Synergistic vasorelaxant and antihypertensive effects of Ligusticum wallichii and Angelica gigas

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 μM), methylene blue (1.0 μM), or atropine (0.1 μM), 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.