selected medicinal plants - World Health Organization

WHO monographs on selected medicinal plants
50.0 mg/kg bw. In dogs, the oral and intravenous LD 50 values were
20.0 mg/kg bw and 200.0 mg/kg bw, respectively.
Subchronic oral administration of visnadin to mice, rats and rabbits at
doses of up to 2.2 g/kg bw, up to 600.0 mg/kg bw and 6.0 mg/kg bw,
respectively, produced no pronounced toxicity (25). In dogs, daily intramuscular
injections of isolated chemical constituents of the fruits at ten
times the therapeutic concentration for 90 days produced toxic effects
characterized by increases in the serum glutamic-pyruvic and glutamicoxaloacetic
transaminases, increases in plasma urea, haematological
changes and, in some cases, death. Of the six compounds tested, samidin
was the most toxic, dihydrosamidin was the least toxic and khellin, visnagin,
visnadin and khellol glucoside were of intermediate toxicity (29). The
acute toxicities of khellin, visnagin, visnadin and samidin were assessed in
mice and rats after intramuscular injection of doses of 0.316–3.16 mg/kg
bw. The LD 50 values were: khellin, 83.0 mg/kg bw in mice and 309.0 mg/
kg bw in rats; visnagin, 123.0 mg/kg bw and 831.0 mg/kg bw; visnadin,
831.8 mg/kg bw and 1.213 g/kg bw; and samidin, 467.7 mg/kg bw and
1.469 g/kg bw (30).
Administration of Ammi visnaga seeds at 1.25–3% in the diet for
14 days had no toxic effects on turkeys or ducks. However, in chickens,
the 3% dose produced mild signs of photosensitization within 6–8 days
(31). Administration of 2.0 g/day for 4–8 days to goslings at age 3–5 weeks
induced photosensitivity in the form of erythema, haematomas and blisters
on the upper side of the beak (32).
The chemical constituents responsible for the induction of contact
dermatitis in the mouse-ear assay were khellol, visnagin and khellinol,
median irritant doses 0.125 μg/5 μl, 1.02 μg/5 μl and 0.772 μg/5 μl, respectively
(33).
Clinical pharmacology
A placebo-controlled study assessed the effects of oral administration of
50 mg of khellin four times per day for 4 weeks on the plasma lipids of 20
non-obese, normolipaemic male subjects. Plasma lipids were measured
every week during treatment and 1 week after cessation. Plasma total
cholesterol and triglyceride concentrations remained unchanged, while
high-density-lipoprotein cholesterol concentrations were signifi cantly elevated,
the effect lasting until 1 week after cessation of treatment (34).
Adverse reactions
Pseudoallergic reactions and reversible cholestatic jaundice have been reported
(35). High oral doses of khellin (100.0 mg/day) reversibly elevated
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