HERBS: Berberine (plant alkaloid) (REMEDIES)

August 16, 2006

Cardiovascular actions of berberine.

Lau CW, Yao XQ, Chen ZY, Ko WH, Huang Y.

Department of Physiology, Chinese University of Hong Kong, Shatin, Hong

Kong, China.

Berberine, is an alkaloid from Hydrastis canadensis L., Chinese herb

Huanglian, and many other plants. It is widely used in traditional

Chinese medicine as an antimicrobial in the treatment of dysentery and

infectious diarrhea. This manuscript describes cardiovascular effects of

berberine and its derivatives, tetrahydroberberine and 8-oxoberberine.

Berberine has positive inotropic, negative chronotropic, antiarrhythmic,

and vasodilator properties. Both derivatives of berberine have

antiarrhythmic activity. Some cardiovascular effects of berberine and

its derivatives are attributed to the blockade of K+ channels (delayed

rectifier and K(ATP)) and stimulation of Na+ -Ca(2+) exchanger.

Berberine has been shown to prolong the duration of ventricular action

potential. Its vasodilator activity has been attributed to multiple

cellular mechanisms. The cardiovascular effects of berberine suggest its

possible clinical usefulness in the treatment of arrhythmias and/or

heart failure.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_uids=1\

1607041 & dopt=Abstract

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Berberine - Herbal Antimicrobial Agent

An active ingredient of:

-Goldenseal (hydrastis canadensis)

-Coptis (Coptis chinensis)

-Barberry (Berberis vulgaris)

-Oregon grape (Mahonia repens)

-Yerba mansa (Anemopsis californica)

Berberine:

1. Is Antibacterial

2. Increases bile production and secretion1

3. Destroys protozoa in the gastrointestinal system2

4. Increases mucus production

5. Has been shown to be effective for Giardia lamblia3 as well as many

other parasites

Berberine is commonly used as a component of oregon grape and goldenseal

for a variety of bacterial infections, especially of the

gastrointestinal and respiratory systems. One of our favorite uses for

berberine is in the treatment of giardiasis and other protozoan parasites.

1. Kulkarni, SK, et al. Pharmacological investigations of berberine

sulphate. Japanese Journal of Pharmacology, 22, pp 11-16, 1972.

2. Subbaiah, TV. Effects of berberine sulphate on Entamoeba histolytica,

Natyuer, 215, PP 527-28, 1967.

3. Gupe, S. Use of berberine in the treatment of giardiasis. Am J of

Diseases of Childhood, 129, p 866, 1961.

http://www.wellvet.com/berberine_Herbal_Antimicrobial.htm

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Berberine is a plant alkaloid isolated from the roots and bark of

several herbs. Some of these herbs include:

Barberry (Berberis vulgaris), Berberis integerrima

Coptis chinensis or Berberis aristata

Goldenseal (Hydrastis canadensis)

Oregon Grape (Berberis aquifolium)

Phellodendron Amurense

Yerba mansa (Anemopsis californica).

The berberine alkaloid can be found in the roots, rhizomes, stem, and

bark of the plants. Berberine-containing plants are used medicinally in

many traditional medical systems, including Ayurvedic and Chinese herbal

medicine.

Coptis chinensis rhizome -- Golden Thread -- Huang Lian -- Intense

yellow color most likely due to high content of berberine, which is very

bitter in taste.

Berberine potential benefits:

Some people claim berberine is useful for fungal, candida, yeast,

parasites and bacterial, viral infections. Berberine extracts and

decoctions have demonstrated antimicrobial activity against a variety of

organisms including bacteria, viruses, fungi, protozoans, helminths, and

chlamydia. Currently, the predominant clinical uses of berberine include

bacterial diarrhea, intestinal parasite infections, and ocular trachoma

infections.

Berberine has been tested in diabetes, cardiac arrhythmia and leukemia.

Berberine and Diabetes:

A collaboration between Chinese, Korean, and Australian scientists at

Sydney's Garvan Institute indicates berberine could be helpful. They say

" Our studies in animal models of diabetes show that berberine acts in

part by activating an enzyme in the muscle and liver that is involved in

improving sensitivity of the tissue to insulin – this in turn helps

lower blood sugar levels. In addition, it seems berberine can help

reduce body weight " . " Berberine has been used for decades, if not

centuries, with few reported side effects. Given the limitations of

existing medicines we are excited to have evidence that berberine may be

a helpful new treatment for type 2 diabetes; however, despite its

widespread use in traditional medicine practices, it will still have to

be evaluated properly following the defined clinical trials process " ,

said Professor James, head of the Garvan's Diabetes & Obesity Research

Program and co-author of the Diabetes paper.

Berberine Research Update:

Antimicrobial activity of berberine alone and in combination with

ampicillin or oxacillin against methicillin-resistant Staphylococcus aureus.

J Med Food. 2005 Winter;8(4):454-61. Department of Food and Nutrition,

Kunsan National University, Kunsan.

Methicillin-resistant Staphylococcus aureus (MRSA) bacteria have been

responsible for substantial morbidity and mortality in hospitals because

they usually have multidrug resistance. Some natural products are

candidates as new antibiotic substances. In the present study, we

investigated the antimicrobial activity of berberine, the main

antibacterial substance of Coptidis rhizoma (Coptis chinensis Franch)

and Phellodendri cortex (Phellodendron amurense Ruprecht), against

clinical isolates of MRSA, and the effects of berberine on the adhesion

to MRSA and intracellular invasion into human gingival fibroblasts

(HGFs). Berberine showed antimicrobial activity against all tested

strains of MRSA. These results suggest that berberine may have

antimicrobial activity and the potential to restore the effectiveness of

beta-lactam antibiotics against MRSA, and inhibit the MRSA adhesion and

intracellular invasion in HGFs.

Hepatobiliary excretion of berberine.

Drug Metab Dispos. 2004 Apr;32(4):405-12.

To investigate the detailed pharmacokinetics of berberine and its

mechanisms of hepatobiliary excretion, an in vivo microdialysis coupled

with high-performance liquid chromatography was performed. In the

control group, rats received berberine alone; in the drug-treated group,

10 min before berberine administration, the rats were injected with

cyclosporin A (CsA), a P-glycoprotein (P-gp) inhibitor; quinidine, both

organic cation transport (OCT) and P-gp inhibitors; SKF-525A

(proadifen), a cytochrome P450 inhibitor; and probenecid to inhibit the

glucuronidation. The results indicate that berberine displays a linear

pharmacokinetic phenomenon in the dosage range from 10 to 20 mg kg(-1),

since a proportional increase in the area under the concentration-time

curve (AUC) of berberine was observed in this dosage range. Moreover,

berberine was processed through hepatobiliary excretion against a

concentration gradient based on the bile-to-blood distribution ratio

(AUC(bile)/AUC(blood)); the active berberine efflux might be affected by

P-gp and OCT since coadministration of berberine and CsA or quinidine at

the same dosage of 10 mg kg(-1) significantly decreased the berberine

amount in bile. In addition, berberine was metabolized in the liver with

phase I demethylation and phase II glucuronidation, as identified by

liquid chromatography/tandem mass spectrometry. Also, the phase I

metabolism of berberine was partially reduced by SKF-525A treatment, but

the phase II glucuronidation of berberine was not obviously affected by

probenecid under the present study design.

Cytotoxic effects of Coptis chinensis and Epimedium sagittatum extracts

and their major constituents (berberine, coptisine and icariin) on

hepatoma and leukemia cell growth.

Clin Exp Pharmacol Physiol. 2004 Jan-Feb;31(1-2):65-9.

1. The present study was conducted to evaluate the cytotoxic effects of

Coptis chinensis and Epimedium sagittatum extracts and their major

constituents on hepatoma and leukemia cells in vitro. 2. Four human

liver cancer cell lines, namely HepG2, Hep3B, SK-Hep1 and PLC/PRF/5, and

four leukemia cell lines, namely K562, U937, P3H1 and Raji, were used in

the present study. 3. Of the two crude drugs, C. chinensis exhibited the

strongest activity against SK-Hep1 (IC50 = 7 microg/mL) and Raji (IC50 =

4 microg/mL) cell lines. The IC50 values for Coptis chinensis on HepG2,

Hep3B and PLC/PRF/5 cell lines were 20, 55 and 35 microg/mL,

respectively. The IC50 values for Coptis chinensis on K562, U937 and

P3H1 cell lines were 29, 29 and 31 microg/mL, respectively. 4. With the

exception of HepG2 and Hep3B, the E. sagittatum extract inhibited the

proliferation of all cell lines (SK-Hep1, PLC/PRF/5, K562, U937, P3H1

and Raji), with IC50 values of 15, 57, 74, 221, 40 and 80 microg/mL,

respectively. 5. Interestingly, the two major compounds of Coptis

chinensis, berberine and coptisine, showed a strong inhibition on the

proliferation of both hepatoma and leukemia cell lines, with IC50 values

varying from 1.4 to 15.2 microg/mL and from 0.6 to 14.1 microg/mL,

respectively. However, icariin (the major compound of E. sagittatum)

showed no inhibition of either the hepatoma or leukemia cell lines. 6.

The results of the present study suggest that the Coptis chinensis

extract and its major constituents berberine and coptisine possess

active antihepatoma and anti leukemia activities.

Effect of berberine on regression of pressure-overload induced cardiac

hypertrophy in rats.

Am J Chin Med. 2002;30(4):589-99.

Berberine is the basic chemical component of a Chinese herb, Coptis

chinensis Franch (coptis), considered to be useful in treating some

diseases of the cardiovascular system, such as hypertension and chronic

heart failure (CHF). In this study, we investigate the inhibitory effect

of berberine on experimental cardiac hypertrophy, which is regarded as a

risk factor of CHF and other heart diseases. Forty-two male SD rats were

divided into four groups: age-matched control, aortic banding model,

berberine-treated group and captopril-treated group. Cardiac hypertrophy

was induced by suprarenal abdominal aorta constriction (banding). The

drugs were orally administered for 8 weeks starting from 4 weeks after

surgery at dosage of berberine 10 mg/kg and captopril 50 mg/kg. Blood

pressure (BP) was measured four times during the period of the

experiment, and hemodynamic parameters, cardiac index, cell size of left

ventricular myocardium and total protein of left ventricular tissue were

detected 8 weeks after treatment with drugs. The data from the present

study showed that: (1) The BP of the aorta banded rats was increased

compared with those of the normal (p < 0.001) and the age-matched

control rats (p < 0.001), and berberine showed no significant effect on

it. (2) After 8 weeks of treatment with berberine, the elevated left

ventricular end diastolic pressure (LVEDP) was slightly decreased

compared with the aortic banded rats. Meanwhile, the maximum rates of

contraction and relaxation (+/- dp/dtmax) was increased (p < 0.05) and

the time to reach the point of maximum rate from beginning of

contraction (t-dp/dt) was shortened (p < 0.01), indicating that the

functions of heart, both contraction and relaxation, were improved. (3)

Cardiac growth was inhibited by treatment with berberine. Both whole

heart and left ventricular weight were notably decreased compared with

the banded rats (p < 0.05 and p < 0.01). (4) The cell size of left

ventricular myocardium was significantly reduced (p < 0.001) and the

total protein of left ventricular tissue was slightly down-regulated by

treatment with berberine. These data suggest that berberine can improve

abnormal cardiac function and can prevent the development of left

ventricular hypertrophy induced by pressure-overload. This indicates

that it may have therapeutic potential in the treatment of CHF.

Efficacy and safety of berberine for congestive heart failure secondary

to ischemic or idiopathic dilated cardiomyopathy.

Am J Cardiol. 2003 Jul 15;92(2):173-6.

This study was designed to assess the efficacy and safety of berberine

for chronic congestive heart failure. One hundred fifty-six patients

with CHF and >90 ventricular premature complexes (VPCs) and/or

nonsustained ventricular tachycardia (VT) on 24-hour Holter monitoring

were randomly divided into 2 groups. All patients were given

conventional therapy for congestive heart failure, consisting of

angiotensin-converting enzyme inhibitors, digoxin, diuretics, and

nitrates. Patients in the treatment group (n = 79) were also given

berberine 1.2 to 2.0 g/day. The remaining 77 patients were given

placebo. Symptoms, a 6-minute walk test, left ventricular (LV) ejection

fraction (EF), frequency and complexity of VPCs, and quality of life

were assessed after 8 weeks of treatment and during a mean 24-month

follow-up. After treatment with berberine, there was a significantly

greater increase in LVEF, exercise capacity, improvement of the

dyspnea-fatigue index, and a decrease of frequency and complexity of

VPCs compared with the control group. There was a significant decrease

in mortality in the berberine-treated patients during long-term

follow-up (7 patients receiving treatment died vs 13 on placebo, p

<0.02). Proarrhythmia was not observed, and there were no apparent side

effects. Thus, berberine improved quality of life and decreased VPCs and

mortality in patients with congestive heart failure.

Effect of berberine on bone mineral density in SAMP6 as a senile

osteoporosis model.

Biol Pharm Bull. 2003 Jan;26(1):110-1.

The effects of berberine in senescence accelerated mice P6 (SAMP6) were

investigated to learn whether the alkaloid affects bone mineral density

(BMD). Oral administration of berberine (10 mg/kg/d) to male and female

mice for 22 weeks resulted in an increase in BMD in both sexes. A

decreased concentration of deoxypyridinoline (Dpd) in urine was only

observed in female mice. There was no effect on body or tibia weight or

on the concentration of procollagen type I carboxyterminal extension

peptide (PICP) in serum.

A comparative study on the anti-inflammatory, antinociceptive and

antipyretic effects of isoquinoline alkaloids from the roots of Turkish

Berberis species.

Life Sci. 2002 Dec 27;72(6):645-57.

Roots and barks of various Berberis species are used as folk remedy for

the treatment of various inflammatory diseases such as lumbago,

rheumatism and to reduce fever. Six isoquinoline alkaloids namely

berberine, berbamine, palmatine, oxyacanthine, magnoflorine, and

columbamine were isolated as the main components of alkaloidal fraction

from the roots of Turkish Berberis species and effects were studied

using various in vivo models in mice. All alkaloids inhibited

inflammations in varying degrees, among them berberine, berbamine and

palmatine were shown to possess significant and dose-dependent

inhibitory activity against serotonin-induced hind paw oedema both on

oral and topical applications and acetic acid-induced increase in

vascular permeability on oral administration. Moreover, these three

alkaloids were also shown to possess dose-dependent antinociceptive

activity, which assessed by using the model based on the inhibition of

p-benzoquinone-induced writhing movements as well as antipyretic

activity on FCA-induced increased rectal temperature on subacute

administration. However, all alkaloids induced gastric lesions in

varying degrees.

Inhibitory effects of berberine on IK1, IK, and HERG channels of cardiac

myocytes.

Acta Pharmacol Sin. 2001 Feb;22(2):125-31.

AIM: To study the effects of berberine on inward rectifier potassium

current (IK1) and outward delayed rectifier potassium current (IK) of

guinea pig ventricular myocytes, and on human ether-a-go-go related gene

(HERG) channel expressed in Xenopus oocytes. RESULTS: Berberine

prolonged action potential duration (APD) and inhibited IK1 and IK in a

concentration-dependent manner. Berberine 100 micromol/L increased APD90

from (450 +\- 48) ms to (888 +\- 90) ms (n = 6, P < 0.01), and inhibited

IK1 by 65 % +\- 7 % (n = 6, P < 0.01). Berberine 50 micromol/L inhibited

IK by 57 % +\- 6 %, IKtail by 53 % +\- 6 % (n = 6, P < 0.01). Berberine

produced a voltage-dependent block on IK that increased with stronger

depolarization, and once all channels were activated, there was no

further block at positive potentials. Berberine blocked the HERG

channels potently with an IC50 value of approximately 75 micromol/L.

This block was voltage-dependent, suggesting that it probably bind to

either open or inactivated HERG channels. CONCLUSION: Berberine

prolonged APD and possessed blocking effect on IK1, IK, and HERG channel

expressed in Xenopus oocytes. The antiarrhythmic mechanism of berberine

is related to its inhibitory effects on IK1, IK, and HERG channel.

Cardiovascular actions of berberine.

Cardiovasc Drug Rev. 2001 Fall;19(3):234-44.