A Case Report on Cholestatic Jaundice Secondary to Adverse Effect of Phaleria macrocarpa (Mahkota Dewa).

Drug induced cholestatic liver injury can posed a great diagnostic difficulty as a result of its long non-exhaustive list of potential offending causes which can be either prescribed or over-the-counter medications, such as medicinal herbs and remedies. Phaleria macrocarpa, or more commonly known as the 'God's crown' by the local people of South East Asia, is not listed as one of the causes. This medicinal plant extract has been increasingly used for traditional treatment for various ailments. Here, we report a case of a young man who has no known medical illness presented with cholestatic pattern of liver injury which caused by chronic ingestion of Phaleria macrocarpa. The objective of this case report is to share the uncommon side effect of taking this traditional product which may have been under-reported due to the unknown effect.

Toxicity of daphnane-type diterpenoids from Genkwa Flos and their pharmacokinetic profile in rat.

Daphnane-type diterpenoids (DDs) are the main types of plant diterpene orthoesters known and have remarkable biological activities. However, the in vivo toxicity and pharmacokinetic profile of DDs remains unkonwn. The aim of this study was to investigate the toxicity and pharmacokinetic profile of DDs from Genkwa Flos (Thymelaeaceae). The toxicity of diterpenoids was evaluated after oral administration of total diterpenoids extract from Genkwa Flos to rats, and the blood concentration of diterpenoids was analyzed by ultra performance liquid chromatography tandem triple-quadrupole mass spectrometry (UPLC-TQ-MS). The diterpenoids were confirmed to be the toxic components of Genkwa Flos. The pharmacokinetic profile of these diterpenoids was quite different due to their different structures. Although the contents of yuanhuafine and yuanhuapine were low in the extract, the blood concentrations were extremely high. In contrary, the contents of genkwanine F and Wikstroemia factor M1 in the extract were much higher, but they could not be detected in the blood. This result implied that yuanhuafine and yuanhuapine but not genkwanine F and Wikstroemia factor M1 were the potentail toxic components of Genkwa Flos in vivo. This paper shows for the first time the toxicity of diterpenoids from Genkwa Flos was correlated with their blood concentration and when DDs were used for medicinal purposes, their contents in herb as well as their blood concentrations should be considered.