Caffeic acid is an inhibitor of both TRPV1 ion channel and 5-Lipoxygenase (5-LO).

Caffeic acid has inhibitory effects on histamine-induced responses and the inhibitory effect of Caffeic acid is gradually increased when the concentration used for pretreatment is increased from 0.1 to 1 mM, similar to typical dose-dependent responses. Pretreatment of HEK293T-TRPV1 cells with 1 mM Caffeic acid results in significant inhibition of capsaicin-induced responses. When lower concentration of Caffeic acid is used, the inhibitory effect for capsaicin-induced responses is less evident. Calcium imaging experiments show that Caffeic acid incubation results in significant inhibition in histamine-sensitive dorsal root ganglion (DRG) neurons. Pretreatment with Caffeic acid (1 mM) results in a significant decrease in the percentage of responsive DRG neurons to histamine application from 12.5% to 2.1%. Pretreatment with 1 mM Caffeic acid dramatically blocks the allylisothiocyanate (AITC)-induced intracellular calcium increase in TRPA1-expressing cells. Caffeic acid is also able to block the AITC-induced activation of TRPA1[1].

Mice pretreated with Caffeic acid (500 mg/kg) exhibit significantly less histamine-induced scratching (30.50±10.87 bouts/1 h, n=6). It is further found that the lower dose of Caffeic acid (100 mg/kg) is not significantly effective in terms of anti-scratching effects in histamine-induced scratching, although there appears to be a tendency of reduction (49.40±12.35 bouts/1 h, n=5). The chloroquine induced scratching is significantly inhibited by pretreatment with 500 mg/kg of Caffeic acid (161.6±31.42 bouts/1 h, n=5)[1].Caffeic acid significantly reduces the expression of 5-LO mRNA (P<0.01) dose-dependently in hippocampus. Compare with the ischemia-reperfusion (I/R) non-treated group, 5-LO protein expression is significantly reduced in the I/R-Caffeic acid group (P<0.05 or P<0.01), especially in the I/R-Caffeic acid group (50 mg/kg). Compare with the I/R non-treated group, the latency to find platform is significantly shortened in low- and high-dose Caffeic acid groups, the shortened platform latency is most evident in the I/R- Caffeic acid group (50 mg/kg) (P<0.01). In the low-dose Caffeic acid group, cell injury is still marked, the pyknosis ratio is (63.6±2.8)%, whereas in the high-dose Caffeic acid group, hippocampal neuron karyopyknosis is significantly reduced and the pyknosis ratio is (13.3±3.0)%[2].

References:

[1]. Pradhananga S, et al. Caffeic acid exhibits anti-pruritic effects by inhibition of multiple itch transmission pathways in mice. Eur J Pharmacol. 2015 Sep 5;762:313-21.

[2]. Liang G, et al. The protective effect of caffeic acid on global cerebral ischemia-reperfusion injury in rats. Behav Brain Funct. 2015 Apr 18;11:18.

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