NIS - libdoc.who.int - World Health Organization

WHO monographs on medicinal plants commonly used in the Newly Independent States (NIS)
creased the numbers of granulocyte macrophage-colony forming cells
1.48-fold as compared to the untreated splenocytes (70).
Toxicology
No harmful or toxic effects from therapeutic doses have been reported in
rodent models. In mice, the median lethal dose (LD 50
) of a decoction of the
crude drug was 9.5 g/kg bw after intraperitoneal administration. The LD 50
of the isoquinoline alkaloids in mice was 300 mg/kg bw after subcutaneous
administration. Intraperitoneal administration of 350 mg/kg bw of a methanol
extract of the herb to mice for 7 days resulted in a 20% mortality rate
(60). The median lethal intraperitoneal dose for chelidonine was 1300 mg/
kg bw in mice and 2000 mg/kg bw in rats. Sublethal doses of chelidonine
induced sedation, ptosis, tremor and decreased body temperature (73). The
methanol and aqueous extracts of Herba Chelidonii were examined for
acute oral toxicity in mice. The LD 50
for the methanol extract was 12.5 g/kg
bw and that for the aqueous extract was 10.1 g/kg bw (74). Oral administration
of 5 mg/kg bw of sanguinarine and chelerythrine (3:1) to pigs for
90 days did not result in any histological or biochemical changes (75).
The alkaloids sanguinarine and chelerythrine, present in low concentrations
in the herb, are known to cause hepatotoxicity in rats. Intraperitoneal
administration to rats of 10 mg/kg bw of sanguinarine or chelerythrine
induced hepatic cell injury and increased alanine aminotransferase
and aspartate aminotransferase activities by 50 and 100%, respectively.
However, intraperitoneal administration of 0.2 mg/kg bw of sanguinarine
or chelerythrine to rats for 55 days did not result in signs of hepatotoxicity
(76, 77). Investigation of extracts of the herb, as well as of the individual
alkaloids, coptisine, chelidonine, protopine, chelerythrine and sanguinarine,
in primary rat hepatocytes indicated a direct correlation
between the alkaloid content of the extract and hepatotoxicity. The mean
hepatotoxic concentration for the extracts was 5 mg/ml, for sanguinarine
5 µg/ml, and chelerythrine 8 µg/ml.
Clinical pharmacology
A prospective observational study involving 608 patients treated orally
with an aqueous-ethanol extract of the crude drug (5–7:1, mean daily dose
375–500 mg extract, corresponding to 9–12 mg of total alkaloids) has been
reported. The outcomes were measured using the Physicians’ Global Assessment
of Efficacy (4-point scale). After an average of 22 days of treatment,
symptoms (dyspepsia or cramps in the upper gastrointestinal tract)
were reduced in most patients and the outcome was assessed as good or
very good in 87.4% of the patients (55).
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