C. elegans is a useful and cost effective model for initial drug screening. In mammmals, activation of the Ras/MAPK signaling cascade promotes cellular proliferation, and activating mutations of Ras are involved in tumorigenesis. This pathway is highly conserved and required for vulval development in C. elegans. Gain-of-function mutations of the Ras ortholog,
let-60, lead to constitutive pathway signaling and cause a multivulva (Muv) phenotype. Using a gain-of-function mutant
let-60(
n1046), we screened 19 herbal medicines for inhibiting activity of the Ras/MAPK pathway signaling and found that an extract from Tetradium ruticarpum suppresses the Muv phenotype of the mutant. Indolequinazoline alkaloids evodiamine (Evo) and rutaecarpine (Rut) are known major bioactive components of T. ruticarpum. They have been reported to have various pharmacological activities including thermoregulation, vascular regulation, anti-allergic, anti-nociceptive and anti-inflammatory activities, and so on. We examined the effects of Evo and Rut on the
let-60(
n1046) mutant, and found that both the compounds of the concentration of 0.1 mM suppressed the Muv phenotype by 40%, which was comparable to effect of gliotoxin, an inhibitor of farnesyl transferase involved in activation of Ras. Transcription factors
lin-1/ETS and
lin-31/Forkhead are known downstream targets of the RAS/MAPK pathway. Neither Evo nor Rut, as well as gliotoxin, suppressed the Muv phenotype of
lin-1(
sy254),
lin-1(
e1777), and
lin-31(
n301). These results suggest that Evo and Rut suppress the Muv phenotype of
let-60(
n1046) by inhibiting Ras/MAPK pathway or farnesyl transferase.