9000-38-8 Usage
Uses
Used in Traditional Medicine:
Kavakavaresin is used as a traditional medicine in the South Pacific for treating various illnesses, including migraines and bladder disorders. It is also used as a ceremonial and intoxicating drink due to its sedative and anesthetic effects.
Used in Western Herbal Supplements:
In Western countries, organic kava extracts containing kavakavaresin have gained popularity as herbal supplements for treating anxiety and insomnia. The kava lactones are believed to possess analgesic, anticonvulsive, spasmolytic, and antimycotic effects.
Used in Pharmaceutical Industry:
Kavakavaresin has potential applications in the pharmaceutical industry due to its various therapeutic properties. However, it is important to note that the use of kava products has been associated with hepatotoxic events, leading to bans and warnings in some countries. Further research and development are needed to ensure the safety and efficacy of kavakavaresin-based pharmaceutical products.
Toxicity evaluation
Mechanisms of action to explain kava’s pharmacological and
toxicological properties are still incompletely understood.
Known side effects are relatively mild and include allergic
reactions and gastrointestinal complaints. Kava dermopathy is
a well-recognized symptom in heavy kava users. It appears after
weeks of ingestion as a scaly rash; however, the skin returns to
normal upon cessation. There is an apparent dose–response
relationship and the prevalence in heavy kava users has been
reported to be 78%.
Amore serious issue is suspectedkava-induced hepatotoxicity.
This has resulted in extensive studies of kava lactones, chalcones,
and alkaloids. To date, there are no indisputable explanations
and, due to the lack of dose dependency, kava-induced hepatotoxicity
has been classified as idiosyncratic, possibly with
involvement of the immune system.
Ninety-three cases of suspected kava-induced hepatotoxicity
have been reviewed by the World Health Organization (WHO).
However, in most cases the information was inadequate to
determine whether hepatotoxicity was caused by kava. The
reported symptoms were hepatitis, hepatic failure, cholestatic
hepatitis, jaundice, abnormal hepatic function, and cirrhosis.
The outcome in seven of the reviewed cases was death and 14 of
the cases resulted in liver transplant. The mean duration to
onset was 111 days and positive rechallenge tests were seen in
five patients.
The form of kava use in the South Pacific and in Aboriginal
communities is apparently not associated with the hepatotoxicity
reported in Western countries. Elevated liver enzymes (gammaglutamyl
transferase (GGT) and alkaline phosphatase (ALP))
have been reported in these kava users, consuming an average
118 g week-1. The symptoms were reversible upon cessation.
Involvement of glutathione (GSH) and possibly depletion
of endogenous GSH has been proposed to be involved in the
toxic mechanism. A recent study revealed that in vitro toxicity
of kava and acetaminophen (APAP) was intensified by coadministration.
Toxicity of APAP is due to formation of a reactive
metabolite causing depletion of GSH. The increase in
toxicity when kava was coadministered suggests that GSH
somehow could be involved in detoxification of kava.
The possibility of kava acting as an inhibitor of specific
metabolic enzymes has been investigated. In vitro results have
shown that kava is indeed capable of altering the metabolic
capacity of a number of P-450 enzymes; however, the relation
to hepatotoxicity remains unclear.
Flavokavains have been identified as the most potent
cytotoxic compounds in kava. Recently, the flavokavains
gained attention as they have shown apoptotic effects on cancer
cells. Among others, the targets include nuclear factor kappa
beta (NF-kB), Bax, reactive oxygen species, and growth arrest
and DNA-damage-inducible protein (GADD153). Like the
lactones, these compounds have very low solubility in water.
Thus, an organic extract would be expected to contain much
higher concentrations than an aqueous extract. The toxicity of
flavokavains is yet to be examined in vivo.
Poor quality kava products have been accused of being
involved in the increased prevalence of kava-induced hepatotoxicity
in Western countries. Due to the popularity boom,
aerial parts of the shrub allegedly have been included in the
material used to produce commercial kava preparations.
Aerial parts are generally avoided in the South Pacific as they
contain a relatively high amount of alkaloids such as pipermethystine,
which has been reported to decrease cellular
ATP levels and mitochondrial membrane potential and
induce apoptosis in human HepG2 cells. Pipermethystine
has, however, not been identified in commercial products in
clinically significant amounts.
Another aspect of poor quality kava has recently been
addressed. It has been proposed that, due to high temperatures
and humidity in the South Pacific, mold would be able to
develop rapidly in kava plant material not stored correctly. It
has been suggested consequently that hepatotoxins including
aflatoxins could be present in poor quality kava plant material.
Check Digit Verification of cas no
The CAS Registry Mumber 9000-38-8 includes 7 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 4 digits, 9,0,0 and 0 respectively; the second part has 2 digits, 3 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 9000-38:
(6*9)+(5*0)+(4*0)+(3*0)+(2*3)+(1*8)=68
68 % 10 = 8
So 9000-38-8 is a valid CAS Registry Number.
InChI:InChI=1/C15H14O5/c1-17-12-7-11(20-15(16)8-12)4-2-10-3-5-13-14(6-10)19-9-18-13/h2-6,8,11H,7,9H2,1H3/b4-2+
