Korean Red Ginseng extract and ginsenoside Rg3 have anti-pruritic effects on chloroquine-induced itch by inhibition of MrgprA3/TRPA1-mediated pathway

BACKGROUND: It was previously found that Korean Red Ginseng water extract (KRGE) inhibits the histamine-induced itch signaling pathway in peripheral sensory neurons. Thus, in the present study, we investigated whether KRGE inhibited another distinctive itch pathway induced by chloroquine (CQ); a representative histamine-independent pathway mediated by MrgprA3 and TRPA1. METHODS: Intracellular calcium changes were measured by the calcium imaging technique in the HEK293T cells transfected with both MrgprA3 and TRPA1 (“MrgprA3/TRPA1”), and in primary culture of mouse dorsal root ganglia (DRGs). Mouse scratching behavior tests were performed to verify proposed antipruritic effects of KRGE and ginsenoside Rg3. RESULTS: CQ-induced Ca(2+) influx was strongly inhibited by KRGE (10 μg/mL) in MrgprA3/TRPA1, and notably ginsenoside Rg3 dose-dependently suppressed CQ-induced Ca(2+) influx in MrgprA3/TRPA1. Moreover, both KRGE (10 μg/mL) and Rg3 (100 μM) suppressed CQ-induced Ca(2+) influx in primary culture of mouse DRGs, indicating that the inhibitory effect of KRGE was functional in peripheral sensory neurons. In vivo tests revealed that not only KRGE (100 mg) suppressed CQ-induced scratching in mice [bouts of scratching: 274.0 ± 51.47 (control) vs. 104.7 ± 17.39 (KRGE)], but also Rg3 (1.5 mg) oral administration significantly reduced CQ-induced scratching as well [bouts of scratching: 216.8 ± 33.73 (control) vs. 115.7 ± 20.94 (Rg3)]. CONCLUSION: The present study verified that KRGE and Rg3 have a strong antipruritic effect against CQ-induced itch. Thus, KRGE is as a promising antipruritic agent that blocks both histamine-dependent and -independent itch at peripheral sensory neuronal levels.