Bulk Herbs & Herb Infused Olive Oil
Research regarding the potential diabetic health enhancement activity of Hydrastis canadensis (goldenseal) and/or its active compounds berberine and hydrastine
This information has been complied in order to facilitate the research efforts of health care professionals and others. These statements have not been evaluated by the Food and Drug Administration and are not intended diagnose, treat, cure, prevent, mitigate, or prevent any disease. The information is presented with the latest publications first. This is an ongoing work so check back often as we will update these pages as more information becomes available. Also see the anti-parasitic and anti-diarrhea pages. Last Updated : 08/25/2008
Berberine-stimulated glucose uptake in L6 myotubes involves both AMPK and p38 MAPK.
Cheng Z, Pang T, Gu M, Gao AH, Xie CM, Li JY, Nan FJ, Li J.
Biochim Biophys Acta. 2006 Sep 20;
Berberine is a plant alkaloid used in traditional Chinese medicine and has
been reported to have antihyperglycemic activity in NIDDM patients. However,
the molecular basis for this action is yet to be elucidated. Here we
investigate the effects and signaling pathways of berberine on L6 rat
skeletal muscles. Our study demonstrates that berberine stimulates glucose
uptake in a time- and dose-dependent manner. Intriguingly,
berberine-stimulated glucose uptake does not vary as insulin concentration
increases, and could not be blocked by the PI 3-kinase inhibitor wortmannin.
Berberine only weakly stimulates the phosphorylation of Akt/PKB, a key
molecule in the insulin signaling pathway, but strongly promotes the
phosphorylation of AMPK and p38 MAPK. The effects of berberine are not a
result of pro-oxidant action, but a consequence of an increased cellular
AMP:ATP ratio. Moreover, berberine-stimulated glucose uptake is inhibited by
the AMPK inhibitor Compound C and the p38 MAPK inhibitor SB202190.
Inhibition of AMPK reduces p38 MAPK phosphorylation, suggesting that AMPK
lies upstream of p38 MAPK. These results suggest that berberine
circumvents insulin signaling pathways and stimulates glucose uptake through
the AMP-AMPK-p38 MAPK pathway, which may account for the antihyperglycemic
effects of this drug.
Identification of medicinal plant goldenseal as a natural cholesterol-lowering agent: Mechanisms of actions and new modulators of LDL receptor expression.
Abidi P, Chen W, Kraemer FB, Li H, Liu J.
J Lipid Res. 2006 Aug 2;
Our previous studies have identified berberine (BBR), an alkaloid isolated
from Chinese herb Huanglian, as a unique cholesterol-lowering drug that
upregulates hepatic LDLR expression through a mechanism of mRNA
stabilization. Here we demonstrate that the root extract of goldenseal, a
BBR-containing medicinal plant, is highly effective in upregulation of liver
LDLR expression in HepG2 cells and in reducing plasma cholesterol and LDL-cholesterol
in hyperlipidemic hamsters with greater activities than the pure compound
BBR. By conducting bioassay driven semi-purifications we demonstrate that
the higher potency of goldenseal is achieved through concerted actions of
multiple bioactive compounds in addition to BBR. We identify canadine and
two other constituents of goldenseal as new upregulators of LDLR expression.
We further show that the activity of BBR on LDLR expression is attenuated by
MDR1-mediated efflux from liver cells, whereas canadine is resistant to
MDR1. This finding defines a molecular mechanism for the higher activity of
canadine than BBR. We also provide substantial evidence to show that
goldenseal contains natural MDR1 antagonist(s) that accentuate the
upregulatory effect of BBR on LDLR mRNA expression. These new findings
identify goldenseal as a natural LDL-cholesterol lowering agent and our
studies provide a molecular basis for the mechanisms of actions.
Berberine, a Natural Plant Product, Activates AMP-Activated Protein Kinase With Beneficial Metabolic Effects in Diabetic and Insulin-Resistant States.
Lee YS, Kim WS, Kim KH, Yoon MJ, Cho HJ, Shen Y, Ye JM, Lee
CH, Oh WK, Kim CT, Hohnen-Behrens C, Gosby A, Kraegen EW, James DE, Kim JB.
Diabetes. 2006 Aug;55(8):2256-64.
Berberine has been shown to have antidiabetic properties, although its mode
of action is not known. Here, we have investigated the metabolic effects of
berberine in two animal models of insulin resistance and in
insulin-responsive cell lines. Berberine reduced body weight and caused a
significant improvement in glucose tolerance without altering food intake in
db/db mice. Similarly, berberine reduced body weight and plasma
triglycerides and improved insulin action in high-fat-fed Wistar rats.
Berberine downregulated the expression of genes involved in lipogenesis and
upregulated those involved in energy expenditure in adipose tissue and
muscle. Berberine treatment resulted in increased AMP-activated protein
kinase (AMPK) activity in 3T3-L1 adipocytes and L6 myotubes, increased GLUT4
translocation in L6 cells in a phosphatidylinositol 3' kinase-independent
manner, and reduced lipid accumulation in 3T3-L1 adipocytes. These
findings suggest that berberine displays beneficial effects in the treatment
of diabetes and obesity at least in part via stimulation of AMPK activity.
Berberine inhibits 3T3-L1 adipocyte differentiation through the PPARgamma pathway.
Huang C, Zhang Y, Gong Z, Sheng X, Li Z, Zhang W, Qin Y.
Biochem Biophys Res Commun. 2006 Jul 28;
Berberine (BBR), a compound purified from Cortidis rhizoma, reduces serum
cholesterol, triglycerides, and LDL-cholesterol of hypercholesterolemic
patients and high fat diet fed animals, and increases hepatic LDLR mRNA and
protein levels through a post-transcriptional mechanism. BBR also enhances
the hypoglycemic action of insulin in diabetic animal models. Here, we show
that BBR inhibits the differentiation of 3T3-L1 preadipocytes induced by DM
and suppresses the mitotic clonal expansion of 3T3-L1 preadipocytes in a
time- and dose-dependent manner. Gene expression analysis and Western blot
analysis reveal that the BBR inhibits the mRNA and protein levels of
adipogenesis related transcription factors PPARgamma and C/EBPalpha and
their upstream regulator, C/EBPbeta. Reporter gene assays demonstrate that
the full-length PPARgamma and alpha transcription activities are inhibited
by BBR. Using real-time PCR, we have also found that the PPAR target genes
that are involved in adipocyte differentiation, such as aP2, CD36, ACO, LPL,
and other adipocyte markers, are suppressed by BBR. These studies suggest
that BBR works on multiple molecular targets as an inhibitor of PPARgamma
and alpha, and is a potential weight reducing, hypolipidemic, and
hypoglycemic drug.
Effects of berberine on diabetes induced by alloxan and a
high-fat/high-cholesterol diet in rats.
Tang LQ, Wei W, Chen LM, Liu S.
J Ethnopharmacol. 2006 May 2;
Berberine is the major active constituent of Rhizoma coptidis. The present
study was carried out to investigate the effect of berberine on diabetes in
rats and its possible mechanisms. Diabetes was induced by tail vein
injection with alloxan in Wistar rats. The amount of alloxan administered
was 55mg/kg. Diabetic rats were fed with a high-cholesterol diet. The
fasting blood glucose, total cholesterol (TC), triglyceride (TG) and low
density lipoprotein-cholesterol (LDL-c), high density
lipoprotein-cholesterol (HDL-c), nitric oxide (NO) levels in serum and
malondialdehyde (MDA),superoxide dismutase (SOD),glutathione peroxidase (GSH-px)
contents in heart tissue were assayed by spectrophotometry. Pancreas samples
collected after 3 weeks of alloxan treatment were stained with hematoxylin-eosin
(HE) and examined under a light microscope, and scored. Intragastric
administration of berberine (100 and 200mg/kg) significantly decreased
fasting blood glucose levels, serum content of TC, TG, LDL-c, and
effectively increased HDL-c, NO level in diabetic rats. Furthermore,
berberine treatment significantly blocked the increase of MDA, increased SOD
and GSH-px levels in diabetic rats. Histopathological scores showed that
berberine had restored the damage of pancreas tissues in rats with diabetes
mellitus. The results showed berberine significantly inhibited the
progression of diabetes induced by alloxan, and the inhibitory effect of
berberine on diabetes might be associated with its hypoglycemic effect,
modulating lipids metabolic effects and its ability to scavenge free
radical.
Berberine potently inhibits protein tyrosine phosphatase
1B: investigation by docking simulation and experimental validation.
Bustanji Y, Taha MO, Yousef AM, Al-Bakri AG.
J Enzyme Inhib Med Chem. 2006 Apr;21(2):163-71.
Berberine was investigated as an inhibitor of human protein tyrosine
phosphatase 1B (h-PTP 1B) in an attempt to explain its anti-hyperglycemic
activitiy. The investigation included simulated docking experiments to fit
berberine within the binding pocket of h-PTP 1B. Berberine was found to
readily fit within the binding pocket of h-PTP 1B in a low energy
orientation characterized with optimal electrostatic attractive interactions
bridging the isoquinolinium positively charged nitrogen atom of berberine
and the negatively charged acidic residue of ASP 48 of h-PTP 1B.
Experimentally, berberine was found to potently competitively inhibit
recombinant h-PTP 1B in vitro (Ki value = 91.3 nM). Our findings strongly
suggest that h-PTP 1B inhibition is at least one of the reasons for the
reported anti-hyperglycemic activities of berberine.
Inhibition of lipid synthesis through activation of AMP-kinase:
An additional mechanism for the hypolipidemic effects of Berberine.
Brusq JM, Ancellin N, Grondin P, Guillard R, Martin S, Saintillan Y,
Issandou M.
J Lipid Res. 2006 Feb 28;
The alkaloid drug Berberine (BBR) was recently described to decrease plasma
cholesterol and triglycerides in hypercholesterolemic patients by increasing
expression of the hepatic LDL receptor. Using HepG2 human hepatoma cells, we
found that BBR inhibits cholesterol and triglyceride synthesis in a similar
fashion to the AMP-activated protein kinase (AMPK) activator,
5-aminoimidazole-4-carboxamide 1--ribofuranoside (AICAR). A significant
increase in AMPK phosphorylation as well as in AMPK activity was observed
when the cells were incubated with BBR. Activation of AMPK was also
demonstrated by measuring the phosphorylation of acetyl CoA carboxylase, a
substrate of AMPK, correlated with a subsequent increase in fatty acid
oxidation. All these effects were abolished by the mitogen-activated protein
kinase kinase inhibitor PD98059. Treatment of hyperlipidemic hamsters
with BBR decreased plasma LDL cholesterol and strongly reduced fat storage
in the liver. These findings indicate that BBR, in addition to
up-regulating the LDL receptor, inhibits lipid synthesis in human
hepatocytes through activation of AMPK. These effects could account for
the strong reduction of plasma triglycerides observed with this drug in
clinical trials.
Extracellular Signal-Regulated Kinase-Dependent
Stabilization of Hepatic Low-Density Lipoprotein Receptor mRNA by Herbal
Medicine Berberine
Abidi P. Zhou Y, Jaing JG, Liu J.
Arterioscler Thromb Vasc Biol.
2005 Aug 11;
OBJECTIVE: Our recent studies identified berberine (BBR) as a novel
cholesterol-lowering drug that upregulates low-density lipoprotein (LDL)
receptor expression through mRNA stabilization. Here, we investigated
mechanisms underlying regulatory effects of BBR on LDL receptor (LDLR)
messenger. METHODS AND RESULTS: We show that the extracellular
signal-regulated kinase (ERK) signaling pathway is used primarily by BBR to
attenuate the decay of LDLR mRNA in HepG2 cells. Using different reporter
constructs, we demonstrate that BBR affects LDLR mRNA stability entirely
through 3' untranslated region (UTR) in an ERK-dependent manner, and this
stabilizing effect is more prominent in liver-derived cells than nonhepatic
cell lines. In contrast to BBR, the mRNA stabilizing effect of bile acid
CDCA is mediated through the LDLR coding sequence, whereas the 5'UTR, 3'UTR,
and the coding sequence of LDLR mRNA are all implicated in the action of
phorbol 12-myristate 13-acetate. By performing UV cross-linking and SDS-PAGE,
we identify 2 cytoplasmic proteins of 52 and 42 kDa that specifically bind
to the LDLR 3'UTR in BBR-inducible and ERK-dependent manners. CONCLUSIONS:
These new findings demonstrate that the BBR-induced stabilization of LDLR
mRNA is mediated by the ERK signaling pathway through interactions of cis-regulatory
sequences of 3'UTR and mRNA binding proteins that are downstream effectors
of this signaling cascade.
Insulin sensitizing and insulinotropic action of berberine
from Cortidis rhizoma.
Ko BS, Choi SB, Park SK, Jang JS, Kim YE, Park S.
Biol Pharm Bull. 2005 Aug;28(8):1431-7.
Our preliminary study demonstrated that 70% ethanol Cortidis Rhizoma extracts (CR) had a hypoglycemic action in diabetic animal models. We determined whether CR fractions acted as anti-diabetic agent, and a subsequent investigation of the action mechanism of the major compound, berberine ([C(20)H(18)NO(4)](+)), was carried out in vitro. The 20, 40 and 60% methanol fractions from the XAD-4 column contained the most insulin sensitizing activities in 3T3-L1 adipocytes. The common major peak in these fractions was berberine. Treatment with 50 microM berberine plus differentiation inducers significantly reduced triglyceride accumulation by decreased differentiation of 3T3-L1 fibroblasts to adipocytes and triglyceride synthesis. Significant insulin sensitizing activity was observed in 3T3-L1 adipocytes which were given 50 microM berberine plus 0.2 nM insulin to reach a glucose uptake level increased by 10 nM of insulin alone. This was associated with increased glucose transporter-4 translocation into the plasma membrane via enhancing insulin signaling pathways and the insulin receptor substrate-1-phosphoinositide 3 Kinase-Akt. Berberine also increased glucose-stimulated insulin secretion and proliferation in Min6 cells via an enhanced insulin/insulin-like growth factor-1 signaling cascade. Data suggested that berberine can act as an effective insulin sensitizing and insulinotropic agent. Therefore, berberine can be used as anti-diabetic agent for obese diabetic patients.
Therapeutic effects of berberine in impaired glucose tolerance rats and its influence on insulin secretion.
Acta Pharmacol Sin. 2004 Apr;25(4):496-502.
AIM: To explore the anti-diabetic effects of berberine and its influence on insulin secretion. METHODS: Impaired glucose tolerance rats induced by iv injection of streptozotocin 30 mg/kg were treated with berberine 187.5 and 562.5 mg/kg while fed with high fat laboratory chow. After rats were treated for 4 weeks, oral glucose tolerance was determined, and for 8 weeks, the fasting blood glucose, insulin, lipid series were determined. In insulin secretion experiments, berberine 93.75, 187.5, and 562.5 mg/kg was administered orally to BALB/c mice at a bolus. The murine serum was collected 2 h after the berberine administration for insulin determination. Insulin released from HIT-T15 cells and pancreatic islets incubated with berberine 1-100 micromol/L for 12 h was determined. RESULTS: The levels of fasting blood glucose (7.4+/-1.5 or 7.3+/-1.3 vs 9.3+/-1.3 mmol/L), triglycerides (0.61+/-0.22 or 0.63+/-0.17 vs 1.8+/-0.7 mmol/L), total cholesterol (1.8+/-0.3 or 1.9+/-0.3 vs 2.2+/-0.2 mmol/L), free fatty acid (456+/-93 or 460+/-72 vs 550+/-113 micromol/L) and apolipoprotein B (0.37+/-0.02 or 0.42+/-0.05 vs 0.46+/-0.04 g/L) were reduced greatly in berberine-treated groups at doses of 187.5 and 562.5 mg/g/d, respectively as compared with those in control group (P<0.05 or P<0.01), whereas high density lipoprotein-cholesterol (1.5+/-0.3 or 1.4+/-0.3 vs 1.1+/-0.1 g/L), apolipoprotein AI (0.80+/-0.08 or 0.87+/-0.08 vs 0.71+/-0.06 g/L) were significantly increased (P<0.05 or P<0.01), and oral glucose tolerance was improved. In vitro experiment showed that berberine 1-10 micromol/L facilitated insulin secretion of HIT-T15 cells and murine pancreatic islets in a dose-dependent manner. Meanwhile murine serum insulin level (27.5+/-2.7 or 29+/-4 or 29+/-4 vs 24.3+/-2.8 pIU/L) was undoubtedly promoted and blood glucose (4.52+/-0.31 or 4.45+/-0.29 or 4.30+/-0.19 vs 4.87+/-0.21 mmol/L) was reduced after berberine administration at doses of 93.75, 187.5, and 562.5 mg/kg, respectively in the BALB/c mice. CONCLUSION: Berberine possesses anti-diabetic effects, which is related to the property of stimulating insulin secretion and modulating lipids.
Effect of Astragalus polysaccharides and berberine on carbohydrate metabolism and cell differentiation in 3T3-L1 adipocytes
Wang SH, Wang WJ, Wang XF, Chen W.
Zhongguo Zhong Xi Yi Jie He Za Zhi. 2004 Oct;24(10):926-8.
To compare the effects of Astragalus polysaccharides (AP) and berberine (BB) on the adipocyte's carbohydrate metabolism and cell differentiation, for assessing the possible mechanism of them in improving carbohydrate metabolism. METHODS: Adipocytes were treated with AP or BE, the 3H-glucose up-take rate in them was investigated, those of differentiation phase were stained by oil red O to analyze the degree of cell differentiation by spectrophotography quantitatively. The adipocyte differentiation related expression of PPARgamma mRNA and C/EBPalpha mRNA were determined by RT-PCR. RESULTS: The 3H-glucose up-take rate in the AP group and BE group were 109.3% and 182.7% of that in the blank control group respectively. AP obviously promoted the cell differentiation and up-regulated expression of PPARgamma mRNA, while BE suppressed the differentiation and expression of PPARgamma and C/EBPalpha mRNA distinctly, all showing significant difference as compared with that in the blank control (P<0.01). CONCLUSION: AP could promote glucose up-take, cell differentiation and PPARgamma mRNA expression, BB also promote glucose up-take, but suppress the cell differentiation, and inhibit expressions of PPARgamma and C/EBPalpha mRNA in 3T3-L1 adipocytes.
Inhibitory action of berberine on glucose absorption
Pan GY, Wang GJ, Sun JG, Huang ZJ, Zhao XC, Gu Y, Liu XD.
Yao Xue Xue Bao. 2003 Dec;38(12):911-4.
AIM: To study the absorption characteristics of berberine and its influence on glucose absorption. METHODS: Rat recirculating perfusion model was used to study berberine absorption characteristics and Caco-2 cell model was used to explore the influence of berberine on disaccharidase, using HPLC to assay the appearance of glucose to indicate enzyme activities. RESULTS: Berberine was found to be hardly absorbed in the intestine (less than 5% in 2.5 h). However, sucrase and maltase activities were found to be inhibited by berberine, its ID50 to sucrase is 1.830 mg.L-1, and showed no dose dependent influence on maltase activity. Berberine also showed influence on glucose absorption. However, this effect is not significant. CONCLUSION: Berberine may act as an alpha-glucosidase inhibitor, which is its main mechanism in diabetes treatment.
The antihyperglycaemic activity of berberine arises from a decrease of glucose absorption.
Pan GY, Huang ZJ, Wang GJ, Fawcett JP, Liu XD, Zhao XC, Sun JG, Xie
Planta Med. 2003 Jul;69(7):632-6.
The mechanism of action of berberine as an antihyperglycaemic agent was investigated in the Caco-2 cell line. Berberine was found to effectively inhibit the activity of disaccharidases in Caco-2 cells. It also decreased sucrase activity after preincubation with Caco-2 cells for 72 hours. However gluconeogenesis and glucose consumption of Caco-2 cells were not influenced. 2-Deoxyglucose transporting through Caco-2 cell monolayers was decreased by berberine but the effect was not statistically significant. These results suggest that the antihyperglycaemic activity of berberine is at least partly due to its ability to inhibit alpha-glucosidase and decrease glucose transport through the intestinal epithelium.
Effect of berberine on the differentiation of adipocyte
Zhou LB, Chen MD, Wang X, Song HD, Yang Y, Tang JF, Li FY, Xu MY, Chen JL.
Zhonghua Yi Xue Za Zhi. 2003 Feb 25;83(4):338-40.
OBJECTIVE: To observe the effect of berberine on the differentiation of 3T3-L1 preadipocytes into adipocytes and to elucidate its mechanism. METHODS: 3T3-L1 preadipocytes were cultured and then divided into 7 groups into whose media were added berberine of the concentrations of 0, 0.1, 1, 10, and 100 micro mol/L, 100 nmol/Linsulin, and 10 micro mol/L berberine + 100 nmol/L insulin. The proliferation of 3T3-L1 preadipocytes was detected by MTT method. The accumulation of lipid in the cytoplasm of differentiated adipocytes was observed by oil red O staining. The peroxisome proliferation activated receptor gamma2 (PPARgamma2) mRNA and protein were detected by RT-PCR and Western blotting respectively. RESULTS: MTT method showed that the absorbance at 570 nm of 3T3-L1 preadipocytes increased by 17% (P < 0.01), 36% (P < 0.001), and 22% (P < 0.05) in the groups of 1, 10, and 100 micro mol/L berberine, by 53% (P < 0.0001)in the group of 100 nmol/L insulin, and by 66% in the group of 10 micro mol/L berberine + 100 nmol/L insulin. There were less and smaller lipid droplets in the 3T3-L1 adipocytes treated with berberine as compared with the untreated control cells and only 10% - 20% of the treated cells displayed big lipid drops. RT-PCR showed that berberine significantly reduced the expression of PPARgamma2 mRNA by 48% (P < 0.01) in the course of 3T3-L1 adipocyte differentiation. Western blotting showed that berberine inhibited the expression of PPARgamma2 protein. CONCLUSION: Berberine promotes the proliferation of 3T3-L1 preadipocytes, decreases the accumulation of lipid drops therein, and inhibits the terminal differentiation of adipocyte, which may be associated with its effect on decreasing the expression of PPARgamma2 mRNA and protein, suggesting that berberine has advantages in the treatment of obesity patients with type 2 diabetes.
Effects of berberine on glucose metabolism in vitro.
Yin J, Hu R, Chen M, Tang J, Li F, Yang Y, Chen J.
Metabolism. 2002 Nov;51(11):1439-43.
The action of berberine was compared with metformin and troglitazone (TZD) with regard to the glucose-lowering action in vitro. HepG2 cell line, phenotypically similar to human hepatocytes, was used for glucose consumption (GC) studies. Cell proliferation was measured by methylthiotetrazole (MTT) assay. In moderate high glucose concentration (11.1 mmol/L), GC of HepG2 cells was increased by 32% to 60% (P <.001 to P <.0001) with 5 x 10(-6) mol/L to 1 x 10(-4) mol/L berberine, which was comparable to that with 1 x 10(-3) mol/L metformin. The glucose-lowering effect of berberine decreased as the glucose concentration increased. The maximal potency was reached in the presence of 5.5 mmol/L glucose, and it was abolished when the glucose concentration increased to 22.2 mmol/L. The effect was not dependent on insulin concentration, which was similar to that of metformin and was different from that of TZD, whose glucose-lowering effect is insulin dependent. TZD had a better antihyperglycemic potency than metformin when insulin was added (P <.001). In the meantime, a significant toxicity of the drug to HepG2 cells was also observed. The betaTC3 cell line was used for insulin release testing, and no secretogogue effect of berberine was observed. These observations suggest that berberine is able to exert a glucose-lowering effect in hepatocytes, which is insulin independent and similar to that of metformin, but has no effect on insulin secretion.
Shop in Confidence with Our Secure On-Line Ordering System
© Copyright 2002-2003 Sleepy Hollow Herb Farm All Rights Reserved