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Evidence-Based Complementary and Alternative Medicine
Volume 2016 (2016), Article ID 3160247, 10 pages
Research Article

Synergistic Effect of Ferulic Acid and Z-Ligustilide, Major Components of A. sinensis, on Regulating Cold-Sensing Protein TRPM8 and TPRA1 In Vitro

1Department of Traditional Chinese Medicine, College of Medicine, Jinan University, Guangzhou 510630, China
2Shipai District Community Health Service Center, Guangzhou 510630, China
3Guangdong Food and Drug Vocational College, Guangzhou 510520, China

Received 23 February 2016; Revised 16 May 2016; Accepted 31 May 2016

Academic Editor: Alfredo Vannacci

Copyright © 2016 Yuwei Pan et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Angelica sinensis has been used to attenuate cold-induced cutaneous vasospasm syndrome, such as Raynaud’s disease and frostbite, in China for many years. Ferulic acid (PubChem CID: 445858) and Z-ligustilide (PubChem CID: 529865), two major components extracted from Angelica sinensis, had been reported to inhibit vasoconstriction induced by vasoconstrictors. In this study, the pharmacological interaction in regulating cold-induced vascular smooth muscle cell contraction via cold-sensing protein TRPM8 and TRPA1 was analyzed between ferulic acid and Z-ligustilide. Pharmacological interaction on inhibiting influx evoked by TRPM8 agonist WS-12 or TRPA1 agonist ASP 7663 as well as cold-induced upregulation of TRPM8 was determined using isobolographic analysis. The isobolograms demonstrated that the combinations investigated in this study produced a synergistic interaction. Combination effect of two components in inhibiting RhoA activation and phosphorylation of MLC20 induced by WS-12 or ASP 7663 was also being quantified. These findings suggest that the therapeutic effect of Angelica sinensis on cold-induced vasospasm may be partially attributed to combinational effect, via TRPM8 and TPRA1 way, between ferulic acid and Z-ligustilide.