There have been a number of reported cases of interactions between Chinese herbal medicines and warfarin. It is possible that Chinese herbal medicines alter the anticoagulant activity of warfarin by affecting the activation (carboxylation) of clotting proteins. This study evaluated such a possibility as the basis for the purported interactions between Ginseng, Danshen , Danggui and warfarin using rat hepatic microsomes in vitro.

Purified hepatic microsomal fraction was prepared from livers of male Wistar rats according to an established method [1]. Incubations were performed for 30 min at room temperature in a total volume of 125  µl, which contained Tris buffer pH 7.5, microsomes (8 mg protein ml^-1), CHAPS (0.4%), tripeptide (Boc-Glu-Glu-Leu-OMe) (4 mM) as a surrogate marker for prothrombin, ammonium sulphate (1.2  m), ¹⁴CO₂ (5  µCi), and either vitamin KH₂, or vitamin K or vitamin K 2,3-epoxide (0.2 m m), with or without racemic warfarin (10  µm). Extracts of Ginseng (0.13 or 1.30 mg ml^-1), Danshen (0.41 or 4.01mg ml^-1) and Dangui (0.49 or 4.90 mg ml^-1) were added to the incubation medium with or without the presence of warfarin (10  µm). The carboxylation reaction was monitored by measurement of the incorporation of ¹⁴CO₂ (derived from NaH¹⁴CO₂) into the tripeptide.

Warfarin caused significant inhibition of tripeptide carboxylation in the presence of either vitamin K (by 89.1%; p < 0.0001) or vitamin K 2, 3-epoxide (by 79.6%; p < 0.0001) but not in the presence of vitamin KH₂. The results showed that although Ginseng increased tripeptide carboxylation in the presence of vitamin K 2, 3-epoxide (by 31.6% at 0.13mg ml^-1, p < 0.05; 62.9% at 1.3mg ml^-1, p = 0.007), it had no significant effect on the inhibitory effect of warfarin on tripeptide carboxylation. Danshen alone (4.01 mg ml^-1) caused significant inhibition of carboxylation in the presence of either vitamin KH₂ (by 65. 1%; p < 0.0001), or vitamin K (60.7%; p < 0.0001) or vitamin K 2, 3-epoxide (by 24.0%; p = 0.024). Danshen (4.01 mg ml^-1) was also shown to promote the inhibitory effect of warfarin in the presence of either vitamin KH₂ (by 20.4%, p = 0.042), or vitamin K (45.2%, p = 0.001) or vitamin K 2, 3-epoxide (45.1%, p = 0.001). Dangui had no significant effect on tripeptide carboxylation in the presence of either vitamin KH₂, or vitamin K, or vitamin K 2, 3-epoxide. Dangui also had no significant effect on the inhibitory effect of warfarin on tripeptide carboxylation.

The results suggest that both Ginseng and Danshen could affect the activation of prothrombin and that interference with either the vitamin K cycle and/or the carboxylation of prothrombin could, at least in part, be the basis for the reported interaction between Danshen and warfarin. However, it appears that neither Ginseng nor Danggui affect the anticoagulant activity of warfarin.

1. Hickmott H.R., Kamali F. Br J Clin Pharmacol 2000; 47: 585.