Synergistic vasorelaxant and antihypertensive effects of Ligusticum wallichii and Angelica gigas

Abstract

Aim of the study: The synergistic vasorelaxant and antihypertensive effects of Ligusticum wallichii and Angelica gigas were examined in isolated rat aorta rings and spontaneously hypertensive rats (SHRs).

Materials and methods: The ethanol extract of Ligusticum wallichii (LwEx) or Angelica gigas (AgEx) or their combinations at ratios Ligusticum wallichii:Angelica gigas = 1:1 (MxEx11), 1:3 (MxEx13), and 3:1 (and MxEx31), and their successive water soluble (LwDw, AgDw, MxDw11, MxDw13 and MxDw31) or n-butanol soluble fractions (LwBt, AgBt, MxBt11, MxBt13, and MxBt31) were examined for their vasorelaxant effects. In an antihypertensive study, LwEx, AgEx, or MxEx11 (100 mg/kg) was orally administered to SHRs, and the systolic, diastolic, and mean blood pressure were measured using the tail-cuff method before and 1, 3, 5, 7, and 24 h after oral administration.

Results: Each of the ethanol extracts caused long-term relaxation in endothelium-intact or endothelium-denuded rat aorta preconstricted with norepinephrine (NE, 300 nM). All of the water phases of the ethanol extracts elicited an endothelium-dependent acute relaxation, and the water phase of MxDw11 (EC50 values: 1.08 mg/mL, P < 0.05) had the highest activity. MxDw11-induced acute relaxation was abolished by pretreatment with N(G)-nitro-L-arginine (10 microM), methylene blue (1.0 microM), or atropine (0.1 microM), indicating that the response to MxDw involves the enhancement of the nitric oxide-cGMP system. On the other hand, all of the butanol phases showed an endothelium-independent long-term relaxation, and MxBt11 (85 +/- 7% relaxation of NE-preconstricted active tone at 20 min after the addition, P < 0.05) displayed the highest activity. MxBt11-induced gradual relaxation was significantly attenuated by an inward rectifier potassium-channel inhibitor, but not by an ATP-sensitive or a large conductance Ca2+-activated potassium-channel blocker. Calcium concentration-dependent contraction curves in high-potassium, depolarizing medium were shifted significantly to the right and downward after incubation with MxBt11 (0.03, 0.1, and 0.3 mg/mL), implying that MxBt11 is also involved in the inhibition of extracellular calcium influx to vascular smooth muscle. MxEx11 (100 mg/kg) significantly reduced systolic blood pressure of SHRs at 3, 5, and 7 h after oral administration, but this effect was not induced by Ligusticum wallichii or Angelica gigas alone.

Conclusions: The combination of Ligusticum wallichii and Angelica gigas elicits a synergistic effect on vasorelaxation in isolated rat aortas and antihypertension in SHRs. The ratio of Ligusticum wallichii: Angelica gigas = 1:1 was the most effective of all combinations tested.