Cited by 578Berberine and alkaloids researchNatural Antidiabetic Agents StudiesMetabolism, Diabetes, and Cancer

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Treatment of Type 2 Diabetes and Dyslipidemia with the Natural Plant Alkaloid Berberine

Zhang, Yifei, Li, Xiaoying, Zou, Dajin, Liu, Wei, Yang, Jialin, Zhu, Na, Huo, Li, Wang, Miao, Hong, Jie, Wu, Peihong, Ren, Guoguang, Ning, Guang·2008·The Journal of Clinical Endocrinology & Metabolism

DOI 10.1210/jc.2007-2404

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Abstract

Context: Berberine, a natural plant alkaloid, is usually used as an antibiotic drug. The potential glucose-lowering effect of berberine was noted when it was used for diarrhea in diabetic patients. In vitro and in vivo studies have then showed its effects on hyperglycemia and dyslipidemia. Objective: The objective of the study was to evaluate the efficacy and safety of berberine in the treatment of type 2 diabetic patients with dyslipidemia. Design: One hundred sixteen patients with type 2 diabetes and dyslipidemia were randomly allocated to receive berberine (1.0 g daily) and the placebo for 3 months. The primary outcomes were changes in plasma glucose and serum lipid concentrations. Glucose disposal rate (GDR) was measured using a hyperinsulinemic euglycemic clamp to assess insulin sensitivity. Results: In the berberine group, fasting and postload plasma glucose decreased from 7.0 ± 0.8 to 5.6 ± 0.9 and from 12.0 ± 2.7 to 8.9 ± 2.8 mm/liter, HbA1c from 7.5 ± 1.0% to 6.6 ± 0.7%, triglyceride from 2.51 ± 2.04 to 1.61 ± 1.10 mm/liter, total cholesterol from 5.31 ± 0.98 to 4.35 ± 0.96 mm/liter, and low-density lipoprotein-cholesterol from 3.23 ± 0.81 to 2.55 ± 0.77 mm/liter, with all parameters differing from placebo significantly (P < 0.0001, P < 0.0001, P < 0.0001, P = 0.001, P < 0.0001, and P <0.0001, respectively). The glucose disposal rate was increased after berberine treatment (P = 0.037), although no significant change was found between berberine and placebo groups (P = 0.063). Mild to moderate constipation was observed in five participants in the berberine group. Conclusions: Berberine is effective and safe in the treatment of type 2 diabetes and dyslipidemia.

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Items 101–200 of 578

Lipid profiling of the therapeutic effects of berberine in patients with nonalcoholic fatty liver disease
Chang, X., Wang, Z., Zhang, J., Yan, H., Bian, H., Xia, M., Lin, H., Jiang, J., & Gao, X. (2016) · Journal of Translational Medicine · doi:10.1186/s12967-016-0982-x · Cited by 96
“BBR significantly lowered fasting blood glucose (FBG), hemoglobin A1C, triglyceride, and insulin levels in patients with type 2 diabetes mellitus (T2DM) in the clinical study [7].”
BackgroundResultInfluential
Preparation of an anhydrous reverse micelle delivery system to enhance oral bioavailability and anti-diabetic efficacy of berberine
Wang, T., Wang, N., Song, H., Xi, X., Wang, J., Hao, A., & Li, T. (2011) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2011.06.015 · Cited by 96
Antiviral and antioxidant properties of green synthesized gold nanoparticles using Glaucium flavum leaf extract
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“Research has shown the antimicrobial function of this plant that some medications derived from this plant extract applied as adjuvant treatment in respiratory disorders or antibiotic (Zhang et al. 2008).”
Background
Berberine Promotes Glucose Consumption Independently of AMP-Activated Protein Kinase Activation
Xu, M., Xiao, Y., Yin, J., Hou, W., Xue-ying, Y., Shen, L., Liu, F., Wei, L., & Jia, W. (2014) · PLoS ONE · doi:10.1371/journal.pone.0103702 · Cited by 101
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Liu, Q., Jiang, H., Liu, Z., Wang, Y., Zhao, M., Hao, C., Feng, S., Guo, H., Xu, B., Yang, Q., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0023427 · Cited by 94
“trials for type 2 diabetes mellitus [41,42] and on hypercholester-”
Background
Cardiovascular and metabolic effects of Berberine
Affuso, F. (2010) · World Journal of Cardiology · doi:10.4330/wjc.v2.i4.71 · Cited by 94
Therapeutic potential of berberine against neurodegenerative diseases
Jiang, W., Li, S., & Li, X. (2015) · Science China Life Sciences · doi:10.1007/s11427-015-4829-0 · Cited by 93
Self-citation
Berberine: New Insights from Pharmacological Aspects to Clinical Evidences in the Management of Metabolic Disorders
Caliceti, C., Franco, P., Spinozzi, S., Roda, A., & Cicero, A. F. G. (2016) · Current Medicinal Chemistry · doi:10.2174/0929867323666160411143314 · Cited by 93
“Zhang (2008) [121] Type 2 diabetes 116 1000 mg/day 12 weeks Reduction of BMI by 0.”
Background
Glucose-lowering effect of berberine on type 2 diabetes: A systematic review and meta-analysis
Xie, W., Su, F., Wang, G., Peng, Z., Xu, Y., Zhang, Y., Xu, N., Hou, K., Hu, Z., Chen, Y., et al. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.1015045 · Cited by 100
“Of these 37 studies, seven studies (Wang, 2008; Zhang et al., 2008; Gu et al., 2010; Xiang et al., 2011; Li, 2014; Lang and Zhu, 2016; Rashidi et al., 2018) compared BBR with placebo or no drug, while 20 studies (Liu, 2004; You and Liu, 2007; Liu and Hu, 2008; Xu, 2008; Sheng, 2009; Yang, 2010; Ye, 2010; Yin, 2011; Zh…”
BackgroundMethodResultInfluentialSelf-citation
Modulation of Microbiota-Gut-Brain Axis by Berberine Resulting in Improved Metabolic Status in High-Fat Diet-Fed Rats
Sun, H., Wang, N., Cang, Z., Zhu, C., Zhao, L., Nie, X., Cheng, J., Xia, F., Zhai, H., & Lu, Y. (2016) · Obesity Facts · doi:10.1159/000449507 · Cited by 90
Expatiating the Pharmacological and Nanotechnological Aspects of the Alkaloidal Drug Berberine: Current and Future Trends
Behl, T., Singh, S., Sharma, N., Zahoor, I., Albarrati, A., Albratty, M., Meraya, A. M., Najmi, A., & BUNGAU, S. G. (2022) · Molecules · doi:10.3390/molecules27123705 · Cited by 94
“In addition to a similar reduction in plasma lipids, the BBR-treated individuals had lower glycohemoglobin, fasting blood glucose, and 2 h postprandial blood glucose levels than the placebo group [98].”
Background
Berberine alleviates nonalcoholic fatty liver induced by a high‐fat diet in mice by activating SIRT3
Xu, X., Zhu, X., Bai, J., Xia, P., Li, Y., Lü, Y., Li, X.-Y., & Gao, X. (2019) · The FASEB Journal · doi:10.1096/fj.201802316r · Cited by 86
Self-citation
Amorphous solid dispersion of berberine with absorption enhancer demonstrates a remarkable hypoglycemic effect via improving its bioavailability
Meng, Z., Zhang, M., Shengnan, W., Xiaojia, B., Hatch, G. M., Gu, J., & Li, C. (2014) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2014.03.017 · Cited by 86
Berberine protects against diet-induced obesity through regulating metabolic endotoxemia and gut hormone levels
Xu, J. H., Liu, X., Pan, W., & Zou, D. J. (2017) · Molecular Medicine Reports · doi:10.3892/mmr.2017.6321 · Cited by 86
“Previous clinical research and animal studies have demonstrated that berberine can regulate glucose and lipid metabolism, and attenuate insulin resistance (1-3).”
BackgroundSelf-citation
Berberine in combination with doxorubicin suppresses growth of murine melanoma B16F10 cells in culture and xenograft
Mittal, A., Tabasum, S., & Singh, R. P. (2013) · Phytomedicine · doi:10.1016/j.phymed.2013.09.002 · Cited by 82
Dietary management of the metabolic syndrome beyond macronutrients
Minich, D. M., & Bland, J. S. (2008) · Nutrition Reviews · doi:10.1111/j.1753-4887.2008.00075.x · Cited by 84
Chinese Herbal Medicine for the Optimal Management of Polycystic Ovary Syndrome
Ong, M., Peng, J., Jin, X., & Qu, X. (2017) · The American Journal of Chinese Medicine · doi:10.1142/s0192415x17500252 · Cited by 80
Berberine: A Plant-derived Alkaloid with Therapeutic Potential to Combat Alzheimer’s disease
Singh, A. K., Singh, S. K., Nandi, M. K., Mishra, G., Maurya, A., Rai, A., Rai, G. K., Awasthi, R., Sharma, B., & Kulkarni, G. T. (2019) · Central Nervous System Agents in Medicinal Chemistry · doi:10.2174/1871524919666190820160053 · Cited by 79
Protective effect of berberine on antioxidant enzymes and positive transcription elongation factor b expression in diabetic rat liver
Zhou, J., & Zhou, S.-W. (2010) · Fitoterapia · doi:10.1016/j.fitote.2010.08.019 · Cited by 79
Dose-response of berberine on hepatic cytochromes P450 mRNA expression and activities in mice
Guo, Y., Pope, C., Cheng, X., Zhou, H., & Klaassen, C. D. (2011) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2011.08.058 · Cited by 77
“In recent years, berberine has been used for cardiovascular, nervous, and endocrine system diseases as well as cancer therapy (Kulkarni and Dhir, 2010; Vuddanda et al., 2010; Zhang et al., 2011; Zhang et al., 2008).”
Background
Recent formulation approaches to oral delivery of herbal medicines
Byeon, J. C., Ahn, J. B., Jang, W. S., Lee, S., Choi, J., & Park, J. (2018) · Journal of Pharmaceutical Investigation · doi:10.1007/s40005-018-0394-4 · Cited by 78
“Diabetes mellitus Type 2, Dyslipidemia Berberine Zhang et al. (2008)”
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
Pierro, F. D., Putignano, P., Montesi, L., Moscatiello, S., Marchesini, G., & Villanova, N. (2013) · Clinical Pharmacology Advances and Applications · doi:10.2147/cpaa.s54308 · Cited by 78
Gut Microbiota-Regulated Pharmacokinetics of Berberine and Active Metabolites in Beagle Dogs After Oral Administration
Feng, R., Zhao, Z., Ma, S.-R., Guo, F., Wang, Y., & Jiang, J.-D. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.00214 · Cited by 79
“…anticancer (Iizuka et al., 2000), cardioprotective (Wang et al., 1994), anti-inflammatory (Chang et al., 1990), and especially, anti-hyperlipidemia (Zhang et al., 2008, 2010; Derosa et al., 2013; Dong et al., 2013) effects, that lower the total cholesterol (TC), triglyceride (TG), and…”
Background
Dose-Dependent AMPK-Dependent and Independent Mechanisms of Berberine and Metformin Inhibition of mTORC1, ERK, DNA Synthesis and Proliferation in Pancreatic Cancer Cells
Ming, M., Sinnett‐Smith, J. W., Wang, J., Soares, H. P., Young, S. H., Eibl, G., & Rozengurt, E. (2014) · PLoS ONE · doi:10.1371/journal.pone.0114573 · Cited by 78
Protective mechanisms of berberine against experimental autoimmune myocarditis in a rat model
Liu, X., Zhang, X., Ye, L., & Yuan, H. (2016) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2016.02.015 · Cited by 77
Anticancer effect of berberine based on experimental animal models of various cancers: a systematic review and meta-analysis
Xu, J., Long, Y., Ni, L., Yuan, X., Yu, N. H., Wu, R., Tao, J., & Zhang, Y. (2019) · BMC Cancer · doi:10.1186/s12885-019-5791-1 · Cited by 78
Self-citation
Metformin and Berberine Prevent Olanzapine-Induced Weight Gain in Rats
Hu, Y., Young, A. J., Ehli, E. A., Nowotny, D., Davies, P. S., Droke, E. A., Soundy, T. J., & Davies, G. E. (2014) · PLoS ONE · doi:10.1371/journal.pone.0093310 · Cited by 76
“In the last decade, emerging evidence demonstrated that berberine treatment can induce weight loss in rodents [29,30] and human subjects [31,32].”
Background
A nutraceutical combination improves insulin sensitivity in patients with metabolic syndrome
Affuso, F. (2012) · World Journal of Cardiology · doi:10.4330/wjc.v4.i3.77 · Cited by 75
MYC is a positive regulator of choline metabolism and impedes mitophagy-dependent necroptosis in diffuse large B-cell lymphoma
Xiong, J., Wang, L., Fei, X.-C., Jiang, X.-F., Zheng, Z., Zhao, Y., Wang, C., Li, B., Chen, S.-J., Janin, A., et al. (2017) · Blood Cancer Journal · doi:10.1038/bcj.2017.61 · Cited by 75
Optimization of yeast-based production of medicinal protoberberine alkaloids
Galanie, S. S., & Smolke, C. D. (2015) · Microbial Cell Factories · doi:10.1186/s12934-015-0332-3 · Cited by 75
“Protoberberine alkaloids possess many reported bioactivities, including amelioration of multiple sclerosis in a mouse model [2], mitochondrially-mediated arrest of cell proliferation [3], and decreased blood sugar and cholesterol in diabetic patients [4].”
Background
Berberine Acutely Inhibits Insulin Secretion from β-Cells through 3′,5′-Cyclic Adenosine 5′-Monophosphate Signaling Pathway
Zhou, L., Wang, X., Shao, L., Yang, Y., Shang, W., Yuan, G., Jiang, B., Li, F., Tang, J., Hua, J., et al. (2008) · Endocrinology · doi:10.1210/en.2007-1752 · Cited by 73
“In a randomized, double-blind, and placebo-controlled trial, berberine decreased fasting and postprandial plasma glucose with slightly decreasing postprandial insulin and body weight reduction in type 2 diabetics after 3 months treatment (29), in agreement with the current animal experiment.”
Result
Redox regulation in health and disease — Therapeutic potential of berberine
Siow, Y. L., Sarna, L. K., & Karmin, O. (2011) · Food Research International · doi:10.1016/j.foodres.2010.12.038 · Cited by 72
8,8-Dimethyldihydroberberine with improved bioavailability and oral efficacy on obese and diabetic mouse models
Cheng, Z., Chen, A.-F., Wu, F., Li, S., Zhang, H., Gu, M., Li, Y., Zhang, L.-N., Hu, L., Li, J.-Y., et al. (2010) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2010.06.085 · Cited by 71
In vitro and in vivo antidiabetic activity of isolated fraction of Prosopis cineraria against streptozotocin-induced experimental diabetes: A mechanistic study
Soni, L. K., Dobhal, M. P., Arya, D. V., Bhagour, K., Parasher, P., & Gupta, R. S. (2018) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2018.09.099 · Cited by 72
Natural Alkaloids and Diabetes Mellitus: A Review
Ajebli, M., Khan, H., & Eddouks, M. (2020) · Endocrine Metabolic & Immune Disorders - Drug Targets · doi:10.2174/1871530320666200821124817 · Cited by 74
Medicinal plants and bioactive natural compounds as inhibitors of HMG‐CoA reductase: A literature review
Mahdavi, A., Bagherniya, M., Fakheran, O., Reiner, Ž., Xu, S., & Sahebkar, A. (2020) · BioFactors · doi:10.1002/biof.1684 · Cited by 74
State of the art papers Dietary and nutraceutical approach to type 2 diabetes
Derosa, G., Limas, C. P., Macías, P. C., Estrella, A., & Maffioli, P. (2014) · Archives of Medical Science · doi:10.5114/aoms.2014.42587 · Cited by 74
“[39] described similar results when they treated type 2 diabetic and dyslipidemic patients with berberine.”
Result
Berberine Suppresses Adipocyte Differentiation via Decreasing CREB Transcriptional Activity
Zhang, J., Tang, H., Deng, R., Wang, N., Zhang, Y., Wang, Y., Liu, Y., Li, F., Wang, X., & Zhou, L. (2015) · PLoS ONE · doi:10.1371/journal.pone.0125667 · Cited by 70
“In a randomized, double-blind, and placebo-controlled trial, berberine decreased fasting and postprandial plasma glucose with a slight decrease in body weight in type 2 diabetics after 3 months treatment [6].”
BackgroundSelf-citation
Hippocampal synaptic plasticity restoration and anti-apoptotic effect underlie berberine improvement of learning and memory in streptozotocin-diabetic rats
Moghaddam, H. K., Baluchnejadmojarad, T., Roghani, M., Goshadrou, F., & Ronaghi, A. (2012) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2012.10.020 · Cited by 70
“A number of clinical and preclinical investigations have shown beneficial effects of berberine in diabetes (Bhutada et al., 2011; Cok et al., 2011; Gu et al., 2010; Zhang et al., 2008).”
Background
Berberine attenuates autophagy in adipocytes by targeting BECN1
Deng, Y., Xu, J., Zhang, X., Yang, J., Zhang, D., Huang, J. Y., Lv, P., Shen, W., & Yang, Y. (2014) · Autophagy · doi:10.4161/auto.29746 · Cited by 69
“However, in rodents and humans, BBR has been verified as having many beneficial metabolic effects in diabetic and insulin-resistant states, although the precise mechanisms are not yet entirely clear.(10,14) Here, we identify a novel target of BBR activity in adipocytes, BECN1-dependent autophagy that may have importan…”
BackgroundSelf-citation
Role of plant-derived alkaloids against diabetes and diabetes-related complications: a mechanism-based approach
Kumar, A., Aswal, S., Semwal, R. B., Chauhan, A., Joshi, S. K., & Semwal, D. K. (2019) · Phytochemistry Reviews · doi:10.1007/s11101-019-09648-6 · Cited by 68
Functional inhibition of lactate dehydrogenase suppresses pancreatic adenocarcinoma progression
Cheng, C., Tan, H., Wang, N., Chen, L., Meng, Z., Chen, Z., & Feng, Y. (2021) · Clinical and Translational Medicine · doi:10.1002/ctm2.467 · Cited by 70
Update on the Benefits and Mechanisms of Action of the Bioactive Vegetal Alkaloid Berberine on Lipid Metabolism and Homeostasis
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Alteration of hepatic glutathione peroxidase and superoxide dismutase expression in streptozotocin-induced diabetic mice by berberine
Lao‐ong, T., Chatuphonprasert, W., Nemoto, N., & Jarukamjorn, K. (2012) · Pharmaceutical Biology · doi:10.3109/13880209.2012.655377 · Cited by 68
“Intragastric administration of berberine at a dose of 100 mg/kg/d for 2 weeks, or 250 mg/kg/d (orally) for 4 weeks, decreased level of FBG in mice (Zhang et al., 2008; Wang et al., 2010; Tang et al., 2006).”
Background
Berberine suppresses intestinal disaccharidases with beneficial metabolic effects in diabetic states, evidences from in vivo and in vitro study
Liu, L., Yu, Y., Yang, J., Yang, L., Liu, Y., Liang, Y., Liu, X., Xie, L. Y., & Wang, G. (2010) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-010-0502-0 · Cited by 68
“The results indicated that berberine may reduce intestinal disaccharidase activities, resulting in the decrease of blood glucose levels in diabetic rats, which may be beneficial for the amelioration of diabetic states (Zhang et al. 2009; Yin et al. 2008; Zhang et al. 2008 ).”
BackgroundInfluentialSelf-citation
The Influence of Plant Extracts and Phytoconstituents on Antioxidant Enzymes Activity and Gene Expression in the Prevention and Treatment of Impaired Glucose Homeostasis and Diabetes Complications
Mihailović, M., Dinić, S., Јovanović, J. A., Uskoković, A. S., Grdović, N., & Vidaković, M. (2021) · Antioxidants · doi:10.3390/antiox10030480 · Cited by 72
“) has been shown to regulate hyperglycemia and dyslipidemia in T2D patients [65] and to induce hepatic expression of CuZnSOD in STZ-NA diabetic mice [66].”
Background
Hypoglycemic effect of Gynostemma pentaphyllum saponins by enhancing the Nrf2 signaling pathway in STZ-inducing diabetic rats
Gao, D., Zhao, M., Qi, X., Liu, Y., Li, N., Liu, Z., & Bian, Y. (2014) · Archives of Pharmacal Research · doi:10.1007/s12272-014-0441-2 · Cited by 66
Berberine Pretreatment Confers Cardioprotection Against Ischemia–Reperfusion Injury in a Rat Model of Type 2 Diabetes
Chang, W., Li, K., Guan, F., Yao, F., Yu, Y., Zhang, M., Hatch, G. M., & Chen, L. (2016) · Journal of Cardiovascular Pharmacology and Therapeutics · doi:10.1177/1074248415627873 · Cited by 68
“The dose of BBR utilized in our study was similar to the dose utilized for controlling BG in a previous clinical study, which recommended 1000 mg/60 kg/d for optimum BG control in diabetic patients.(22) In the current study, short-term (7 days) BBR treatment profoundly reduced myocardial IS in the NIA of the heart in…”
Method
Chinese Medicine in the Battle Against Obesity and Metabolic Diseases
Xu, L., Zhao, W., Wang, D., & Ma, X. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.00850 · Cited by 65
“Later, Ning’s group showed the effectiveness of berberine in lipid and glycemic control in larger cohort of patients with Type 2 diabetes and hyperlipidemia based on comprehensive metabolomics (Zhang et al., 2008; Gu et al., 2010).”
Background
Berberine Influences Blood Glucose via Modulating the Gut Microbiome in Grass Carp
Pan, H., Li, Z., Xie, J., Liu, D., Wang, H., Yu, D., Zhang, Q., Hu, Z., & Shi, C. (2019) · Frontiers in Microbiology · doi:10.3389/fmicb.2019.01066 · Cited by 67
“Recently, accumulative evidence demonstrated that berberine is clinically effective in anti-diabetes in mammals due to its significant hypoglycemic (glucose-lowering) and hypolipidemic (lipid-lowering) effects (Chen and Xie, 1986; Zhang et al., 2008; Zhang H. et al., 2010; Cicero and Tartagni, 2012; Dong et al., 2013;…”
Background
Renoprotective effect of berberine on type 2 diabetic nephropathy in rats
Sun, S., Zhao, T., Zhang, H., Huang, X., Zhang, W., Zhang, L., Yan, M., Dong, X., Wang, H., Wen, Y., et al. (2015) · Clinical and Experimental Pharmacology and Physiology · doi:10.1111/1440-1681.12402 · Cited by 65
Activation of AMPK by berberine induces hepatic lipid accumulation by upregulation of fatty acid translocase CD36 in mice
Choi, Y., Lee, K.-Y., Jung, S.-H., Kim, H. S., Shim, G., Kim, M.-G., Oh, Y., Oh, S., Jun, D. W., & Lee, B. (2016) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2016.12.019 · Cited by 67
PCSK9 and diabetes: is there a link?
Momtazi‐Borojeni, A. A., Banach, M., Pirro, M., Stein, E. A., & Sahebkar, A. (2017) · Drug Discovery Today · doi:10.1016/j.drudis.2017.01.006 · Cited by 65
Tinospora cordifolia (Giloy): An insight on the multifarious pharmacological paradigms of a most promising medicinal ayurvedic herb
Gupta, A. K., Gupta, P., & Bajpai, G. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e26125 · Cited by 82
“Clinical trial Decrease plasma glucose and serum lipid concentrations [46].”
Background
Interaction of Herbal Compounds with Biological Targets: A Case Study with Berberine
Chen, X.-W., Di, Y. M., Zhang, J., Zhou, Z.-W., Li, C. G., & Zhou, S.-F. (2012) · The Scientific World JOURNAL · doi:10.1100/2012/708292 · Cited by 62
“[61] conducted a randomized, double-blind, placebo-controlled multicenter trial (n = 116).”
Background
Effects of Berberine on Amelioration of Hyperglycemia and Oxidative Stress in High Glucose and High Fat Diet-Induced Diabetic Hamsters In Vivo
Liu, C., Wang, Z., Song, Y., Wu, D., Zheng, X., Li, P., Jin, J., Xu, N., & Li, L. (2015) · BioMed Research International · doi:10.1155/2015/313808 · Cited by 63
Positive correlations of liver enzymes with metabolic syndrome including insulin resistance in newly diagnosed type 2 diabetes mellitus
Zhang, Y., Lu, X., Hong, J., Chao, M., Gu, W., Wang, W., & Ning, G. (2010) · Endocrine · doi:10.1007/s12020-010-9369-6 · Cited by 61
Self-citation
Inhibition of M1 macrophage activation in adipose tissue by berberine improves insulin resistance
Ye, L., Shu, L., Guo, C., Yu, X., Zhao, J., Zhang, H., & Shang, W. (2016) · Life Sciences · doi:10.1016/j.lfs.2016.09.025 · Cited by 63
A Novel Promising Frontier for Human Health: The Beneficial Effects of Nutraceuticals in Cardiovascular Diseases
Carrizzo, A., Izzo, C., Forte, M., Sommella, E., Pietro, P. D., Venturini, E., Ciccarelli, M., Galasso, G., Rubattu, S. D., Campiglia, P., et al. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21228706 · Cited by 65
“Berberine, similar to curcumin, has been associated with antioxidant and anti-inflammatory properties [327,328].”
Background
Natural products and analogs as preventive agents for metabolic syndrome via peroxisome proliferator-activated receptors: An overview
Villarroel-Vicente, C., Gutiérrez-Palomo, S., Ferri, J., Cortés, D., & Cabedo, N. (2021) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2021.113535 · Cited by 63
Berberine regulates peroxisome proliferator-activated receptors and positive transcription elongation factor b expression in diabetic adipocytes
Zhou, J., & Zhou, S. (2010) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2010.09.030 · Cited by 61
Improvement of superoxide dismutase and catalase in streptozotocin–nicotinamide-induced type 2-diabetes in mice by berberine and glibenclamide
Chatuphonprasert, W., Lao‐ong, T., & Jarukamjorn, K. (2013) · Pharmaceutical Biology · doi:10.3109/13880209.2013.839714 · Cited by 61
“These observations supported the hypoglycemic potential of berberine on the DM type 2 (Lao-ong et al., 2012; Zhang et al., 2008, 2011).”
BackgroundResultInfluential
Dietary Supplements and Natural Products: An Update on Their Clinical Effectiveness and Molecular Mechanisms of Action During Accelerated Biological Aging
Chen, Y., Hamidu, S., Yang, X., Yan, Y., Wang, Q., Li, L., Oduro, P. K., & Li, Y. (2022) · Frontiers in Genetics · doi:10.3389/fgene.2022.880421 · Cited by 62
Berberine inhibits intestinal carcinogenesis by suppressing intestinal pro-inflammatory genes and oncogenic factors through modulating gut microbiota
Chen, H., Ye, C., Cai, B., Zhang, F., Wang, X., Zhang, J., Zhang, Z., Guo, Y., & Yao, Q. (2022) · BMC Cancer · doi:10.1186/s12885-022-09635-9 · Cited by 60
Synthesis and structure–activity relationship of berberine analogues in LDLR up-regulation and AMPK activation
Wang, Y., Kong, W., Li, Y., Tang, S., Li, Z., Li, Y.-B., Shan, Y., Bi, C., Jiang, J., & Song, D. (2012) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2012.09.029 · Cited by 60
Dietary supplementation with berberine improves growth performance and modulates the composition and function of cecal microbiota in yellow-feathered broilers
Zhu, C., Huang, K., Bai, Y., Feng, X., Gong, L., Wei, C., Huang, H., & Zhang, H. (2020) · Poultry Science · doi:10.1016/j.psj.2020.10.071 · Cited by 58
“Other studies in dyslipidemia patients and hyperlipidemic mice have also shown that serum total cholesterol, triglyceride, and LDL-C levels were reduced by BBR (Zhang et al., 2008).”
Background
Effect ofRhizoma coptidis(Huang Lian) on Treating Diabetes Mellitus
Pang, B., Yu, X., Zhou, Q., Zhao, T., Wang, H., Gu, C., & Tong, X. (2015) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2015/921416 · Cited by 59
“After referring to the documents, we found that several preparation formulations were mentioned to demonstrate hypoglycemic effects of RC, such as compound formula, decocting-free granules, BBR, total coptis alkaloids (TCA), pill, and tablet [17, 18, 65, 69, 75, 79, 80].”
Background
Berberine produces antidepressant-like effects in ovariectomized mice
Fan, J., Li, B., Ge, T., Zhang, Z., Lv, J., Zhao, J., Wang, P., Liu, W., Wang, X., Młyniec, K., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-01035-5 · Cited by 61
Self-citation
Effect of Berberine on Cardiovascular Disease Risk Factors: A Mechanistic Randomized Controlled Trial
Zhao, J. V., Yeung, W.-F., Chan, Y.-H., Vackova, D., Leung, J. Y. Y., Ip, D. K. M., Zhao, J., Ho, W.-K., Tse, H.-F., & Schooling, C. M. (2021) · Nutrients · doi:10.3390/nu13082550 · Cited by 58
“The sample size was estimated based on previous studies [32,43].”
Method
Berberine Reduces Lipid Accumulation by Promoting Fatty Acid Oxidation in Renal Tubular Epithelial Cells of the Diabetic Kidney
Rong, Q., Han, B., Li, Y., Yin, H., Li, J., & Hou, Y. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.729384 · Cited by 59
Phytochemicals for the treatment of metabolic diseases: Evidence from clinical studies
Luo, Y., Zeng, Y., Peng, J., Zhang, K., Wang, L., Feng, T., Nhamdriel, T., & Fan, G. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.115274 · Cited by 63
Berberine Nanosuspension Enhances Hypoglycemic Efficacy on Streptozotocin Induced Diabetic C57BL/6 Mice
Wang, Z., Wu, J., Zhou, Q. Y., Wang, Y., & Chen, T. (2015) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2015/239749 · Cited by 60
Effects of Berberine on Atherosclerosis
Rui, R., Yang, H., Liu, Y., Zhou, Y., Xu, X., Li, C., & Liu, S. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.764175 · Cited by 62
Significant pharmacokinetic differences of berberine are attributable to variations in gut microbiota between Africans and Chinese
Alolga, R. N., Fan, Y., Chen, Z., Liu, L., Zhao, Y., Li, J., Chen, Y., Lai, M., Li, P., & Qi, L. (2016) · Scientific Reports · doi:10.1038/srep27671 · Cited by 57
Berberine Suppresses Th17 and Dendritic Cell Responses
Yang, Y., Qi, J., Wang, Q., Du, L., Zhou, Y. N., Yu, H., Kijlstra, A., & Yang, P. (2013) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.12-11217 · Cited by 56
Renoprotective effects of berberine and its possible molecular mechanisms in combination of high-fat diet and low-dose streptozotocin-induced diabetic rats
Wang, F. L., Tang, L. Q., Yang, F., Zhu, L. N., Cai, M., & Wei, W. (2012) · Molecular Biology Reports · doi:10.1007/s11033-012-2321-5 · Cited by 56
“In addition, BBR has been shown to reduce serum TC, TG, and LDL-c in the patients with hypercholesterolemia and high- fat diet fed animals [8, 12].”
Background
Organic cation transporter-mediated drug-drug interaction potential between berberine and metformin
Kwon, M., Choi, Y. A., Choi, M.-K., & Song, I.-S. (2015) · Archives of Pharmacal Research · doi:10.1007/s12272-014-0510-6 · Cited by 56
A bird's eye view on a therapeutically ‘wonder molecule’: Berberine
Patel, P. K. (2021) · Phytomedicine Plus · doi:10.1016/j.phyplu.2021.100070 · Cited by 57
Effectiveness and safety of Bifidobacterium and berberine in human hyperglycemia and their regulatory effect on the gut microbiota: a multi-center, double-blind, randomized, parallel-controlled study
Ming, J., Yu, X., Xu, X., Wang, L., Ding, C., Wang, Z., Xie, X., Li, S., Yang, W., Luo, S., et al. (2021) · Genome Medicine · doi:10.1186/s13073-021-00942-7 · Cited by 52
“Berberine administered orally has poor intestinal absorption and bioavailability [7] and low serum concentration [8], resulting in concerns over its effect on the gut microbiota.”
Background
Berberine-induced activation of 5′-adenosine monophosphate–activated protein kinase and glucose transport in rat skeletal muscles
Ma, X., Egawa, T., Kimura, H., Karaike, K., Masuda, S., Iwanaka, N., & Hayashi, T. (2010) · Metabolism · doi:10.1016/j.metabol.2010.03.009 · Cited by 54
“5 g daily) [20, 21] results in AMPK activation in human skeletal muscle.”
Background
Repurposing Drugs to Target the Diabetes Epidemic
Turner, N. A., Zeng, X., Osborne, B., Rogers, S., & Ye, J.-M. (2016) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2016.01.007 · Cited by 59
“Berberine Infectious diarrhea Activates AMPK by inhibiting mitochondrial complex 1 [74,75,77,78] [76,83] NCT02084004”
Therapeutic potential and recent delivery systems of berberine: A wonder molecule
Raju, M., Kulkarni, Y. A., & Wairkar, S. (2019) · Journal of Functional Foods · doi:10.1016/j.jff.2019.103517 · Cited by 52
Berberine Phospholipid Is an Effective Insulin Sensitizer and Improves Metabolic and Hormonal Disorders in Women with Polycystic Ovary Syndrome: A One-Group Pretest–Post-Test Explanatory Study
Rondanelli, M., Riva, A., Petrangolini, G., Allegrini, P., Giacosa, A., Fazia, T., Bernardinelli, L., Gasparri, C., Peroni, G., & Perna, S. (2021) · Nutrients · doi:10.3390/nu13103665 · Cited by 56
Enhancement of Sodium Caprate on Intestine Absorption and Antidiabetic Action of Berberine
Lv, X., Li, J., Zhang, M., Wang, C., Fan, Z., Wang, C., & Chen, L. (2010) · AAPS PharmSciTech · doi:10.1208/s12249-010-9386-z · Cited by 53
Efficacy and safety of berberine alone or combined with statins for the treatment of hyperlipidemia: A systematic review and meta-analysis of randomized controlled clinical trials
Zhang, L.-S., Zhang, J.-H., Feng, R., Jin, X.-Y., Yang, F.-W., Ji, Z.-C., Zhao, M.-Y., Zhang, M.-Y., Zhang, B.-L., & Li, X.-M. (2019) · The American Journal of Chinese Medicine · doi:10.1142/s0192415x19500393 · Cited by 50
Self-citation
Berberine improves free-fatty-acid–induced insulin resistance in L6 myotubes through inhibiting peroxisome proliferator–activated receptor γ and fatty acid transferase expressions
Chen, Y., Li, Y., Wang, Y., Wen, Y., & Sun, C. (2009) · Metabolism · doi:10.1016/j.metabol.2009.06.009 · Cited by 52
“Recent studies have shown that dietary supplementation of BBR improves the conditions of diabetes [21,22] by increasing insulin secretion [23,24] and glucose uptake [23,25,26].”
Background
Berberine ameliorates intrahippocampal kainate-induced status epilepticus and consequent epileptogenic process in the rat: Underlying mechanisms
Sedaghat, R., Taab, Y., Kiasalari, Z., Afshin‐Majd, S., Baluchnejadmojarad, T., & Roghani, M. (2017) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2016.12.109 · Cited by 52
New Therapeutic Approaches in Obesity and Metabolic Syndrome Associated with Polycystic Ovary Syndrome
Saleem, F., & Rizvi, S. W. (2017) · Cureus · doi:10.7759/cureus.1844 · Cited by 56
Targeting metabolic syndrome: Candidate natural agents
Xia, X., & Weng, J. (2010) · Journal of Diabetes · doi:10.1111/j.1753-0407.2010.00090.x · Cited by 51
“Recently, Zhang et al.5 and Kong et al.6 reported on the beneficial effects of BBR in Type 2 diabetes and dyslipidemia.”
Background
Berberine ameliorates hyperglycemia in alloxan-induced diabetic C57BL/6 mice through activation of Akt signaling pathway
Xie, X., Li, W., Lan, T., Liu, W., Peng, J., Huang, K., Huang, J., Shen, X., Liu, P., & Huang, H. (2011) · Endocrine Journal · doi:10.1507/endocrj.k11e-024 · Cited by 52
“BBR has exhibited hypoglycemic, hypolipidemic, anti-oxidation, antitumor and anti-aldose reductase effect, which presents wide clinical values and perspectives in treating diabetes and its complications [13-18].”
BackgroundSelf-citation
Design, synthesis, and cholesterol-lowering efficacy for prodrugs of berberrubine
Li, Y., Li, Y., Yang, P., Kong, W., You, X., Ren, G., Deng, H., Wang, Y., Wang, Y., Jiang, J., et al. (2010) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2010.06.106 · Cited by 51
Self-citation
The Effect of Berberis Vulgaris Extract on Transaminase Activities in Non-Alcoholic Fatty Liver Disease
Kashkooli, R. I., Najafi, S. S., Sharif, F., Hamedi, A., Asl, M. K. H., Kalyani, M. N., & Birjandi, M. (2015) · Hepatitis Monthly · doi:10.5812/hepatmon.25067 · Cited by 51
Antidiabetic and Hypolipidemic Activities ofCurculigo latifoliaFruit:Root Extract in High Fat Fed Diet and Low Dose STZ Induced Diabetic Rats
Ishak, N. A., Ismail, M., Hamid, M., Ahmad, Z., & Ghafar, S. A. A. (2013) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2013/601838 · Cited by 50
“Meanwhile, low dose of STZ has known to induce mild defect in insulin secretion, which is similar to the characteristics of the later stage of type 2 diabetes [14].”
Result
New Insights into the Mechanisms of Chinese Herbal Products on Diabetes: A Focus on the “Bacteria-Mucosal Immunity-Inflammation-Diabetes” Axis
Gao, Z., Li, Q., Wu, X., Zhao, X., Zhao, L., & Tong, X. (2017) · Journal of Immunology Research · doi:10.1155/2017/1813086 · Cited by 50
The Hypoglycemic Effect of Berberine and Berberrubine Involves Modulation of Intestinal Farnesoid X Receptor Signaling Pathway and Inhibition of Hepatic Gluconeogenesis
Sun, R., Kong, B., Yang, N., Cao, B., Feng, D., Yu, X., Ge, C., Feng, S., Fei, F., Huang, J., et al. (2020) · Drug Metabolism and Disposition · doi:10.1124/dmd.120.000215 · Cited by 50
“…diseases including diarrhea, obesity, NAFLD, and various tumors in both animal models and human because of its antimicrobial, antiprotozoal, antioxidant, anti-inflammatory, and immunomodulatory properties (Yin et al., 2008; Zhang et al., 2008; Xing et al., 2011; Yu et al., 2015; Zou et al., 2017).”
BackgroundMethod
Efficacy of berberine alone and in combination for the treatment of hyperlipidemia: A systematic review
Koppen, L. M., Whitaker, A., Rosene, A., & Beckett, R. D. (2017) · Journal of Evidence-Based Complementary & Alternative Medicine · doi:10.1177/2156587216687695 · Cited by 47
“The average blood pressure in both groups was 122/76 mm Hg.21 The least square mean change in LDL from baseline to week 12 was 12 mg/dL (95% confidence interval [CI] 20.06 to 4.03 mg/dL) in the placebo group and 23.25 mg/dL (95% CI 27.08 to 15.34 mg/dL) in the NC group.”
BackgroundMethodInfluential
Berberine prevents NAFLD and HCC by modulating metabolic disorders
Lin, X., Zhang, J., Chu, Y., Nie, Q., & Zhang, J. (2024) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2024.108593 · Cited by 56
Efficacy and Tolerability of a Nutraceutical Combination (Red Yeast Rice, Policosanols, and Berberine) in Patients with Low-Moderate Risk Hypercholesterolemia: A Double-Blind, Placebo-Controlled Study
Gonnelli, S., Caffarelli, C., Stolakis, K., Cuda, C., Giordano, N. G., & Nuti, R. (2014) · Current Therapeutic Research · doi:10.1016/j.curtheres.2014.07.003 · Cited by 49
“5 g/d) were often associated with gastrointestinal disorders.(22) Therefore, berberine and”
Background
Beneficial Effects of Berberine on Oxidized LDL-Induced Cytotoxicity to Human Retinal Müller Cells
Fu, D., Yu, Y., Connell, A. R., Yang, S., Hookham, M. B., McLeese, R. H., & Lyons, T. J. (2016) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.16-19291 · Cited by 49
NMR-based metabonomic study of Chinese medicine Gegen Qinlian Decoction as an effective treatment for type 2 diabetes in rats
Tian, N., Wang, J., Wang, P., Song, X., Yang, M., & Kong, L. (2013) · Metabolomics · doi:10.1007/s11306-013-0535-8 · Cited by 48
“Nowadays, metabonomics has been widely used in various diseases such as diabetes (Gu et al. 2010; Zhang et al. 2008b; Jankevics et al. 2009), cancer (Odunsi et al. 2005) and inborn errors of metabolism (Nicholson et al. 2002; Bino et al. 2004).”
MethodResultInfluential

Authors: Zhang, Y., Li, X., Zou, D., Liu, W., Yang, J., Zhu, N., Huo, L., Wang, M., Hong, J., Wu, P., Ren, G., & Ning, G.
Affiliations: Shanghai Jiao Tong University (CN)
Second Military Medical University (CN)
Department of Endocrinology (J.Y., G.R.), Min-Hang Hospital, Shanghai 201100, People’s Republic of China
Corresponding author: Ning, Guang
ORCID: Zhang, Yifei
Liu, Wei
Yang, Jialin
Zhu, Na
Wang, Miao
Hong, Jie
Ning, Guang
Venue: The Journal of Clinical Endocrinology & Metabolism
Publisher: The Endocrine Society
Published: 2008-07-01
Volume: 93
Issue: 7
Pages: 2559-2565
ISSN: 0021-972X (ISSN-L)
1945-7197
DOI: 10.1210/jc.2007-2404
OpenAlex: W1969395627
Cited by: 573
References: 23
Citations by year: 2026: 30 · 2025: 27 · 2024: 28 · 2023: 33 · 2022: 41 · 2021: 54 · 2020: 46 · 2019: 42 · 2018: 33 · 2017: 23 · 2016: 29 · 2015: 32 · 2014: 34 · 2013: 31 · 2012: 25
FWCI: 14.72
Type: journal article
Language: en
Open access: closed
Locations: The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Pharmacology (medical) › Berberine and alkaloids research
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Natural Antidiabetic Agents Studies
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords: berberine, type 2 diabetes, dyslipidemia, glucose-lowering effect, insulin sensitivity, glucose disposal rate, hyperinsulinemic-euglycemic clamp, HbA1c, serum lipids, triglycerides, LDL cholesterol, total cholesterol, plant alkaloids, constipation, drug safety, antidiabetic therapy, lipid-lowering therapy
MeSH terms: Adult, Aged, Berberine, Diabetes Mellitus, Type 2, Double-Blind Method, Female, Glycated Hemoglobin, Humans, Insulin, Insulin Resistance, Cholesterol, LDL, Male, Middle Aged, Triglycerides, Dyslipidemias

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Treatment of Type 2 Diabetes and Dyslipidemia with the Natural Plant Alkaloid Berberine

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