. C., He, J., & Vupputuri, S. X. (2000) · Survey of Anesthesiology · doi:10.1097/00132586-200012000-00024 · Cited by 157 · see citing works
An Evidence-Based Assessment of the NCEP Adult Treatment Panel II Guidelines
Ansell, B., Watson, K., & Fogelman, A. (1999) · JAMA · doi:10.1001/jama.282.21.2051 · Cited by 102 · see citing works
Horton, J. D., Cuthbert, J. A., & Spady, D. K. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116645 · Cited by 100 · see citing works
Nakahara, M., Fujii, H., Maloney, P., Shimizu, M., & Sato, R. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m206749200 · Cited by 93 · see citing works
Yang, T., Goldstein, J. L., & Brown, M. S. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m005439200 · Cited by 87 · see citing works
Feedback regulation of MAPK signalling by an RNA-binding protein
Sugiura, R., Kita, A., Shimizu, Y., Shuntoh, H., Sio, S. O., & Kuno, T. (2003) · Nature · doi:10.1038/nature01907 · Cited by 86 · see citing works
Sakai, J., & Rawson, R. B. (2001) · Current Opinion in Lipidology · doi:10.1097/00041433-200106000-00004 · Cited by 73 · see citing works
Liu, J., Hadjokas, N. E., Mosley, B., Estrov, Z., Spence, M. J., & Vestal, R. E. (1998) · Cytokine · doi:10.1006/cyto.1997.0283 · Cited by 72 · see citing works
Self-citationSCAP ligands are potent new lipid-lowering drugs
Grand‐Perret, T., Bouillot, A., Perrot, A., Commans, S., Walker, M., & Issandou, M. (2001) · Nature Medicine · doi:10.1038/nm1201-1332 · Cited by 61 · see citing works
Wilson, G. M., Vasa, M. Z., & Deeley, R. G. (1998) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)33870-0 · Cited by 58 · see citing works
Liu, J., Ahlborn, T. E., Briggs, M. R., & Kraemer, F. B. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.7.5214 · Cited by 54 · see citing works
Self-citationYeung, A. C., & Tsao, P. S. (2002) · Circulation · doi:10.1161/01.cir.0000023397.12047.03 · Cited by 42 · see citing works
Novel mechanism of transcriptional activation of hepatic LDL receptor by oncostatin M
Liu, J., Streiff, R. J., Zhang, Y. L., Vestal, R. E., Spence, M. J., & Briggs, M. R. (1997) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)37134-0 · Cited by 40 · see citing works
Self-citationKnouff, C. W., Malloy, S. I., Wilder, J., Altenburg, M. K., & Maeda, N. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m009423200 · Cited by 36 · see citing works
Zhang, F., Ahlborn, T. E., Li, C., Kraemer, F. B., & Liu, J. (2002) · Journal of Lipid Research · doi:10.1194/jlr.m200126-jlr200 · Cited by 23 · see citing works
Self-citationSynergistic Activation of Human LDL Receptor Expression by SCAP Ligand and Cytokine Oncostatin M
Liu, J., Zhang, F., Li, C., Lin, M., & Briggs, M. R. (2003) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000046229.77566.e5 · Cited by 20 · see citing works
Self-citationUgawa, T., Kakuta, H., Moritani, H., & Inagaki, O. (2002) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0704906 · Cited by 18 · see citing works
Bensch, W. R., Gadski, R. A., Bean, J. S., Beavers, L. S., Schmidt, R. J., Perry, D. N., Murphy, A., McClure, D., Eacho, P. I., Breau, A. P., et al. (1999) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)38110-8 · Cited by 16 · see citing works
Flagged first, then by citations
2 of the 40 references couldn’t be matched to a known paper.
Research works printed but not linked: 4
- Cho, E. Berberini hydrochloride. in Pharmacopoeia of the People's Republic of China 2, 437–439 (1990).
- Luo, L.J. Experience of berberine in the treatment of diarrhea. Chin. J. Med. 41, 452–455 (1955).
- Liu . Berberine. Altern. Med. Rev. 5, 175–177 (2000).
- Zhao, S.P. Etiology and diagnosis of hyperlipidemia. Clinical Serum and Lipid 1, 72–94 (1997).
Cited by
Sorted by citations
Steinberg, G. R., & Kemp, B. E. (2009) · Physiological Reviews · doi:10.1152/physrev.00011.2008 · Cited by 1,633 · see citing works
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. (2006) · Diabetes · doi:10.2337/db06-0006 · Cited by 1,054 · see citing works
Efficacy of berberine in patients with type 2 diabetes mellitus
Yin, J., Xing, H., & Ye, J. (2008) · Metabolism · doi:10.1016/j.metabol.2008.01.013 · Cited by 801 · see citing works
Pharmacological and therapeutic effects of Berberis vulgaris and its active constituent, berberine
Imanshahidi, M., & Hosseinzadeh, H. (2008) · Phytotherapy Research · doi:10.1002/ptr.2399 · Cited by 636 · see citing works
Zhang, X., Zhao, Y., Xu, J., Xue, Z., Zhang, M., Pang, X., Zhang, X., & Zhao, L. (2015) · Scientific Reports · doi:10.1038/srep14405 · Cited by 630 · see citing works
Zhang, X., Zhao, Y., Zhang, M., Pang, X., Xu, J., Kang, C., Li, M., Zhang, C., Zhang, Z., Zhang, Y., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0042529 · Cited by 615 · see citing works
Treatment of Type 2 Diabetes and Dyslipidemia with the Natural Plant Alkaloid Berberine
Zhang, Y., Li, X., Zou, D., Liu, W., Yang, J., Zhu, N., Huo, L., Wang, M., Hong, J., Wu, P., et al. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-2404 · Cited by 573 · see citing works
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., et al. (2008) · Diabetes · doi:10.2337/db07-1552 · Cited by 535 · see citing works
Biological properties and clinical applications of berberine
Song, D., Hao, J., & Fan, D. (2020) · Frontiers of Medicine · doi:10.1007/s11684-019-0724-6 · Cited by 510 · see citing works
Tang, J., Feng, Y., Tsao, S., Wang, N., Curtain, R., & Wang, Y. (2009) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2009.08.009 · Cited by 491 · see citing works
Self-citationBerberine in Cardiovascular and Metabolic Diseases: From Mechanisms to Therapeutics
Feng, X., Sureda, A., Jafari, S., Memariani, Z., Tewari, D., Annunziata, G., Barrea, L., Hassan, S. T. S., Šmejkal, K., Malaník, M., et al. (2019) · Theranostics · doi:10.7150/thno.30787 · Cited by 465 · see citing works
Lan, J., Zhao, Y., Dong, F., Yan, Z., Zheng, W., Fan, J., & Sun, G. (2015) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2014.09.049 · Cited by 458 · see citing works
Berberine suppresses proinflammatory responses through AMPK activation in macrophages
Jeong, H. W., Hsu, K. C., Lee, J.-W., Ham, M., Huh, J. Y., Shin, H. J., Kim, W. S., & Kim, J. B. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90599.2008 · Cited by 454 · see citing works
Mo, C., Wang, L., Zhang, J., Numazawa, S., Tang, H. W., Tang, X., Han, X., Li, J., Yang, M., Wang, Z., et al. (2013) · Antioxidants and Redox Signaling · doi:10.1089/ars.2012.5116 · Cited by 442 · see citing works
Self-citationZhang, H., Wei, J., Xue, R., Wu, J.-D., Zhao, W., Wang, Z., Wang, S., Zhou, Z.-X., Song, D., Wang, Y., et al. (2009) · Metabolism · doi:10.1016/j.metabol.2009.07.029 · Cited by 442 · see citing works
Self-citationBerberine activates thermogenesis in white and brown adipose tissue
Zhang, Z., Zhang, H., Li, B., Meng, X.-J., Wang, J., Zhang, Y., Yao, S., Ma, Q., Jin, L., Yang, J., et al. (2014) · Nature Communications · doi:10.1038/ncomms6493 · Cited by 439 · see citing works
AMPK activation: a therapeutic target for type 2 diabetes?
Saha, A. K., Coughlan, K. A., Valentine, R. J., & Ruderman, N. B. (2014) · Diabetes Metabolic Syndrome and Obesity · doi:10.2147/dmso.s43731 · Cited by 440 · see citing works
Zhu, Y., Ouyang, Z., Du, H., Wang, M., Wang, J., Sun, H., Kong, L., Xu, Q., Ma, H., & Sun, Y. (2022) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2022.08.022 · Cited by 422 · see citing works
Maxwell, K. N., Fisher, E. A., & Breslow, J. L. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409736102 · Cited by 415 · see citing works
Cai, Y., Song, W., Li, J., Jing, Y., Liang, C., Zhang, L., Zhang, X., Zhang, W., Liu, B., An, Y., et al. (2022) · Science China Life Sciences · doi:10.1007/s11427-022-2161-3 · Cited by 436 · see citing works
Self-citationTraditional medicine-inspired approaches to drug discovery: can Ayurveda show the way forward?
Patwardhan, B., & Mashelkar, R. A. (2009) · Drug Discovery Today · doi:10.1016/j.drudis.2009.05.009 · Cited by 390 · see citing works
Gut microbiome-related effects of berberine and probiotics on type 2 diabetes (the PREMOTE study)
Zhang, Y., Gu, Y., Ren, H., Wang, S., Zhong, H., Zhao, X., Ma, J., Gu, X., Xue, Y., Huang, S., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-18414-8 · Cited by 380 · see citing works
Self-citationGut microbiota, a new frontier to understand traditional Chinese medicines
Feng, W., Ao, H., Peng, C. Y., & Yan, D. (2019) · Pharmacological Research · doi:10.1016/j.phrs.2019.02.024 · Cited by 379 · see citing works
Analysis of alkaloids (indole alkaloids, isoquinoline alkaloids, tropane alkaloids)
Dey, P. K., Kundu, A. B., Kumar, A., Gupta, M., Lee, B. M., Bhakta, T., Dash, S., & Kim, H. S. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-816455-6.00015-9 · Cited by 403 · see citing works
Traditional Chinese Medicine in Treatment of Metabolic Syndrome
Yin, J., Zhang, H., & Ye, J. (2008) · Endocrine Metabolic & Immune Disorders - Drug Targets · doi:10.2174/187153008784534330 · Cited by 374 · see citing works
Berberine: a plant alkaloid with therapeutic potential for central nervous system disorders
Kulkarni, S. K., & Dhir, A. (2009) · Phytotherapy Research · doi:10.1002/ptr.2968 · Cited by 367 · see citing works
Chen, W., Miao, Y.-Q., Fan, D.-J., Yang, S.-S., Lin, X., Meng, L.-K., & Tang, X. (2011) · AAPS PharmSciTech · doi:10.1208/s12249-011-9632-z · Cited by 363 · see citing works
Research progress on berberine with a special focus on its oral bioavailability
Liu, C.-S., Zheng, Y.-R., Zhang, Y.-F., & Long, X.-Y. (2016) · Fitoterapia · doi:10.1016/j.fitote.2016.02.001 · Cited by 363 · see citing works
Liu, Y.-T., Hao, H.-P., Xie, H.-G., Lai, L., Wang, Q., Liu, C.-X., & Wang, G.-J. (2010) · Drug Metabolism and Disposition · doi:10.1124/dmd.110.033936 · Cited by 356 · see citing works
Molecular Insights and Therapeutic Targets for Diabetic Endothelial Dysfunction
Xu, J., & Zou, M. (2009) · Circulation · doi:10.1161/circulationaha.108.835223 · Cited by 348 · see citing works
Berberine pharmacology and the gut microbiota: A hidden therapeutic link
Habtemariam, S. (2020) · Pharmacological Research · doi:10.1016/j.phrs.2020.104722 · Cited by 352 · see citing works
Nutraceuticals and dyslipidaemia: Beyond the common therapeutics
Scicchitano, P., Cameli, M., Maiello, M. R., Modesti, P. A., Muiesan, M. L., Novo, S., Palmiero, P., Saba, P. S., Pedrinelli, R., & Ciccone, M. M. (2014) · Journal of Functional Foods · doi:10.1016/j.jff.2013.12.006 · Cited by 351 · see citing works
Li, H., Dong, B., Park, S. W., Lee, H.-S., Chen, W., & Liu, J. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.052407 · Cited by 349 · see citing works
Self-citationBrusq, J.-M. G., Ancellin, N., Grondin, P., Guillard, R., Martin, S., Saintillan, Y., & Issandou, M. (2006) · Journal of Lipid Research · doi:10.1194/jlr.m600020-jlr200 · Cited by 344 · see citing works
Microbial production of plant benzylisoquinoline alkaloids
Minami, H., Kim, J., Ikezawa, N., Takemura, T., Katayama, T., Kumagai, H., & Sato, F. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0802981105 · Cited by 340 · see citing works
Wang, Y., Tong, Q., Ma, S.-R., Zhao, Z.-X., Pan, L.-B., Cong, L., Han, P., Peng, R., Yu, H., Lin, Y., et al. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00456-5 · Cited by 319 · see citing works
Self-citationBerberine: a potential phytochemical with multispectrum therapeutic activities
Vuddanda, P. R., Chakraborty, S., & Singh, S. (2010) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.2010.517745 · Cited by 317 · see citing works
The strategies and techniques of drug discovery from natural products
Zhang, L., Song, J., Kong, L., Yuan, T., Li, W., Zhang, W., Hou, B., Lü, Y., & Du, G. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107686 · Cited by 319 · see citing works
Transforming berberine into its intestine-absorbable form by the gut microbiota
Feng, R., Shou, J.-W., Zhao, Z.-X., He, C.-Y., Ma, C., Huang, M., Fu, J., Tan, X.-S., Li, X.-Y., Wen, B.-Y., et al. (2015) · Scientific Reports · doi:10.1038/srep12155 · Cited by 307 · see citing works
Self-citationPirillo, A., & Catapano, A. L. (2015) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2015.09.032 · Cited by 308 · see citing works
Bhadra, K., & Kumar, G. S. (2010) · Medicinal Research Reviews · doi:10.1002/med.20202 · Cited by 308 · see citing works
Nutraceuticals: A paradigm of proactive medicine
Santini, A., Tenore, G. C., & Novellino, E. (2016) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2016.09.003 · Cited by 294 · see citing works
Inhibition of inflammation by berberine: Molecular mechanism and network pharmacology analysis
Wang, K., Yin, J., Chen, J., Ma, J., Si, H., & Xia, D. (2024) · Phytomedicine · doi:10.1016/j.phymed.2023.155258 · Cited by 301 · see citing works
Berberine and Its Role in Chronic Disease
Cicero, A. F. G., & Baggioni, A. (2016) · Advances in Experimental Medicine and Biology · doi:10.1007/978-3-319-41334-1_2 · Cited by 285 · see citing works
Berberine inhibits 3T3-L1 adipocyte differentiation through the PPARγ pathway
Huang, C., Zhang, Y., Gong, Z., Sheng, X., Li, Z., Zhang, W., & Qin, Y. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.07.095 · Cited by 277 · see citing works
Self-citationBerberine attenuates nonalcoholic hepatic steatosis through the AMPK-SREBP-1c-SCD1 pathway
Zhu, X., Bian, H., Wang, L., Sun, X., Xu, X., Yan, H., Xia, M., Chang, X., Lü, Y., Li, Y., et al. (2019) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2019.06.019 · Cited by 274 · see citing works
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. (2012) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2012.02.016 · Cited by 271 · see citing works
Tissue Distribution of Berberine and Its Metabolites after Oral Administration in Rats
Tan, X.-S., Ma, J.-Y., Feng, R., Ma, C., Chen, W.-J., Sun, Y.-P., Fu, J., Huang, M., He, C.-Y., Shou, J.-W., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0077969 · Cited by 266 · see citing works
Self-citationKong, W., Zhang, H., Song, D., Xue, R., Zhao, W., Wei, J., Wang, Y., Shan, N., Zhou, Z., Yang, P., et al. (2008) · Metabolism · doi:10.1016/j.metabol.2008.08.013 · Cited by 266 · see citing works
Self-citationDong, B., Wu, M., Li, H., Kraemer, F. B., Adeli, K., Seidah, N. G., Park, S. W., & Liu, J. (2010) · Journal of Lipid Research · doi:10.1194/jlr.m003566 · Cited by 266 · see citing works
Self-citationBerberine Improves Glucose Metabolism in Diabetic Rats by Inhibition of Hepatic Gluconeogenesis
Xia, X., Yan, J., Shen, Y., Tang, K., Yin, J., Zhang, Y., Yang, D., Liang, H., Ye, J., & Weng, J. (2011) · PLoS ONE · doi:10.1371/journal.pone.0016556 · Cited by 262 · see citing works
Berberine Targets Assembly of Escherichia coli Cell Division Protein FtsZ
Domadia, P. N., Bhunia, A., Sivaraman, J., Swarup, S., & Dasgupta, D. (2008) · Biochemistry · doi:10.1021/bi7018546 · Cited by 253 · see citing works
Application of Berberine on Treating Type 2 Diabetes Mellitus
Pang, B., Zhao, L., Zhou, Q., Zhao, T., Wang, H., Gu, C., & Tong, X. (2015) · International Journal of Endocrinology · doi:10.1155/2015/905749 · Cited by 254 · see citing works
Engineering microbial factories for synthesis of value-added products
Du, J., Shao, Z., & Zhao, H. (2011) · Journal of Industrial Microbiology & Biotechnology · doi:10.1007/s10295-011-0970-3 · Cited by 246 · see citing works
Méndez-del Villar, M., González-Ortiz, M., Martínez-Abundis, E., Pérez-Rubio, K. G., & Lizárraga-Valdez, R. (2014) · Metabolic Syndrome and Related Disorders · doi:10.1089/met.2014.0082 · Cited by 246 · see citing works
The influence of the gut microbiota on the bioavailability of oral drugs
Zhang, X., Han, Y., Huang, W., Jin, M., & Gao, Z. (2020) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2020.09.013 · Cited by 246 · see citing works
AMP-activated protein kinase, stress responses and cardiovascular diseases
Wang, S., Song, P., & Zou, M. (2012) · Clinical Science · doi:10.1042/cs20110625 · Cited by 243 · see citing works
Self-citationZhu, L., Zhang, D., Zhu, H., Zhu, J., Weng, S., Dong, L., Liu, T., Hu, Y., & Shen, X. (2017) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2017.11.023 · Cited by 243 · see citing works
Zhang, W., Xu, J., Yu, T., & Chen, Q. (2019) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2019.109131 · Cited by 242 · see citing works
RetractedXu, X., Yi, H., Wu, J., Kuang, T., Zhang, J., Li, Q., Du, H., Xu, T., Jiang, G., & Fan, G. (2020) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2020.110984 · Cited by 246 · see citing works
Self-citationKim, W. S., Lee, Y. S., Cha, S. H., Jeong, H. W., Choe, S. S., Lee, M., Oh, G. T., Park, H., Lee, K., Lane, M. D., et al. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90710.2008 · Cited by 239 · see citing works
Acute toxicity of berberine and its correlation with the blood concentration in mice
Kheir, M. M., Wang, Y., Hua, L., Hu, J., Li, L., Lei, F., & Du, L. (2010) · Food and Chemical Toxicology · doi:10.1016/j.fct.2010.01.033 · Cited by 235 · see citing works
Self-citationEfficacy of Berberine in Patients with Non-Alcoholic Fatty Liver Disease
Yan, H., Xia, M., Wang, Y., Chang, X., Yao, X., Rao, S., Zeng, M., Tu, Y., Feng, R., Jia, W., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0134172 · Cited by 233 · see citing works
Self-citationBerberine decreases PCSK9 expression in HepG2 cells
Cameron, J., Ranheim, T., Kulseth, M. A., Leren, T. P., & Berge, K. E. (2008) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2008.02.004 · Cited by 232 · see citing works
The Anti-Cancer Mechanisms of Berberine: A Review
Wang, Y., Liu, Y., Du, X., Ma, H., & Yao, J. (2020) · Cancer Management and Research · doi:10.2147/cmar.s242329 · Cited by 238 · see citing works
Self-citationTargeting Foam Cell Formation in Atherosclerosis: Therapeutic Potential of Natural Products
Wang, D., Yang, Y., Lei, Y., Tzvetkov, N. T., Liu, X., Yeung, A. W. K., Xu, S., & Atanasov, A. G. (2019) · Pharmacological Reviews · doi:10.1124/pr.118.017178 · Cited by 223 · see citing works
Berberine in the treatment of type 2 diabetes mellitus: A systemic review and meta-analysis
Dong, H., Wang, N., Zhao, L., & Lu, F. (2012) · Evidence-Based Complementary and Alternative Medicine · doi:10.1155/2012/591654 · Cited by 225 · see citing works
Functional foods and dietary supplements for the management of dyslipidaemia
Hunter, P. M., & Hegele, R. A. (2017) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2016.210 · Cited by 226 · see citing works
Herbal drug discovery for the treatment of nonalcoholic fatty liver disease
Yan, T., Yan, N., Wang, P., Xia, Y., Hao, H., Wang, G., & Gonzalez, F. J. (2019) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2019.11.017 · Cited by 225 · see citing works
Amasheh, M., Fromm, A., Krug, S. M., Amasheh, S., Andres, S., Zeitz, M., Fromm, M., & Schulzke, J. (2010) · Journal of Cell Science · doi:10.1242/jcs.070896 · Cited by 224 · see citing works
On the mechanism of antidepressant-like action of berberine chloride
Kulkarni, S. K., & Dhir, A. (2008) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2008.05.043 · Cited by 223 · see citing works
Plant isoquinoline alkaloids: Advances in the chemistry and biology of berberine
Singh, S., Pathak, N., Fatima, E., & Negi, A. S. (2021) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2021.113839 · Cited by 221 · see citing works
Berberine and neurodegeneration: A review of literature
Ahmed, T., Gilani, A. H., Abdollahi, M. R., Daglia, M., Nabavi, S. F., & Nabavi, S. M. (2015) · Pharmacological Reports · doi:10.1016/j.pharep.2015.03.002 · Cited by 210 · see citing works
Varghese, F. S., Kaukinen, P., Gläsker, S., Bespalov, M. M., Hanski, L. L., Wennerberg, K., Kümmerer, B. M., & Ahola, T. (2016) · Antiviral Research · doi:10.1016/j.antiviral.2015.12.012 · Cited by 209 · see citing works
Zhou, J., Zhou, S., Tang, J., Zhang, K., Guang, L.-X., Huang, Y., Xu, Y. X., Ying, Y., Zhang, L., & Li, D. (2009) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2008.12.056 · Cited by 208 · see citing works
Berberine-induced bioactive metabolites of the gut microbiota improve energy metabolism
Wang, Y., Shou, J., Li, X., Zhao, Z., Fu, J., He, C., Feng, R., Ma, C., Wen, B., Guo, F., et al. (2017) · Metabolism · doi:10.1016/j.metabol.2017.02.003 · Cited by 206 · see citing works
Self-citationMulvihill, E. E., Assini, J. M., Lee, J. K., Allister, E. M., Sutherland, B. G., Koppes, J. B., Sawyez, C. G., Edwards, J. Y., Telford, D. E., Charbonneau, A., et al. (2011) · Diabetes · doi:10.2337/db10-0589 · Cited by 202 · see citing works
Wu, M., Yang, S., Wang, S., Cao, Y., Zhao, R., Li, X., Xing, Y., & Liu, L. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.00223 · Cited by 201 · see citing works
Self-citationAnticancer Effects and Mechanisms of Berberine from Medicinal Herbs: An Update Review
Xiong, R.-G., Huang, S., Wu, S.-X., Zhou, D.-D., Yang, Z., Saimaiti, A., Zhao, C., Shang, A., Zhang, Y., Gan, R., et al. (2022) · Molecules · doi:10.3390/molecules27144523 · Cited by 204 · see citing works
Sun, R., Yang, N., Kong, B., Cao, B., Feng, D., Yu, X., Ge, C., Huang, J., Shen, J., Wang, P., et al. (2017) · Molecular Pharmacology · doi:10.1124/mol.116.106617 · Cited by 199 · see citing works
Zhu, F., & Qian, C. (2006) · BMC Neuroscience · doi:10.1186/1471-2202-7-78 · Cited by 197 · see citing works
Cui, G., Qin, X., Zhang, Y., Gong, Z., Ge, B., & Zang, Y. Q. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.012674 · Cited by 197 · see citing works
Ma, S., Tong, Q., Lin, Y., Pan, L., Fu, J., Peng, R., Zhang, X., Zhao, Z., Li, Y., Yu, J., et al. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01027-6 · Cited by 193 · see citing works
Self-citationLipid-modifying effects of nutraceuticals: An evidence-based approach
Sahebkar, A., Șerban, M.-C., Gluba-Brzózka, A., Mikhailidis, D. P., Cicero, A. F. G., Rysz, J., & Banach, M. (2016) · Nutrition · doi:10.1016/j.nut.2016.04.007 · Cited by 188 · see citing works
Targeting proprotein convertase subtilisin/kexin type 9 (PCSK9): From bench to bedside
Bao, X., Liang, Y., Chang, H., Cai, T., Feng, B., Gordon, K., Zhu, Y., Shi, H., He, Y., & Xie, L. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01690-3 · Cited by 187 · see citing works
Nutraceutical therapies for atherosclerosis
Moss, J. W. E., & Ramji, D. P. (2016) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2016.103 · Cited by 186 · see citing works
Berberine stimulates glucose transport through a mechanism distinct from insulin
Zhou, L., Yang, Y., Wang, X., Liu, S., Shang, W., Yuan, G., Li, F., Tang, J., Chen, M., & Chen, J. (2007) · Metabolism · doi:10.1016/j.metabol.2006.10.025 · Cited by 187 · see citing works
Berberine alters the processing of Alzheimer’s amyloid precursor protein to decrease Aβ secretion
Asai, M., Iwata, N., Yoshikawa, A., Aizaki, Y., Ishiura, S., Saido, T. C., & Maruyama, K. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.11.043 · Cited by 182 · see citing works
Peng, W., Lo, K.-L., Lee, Y.-H., Hung, T.-H., & Lin, Y.-C. (2007) · Life Sciences · doi:10.1016/j.lfs.2007.08.003 · Cited by 183 · see citing works
Xie, W., Gu, D., Li, J., Cui, K., & Zhang, Y. (2011) · PLoS ONE · doi:10.1371/journal.pone.0024520 · Cited by 183 · see citing works
Kato, N., Dubouzet, E. G., Kokabu, Y., Yoshida, S., Taniguchi, Y., Dubouzet, J. G., Yazaki, K., & Sato, F. (2006) · Plant and Cell Physiology · doi:10.1093/pcp/pcl041 · Cited by 182 · see citing works
Yan, F., Wang, L., Shi, Y., Cao, H., Liu, L., Washington, M. K., Chaturvedi, R., Israel, D. A., Cao, H., Wang, B., et al. (2011) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00312.2011 · Cited by 182 · see citing works
Insulin Sensitizing and Insulinotropic Action of Berberine from Cortidis Rhizoma
Ko, B., Choi, S. B., Park, S. K., Jang, J. S., Kim, Y. E., & Park, S. (2005) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.28.1431 · Cited by 181 · see citing works
Maiti, M., & Kumar, G. S. (2006) · Medicinal Research Reviews · doi:10.1002/med.20087 · Cited by 180 · see citing works
Treatment for liver cancer: From sorafenib to natural products
Man, S., Luo, C., Yan, M., Zhao, G., Ma, L., & Gao, W. (2021) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2021.113690 · Cited by 179 · see citing works
Effects and mechanisms of berberine in diabetes treatment
Yin, J., Ye, J., & Jia, W. (2012) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2012.06.003 · Cited by 183 · see citing works
Abidi, P., Zhou, Y., Jiang, J., & Liu, J. (2005) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000181761.16341.2b · Cited by 176 · see citing works
Self-citationPharmacological effects of berberine and its derivatives: a patent update
Jin, Y., Khadka, D. B., & Cho, W. (2015) · Expert Opinion on Therapeutic Patents · doi:10.1517/13543776.2016.1118060 · Cited by 174 · see citing works
Liu, D., Meng, X. W., Wu, D., Qiu, Z., & Luo, H. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.00009 · Cited by 174 · see citing works
Antiatherogenic properties of flavonoids: Implications for cardiovascular health
Mulvihill, E. E., & Huff, M. W. (2010) · Canadian Journal of Cardiology · doi:10.1016/s0828-282x(10)71056-4 · Cited by 172 · see citing works
- Authors
- 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.
- Affiliations
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Nanjing First Hospital (CN)
- VA Palo Alto Health Care System (US)
- Icahn School of Medicine at Mount Sinai (US)
- Corresponding author
- Liu, Jingwen
- Jiang, Jian-Dong
- ORCID
- Venue
- Nature Medicine
- Published
- 2004-11-07
- Volume
- 10
- Issue
- 12
- Pages
- 1344-1351
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2129582474
- Cited by
- 1,391
- References
- 40
- Citations by year
- 2026: 48 · 2025: 67 · 2024: 57 · 2023: 72 · 2022: 84 · 2021: 99 · 2020: 98 · 2019: 79 · 2018: 88 · 2017: 84 · 2016: 72 · 2015: 71 · 2014: 65 · 2013: 62 · 2012: 60
- FWCI
- 15.08
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ca083648-05)
- National Cancer Institute (1R01CA83648-01)
- Topics
- Health Sciences › Medicine › Pharmacology › Berberine and alkaloids research
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Keywords
- berberine, hypercholesterolemia, LDL receptor upregulation, ERK signaling, mRNA stability, 3' untranslated region, post-transcriptional regulation, SREBP, lipid-lowering drugs, hyperlipidemia
- MeSH terms
- Animals, Anticholesteremic Agents, Berberine, China, Cholesterol, Flow Cytometry, Gene Expression Regulation, Cricetinae, Humans, Hypercholesterolemia, Cholesterol, LDL, Liver, Plasmids, Receptors, LDL, Regulatory Sequences, Nucleic Acid, Triglycerides, Tumor Cells, Cultured, Blotting, Northern, DNA Primers, Reverse Transcriptase Polymerase Chain Reaction
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