title: Synergistic Effect of Ferulic Acid and Z-Ligustilide, Major Components of A. sinensis, on Regulating Cold-Sensing Protein TRPM8 and TPRA1 In Vitro.
abstract: 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 [Ca(2+)]i 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.
authors.affiliation: Department of Traditional Chinese Medicine, College of Medicine, Jinan University, Guangzhou 510630, China.
authors.forename: Yuwei
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Department of Traditional Chinese Medicine, College of Medicine, Jinan University, Guangzhou 510630, China.
authors.forename: Guoping
authors.initials: G
authors.lastname: Zhao
authors.affiliation: Shipai District Community Health Service Center, Guangzhou 510630, China.
authors.forename: Zejian
authors.initials: Z
authors.lastname: Cai
authors.affiliation: Department of Traditional Chinese Medicine, College of Medicine, Jinan University, Guangzhou 510630, China.
authors.forename: Fengguo
authors.initials: F
authors.lastname: Chen
authors.affiliation: Guangdong Food and Drug Vocational College, Guangzhou 510520, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Xu
authors.affiliation: Department of Traditional Chinese Medicine, College of Medicine, Jinan University, Guangzhou 510630, China.
authors.forename: Si
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Traditional Chinese Medicine, College of Medicine, Jinan University, Guangzhou 510630, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Lan
authors.affiliation: Department of Traditional Chinese Medicine, College of Medicine, Jinan University, Guangzhou 510630, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Tong