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beriberine
1. 1
University of sulaimani
College of pharmacy
Pharmacognocy and pharmaceutical chemistry department
(Beriberine) natural products and pharmacological activity
Prepared by: Dr. Muhammad Koksh Sdiq
B.Sc. in pharmacy
3. 3
Introduction
Alkaloids are group of secondary metabolites, they are natural and
contain nitrogen atom (should be heterocyclic), possess significant
pharmacological action; Often highly reactive in small amounts, their effects
on the human physiology is most notable on the nervous system (1).
The Isoquinoline alkaloids are Heterocyclic alkaloids group .They are
typically found in the Papaveraceae, Berberidaceae and Ranunculaceae
families. This class notably includes morphine and codeine and berberine .
They are derived from the amino acids tyrosine. They are formed from
dopamine linked to an aldehyde or ketone (2).
Berberine is one of the isoquinoline alkaloids, it have many
pharmacological use while being relatively non-toxic to man making it widely
applicable in its use. Berberine is chief alkaloid from roots and stem-bark of
Berberis species.It is major type of protoberberine alkaloids which are organic
cations characteristically yellow, have four linked benzene rings with a
nitrogen atom joining two ring pairs, and are modified variously via two
oxygen atoms at each end (3). It is water solube and acidic compound.
Aim
1) To provide the information about the botany of the isoquinoline alkaloid ( berberine) .
2) To know the pharmacological activity of the berberine .
4. 4
Literature review
# plant : table -1
Plant Content % Action
Coptis chinensis
(golden thread) (4)
4-8% berberine Antiviral , antibacterial,
analgesic,antispasm,antidiabetic
Cholagogue , sedative ,
antidiarrheal drug .
Phellodendron amurense (5) 4-8% berberine gastric ulcers, bacterial
infections, fungal infections,
and diabetes. It has also been
used for immunosuppression.
Hydrastis canadensis
(Golden seal) (6)
2-4.5% berberine also
Hydrastine
infectious condition of the
mucus membranes .
Berberis aquifolium
(Oregon mountain grape)(7)
4-6% berberine a tonic for the body and
particularly indicated for
skin problems.
Berberis aristate
(Tree turmeric)
3- 5% berberine treatment of gastroenteritis,
skin and eye infections.
Coccinia fenestratum
(‘Columbo Tree’)
4-5.5% berberine antioxidant, hypotensive,
antiseptic actions and is the
subject of research for
diabetic use.
Berberis vulgaris
(Barberry) (8)
6% berberine Cholagogue, choleretic, mild
laxative, Antibacterial
# Plant Part Used
Root, root bark( rhezomes ) and stem bark
# Family
Papaveraceae, Berberidaceae and Ranunculaceae .
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Figure -3
Physicochemical properties
1- It is quaternary amonium compound .
2- It is soluble in water and sparingly soluble in organic solvent.
3- It has yellow color .
4- It has acidic properties .
5- React with acid to form salt .
Process of extraction
8. 8
Figure -4
Pharmacology
The pharmacologic actions of berberine include metabolic inhibition of certain
organisms, inhibition of bacterial enterotoxin formation, inhibition of intestinal fluid
accumulation and ion secretion, inhibition of smooth muscle contraction, reduction of
inflammation, platelet aggregation inhibition, platelet count elevation in certain types of
thrombocytopenia, stimulation of bile and bilirubin secretion, and inhibition of ventricular
tachyarrhythmias.(12)(13)
The investigation of the interactions of QPA with bio-macromolecules at the atomic
level and the structural description of their complexes represent key steps in the real
understanding of the biological function of the QPA.
Clinical uses
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Antimicrobial activity
Bacterial Diarrhea :
Diarrhea caused by Vibrio cholera and Escherichia coli has been the focus of
numerous berberine studies . An animal study found berberine reduced the intestinal
secretion of water and electrolytes induced by cholera toxin. (15)
Other studies have shown berberine directly inhibits some V. cholera and E. coli
enterotoxins,(16) significantly reduces smooth muscle contraction and intestinal
motility,(14) and delays intestinal transit time in humans. (17) directly bactericidal to V.
cholera. (18) Other study shows that berberine capable of inhibiting bacterial adherence
to mucosal or epithelial surfaces, the first step in the infective process.(19)
Intestinal Parasites:
Berberine extracts and salts have demonstrated growth inhibition of Giardia lamblia,
Entamoeba histolytica, Trichomonas vaginalis, (20) and Leishmania donovani,(21) with
crude extracts being more effective than berberine salts. (22)
In tropical climates Giardia lamblia infestation (giardiasis) is a common occurrence,
particularly in pediatric populations.(23) Clinical trials conducted in India showed
berberine administration improved gastrointestinal symptoms and resulted in a marked
reduction in Giardia-positive stools. In comparison to metronidazole (Flagyl), another
popular giardiasis medication, berberine was nearly as effective at half the dose.
(24)Both in vivo and in vitro studies of berberine’s effects on E. histolytica indicated
berberine sulfate was rapidly amoebicidal and caused encystation, degeneration, and
eventual lysis of the trophozoite forms. (25)Berberine sulfate rapidly inhibited the
growth of Trichomonas vaginalis via formation of large autophagic vacuoles that
eventually result in lysis of the trophozoite forms.(20)
Ocular Trachoma Infections :
10. 10
A clinical study of aqueous berberine versus sulfacetamide for the treatment of
Chlamydia trachomatis infection was conducted on 51 subjects in an outpatient eye
clinic. It was determined that while sulfacetamide eye drops produced slightly better
clinical results, conjunctival scrapings of these patients remained positive for the
infective agent and relapses occurred. In contrast, the conjunctival scrapings of patients
receiving the berberine chloride eye drops were negative for C. trachomatis and there
were no relapses, even one year after treatment. It was also concluded that, while
berberine chloride had no direct anti-chlamydial properties, it seemed to cure the
infection by stimulating some protective mechanism in the host.(26) A second clinical
study found berberine chloride superior to sulfacetamide in both the clinical course of
trachoma and in achieving a drop in serum antibody against C. trachomatis. (27)
Cardiovascularsystem:
Berberine can affect the timing and force of contraction of the heart and is known for
its cardiotonic ability(31) . In vitro studies indicate that berberine inhibits voltage-
dependent and ATP-sensitive potassium channels, although mechanisms involved in
berberine’s anti arrhythmic activities are still unclear but an animal study indicated it
may be due to suppression of delayed after-depolarization in the ventricular muscle.
(28) Berberine also shows inhibition of platelet aggregation and adhesiveness as well
as decreasing thromboxane B2 levels (32) . and lowered peripheral vascular resistance
and blood pressure , berberine may have a vasodilatory/hypotensive effect attributable
to its potentiation of acetylcholine.(29),(30)
Cholesterol :
In a controlled Chinese study, it was shown that berberine, administered 500 mg
twice per day for 3 months, reduced serum cholesterol by 29%, triglycerides by 35%
and LDL-cholesterol by 25%. It is thought that berberine increases the production of a
receptor protein in the liver which binds the LDL-cholesterol, preparing it for
elimination (33) .
Diabetes mellitus :
11. 11
Oral doses (0.3-0.5gms bid) were administered for 1-3 months with a therapeutic
diet for one month. This resulted in the disappearance of major symptoms. Patients had
less thirst, consumed less water and urinated less. General strength was improved, blood
pressure normalized and blood lipids decreased. Fasting sugar levels were controlled in
60% of the cases. Further tests in animals suggested that the mechanism of action was
by promoting regeneration and functional recovery of pancreatic β-cells(34).It is also
thought that berberine inhibits sugars from being absorbed from the intestine (35) .
Collaboration between Australia, China and Korea with trials on animal models of
diabetes, show that berberine acts in part by activating an enzyme in muscles and liver
that is involved in improving sensitivity of the tissue to insulin which then helped lower
blood sugar levels. Additionally in this trial it was found that berberine may help reduce
body weight (36).
Immune system:
Berberine also shows cytotoxic effects against certain types of tumor cells and
inhibitive action on tumor formation. Berberine has been shown to complex with DNA
and is being used as a specific stain for mast cells because of its specificity of binding
with heparin. It has also been shown that berberine exhibits the ability to induce
apoptosis in promyelocytic leukemia HL-60 and 3T3 fibroblast cells (37). Another trial
with berberine on Growth of human colon cancer cells, has shown its inhibiting effect
on blocking two enzymes needed for their growth; N -acetyltransferase (NAT) and the
cyclooxygenase-2 (COX-2) enzyme (38) .
A Japanese patent published in 1995 discusses the use of berberine as an
immunosuppressant specifically for autoimmune diseases such as rheumatism and also
for treatment of allergies and to prevent rejection of isografts. It was found that
berberine inhibits antibody production by B cells, suppresses humoral immunity and
has no effect on propagation of T cells.
Other Effects :
12. 12
Berberine has demonstrated a number of other beneficial effects, including
immunostimulation via increased blood flow to the spleen, macrophage activation,
elevation of platelet counts in cases of primary and secondary thrombocytopenia, and
increased excretion of conjugated bilirubin in experimental hyperbilirubinemia.(39)
In addition, berberine may possess anti-tumor promoting properties as evidenced by
inhibition of COX-2 transcription and N-acetyltransferase activity in colon and bladder
cancer cell lines, (40),(41) and transient, but marked, inhibitory action on the growth of
mouse sarcoma cells in culture. (42)
Dosage and Toxicity
Berberine is not considered toxic at doses used in clinical situations, nor has it been
shown to be cytotoxic or mutagenic. Side-effects can result from high dosages and may
include gastrointestinal discomfort, dyspnea, lowered blood pressure, flu-like symptoms,
and cardiac damage. Berberine usage should be avoided in pregnancy, due to potential for
causing uterine contractions and miscarriage, and in jaundiced neonates because of its
bilirubin displacement properties. The therapeutic dosage for most clinical situations is
200 mg orally two to four times daily.(39)
Conclution
13. 13
uaternary protoberberine alkaloids (berberine)represent a very interesting and
significant group of natural products with a broad range of biological activities. Owing
to the presence of the polarized bond, positive charge, and relatively planar skeleton,
QPA interact with a range of molecular and biological targets, including nucleic acids
and proteins.
Based on the activities of Berberine many applicable uses may be seen,
particularly in its use as an anti-bactericidal. It may be applied safely internally
(malaria, dysentery, Giardia and a broad range of fungal infections which include
Candida)and externally (Eye infections and most likely other external fungal
infections). Berberine also inhibits bacteria from attaching to human cells making it
useful in preventing infection.(43)
The effects on pancreatic cells are particularly positive for diabetes. It may also
have uses as an adjunct treatment for some heart related conditions due to the
cholesterol lowering activities, platelet aggregation inhibition and cardiotonic effects.
Useful in the treatment of some cancer cases as well as those who may be pre-disposed
to cancer it is seen to inhibit tumour growth and retard development of various types of
cancer by varied mechanisms(44). Due to its bitterness it is also a useful choleretic,
which will have beneficial effects on the Gastro Intestinal tract due to the gentle laxative
effects of bile. Berberine has been the source of much research. It is a therapeutic
constituent which is well tolerated in a range situations and age groups making it a
useful and relatively safe constituent.
Refrence
14. 14
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15. 15
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acetyltransferase activity in human colon tumor cells. Am J Chin Med;27:265-275.
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