Zedoary-Induced Cardiovascular Disorders

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Zedoary-Induced Cardiovascular Disorders case
report

• Usama M. El-Barrany
• Magdy A. Ismail
•  
• Forensic Medicine and Toxicology Department,
  Faculty of Medicine, Cairo and Al-Azhar
• Boys Universities

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• intoduction

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intoduction

• Many people use traditional remedies as a first
  line medication.
• Some herbal toxicity is predictable, based on
  known botanical content.
• Many other adverse effects are idiosyncratic or
  not commonly appreciated.
• Zedoary (Curcuma Zedoaria) is one of these
  commonly used herbs.

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Zedoary (Curcuma Zedoaria)
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Zedoary (Curcuma Zedoaria)

• Species Curcuma zedoaria.
• Family Zingiberaceae (ginger family).
• Origin The plant is native to India and
  Indonesia. but today is widely cultivated in
  India, South-East Asia and China.
• It was introduced to Europe by Arabs around the
  sixth century.
• Etymology The European names for zedoary
  originate from Arabic jadwar and Farsi zedwaar.

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Zedoary (Curcuma Zedoaria)

• Characteristics
• A rhizomatous herb with a 6-foot tall leafy stem.
• The leaves are 1 foot long and 3 inches across.
• The flowers are white or yellowish with a lip
  that is pale yellow-shaded, with a deeper yellow
  color near the base.
• The fruits have 3-valved capsules.
• The rhizome is short, firm, and of externally
  wrinkled gray, ash-colored appearance, but with a
  brownish red color from the inside.

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Zedoary (Curcuma Zedoaria)
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Zedoary (Curcuma Zedoaria)
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Zedoary (Curcuma Zedoaria)
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Zedoary (Curcuma Zedoaria)

• Active ingredients
• Curcumin, berberine, hydrastine, canadline,
  zingiberine, dihydrocurdione, ar-turmerone,
  beta-turmerone, some volatile oils, and resins.
• The highest concentrations of these constituents
  are in the root (rhizomes), the lowest, in the
  leaves and stem.

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Zedoary (Curcuma Zedoaria)

• Uses The used part is the rhizomes.
• Food
• It has a fragrant smell (more similar to ginger,
  except with a very bitter taste).
• Due to its bitter taste, its use as a spice today
  is rare, having been replaced by ginger.
• Although it is seldom used today as an individual
  spice, it may be employed in spice mixtures.

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Zedoary (Curcuma Zedoaria)

• Food
• In Indonesia Thailand, the young rhizomes are
  often eaten as an aromatic vegetable, zedoary can
  also be ground to a powder and added to curry
  pastes.
• In India, it tends to be used fresh or in
  pickling.

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Zedoary (Curcuma Zedoaria)

• Medicinal uses
• Zedoary is used in the form of powdered root,
  tincture, fluid and solid extract the medicinal
  substance obtained has a fragrant smell, and a
  warm bitter aromatic taste.
• It is much used as a medicine in China and Japan.
  It has been used as an antivenom for the Indian
  cobra.
• It has been also used in traditional eastern
  medicines to help digestion, relieve colic, as a
  laxative, antifungal, analgesic and
  anti-inflammatory agent.

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Zedoary (Curcuma Zedoaria)

• Medicinal uses
• Dihydrocurdione, the major component of Zedoary
  has anti-inflammatory potency related to its
  antioxidant effect.
• The anti-inflammatory and cancer chemopreventive
  effect of some components of Zedoary might be due
  to decreased prostaglandin and nitric oxide
  production through respective inhibition of
  cyclooygenase 2 (COX-2) and nitric oxide
  synthase, which have been implicated as important
  mediators in the processes of inflammation and
  carcinogenesis.

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Zedoary (Curcuma Zedoaria)

• Medicinal uses
• Zedoarin, kurdiona and kurkumol are substances
  that can be also found in Zedoary.
• These substances have anti-neoplastic functions
  through breaking ribosome formation in cancer
  cells and wild tissue.
• They enhance the formation of fibroblast tissue
  around the cancer and form a layer of lymphocytes
  in the cells of cancer wrap it.
• So, the tissue cells of cancer can not grow,
  eventually the cancer cells will die.

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Zedoary (Curcuma Zedoaria)

• Medicinal uses
• Zedoary has been used to treat some liver and
  coronary heart disease.
• It has been used to treat anemia, prevent
  leukopenia due to cancer therapies and as an
  agent for purifying the blood.
• It has been also applied locally as poultice for
  skin lesions and eyes.

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Zedoary (Curcuma Zedoaria)

• Others
• The essential oil produced from the dried roots
  of Zedoary is used in perfumery as well as an
  ingredient in bitter tonics.

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Zedoary (Curcuma Zedoaria)

• On the other hand, a protein flour, prepared from
  rhizomes of Zedoary , proved to be highly toxic
  to 5-week-old rats and caused 100 mortality
  within 6 days when given at 320 g/kg diet.
• When a meal formed of fresh minced and dried
  rhizomes of Zedoary was given to weanling rats at
  400 g/kg diet, all the animals lost weight
  rapidly, and two of the five rats died within 4
  days.

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• Case Report

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Case Report

• This study describes 2 cases of Zedoary-induced
  bradyarrhythmias and severe prolonged hypotension
  (during our work in Center of Poison Control and
  Clinical Forensic Chemistry, in Holy Makkah
  region, Saudi Arabia).

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• CASE I

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CASE I

• A 20-year-old woman was admitted to Al-noor
  special hospital in Holy Makkah region, Saudi
  Arabia at 3/11/2003 after ingestion of an unknown
  quantity of Zedoary extract to reduce pain (the
  history was taken from her father).
• On admission, she was unresponsive except for
  painful stimuli, with diaphoresis, cyanosis, and
  respiratory depression.
• Pupils were slightly dilated systolic blood
  pressure was 50 mmHg, with a third degree heart
  block and a ventricular rate 40 beats/minute.

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CASE I

• Following intubation, gastric lavage was done,
  and activated charcoal was given 3 times (every 4
  hours).
• Routine toxicological screening using,
  immunoassay techniques (AxSYM), was negative for
  alcohol, opiates, barbiturates, benzodiazepines,
  amphetamines, cocaine, cannabis, tricyclic
  antidepressants (TCAs), digoxin, theophylline,
  salicylates, acetaminophen, phenytoin,
  carbamazepine as well as valproic acid.

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CASE I

• Color tests, TLC Toxi-Lab System showed ve
  results for other common substances such as
  phenothiazines, antihistamines, beta blockers,
  calcium channel antagonists, NSAIDs, SSRIs,
  organophosphates as well as carbamates.
• Bradycardia and hypotension were unresponsive to
  atropine, infusion of dopamine, saline, or even
  pacemaker insertion.
• She died within 24 hours after admission from
  cardiovascular collapse.

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• CASE Ii

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CASE Ii

• An 18-years old woman was admitted to Al-noor
  special hospital in Holy Makkah region, Saudi
  Arabia at 4/11/2003 after ingestion of a large
  quantity of Zedoary extract as a tonic. (the
  history was taken from the patient).
• On admission, she was alert, but had nausea,
  vomiting, abdominal pain, dizziness and lethargy.
• Systolic blood pressure was 60 mmHg, with
  junctional bradycardia (as slow as 27
  beats/minute) but without evidence of myocardial
  infarction.

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CASE Ii

• Following spontaneous emesis, gastric lavage was
  done, and activated charcoal was given 3 times
  (every 4 hours).
• Routine toxicological screening, using
  immunoassay techniques (AxSYM), was also negative
  for alcohol, opiates, barbiturates,
  benzodiazepines, amphetamines, cocaine, cannabis,
  TCAs, digoxin, theophylline, salicylates,
  acetaminophen, phenytoin, carbamazepine as well
  as valproic acid.

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CASE Ii

• Color tests, TLC Toxi-Lab System showed also
  ve results for other common substances such as
  phenothiazines, antihistamines, beta blockers,
  calcium channel antagonists, NSAIDs, SSRIs,
  organophosphates as well as carbamates.
• Dopamine, intravenous saline, and 20 ml of 10
  calcium gluconate intravenously were
  administered, and a pacemaker was placed.
• Calcium gluconate was repeated and pressor agents
  were infused for additional 18 hours.
• Blood pressure became normal after 24 hours, and
  sinus rhythm returned after 35 hours from
  admission. The patient was discharged free 5 days
  post-admission.

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• Discussion

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Discussion

• The rapid course of the two cases pushed the team
  of center to work in two ways
• One way was the analysis of biological fluids
  from the two patient as well as the possible
  analysis of Zedoary.
• The other one was getting all possible data about
  the mentioned herb.

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Discussion

• In the two cases, routine toxicological screening
  for the previously mentioned substances was done
  to exclude any of them as a cause of toxicity.
• Many substances such as beta blockers,
  antihistamines, CCAs, NSAIDs or SSRIs are not
  analyzed routinely as one group but as individual
  drugs in the group, meaning that getting ve
  results for some drugs in the group does not
  exclude the presence of other ve unknown drugs
  or substances belonging to the same group.

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Discussion

• Although HPLC-MS needed for analysis of zedoary
  into their different components was available in
  the center, we did not have the special method
  for detection of this herb.
• In addition to that, the rapid course of the two
  cases especially the first one enforced all the
  team of the center to depend on the available
  data received from our search about Zedoary.

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Discussion

• Some of these data included that Curcuma herbs
  have showed hypotensive and protective effect on
  the endothelium in spontaneously hypertensive
  rats.
• Especially, C. Zedoaria was more effective than
  C. Longa, and its mechanism was thought to be
  related to a radical scavenging effect and
  improvement of hemorheology.
• Hemorheology is the study of flow properties of
  blood and its elements (plasma and formed
  elements, including red blood cells, white blood
  cells and platelets).

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Discussion

• Dihydrocurdione, the major component of Zedoary
  has calcium channel antagonist-like effects.
• Zedoary contains both hydrastine and berberine,
  which cause a decrease in blood pressure.

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Discussion

• Berberine is thought to be seven times as potent
  as hydrastine in producing hypotension.
• A dose of 1mg/kg of Zedoary extract will produce
  a slight increase then decrease in blood
  pressure, while 2mg/kg will produce significant
  prolonged hypotension.

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Discussion

• On the other hand, hallmarks of CCAs overdose
  include bradyarrhythmias, myocardial depression,
  peripheral vasodilatation, hypotension, and
  syncope.
• These symptoms and signs of toxicity coincided
  with the two cases of Zedoary toxicity, presently
  reported, whereas their main manifestations were
  cardiovascular disorders in the form of severe
  prolonged hypotension and bradyarrhythmias.

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Discussion

• Although plasma concentrations of CCAs correlate
  well with cardiovascular depression in the
  experimental setting, plasma concentrations in
  humans show no significant correlation with the
  amount of drug reportedly ingested by patients.
• Moreover, fatal verapamil overdose has occurred
  with a peak plasma concentration slightly higher
  than the high-therapeutic range (687 ng/mL).

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Discussion

• Thus, managing patients with suspected herbs
  having signs and symptoms similar to CCA overdose
  should be based on clinical features rather than
  analysis.
• Based on these data, calcium gluconate 10 was
  given to the second patient to treat the
  refractory hypotension and to avoid death as in
  the first case.

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• Conclusion AND RECOMMENDATIONS

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Conclusion AND RECOMMENDATIONS

• There is no logic supporting the popular
  conception that herbal products are safer or more
  natural than pharmaceutical medications.
• The use of herbs by most individuals should be
  put under strict medical regulations.

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Conclusion AND RECOMMENDATIONS

• More studies are needed regarding the clinical
  manifestations as well as the chemical analysis
  of most commonly-used herbs.
• Toxicology centers should be equipped with modern
  analytical facilities as well as information
  centers to help clinicians in managing different
  toxic cases.

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