Although the precise molecular mechanism of plant triterpenoids on topoisomerase II remains elusive, accumulated experimental evidence indicates that plant triterpenoids represent a vast potential source of antineoplastic agents. An interesting development from these results would be a massive survey of plant triterpenoids as source of topoisomerase inhibitors. Also, one might have noticed that plant triterpenoids have an affinity to phos-pholipase. Martelli et al. observed that during apoptosis, a phospholipase D-mediated signaling pathway operating at the nuclear level is elicited and may represent an attractive therapeutic target for the modulation of apoptotic events in human disease (39). Macaranga triloba (Reinw.) Muell.-Arg., or mahong merah (Malay), is a treelet that grows wild to a height of 6 m in Malaysia, Burma, Thailand in secondary forests, often gregarious, gaps, and river valleys in primary forests. The stems are hollow with ants ribbed and constricted. The leaves are simple, spiral, and stipulate. The stipules are leathery and persistent. The blades are lobed, membranaceous, with scattered yellow granular glands and conspicuous nerves below (Fig. 94).

Fig. 94. Macaranga triloba. Flora of Malaya. FRI main road side, Kepong. Field collector: Matr. Asri.

In Malaysia, the leaves are used externally to heal boils. In Indonesia, a decoction of fruits and leaves is drunk to mitigate stomachache. The fruits are poisonous. Activity-guided fractionation of the leaves of Macaranga triloba (Reinw.) Muell.-Arg. using an in vitro bioassay based on the inhibition of cyclooxygenase-2, resulted in the isolation of flavonoids, triterpenes, and of 4,5-dihydro-5'a-hydroxy-4'a-methoxy-6a,12a-dehydro-a-toxicarol (40). The inhibition of cyclooxygenase 2 as an important mechanism for cancer chemoprevention has been supported by epidemiological and experimental evidence notably reported by Dannenberg et al. (41).

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