Overview

Berberine is a chemical found in several plants including European barberry, goldenseal, goldthread, Oregon grape, phellodendron, and tree turmeric.

Berberine is most commonly taken by mouth for diabetes, high levels of cholesterol or other fats (lipids) in the blood (hyperlipidemia), and high blood pressure. It is also applied to the skin to treat burns and canker sores, but there is no good scientific evidence to support these uses.

Classification

Is a Form Of:

Chemical found in plants

Primary Functions:

Diabetes, cholesterol

Also Known As:

Alcaloïde de Berbérine, Berberina, Berbérine, Berberine Alkaloid, Berberine Complex,

How Does It Work?

Berberine might cause stronger heartbeats. This might help people with certain heart conditions. Berberine might also help regulate how the body uses sugar in the blood. This might help people with diabetes. It also might also be able to kill bacteria and reduce swelling.

Uses

• Canker sores. Research shows that applying a gel containing berberine can reduce pain, redness, oozing, and the size of ulcers in people with canker sores.
• Diabetes. Berberine seems to slightly reduce blood sugar levels in people with diabetes. Also, some early research suggests that taking 500 mg of berberine 2-3 times daily for up to 3 months might control blood sugar as effectively as metformin or rosiglitazone.
• High levels of cholesterol or other fats (lipids) in the blood (hyperlipidemia). Berberine might help lower cholesterol levels in people with high cholesterol. Taking berberine for up to 2 years seems to reduce total cholesterol, low-density lipoprotein (LDL or "bad") cholesterol, and triglyceride levels in people with high cholesterol. When compared with standard cholesterol-lowering medications, berberine appears to cause similar changes in total cholesterol, LDL cholesterol, and high-density lipoprotein (HDL or "good") cholesterol, and it might be better at reducing triglyceride levels.
• High blood pressure. Taking 0.9 grams of berberine per day along with the blood pressure-lowering drug amlodipine reduces systolic blood pressure (the top number) and diastolic blood pressure (the bottom number) better than taking amlodipine alone in people with high blood pressure.
• A hormonal disorder that causes enlarged ovaries with cysts (polycystic ovary syndrome or PCOS). Research shows that berberine can lower blood sugar, improve cholesterol and triglyceride levels, reduce testosterone levels, and lower waist-to-hip ratio in women with PCOS. Berberine may even lower blood sugar levels similar to metformin and may improve cholesterol levels better than metformin. It is unclear if berberine increases pregnancy rates or live birth rates in women with PCOS.

Recommended Dosing

ADULTS

BY MOUTH:

• For diabetes: 0.9-1.5 grams of berberine has been taken in divided doses daily for 2-4 months.
• For high levels of cholesterol or other fats (lipids) in the blood (hyperlipidemia): 0.6-1.5 grams of berberine has been taken in divided doses daily for 6 to 24 months. Combination products containing 500 mg of berberine, 10 mg of policosanol, and 200 mg of red yeast rice, along with other ingredients, have been taken daily for up to 12 months.
• For high blood pressure: 0.9 grams of berberine has been taken daily for 2 months.
• For a hormonal disorder that causes enlarged ovaries with cysts (polycystic ovary syndrome or PCOS): 1.5 grams of berberine has been taken daily for 3-6 months.

APPLIED TO THE SKIN:

• For canker sores: Gel containing 5 mg of berberine per gram has been applied four times per day for 5 days.

Berberine Supplements Frequently Asked Questions

What does berberine do for the body?

A compound called berberine is one of the most effective natural supplements available. It has very impressive health benefits, and affects your body at the molecular level. Berberine has been shown to lower blood sugar, cause weight loss and improve heart health, to name a few.

What are the side effects of berberine?

Side effects. Most studies have found no serious side effects of berberine. However, it may cause digestive side effects, such as an upset stomach, constipation, or nausea. Berberine can also cause a rash or headache in some people.

Is berberine safe for long term use?

The mechanism for berberine extract is very unclear. For decades it has been a well-researched herbal treatment for intestinal infections, like Giardia, but it came with the warning to avoid long-term use due to the potential undesirable and antimicrobial effect in the gut.

What is the best berberine supplement?

Best Berberine Supplements

• Nutrivein Premium Berberine.
• Purely Optimal Premium Berberine Supplement.
• N1 Nutrition Premium Berberine.

Is berberine bad for liver?

It is normally removed by the liver. Berberine may keep the liver from removing bilirubin fast enough. This can cause brain problems, especially in infants with high levels of bilirubin in the blood. Avoid using.

Is berberine toxic to the liver?

The toxicity of pure compound is greater than the toxicity of plant extract or plant extract fractions. The sub-acute concentrations of berberine lead to altered liver function, gastric troubles, hepato and hematotoxicity, hemorrhagic inflammatory consequences, damage to immune cells and induced apoptosis.

Does berberine kill viruses?

Berberine also kills herpes simplex virus, which is often treated with the prescription drug acyclovir. Berberine protects neurons in your brain and reduces inflammation, so it helps with a traumatic brain injury.

Can berberine cause weight gain?

Berberine may also be effective as a weight loss supplement. So far, two studies have examined the effects on body weight. In a 12-week study in obese individuals, 500 mg taken three times per day caused about 5 pounds of weight loss, on average.

Is berberine bad for kidneys?

Berberine (BBR) has been shown to have antifibrotic effects in liver, kidney and lung. We found that BBR treatment attenuated renal fibrosis by activating the nuclear factor-erythroid 2-related factor 2 (Nrf2) signaling pathway in the diabetic kidneys.

Is turmeric a berberine?

Share on Pinterest Berberine, which is a compound in tree turmeric, is an effective antimicrobial agent. Berberine could be an effective antimicrobial agent. A laboratory study found that berberine helped inhibit the growth of Staphylococcus aureus.

Which is better metformin or berberine?

Berberine, an isoquinoline alkaloid derived from medicinal herbs including Coptis chinensis and Hydrastis canadensis (Goldenseal), has been found in previous studies of type 2 diabetic patients to have hypoglycemic effects comparable to those of metformin at the same dosage (500 mg 3 times/day).

Can berberine be toxic?

The toxicity of pure compound is greater than the toxicity of plant extract or plant extract fractions. The sub-acute concentrations of berberine lead to altered liver function, gastric troubles, hepato and hematotoxicity, hemorrhagic inflammatory consequences, damage to immune cells and induced apoptosis.

What foods contain berberine?

Berberine is a chemical found in several plants including European barberry, goldenseal, goldthread, Oregon grape, phellodendron, and tree turmeric. Berberine is most commonly taken by mouth for diabetes, high levels of cholesterol or other fats (lipids) in the blood (hyperlipidemia), and high blood pressure.

What is the best way to take berberine?

It is common to take 500 mg, 3 times per day, before meals (a total of 1500 mg per day). Berberine has a half-life of several hours, so it is necessary to spread your dosage to several times per day to achieve stable blood levels.

What is the best time of day to take berberine?

Bottom Line: A common dosage recommendation is 500 mg, 3 times per day, half an hour before meals. Berberine may cause digestive side effects in some people.

Will berberine keep me awake?

Berberine might cause sleepiness and drowsiness. Medications that cause sleepiness are called sedatives. Taking berberine along with sedative medications might cause too much sleepiness.

s berberine good for fatty liver?

Berberine is a plant compound that has been shown to significantly reduce blood sugar, insulin and cholesterol levels, along with other health markers. Several studies also suggest that it may benefit people with fatty liver.

What bacteria does berberine kill?

Besides repressing or killing harmful gut bacteria, berberine has some positive effect on beneficial gut microbiota, such as Bifidobacterium adolescentis and Lactobacillus acidophilus.

What drugs interact with berberine?

Taking berberine along with medications that also slow clotting might increase the chances of bruising and bleeding. Some medications that slow blood clotting include aspirin, cilostazol (Pletal), clopidogrel (Plavix), dalteparin (Fragmin), enoxaparin (Lovenox), heparin, ticlopidine (Ticlid), and others.

Can berberine cause depression?

7 Wang et al reported that berberine could easily cross the blood‐brain barrier on systemic administration14 and recent studies show that berberine has a protective effect on central nervous system disorders, such as Alzheimer's, cerebral ischaemia, mental depression, schizophrenia, and anxiety.

Is berberine an antiviral?

Berberine, a natural isoquinoline alkaloid isolated from the berberis species, has a wide array of biological properties such as anti‐inflammatory, antibacterial, antifungal, and antihelminthic effects. We evaluated the antiviral effect of berberine against influenza A/FM1/1/47 (H1N1) in vivo and in vitro.

How long does it take berberine to start working?

How long before I can expect to see results with Berberine? Dr. Whitaker has noted that some people might see an improvement in fasting glucose after about 2 weeks of taking Berberine, however everyone is different.

Is berberine anti inflammatory?

Some research suggests that berberine has anti-inflammatory properties, which means that it could help treat diabetes and other inflammation-related health conditions.

How long can you safely take berberine?

Diabetes. Berberine seems to slightly reduce blood sugar levels in people with diabetes. Also, some early research suggests that taking 500 mg of berberine 2-3 times daily for up to 3 months might control blood sugar as effectively as metformin or rosiglitazone.

Clinical Studies

• ^ a b c d e f g Effects of a nutraceutical combination on left ventricular remodeling and vasoreactivity in subjects with the metabolic syndrome.
• ^ a b c d Cicero AF, Rovati LC, Setnikar I. Eulipidemic effects of berberine administered alone or in combination with other natural cholesterol-lowering agents. A single-blind clinical investigation. Arzneimittelforschung. (2007)
• ^ a b Marazzi G, et al. Long-term effects of nutraceuticals (berberine, red yeast rice, policosanol) in elderly hypercholesterolemic patients. Adv Ther. (2011)
• ^ a b c d e f g h Vuddanda PR, Chakraborty S, Singh S. Berberine: a potential phytochemical with multispectrum therapeutic activities. Expert Opin Investig Drugs. (2010)
• ^ Cernáková M, Kostálová D. Antimicrobial activity of berberine--a constituent of Mahonia aquifolium. Folia Microbiol (Praha). (2002)
• ^ Sheng WD, et al. Treatment of chloroquine-resistant malaria using pyrimethamine in combination with berberine, tetracycline or cotrimoxazole. East Afr Med J. (1997)
• ^ Kaneda Y, et al. In vitro effects of berberine sulphate on the growth and structure of Entamoeba histolytica, Giardia lamblia and Trichomonas vaginalis. Ann Trop Med Parasitol. (1991)
• ^ Ghosh AK, Bhattacharyya FK, Ghosh DK. Leishmania donovani: amastigote inhibition and mode of action of berberine. Exp Parasitol. (1985)
• ^ Kaneda Y, Tanaka T, Saw T. Effects of berberine, a plant alkaloid, on the growth of anaerobic protozoa in axenic culture. Tokai J Exp Clin Med. (1990)
• ^ Grycová L, Dostál J, Marek R. Quaternary protoberberine alkaloids. Phytochemistry. (2007)
• ^ a b c Singh IP, Mahajan S. Berberine and its derivatives: a patent review (2009 - 2012). Expert Opin Ther Pat. (2012)
• ^ Krivogorsky B, et al. Structure-activity studies of some berberine analogs as inhibitors of Toxoplasma gondii. Bioorg Med Chem Lett. (2012)
• ^ Avula B, Wang YH, Khan IA. Quantitative determination of alkaloids from roots of Hydrastis canadensis L. and dietary supplements using ultra-performance liquid chromatography with UV detection. J AOAC Int. (2012)
• ^ a b Chen J, et al. Analysis of major alkaloids in Rhizoma coptidis by capillary electrophoresis-electrospray-time of flight mass spectrometry with different background electrolytes. Electrophoresis. (2008)
• ^ a b c d Tillhon M, et al. Berberine: new perspectives for old remedies. Biochem Pharmacol. (2012)
• ^ a b Wang JR, et al. Formation and conformation of baicalin-berberine and wogonoside-berberine complexes. Chem Pharm Bull (Tokyo). (2012)
• ^ a b c d e f g Turner N, et al. 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)
• ^ a b Cheng Z, et al. 8,8-Dimethyldihydroberberine with improved bioavailability and oral efficacy on obese and diabetic mouse models. Bioorg Med Chem. (2010)
• ^ Subeki, et al. Antibabesial activity of protoberberine alkaloids and 20-hydroxyecdysone from Arcangelisia flava against Babesia gibsoni in culture. J Vet Med Sci. (2005)
• ^ Schramm A, et al. HERG channel inhibitors in extracts of Coptidis rhizoma. Planta Med. (2011)
• ^ Zhang TT, et al. CPU 86017, p-chlorobenzyltetrahydroberberine chloride, attenuates monocrotaline-induced pulmonary hypertension by suppressing endothelin pathway. Acta Pharmacol Sin. (2005)
• ^ Gao J, et al. Raisanberine protected pulmonary arterial rings and cardiac myocytes of rats against hypoxia injury by suppressing NADPH oxidase and calcium influx. Acta Pharmacol Sin. (2012)
• ^ a b c d Pan GY, et al. Inhibitory action of berberine on glucose absorption. Yao Xue Xue Bao. (2003)
• ^ Maeng HJ, et al. P-glycoprotein-mediated transport of berberine across Caco-2 cell monolayers. J Pharm Sci. (2002)
• ^ a b Chen W, et al. Bioavailability study of berberine and the enhancing effects of TPGS on intestinal absorption in rats. AAPS PharmSciTech. (2011)
• ^ Pan GY, et al. The involvement of P-glycoprotein in berberine absorption. Pharmacol Toxicol. (2002)
• ^ a b c Chae HW, et al. Effect of ion-pair formation with bile salts on the in vitro cellular transport of berberine. Arch Pharm Res. (2008)
• ^ Tsai P, Tsai TH. Simultaneous determination of berberine in rat blood, liver and bile using microdialysis coupled to high-performance liquid chromatography. J Chromatogr A. (2002)
• ^ a b Qiu W, et al. Effect of berberine on the pharmacokinetics of substrates of CYP3A and P-gp. Phytother Res. (2009)
• ^ Zhang X, et al. Intestinal absorption mechanisms of berberine, palmatine, jateorhizine, and coptisine: involvement of P-glycoprotein. Xenobiotica. (2011)
• ^ Hwang YH, et al. Effects of berberine and hwangryunhaedok-tang on oral bioavailability and pharmacokinetics of ciprofloxacin in rats. Evid Based Complement Alternat Med. (2012)
• ^ Shan YQ, et al. Berberine analogue IMB-Y53 improves glucose-lowering efficacy by averting cellular efflux especially P-glycoprotein efflux. Metabolism. (2012)
• ^ a b c d Di Pierro F, et al. Pilot study on the additive effects of berberine and oral type 2 diabetes agents for patients with suboptimal glycemic control. Diabetes Metab Syndr Obes. (2012)
• ^ Zhou Y, et al. Drug-drug interactions between ketoconazole and berberine in rats: pharmacokinetic effects benefit pharmacodynamic synergism. Phytother Res. (2012)
• ^ Reversible Increase in Tight Junction Permeability to Macromolecules in Rat Ileal Mucosa In Vitro by Sodium Caprate, a Constituent of Milk Fat.
• ^ a b c d e Zhang M, et al. Sodium caprate augments the hypoglycemic effect of berberine via AMPK in inhibiting hepatic gluconeogenesis. Mol Cell Endocrinol. (2012)
• ^ a b c d Enhancement of Sodium Caprate on Intestine Absorption and Antidiabetic Action of Berberine.
• ^ Fan D, et al. Enhancement by sodium caprate and sodium deoxycholate of the gastrointestinal absorption of berberine chloride in rats. Drug Dev Ind Pharm. (2012)
• ^ a b Zhang Y, et al. Treatment of type 2 diabetes and dyslipidemia with the natural plant alkaloid berberine. J Clin Endocrinol Metab. (2008)
• ^ Khin-Maung-U, et al. Clinical trial of berberine in acute watery diarrhoea. Br Med J (Clin Res Ed). (1985)
• ^ Khan AY, Hossain M, Kumar GS. Binding of plant alkaloids berberine and palmatine to serum albumins: a thermodynamic investigation. Mol Biol Rep. (2013)
• ^ Hazra S, Hossain M, Suresh Kumar G. Binding of isoquinoline alkaloids berberine, palmatine and coralyne to hemoglobin: structural and thermodynamic characterization studies. Mol Biosyst. (2013)
• ^ a b Wang YX, et al. Synthesis and structure-activity relationship of berberine analogues in LDLR up-regulation and AMPK activation. Bioorg Med Chem. (2012)
• ^ a b c d e f Li Y, et al. Bioactivities of berberine metabolites after transformation through CYP450 isoenzymes. J Transl Med. (2011)
• ^ a b Zuo F, et al. 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)
• ^ a b c Qiu F, et al. Isolation and identification of urinary metabolites of berberine in rats and humans. Drug Metab Dispos. (2008)
• ^ Pan JF, et al. Identification of three sulfate-conjugated metabolites of berberine chloride in healthy volunteers' urine after oral administration. Acta Pharmacol Sin. (2002)
• ^ Virtanen P, et al. Natural protoberberine alkaloids from Enantia chlorantha, palmatine, columbamine and jatrorrhizine for thioacetamide-traumatized rat liver. Acta Anat (Basel). (1988)
• ^ a b c Zhao Y, et al. The in vitro inhibition of human CYP1A2, CYP2D6 and CYP3A4 by tetrahydropalmatine, neferine and berberine. Phytother Res. (2012)
• ^ a b c Guo Y, et al. Repeated administration of berberine inhibits cytochromes P450 in humans. Eur J Clin Pharmacol. (2012)
• ^ a b Xin HW, et al. The effects of berberine on the pharmacokinetics of cyclosporin A in healthy volunteers. Methods Find Exp Clin Pharmacol. (2006)
• ^ a b Wu X, et al. Effects of berberine on the blood concentration of cyclosporin A in renal transplanted recipients: clinical and pharmacokinetic study. Eur J Clin Pharmacol. (2005)
• ^ Budzinski JW, et al. Modulation of human cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp) in Caco-2 cell monolayers by selected commercial-source milk thistle and goldenseal products. Can J Physiol Pharmacol. (2007)
• ^ Hermann R, von Richter O. Clinical evidence of herbal drugs as perpetrators of pharmacokinetic drug interactions. Planta Med. (2012)
• ^ Pharmacological and therapeutic effects of Berberis vulgaris and its active constituent, berberine.
• ^ a b Chatuphonprasert W, et al. Modulations of cytochrome P450 expression in diabetic mice by berberine. Chem Biol Interact. (2012)
• ^ Cheng Q, et al. Drug-metabolizing enzyme and transporter expression in a mouse model of diabetes and obesity. Mol Pharm. (2008)
• ^ a b Viollet B, et al. Cellular and molecular mechanisms of metformin: an overview. Clin Sci (Lond). (2012)
• ^ Han Y, et al. Redox regulation of the AMP-activated protein kinase. PLoS One. (2010)
• ^ Cheng Z, et al. Berberine-stimulated glucose uptake in L6 myotubes involves both AMPK and p38 MAPK. Biochim Biophys Acta. (2006)
• ^ a b c d e Wang H, et al. Atrogin-1 affects muscle protein synthesis and degradation when energy metabolism is impaired by the antidiabetes drug berberine. Diabetes. (2010)
• ^ a b c d Liu LZ, et al. The pivotal role of protein kinase C zeta (PKCzeta) in insulin- and AMP-activated protein kinase (AMPK)-mediated glucose uptake in muscle cells. Cell Signal. (2010)
• ^ a b c Kim WS, et al. Berberine improves lipid dysregulation in obesity by controlling central and peripheral AMPK activity. Am J Physiol Endocrinol Metab. (2009)
• ^ a b Brusq JM, et al. Inhibition of lipid synthesis through activation of AMP kinase: an additional mechanism for the hypolipidemic effects of berberine. J Lipid Res. (2006)
• ^ a b c Kong W, et al. Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins. Nat Med. (2004)
• ^ Hypothalamic malonyl-CoA triggers mitochondrial biogenesis and oxidative gene expression in skeletal muscle: Role of PGC-1α.
• ^ Turnley AM, et al. Cellular distribution and developmental expression of AMP-activated protein kinase isoforms in mouse central nervous system. J Neurochem. (1999)
• ^ Neidle S. Human telomeric G-quadruplex: the current status of telomeric G-quadruplexes as therapeutic targets in human cancer. FEBS J. (2010)
• ^ Ou TM, et al. G-quadruplexes: targets in anticancer drug design. ChemMedChem. (2008)
• ^ Monchaud D, Teulade-Fichou MP. A hitchhiker's guide to G-quadruplex ligands. Org Biomol Chem. (2008)
• ^ Arora A, et al. Binding of berberine to human telomeric quadruplex - spectroscopic, calorimetric and molecular modeling studies. FEBS J. (2008)
• ^ Zhang WJ, et al. 9-Substituted berberine derivatives as G-quadruplex stabilizing ligands in telomeric DNA. Bioorg Med Chem. (2007)
• ^ Ma Y, et al. Synthesis and evaluation of 9-O-substituted berberine derivatives containing aza-aromatic terminal group as highly selective telomeric G-quadruplex stabilizing ligands. Bioorg Med Chem Lett. (2009)
• ^ a b Bazzicalupi C, et al. The crystal structure of human telomeric DNA complexed with berberine: an interesting case of stacked ligand to G-tetrad ratio higher than 1:1. Nucleic Acids Res. (2012)
• ^ Naasani I, et al. FJ5002: a potent telomerase inhibitor identified by exploiting the disease-oriented screening program with COMPARE analysis. Cancer Res. (1999)
• ^ Mahata S, et al. Berberine modulates AP-1 activity to suppress HPV transcription and downstream signaling to induce growth arrest and apoptosis in cervical cancer cells. Mol Cancer. (2011)
• ^ Wang X, et al. The uptake and transport behavior of berberine in Coptidis Rhizoma extract through rat primary cultured cortical neurons. Neurosci Lett. (2005)
• ^ a b Olmez E, Ilhan M. Evaluation of the alpha-adrenoceptor antagonistic action of berberine in isolated organs. Arzneimittelforschung. (1992)
• ^ a b Hui KK, et al. Interaction of berberine with human platelet alpha 2 adrenoceptors. Life Sci. (1991)
• ^ Vizi ES, et al. Berbanes: a new class of selective alpha 2-adrenoceptor antagonists. J Med Chem. (1987)
• ^ Zhao X, et al. Screening the bioactive compounds in aqueous extract of Coptidis rhizoma which specifically bind to rabbit lung tissues beta2-adrenoceptor using an affinity chromatographic selection method. J Chromatogr B Analyt Technol Biomed Life Sci. (2010)
• ^ a b c d e f g h i j k l m Kulkarni SK, Dhir A. On the mechanism of antidepressant-like action of berberine chloride. Eur J Pharmacol. (2008)
• ^ a b c d e Berberine produces antidepressant-like effects in the forced swim test and in the tail suspension test in mice.
• ^ a b Kong LD, Cheng CH, Tan RX. Monoamine oxidase inhibitors from rhizoma of Coptis chinensis. Planta Med. (2001)
• ^ Castillo J, et al. LED fluorescence spectroscopy for direct determination of monoamine oxidase B inactivation. Anal Biochem. (2005)
• ^ a b Inhibition of Dopamine Biosynthesis by Protoberberine Alkaloids in PC12 Cells.
• ^ a b c Kalalian-Moghaddam H, et al. Hippocampal synaptic plasticity restoration and anti-apoptotic effect underlie berberine improvement of learning and memory in streptozotocin-diabetic rats. Eur J Pharmacol. (2013)
• ^ Reisi P, et al. Treadmill running improves long-term potentiation (LTP) defects in streptozotocin-induced diabetes at dentate gyrus in rats. Pathophysiology. (2010)
• ^ Artola A. Diabetes-, stress- and ageing-related changes in synaptic plasticity in hippocampus and neocortex--the same metaplastic process. Eur J Pharmacol. (2008)
• ^ Ye L, Wang F, Yang RH. Diabetes impairs learning performance and affects the mitochondrial function of hippocampal pyramidal neurons. Brain Res. (2011)
• ^ Bhutada P, et al. Protection of cholinergic and antioxidant system contributes to the effect of berberine ameliorating memory dysfunction in rat model of streptozotocin-induced diabetes. Behav Brain Res. (2011)
• ^ a b Kulkarni SK, Dhir A. Possible involvement of L-arginine-nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) signaling pathway in the antidepressant activity of berberine chloride. Eur J Pharmacol. (2007)
• ^ Kulkarni SK, Dhir A. sigma-1 receptors in major depression and anxiety. Expert Rev Neurother. (2009)
• ^ Understanding the Molecular Mechanism of Sigma-1 Receptors: Towards A Hypothesis that Sigma-1 Receptors are Intracellular Amplifiers for Signal Transduction.
• ^ Current hypotheses on sigma receptors and their physiological role: possible implications in psychiatry.
• ^ Monnet FP. Sigma-1 receptor as regulator of neuronal intracellular Ca2+: clinical and therapeutic relevance. Biol Cell. (2005)
• ^ Fontanilla D, et al. The hallucinogen N,N-dimethyltryptamine (DMT) is an endogenous sigma-1 receptor regulator. Science. (2009)
• ^ a b Huang L, et al. Berberine derivatives, with substituted amino groups linked at the 9-position, as inhibitors of acetylcholinesterase/butyrylcholinesterase. Bioorg Med Chem Lett. (2010)
• ^ Jung HA, et al. Anti-Alzheimer and antioxidant activities of Coptidis Rhizoma alkaloids. Biol Pharm Bull. (2009)
• ^ Ingkaninan K, et al. Acetylcholinesterase inhibitors from Stephania venosa tuber. J Pharm Pharmacol. (2006)
• ^ a b Chen XW, et al. Interaction of herbal compounds with biological targets: a case study with berberine. ScientificWorldJournal. (2012)
• ^ a b c Asai M, et al. Berberine alters the processing of Alzheimer's amyloid precursor protein to decrease Abeta secretion. Biochem Biophys Res Commun. (2007)
• ^ Zhu F, et al. Decrease in the production of β-amyloid by berberine inhibition of the expression of β-secretase in HEK293 cells. BMC Neurosci. (2011)
• ^ Lee B, et al. Phellodendron amurense and Its Major Alkaloid Compound, Berberine Ameliorates Scopolamine-Induced Neuronal Impairment and Memory Dysfunction in Rats. Korean J Physiol Pharmacol. (2012)
• ^ a b c Zhang Q, et al. Hypoxia-inducible factor 1 mediates the anti-apoptosis of berberine in neurons during hypoxia/ischemia. Acta Physiol Hung. (2012)
• ^ Hu J, et al. PI3K p55γ promoter activity enhancement is involved in the anti-apoptotic effect of berberine against cerebral ischemia-reperfusion. Eur J Pharmacol. (2012)
• ^ a b Kwon IH, et al. Effects of berberine on 6-hydroxydopamine-induced neurotoxicity in PC12 cells and a rat model of Parkinson's disease. Neurosci Lett. (2010)
• ^ Segura Aguilar J, Kostrzewa RM. Neurotoxins and neurotoxic species implicated in neurodegeneration. Neurotox Res. (2004)
• ^ Nagatsu T. Isoquinoline neurotoxins in the brain and Parkinson's disease. Neurosci Res. (1997)
• ^ a b Lee B, et al. Effect of berberine on depression- and anxiety-like behaviors and activation of the noradrenergic system induced by development of morphine dependence in rats. Korean J Physiol Pharmacol. (2012)
• ^ a b Chang W, et al. Berberine Attenuates Ischemia-Reperfusion Injury Via Regulation of Adenosine-5'-monophosphate Kinase Activity in Both Non-ischemic and Ischemic Areas of the Rat Heart. Cardiovasc Drugs Ther. (2012)
• ^ Wang LH, et al. Berberine alleviates ischemic arrhythmias via recovering depressed I(to) and I(Ca) currents in diabetic rats. Phytomedicine. (2012)
• ^ Gong LL, et al. Coptisine exert cardioprotective effect through anti-oxidative and inhibition of RhoA/Rho kinase pathway on isoproterenol-induced myocardial infarction in rats. Atherosclerosis. (2012)
• ^ Kim YM, et al. Palmatine from Coptidis rhizoma reduces ischemia-reperfusion-mediated acute myocardial injury in the rat. Food Chem Toxicol. (2009)
• ^ Soloff MS, et al. Cloning, characterization, and expression of the rat relaxin gene. Gene. (2003)
• ^ a b c Gu HP, et al. Up-regulating relaxin expression by G-quadruplex interactive ligand to achieve antifibrotic action. Endocrinology. (2012)
• ^ Du XJ, et al. Cardiovascular effects of relaxin: from basic science to clinical therapy. Nat Rev Cardiol. (2010)
• ^ Salehi S, Filtz TM. Berberine possesses muscarinic agonist-like properties in cultured rodent cardiomyocytes. Pharmacol Res. (2011)
• ^ Effect of berberine on Cdk9 and cyclin T1 expressions in myocardium of diabetic rats.
• ^ Zeng XH, Zeng XJ, Li YY. Efficacy and safety of berberine for congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol. (2003)
• ^ Zheng L, et al. Protective effect of berberine on cardiac myocyte injured by ischemia-reperfusion. Sichuan Da Xue Xue Bao Yi Xue Ban. (2003)
• ^ a b c d e f Xiao HB, et al. Berberine inhibits dyslipidemia in C57BL/6 mice with lipopolysaccharide induced inflammation. Pharmacol Rep. (2012)
• ^ Lee S, et al. Berberine-induced LDLR up-regulation involves JNK pathway. Biochem Biophys Res Commun. (2007)
• ^ Extracellular Signal-Regulated Kinase–Dependent Stabilization of Hepatic Low-Density Lipoprotein Receptor mRNA by Herbal Medicine Berberine.
• ^ Duff CJ, Hooper NM. PCSK9: an emerging target for treatment of hypercholesterolemia. Expert Opin Ther Targets. (2011)
• ^ a b Feingold KR, et al. Inflammation stimulates the expression of PCSK9. Biochem Biophys Res Commun. (2008)
• ^ Inhibition of lipid synthesis through activation of AMP kinase: an additional mechanism for the hypolipidemic effects of berberine.
• ^ a b c d Hu Y, et al. Lipid-lowering effect of berberine in human subjects and rats. Phytomedicine. (2012)
• ^ Derosa G, et al. Effects of berberine on lipid profile in subjects with low cardiovascular risk. Expert Opin Biol Ther. (2013)
• ^ a b c d e f g h i j Dong H, et al. Berberine in the treatment of type 2 diabetes mellitus: a systemic review and meta-analysis. Evid Based Complement Alternat Med. (2012)
• ^ Fatehi-Hassanabad Z, et al. The antihypertensive and vasodilator effects of aqueous extract from Berberis vulgaris fruit on hypertensive rats. Phytother Res. (2005)
• ^ Chun YT, et al. A biochemical study on the hypotensive effect of berberine in rats. Gen Pharmacol. (1979)
• ^ a b Lau CW, et al. Cardiovascular actions of berberine. Cardiovasc Drug Rev. (2001)
• ^ Wong KK. Mechanism of the aortic relaxation induced by low concentrations of berberine. Planta Med. (1998)
• ^ Effects of berberine on angiotensin-converting enzyme and NO/cGMP system in vessels.
• ^ Cheng B, et al. Cardiovascular aspects of pharmacology of berberine: I. Alpha-adrenoceptor blocking action of berberine in isolated rat anococcygeus muscle and rabbit aortic strip. J Tongji Med Univ. (1987)
• ^ Bova S, et al. On the mechanism of vasodilating action of berberine: possible role of inositol lipid signaling system. J Pharmacol Exp Ther. (1992)
• ^ Huang CG, et al. Effect of berberine on arachidonic acid metabolism in rabbit platelets and endothelial cells. Thromb Res. (2002)
• ^ a b c d Imanshahidi M, Hosseinzadeh H. Pharmacological and therapeutic effects of Berberis vulgaris and its active constituent, berberine. Phytother Res. (2008)
• ^ Cao JW, et al. Effects of berberine on intracellular free calcium in smooth muscle cells of Guinea pig colon. Digestion. (2001)
• ^ a b c d Huang Z, et al. Berberine-induced inhibition of adipocyte enhancer-binding protein 1 attenuates oxidized low-density lipoprotein accumulation and foam cell formation in phorbol 12-myristate 13-acetate-induced macrophages. Eur J Pharmacol. (2012)
• ^ Huang Z, et al. Berberine‑attenuated monocyte adhesion to endothelial cells induced by oxidized low‑density lipoprotein via inhibition of adhesion molecule expression. Mol Med Report. (2013)
• ^ Wang Q, et al. Activation of AMP-activated protein kinase is required for berberine-induced reduction of atherosclerosis in mice: the role of uncoupling protein 2. PLoS One. (2011)
• ^ Effect of berberine on glucose transport in adipocyte and its mechanism.
• ^ a b c d Huang C, et al. Berberine inhibits 3T3-L1 adipocyte differentiation through the PPARgamma pathway. Biochem Biophys Res Commun. (2006)
• ^ a b c d e Yang J, et al. Berberine improves insulin sensitivity by inhibiting fat store and adjusting adipokines profile in human preadipocytes and metabolic syndrome patients. Evid Based Complement Alternat Med. (2012)
• ^ Adipocyte stress: The endoplasmic reticulum and metabolic disease.
• ^ a b Pham TP, Kwon J, Shin J. Berberine exerts anti-adipogenic activity through up-regulation of C/EBP inhibitors, CHOP and DEC2. Biochem Biophys Res Commun. (2011)
• ^ Bae S, Yoon Y. Anti-Adipogenic Activity of Berberine is Not Mediated by the WNT/β-Catenin Pathway. Phytother Res. (2012)
• ^ a b Zhou J, Zhou S. Berberine regulates peroxisome proliferator-activated receptors and positive transcription elongation factor b expression in diabetic adipocytes. Eur J Pharmacol. (2010)
• ^ a b c Zhou L, et al. Berberine attenuates cAMP-induced lipolysis via reducing the inhibition of phosphodiesterase in 3T3-L1 adipocytes. Biochim Biophys Acta. (2011)
• ^ a b c d e Zhou L, et al. Berberine acutely inhibits insulin secretion from beta-cells through 3',5'-cyclic adenosine 5'-monophosphate signaling pathway. Endocrinology. (2008)
• ^ Kadowaki T, Yamauchi T. Adiponectin and adiponectin receptors. Endocr Rev. (2005)
• ^ Basu R, et al. Selective downregulation of the high molecular weight form of adiponectin in hyperinsulinemia and in type 2 diabetes: differential regulation from nondiabetic subjects. Diabetes. (2007)
• ^ Wang Y, et al. Post-translational modifications of adiponectin: mechanisms and functional implications. Biochem J. (2008)
• ^ a b c Li Y, et al. Activation of AMPK by berberine promotes adiponectin multimerization in 3T3-L1 adipocytes. FEBS Lett. (2011)
• ^ Lin H, Li Z. Adiponectin self-regulates its expression and multimerization in adipose tissue: an autocrine/paracrine mechanism. Med Hypotheses. (2012)
• ^ a b c Prabhakar PK, Doble M. Effect of Natural Products on Commercial Oral Antidiabetic Drugs in Enhancing 2-Deoxyglucose Uptake by 3T3-L1 Adipocytes. Ther Adv Endocrinol Metab. (2011)
• ^ Wang SH, et al. Effect of Astragalus polysaccharides and berberine on carbohydrate metabolism and cell differentiation in 3T3-L1 adipocytes. Zhongguo Zhong Xi Yi Jie He Za Zhi. (2004)
• ^ a b c Chen C, Zhang Y, Huang C. Berberine inhibits PTP1B activity and mimics insulin action. Biochem Biophys Res Commun. (2010)
• ^ Cok A, et al. Berberine acutely activates the glucose transport activity of GLUT1. Biochimie. (2011)
• ^ Kim SH, et al. Berberine activates GLUT1-mediated glucose uptake in 3T3-L1 adipocytes. Biol Pharm Bull. (2007)
• ^ a b Bustanji Y, et al. Berberine potently inhibits protein tyrosine phosphatase 1B: investigation by docking simulation and experimental validation. J Enzyme Inhib Med Chem. (2006)
• ^ Yi P, et al. Berberine reverses free-fatty-acid-induced insulin resistance in 3T3-L1 adipocytes through targeting IKKbeta. World J Gastroenterol. (2008)
• ^ Choi BH, et al. Berberine reduces the expression of adipogenic enzymes and inflammatory molecules of 3T3-L1 adipocyte. Exp Mol Med. (2006)
• ^ Yi P, Lu FE, Chen G. Molecular mechanism of berberine in improving insulin resistance induced by free fatty acid through inhibiting nuclear trascription factor-kappaB p65 in 3T3-L1 adipocytes. Zhongguo Zhong Xi Yi Jie He Za Zhi. (2007)
• ^ a b c d e f g h Yan HM, et al. Efficacy of Berberine in Patients with Non-Alcoholic Fatty Liver Disease. PLoS One. (2015)
• ^ Pan GY, et al. The antihyperglycaemic activity of berberine arises from a decrease of glucose absorption. Planta Med. (2003)
• ^ a b c d e Liu SZ, et al. Antihyperglycemic effect of the traditional Chinese scutellaria-coptis herb couple and its main components in streptozotocin-induced diabetic rats. J Ethnopharmacol. (2012)
• ^ a b c d Liu L, et al. Berberine suppresses intestinal disaccharidases with beneficial metabolic effects in diabetic states, evidences from in vivo and in vitro study. Naunyn Schmiedebergs Arch Pharmacol. (2010)
• ^ Liu L, et al. Berberine attenuates intestinal disaccharidases in streptozotocin-induced diabetic rats. Pharmazie. (2008)
• ^ Tintu I, et al. An isoquinoline alkaloid, berberine, can inhibit fungal alpha amylase: enzyme kinetic and molecular modeling studies. Chem Biol Drug Des. (2012)
• ^ Ni YX. Therapeutic effect of berberine on 60 patients with type II diabetes mellitus and experimental research. Zhong Xi Yi Jie He Za Zhi. (1988)
• ^ Sterne JA, Gavaghan D, Egger M. Publication and related bias in meta-analysis: power of statistical tests and prevalence in the literature. J Clin Epidemiol. (2000)
• ^ a b c d e f g Zhang H, et al. Berberine lowers blood glucose in type 2 diabetes mellitus patients through increasing insulin receptor expression. Metabolism. (2010)
• ^ a b Pérez-Rubio KG, et al. Effect of berberine administration on metabolic syndrome, insulin sensitivity, and insulin secretion. Metab Syndr Relat Disord. (2013)
• ^ Efficacy of Berberine in Patients with Type 2 Diabetes.
• ^ Berberine-stimulated glucose uptake in L6 myotubes involves both AMPK and p38 MAPK.
• ^ Ma X, et al. Berberine-induced activation of 5'-adenosine monophosphate-activated protein kinase and glucose transport in rat skeletal muscles. Metabolism. (2010)
• ^ Gomes AP, et al. Berberine protects against high fat diet-induced dysfunction in muscle mitochondria by inducing SIRT1-dependent mitochondrial biogenesis. Biochim Biophys Acta. (2012)
• ^ a b Liu LZ, et al. Berberine modulates insulin signaling transduction in insulin-resistant cells. Mol Cell Endocrinol. (2010)
• ^ a b c Kong WJ, et al. Berberine reduces insulin resistance through protein kinase C-dependent up-regulation of insulin receptor expression. Metabolism. (2009)
• ^ Krawiec BJ, et al. AMP-activated protein kinase agonists increase mRNA content of the muscle-specific ubiquitin ligases MAFbx and MuRF1 in C2C12 cells. Am J Physiol Endocrinol Metab. (2007)
• ^ Wang XH, Jiang SM, Sun QW. Effects of berberine on human rheumatoid arthritis fibroblast-like synoviocytes. Exp Biol Med (Maywood). (2011)
• ^ Evidence for metalloproteinase and metalloproteinase inhibitor imbalance in human osteoarthritic cartilage.
• ^ a b Hu PF, et al. Protective effects of berberine in an experimental rat osteoarthritis model. Phytother Res. (2011)
• ^ a b Ivanovska N, Philipov S, Hristova M. Influence of berberine on T-cell mediated immunity. Immunopharmacol Immunotoxicol. (1999)
• ^ a b Yan F, et al. Berberine promotes recovery of colitis and inhibits inflammatory responses in colonic macrophages and epithelial cells in DSS-treated mice. Am J Physiol Gastrointest Liver Physiol. (2012)
• ^ a b c Lee IA, Hyun YJ, Kim DH. Berberine ameliorates TNBS-induced colitis by inhibiting lipid peroxidation, enterobacterial growth and NF-κB activation. Eur J Pharmacol. (2010)
• ^ a b Kuo CL, Chi CW, Liu TY. The anti-inflammatory potential of berberine in vitro and in vivo. Cancer Lett. (2004)
• ^ Park JE, et al. Alkaloids from Chelidonium majus and their inhibitory effects on LPS-induced NO production in RAW264.7 cells. Bioorg Med Chem Lett. (2011)
• ^ a b Huang Z, et al. Suppression of oxLDL-induced MMP-9 and EMMPRIN expression by berberine via inhibition of NF-κB activation in human THP-1 macrophages. Anat Rec (Hoboken). (2012)
• ^ Guan S, et al. Effects of berberine on expression of LOX-1 and SR-BI in human macrophage-derived foam cells induced by ox-LDL. Am J Chin Med. (2010)
• ^ a b c d Kim BH, et al. Inhibition of the signalling kinase JAK3 alleviates inflammation in monoarthritic rats. Br J Pharmacol. (2011)
• ^ Papageorgiou AC, Wikman LE. Is JAK3 a new drug target for immunomodulation-based therapies. Trends Pharmacol Sci. (2004)
• ^ Malaviya R, et al. Targeting Janus kinase 3 in mast cells prevents immediate hypersensitivity reactions and anaphylaxis. J Biol Chem. (1999)
• ^ a b Cecil CE, et al. Inhibition of H1N1 influenza A virus growth and induction of inflammatory mediators by the isoquinoline alkaloid berberine and extracts of goldenseal (Hydrastis canadensis). Int Immunopharmacol. (2011)
• ^ Schröder M, Kaufman RJ. The mammalian unfolded protein response. Annu Rev Biochem. (2005)
• ^ Chen TC, et al. Involvement of reactive oxygen species and caspase-dependent pathway in berberine-induced cell cycle arrest and apoptosis in C6 rat glioma cells. Int J Oncol. (2009)
• ^ Eom KS, et al. Berberine-induced apoptosis in human glioblastoma T98G cells is mediated by endoplasmic reticulum stress accompanying reactive oxygen species and mitochondrial dysfunction. Biol Pharm Bull. (2010)
• ^ a b Lin JP, et al. GADD153 mediates berberine-induced apoptosis in human cervical cancer Ca ski cells. Anticancer Res. (2007)
• ^ Lin CC, et al. Berberine induces apoptosis in human HSC-3 oral cancer cells via simultaneous activation of the death receptor-mediated and mitochondrial pathway. Anticancer Res. (2007)
• ^ Sun Y, et al. A systematic review of the anticancer properties of berberine, a natural product from Chinese herbs. Anticancer Drugs. (2009)
• ^ a b Hao X, et al. Berberine ameliorates pro-inflammatory cytokine-induced endoplasmic reticulum stress in human intestinal epithelial cells in vitro. Inflammation. (2012)
• ^ a b Wang ZS, et al. Berberine reduces endoplasmic reticulum stress and improves insulin signal transduction in Hep G2 cells. Acta Pharmacol Sin. (2010)
• ^ Zha W, et al. Berberine inhibits HIV protease inhibitor-induced inflammatory response by modulating ER stress signaling pathways in murine macrophages. PLoS One. (2010)
• ^ a b c Zhou J, et al. Protective effect of berberine on beta cells in streptozotocin- and high-carbohydrate/high-fat diet-induced diabetic rats. Eur J Pharmacol. (2009)
• ^ a b Liu J, et al. Coptis extracts enhance the anticancer effect of estrogen receptor antagonists on human breast cancer cells. Biochem Biophys Res Commun. (2009)
• ^ Doyle ME, Egan JM. Mechanisms of action of glucagon-like peptide 1 in the pancreas. Pharmacol Ther. (2007)
• ^ Meier JJ, Nauck MA. Glucagon-like peptide 1(GLP-1) in biology and pathology. Diabetes Metab Res Rev. (2005)
• ^ Holst JJ, Gromada J. Role of incretin hormones in the regulation of insulin secretion in diabetic and nondiabetic humans. Am J Physiol Endocrinol Metab. (2004)
• ^ Li J1, et al. Berberine represses DAXX gene transcription and induces cancer cell apoptosis. Lab Invest. (2013)
• ^ Marverti G1, et al. Modulation of the expression of folate cycle enzymes and polyamine metabolism by berberine in cisplatin-sensitive and -resistant human ovarian cancer cells. Int J Oncol. (2013)
• ^ a b Tsang CM, et al. Berberine suppresses tumorigenicity and growth of nasopharyngeal carcinoma cells by inhibiting STAT3 activation induced by tumor associated fibroblasts. BMC Cancer. (2013)
• ^ Wu HL1, et al. Berberine-induced apoptosis of human leukemia HL-60 cells is associated with down-regulation of nucleophosmin/B23 and telomerase activity. Int J Cancer. (1999)
• ^ Fu L1, et al. Berberine Targets AP-2/hTERT, NF-κB/COX-2, HIF-1α/VEGF and Cytochrome-c/Caspase Signaling to Suppress Human Cancer Cell Growth. PLoS One. (2013)
• ^ Ho YT1, et al. Berberine induced apoptosis via promoting the expression of caspase-8, -9 and -3, apoptosis-inducing factor and endonuclease G in SCC-4 human tongue squamous carcinoma cancer cells. Anticancer Res. (2009)
• ^ Peng PL1, et al. Inhibitory effect of berberine on the invasion of human lung cancer cells via decreased productions of urokinase-plasminogen activator and matrix metalloproteinase-2. Toxicol Appl Pharmacol. (2006)
• ^ Hamsa TP1, Kuttan G. Berberine inhibits pulmonary metastasis through down-regulation of MMP in metastatic B16F-10 melanoma cells. Phytother Res. (2012)
• ^ a b Eisenberg-Lerner A1, Kimchi A. The paradox of autophagy and its implication in cancer etiology and therapy. Apoptosis. (2009)
• ^ a b c d Wang N1, et al. Berberine induces autophagic cell death and mitochondrial apoptosis in liver cancer cells: the cellular mechanism. J Cell Biochem. (2010)
• ^ Peng PL1, et al. Synergistic tumor-killing effect of radiation and berberine combined treatment in lung cancer: the contribution of autophagic cell death. Int J Radiat Oncol Biol Phys. (2008)
• ^ a b Chou TC, Talalay P. Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul. (1984)
• ^ Tong N, et al. Berberine sensitizes mutliple human cancer cells to the anticancer effects of doxorubicin in vitro. Oncol Lett. (2012)
• ^ Zhao X, et al. Protective effects of berberine on doxorubicin-induced hepatotoxicity in mice. Biol Pharm Bull. (2012)
• ^ Choi MS1, et al. Berberine inhibits human neuroblastoma cell growth through induction of p53-dependent apoptosis. Anticancer Res. (2008)
• ^ Eom KS1, et al. Berberine induces G1 arrest and apoptosis in human glioblastoma T98G cells through mitochondrial/caspases pathway. Biol Pharm Bull. (2008)
• ^ Patil JB1, Kim J, Jayaprakasha GK. Berberine induces apoptosis in breast cancer cells (MCF-7) through mitochondrial-dependent pathway. Eur J Pharmacol. (2010)
• ^ Marquez RT, Xu L. Bcl-2:Beclin 1 complex: multiple, mechanisms regulating autophagy/apoptosis toggle switch. Am J Cancer Res. (2012)
• ^ Bcl-2 Inhibition of Autophagy: A New Route to Cancer?.
• ^ a b Park KS, et al. Berberine inhibited the growth of thyroid cancer cell lines 8505C and TPC1. Yonsei Med J. (2012)
• ^ a b Wang L, et al. Berberine induces caspase-independent cell death in colon tumor cells through activation of apoptosis-inducing factor. PLoS One. (2012)
• ^ Choi MS1, et al. Berberine inhibits p53-dependent cell growth through induction of apoptosis of prostate cancer cells. Int J Oncol. (2009)
• ^ Meeran SM1, Katiyar S, Katiyar SK. Berberine-induced apoptosis in human prostate cancer cells is initiated by reactive oxygen species generation. Toxicol Appl Pharmacol. (2008)
• ^ a b Letasiová S1, et al. Berberine-antiproliferative activity in vitro and induction of apoptosis/necrosis of the U937 and B16 cells. Cancer Lett. (2006)
• ^ Lin CC1, et al. Apoptosis of human leukemia HL-60 cells and murine leukemia WEHI-3 cells induced by berberine through the activation of caspase-3. Anticancer Res. (2006)
• ^ a b c d Xia X, et al. Berberine improves glucose metabolism in diabetic rats by inhibition of hepatic gluconeogenesis. PLoS One. (2011)
• ^ a b c Li H, et al. Hepatocyte nuclear factor 1alpha plays a critical role in PCSK9 gene transcription and regulation by the natural hypocholesterolemic compound berberine. J Biol Chem. (2009)
• ^ Cameron J, et al. Berberine decreases PCSK9 expression in HepG2 cells. Atherosclerosis. (2008)
• ^ a b Zhang BJ, et al. Protection by and anti-oxidant mechanism of berberine against rat liver fibrosis induced by multiple hepatotoxic factors. Clin Exp Pharmacol Physiol. (2008)
• ^ a b Sun X, et al. Berberine inhibits hepatic stellate cell proliferation and prevents experimental liver fibrosis. Biol Pharm Bull. (2009)
• ^ a b Wang N, et al. A comparative study on the hepatoprotective action of bear bile and coptidis rhizoma aqueous extract on experimental liver fibrosis in rats. BMC Complement Altern Med. (2012)
• ^ Chang X, et al. Berberine reduces methylation of the MTTP promoter and alleviates fatty liver induced by a high-fat diet in rats. J Lipid Res. (2010)
• ^ Wetterau JR, Lin MC, Jamil H. Microsomal triglyceride transfer protein. Biochim Biophys Acta. (1997)
• ^ Lu SS, et al. Berberine promotes glucagon-like peptide-1 (7-36) amide secretion in streptozotocin-induced diabetic rats. J Endocrinol. (2009)
• ^ Sack RB, Froehlich JL. Berberine inhibits intestinal secretory response of Vibrio cholerae and Escherichia coli enterotoxins. Infect Immun. (1982)
• ^ Yuan J, Shen XZ, Zhu XS. Effect of berberine on transit time of human small intestine. Zhongguo Zhong Xi Yi Jie He Za Zhi. (1994)
• ^ Strober W, Fuss I, Mannon P. The fundamental basis of inflammatory bowel disease. J Clin Invest. (2007)
• ^ Xavier RJ, Podolsky DK. Unravelling the pathogenesis of inflammatory bowel disease. Nature. (2007)
• ^ Zhang M, et al. Evidence for the complementary and synergistic effects of the three-alkaloid combination regimen containing berberine, hypaconitine and skimmianine on the ulcerative colitis rats induced by trinitrobenzene-sulfonic acid. Eur J Pharmacol. (2011)
• ^ Zhou H, Mineshita S. The effect of berberine chloride on experimental colitis in rats in vivo and in vitro. J Pharmacol Exp Ther. (2000)
• ^ Kawashima K, et al. Pharmacological properties of traditional medicine (XXIX): effect of Hange-shashin-to and the combinations of its herbal constituents on rat experimental colitis. Biol Pharm Bull. (2004)
• ^ Hong T, et al. Suppressive effect of berberine on experimental dextran sulfate sodium-induced colitis. Immunopharmacol Immunotoxicol. (2012)
• ^ Zhang X, et al. Structural changes of gut microbiota during berberine-mediated prevention of obesity and insulin resistance in high-fat diet-fed rats. PLoS One. (2012)
• ^ Jiang XW, et al. Effects of berberine gelatin on recurrent aphthous stomatitis: a randomized, placebo-controlled, double-blind trial in a Chinese cohort. Oral Surg Oral Med Oral Pathol Oral Radiol. (2012)
• ^ a b Gao N, Zhao TY, Li XJ. The protective effect of berberine on β-cell lipoapoptosis. J Endocrinol Invest. (2011)
• ^ Gu JJ, Gao FY, Zhao TY. A preliminary investigation of the mechanisms underlying the effect of berberine in preventing high-fat diet-induced insulin resistance in rats. J Physiol Pharmacol. (2012)
• ^ Leng SH, Lu FE, Xu LJ. Therapeutic effects of berberine in impaired glucose tolerance rats and its influence on insulin secretion. Acta Pharmacol Sin. (2004)
• ^ Ko BS, et al. Insulin sensitizing and insulinotropic action of berberine from Cortidis rhizoma. Biol Pharm Bull. (2005)
• ^ Yin J, et al. Effects of berberine on glucose metabolism in vitro. Metabolism. (2002)
• ^ Leclerc I, Rutter GA. AMP-activated protein kinase: a new beta-cell glucose sensor?: Regulation by amino acids and calcium ions. Diabetes. (2004)
• ^ Activation of protein kinases and inhibition of protein phosphatases play a central role in the regulation of exocytosis in mouse pancreatic beta cells.
• ^ Tsuboi T, et al. Glucagon-like peptide-1 mobilizes intracellular Ca2+ and stimulates mitochondrial ATP synthesis in pancreatic MIN6 beta-cells. Biochem J. (2003)
• ^ Rayasam GV, et al. Identification of berberine as a novel agonist of fatty acid receptor GPR40. Phytother Res. (2010)
• ^ a b Abdel-Haq H, et al. Relaxant effects of Hydrastis canadensis L. and its major alkaloids on guinea pig isolated trachea. Pharmacol Toxicol. (2000)
• ^ Wang FL, et al. Renoprotective effects of berberine and its possible molecular mechanisms in combination of high-fat diet and low-dose streptozotocin-induced diabetic rats. Mol Biol Rep. (2012)
• ^ Tang LQ, et al. Berberine ameliorates renal injury by regulating G proteins-AC- cAMP signaling in diabetic rats with nephropathy. Mol Biol Rep. (2012)
• ^ Wu D, et al. Ameliorative effect of berberine on renal damage in rats with diabetes induced by high-fat diet and streptozotocin. Phytomedicine. (2012)
• ^ Liu W, et al. Berberine reduces fibronectin and collagen accumulation in rat glomerular mesangial cells cultured under high glucose condition. Mol Cell Biochem. (2009)
• ^ Jiang Q, et al. Berberine attenuates lipopolysaccharide-induced extracelluar matrix accumulation and inflammation in rat mesangial cells: involvement of NF-κB signaling pathway. Mol Cell Endocrinol. (2011)
• ^ Liu W, et al. Effects of berberine on matrix accumulation and NF-kappa B signal pathway in alloxan-induced diabetic mice with renal injury. Eur J Pharmacol. (2010)
• ^ Oh JH, et al. Sequential effects of high glucose on mesangial cell transforming growth factor-beta 1 and fibronectin synthesis. Kidney Int. (1998)
• ^ Mogyorósi A, et al. Utility of serum and urinary transforming growth factor-beta levels as markers of diabetic nephropathy. Nephron. (2000)
• ^ a b c Lan T, et al. Berberine suppresses high glucose-induced TGF-β1 and fibronectin synthesis in mesangial cells through inhibition of sphingosine kinase 1/AP-1 pathway. Eur J Pharmacol. (2012)
• ^ Taha TA, Hannun YA, Obeid LM. Sphingosine kinase: biochemical and cellular regulation and role in disease. J Biochem Mol Biol. (2006)
• ^ Lan T, et al. Sphingosine kinase-1 pathway mediates high glucose-induced fibronectin expression in glomerular mesangial cells. Mol Endocrinol. (2011)
• ^ Lan T, et al. Berberine ameliorates renal injury in diabetic C57BL/6 mice: Involvement of suppression of SphK-S1P signaling pathway. Arch Biochem Biophys. (2010)
• ^ Liu W, et al. Berberine inhibits aldose reductase and oxidative stress in rat mesangial cells cultured under high glucose. Arch Biochem Biophys. (2008)
• ^ a b c Liu WH, et al. Berberine ameliorates renal injury in streptozotocin-induced diabetic rats by suppression of both oxidative stress and aldose reductase. Chin Med J (Engl). (2008)
• ^ a b c Bashir S, Gilani AH. Antiurolithic effect of berberine is mediated through multiple pathways. Eur J Pharmacol. (2011)
• ^ Li HB, et al. Effects and mechanism of berberine on the hypertensive renal injury rats induced by enriched high fat-salt-fructose diet. Zhong Yao Cai. (2011)
• ^ Bashir S, et al. Berberis vulgaris root bark extract prevents hyperoxaluria induced urolithiasis in rats. Phytother Res. (2010)
• ^ Seki T, Morohashi M. Effect of some alkaloids, flavonoids and triterpenoids, contents of Japanese-Chinese traditional herbal medicines, on the lipogenesis of sebaceous glands. Skin Pharmacol. (1993)
• ^ Namba T, et al. Study on baths with crude drug. II.: the effects of coptidis rhizoma extracts as skin permeation enhancer. Yakugaku Zasshi. (1995)
• ^ Inbaraj JJ, et al. Photochemistry and photocytotoxicity of alkaloids from Goldenseal (Hydrastis canadensis L.) 1. Berberine. Chem Res Toxicol. (2001)
• ^ Tan Y, et al. Antioxidant properties of berberine on cultured rabbit corpus cavernosum smooth muscle cells injured by hydrogen peroxide. Acta Pharmacol Sin. (2007)
• ^ Tan Y, et al. Effect of berberine on the mRNA expression of nitric oxide synthase (NOS) in rat corpus cavernosum. J Huazhong Univ Sci Technolog Med Sci. (2005)
• ^ a b c d Chiou WF, Chen J, Chen CF. Relaxation of corpus cavernosum and raised intracavernous pressure by berberine in rabbit. Br J Pharmacol. (1998)
• ^ Tan Y, et al. Effect of berberine on the mRNA expression of phosphodiesterase type 5 (PDE5) in rat corpus cavernosum. Zhonghua Nan Ke Xue. (2004)
• ^ Tan Y, et al. Effects of berberine on cyclic GMP and cyclic AMP levels in rabbit corpus cavernosum in vitro. Zhonghua Nan Ke Xue. (2005)
• ^ Drewes SE, George J, Khan F. Recent findings on natural products with erectile-dysfunction activity. Phytochemistry. (2003)
• ^ Liu GL, et al. Endoplasmic reticulum stress mediating downregulated StAR and 3-beta-HSD and low plasma testosterone caused by hypoxia is attenuated by CPU86017-RS and nifedipine. J Biomed Sci. (2012)
• ^ Zhang GL, et al. CPU86017-RS attenuate hypoxia-induced testicular dysfunction in mice by normalizing androgen biosynthesis genes and pro-inflammatory cytokines. Acta Pharmacol Sin. (2012)
• ^ Wei W, et al. A clinical study on the short-term effect of berberine in comparison to metformin on the metabolic characteristics of women with polycystic ovary syndrome. Eur J Endocrinol. (2012)
• ^ Zhao W, et al. Reduction of blood lipid by berberine in hyperlipidemic patients with chronic hepatitis or liver cirrhosis. Biomed Pharmacother. (2008)
• ^ Prabhakar PK, Doble M. Synergistic effect of phytochemicals in combination with hypoglycemic drugs on glucose uptake in myotubes. Phytomedicine. (2009)
• ^ a b Kwon M, et al. Organic cation transporter-mediated drug-drug interaction potential between berberine and metformin. Arch Pharm Res. (2015)
• ^ Vogel RA. PCSK9 inhibition: the next statin. J Am Coll Cardiol. (2012)
• ^ Rashid S, et al. Decreased plasma cholesterol and hypersensitivity to statins in mice lacking Pcsk9. Proc Natl Acad Sci U S A. (2005)
• ^ Welder G, et al. High-dose atorvastatin causes a rapid sustained increase in human serum PCSK9 and disrupts its correlation with LDL cholesterol. J Lipid Res. (2010)
• ^ Dubuc G, et al. Statins upregulate PCSK9, the gene encoding the proprotein convertase neural apoptosis-regulated convertase-1 implicated in familial hypercholesterolemia. Arterioscler Thromb Vasc Biol. (2004)
• ^ Kong WJ, et al. Combination of simvastatin with berberine improves the lipid-lowering efficacy. Metabolism. (2008)
• ^ a b Affuso F, et al. Effects of a nutraceutical combination (berberine, red yeast rice and policosanols) on lipid levels and endothelial function randomized, double-blind, placebo-controlled study. Nutr Metab Cardiovasc Dis. (2010)
• ^ Pisciotta L, Bellocchio A, Bertolini S. Nutraceutical pill containing berberine versus ezetimibe on plasma lipid pattern in hypercholesterolemic subjects and its additive effect in patients with familial hypercholesterolemia on stable cholesterol-lowering treatment. Lipids Health Dis. (2012)
• ^ Liu J, et al. Chinese red yeast rice (Monascus purpureus) for primary hyperlipidemia: a meta-analysis of randomized controlled trials. Chin Med. (2006)
• ^ Zhou S, Lim LY, Chowbay B. Herbal modulation of P-glycoprotein. Drug Metab Rev. (2004)
• ^ a b Xue L, et al. Effects and interaction of icariin, curculigoside, and berberine in er-xian decoction, a traditional chinese medicinal formula, on osteoclastic bone resorption. Evid Based Complement Alternat Med. (2012)
• ^ Vrzal R, et al. Activation of the aryl hydrocarbon receptor by berberine in HepG2 and H4IIE cells: Biphasic effect on CYP1A1. Biochem Pharmacol. (2005)
• ^ a b c Zhi D, et al. The enhancement of cardiac toxicity by concomitant administration of Berberine and macrolides. Eur J Pharm Sci. (2015)
• ^ Chan E. Displacement of bilirubin from albumin by berberine. Biol Neonate. (1993)
• Affuso F, et al. A nutraceutical combination improves insulin sensitivity in patients with metabolic syndrome. World J Cardiol. (2012)
• Bahadoran Z, et al. The Nitrate-Independent Blood Pressure-Lowering Effect of Beetroot Juice: A Systematic Review and Meta-Analysis. Adv Nutr. (2017)
• Lara J, et al. Effects of inorganic nitrate and beetroot supplementation on endothelial function: a systematic review and meta-analysis. Eur J Nutr. (2016)
• Aune D, et al. Fruit and vegetable intake and the risk of cardiovascular disease, total cancer and all-cause mortality-a systematic review and dose-response meta-analysis of prospective studies. Int J Epidemiol. (2017)
• Ried K. Garlic Lowers Blood Pressure in Hypertensive Individuals, Regulates Serum Cholesterol, and Stimulates Immunity: An Updated Meta-analysis and Review. J Nutr. (2016)
• Ried K, Toben C, Fakler P. Effect of garlic on serum lipids: an updated meta-analysis. Nutr Rev. (2013)
• El Asmar MS, Naoum JJ, Arbid EJ. Vitamin k dependent proteins and the role of vitamin k2 in the modulation of vascular calcification: a review. Oman Med J. (2014)
• Knapen MH, et al. Menaquinone-7 supplementation improves arterial stiffness in healthy postmenopausal women. A double-blind randomised clinical trial. Thromb Haemost. (2015)
• Institute of Medicine (US) Panel on Micronutrients. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc.
• Cockayne S, et al. Vitamin K and the prevention of fractures: systematic review and meta-analysis of randomized controlled trials. Arch Intern Med. (2006)
• Kodama S, et al. Fasting and post-challenge glucose as quantitative cardiovascular risk factors: a meta-analysis. J Atheroscler Thromb. (2012)
• Mannucci E, et al. Is glucose control important for prevention of cardiovascular disease in diabetes?. Diabetes Care. (2013)
• Lan J, et al. Meta-analysis of the effect and safety of berberine in the treatment of type 2 diabetes mellitus, hyperlipemia and hypertension. J Ethnopharmacol. (2015)
• Schaffer SW, et al. Physiological roles of taurine in heart and muscle. J Biomed Sci. (2010)
• Ahmadian M, Dabidi Roshan V, Ashourpore E. Taurine Supplementation Improves Functional Capacity, Myocardial Oxygen Consumption, and Electrical Activity in Heart Failure. J Diet Suppl. (2017)
• Ahmadian M, et al. Taurine supplementation has anti-atherogenic and anti-inflammatory effects before and after incremental exercise in heart failure. Ther Adv Cardiovasc Dis. (2017)
• Beyranvand MR, et al. Effect of taurine supplementation on exercise capacity of patients with heart failure. J Cardiol. (2011)
• Sun Q, et al. Taurine Supplementation Lowers Blood Pressure and Improves Vascular Function in Prehypertension: Randomized, Double-Blind, Placebo-Controlled Study. Hypertension. (2016)
• Militante JD, Lombardini JB. Treatment of hypertension with oral taurine: experimental and clinical studies. Amino Acids. (2002)