Session Speaker

Loureirin B: A novel chemical component which can modulate voltage-gated sodium currents through TRPV1 receptor
M. Zhinan
China

Dragon's Blood is one of the renowned traditional medicines with analgesic activity. Loureirin B is a flavonoid component extracted from dragon's blood and is used as the marker substance for its quality control. To explore the analgetic mechanism of dragon's blood, the effects of loureirin B on the tetrodotoxin-sensitive and tetrodotoxin-resistant voltage-gated sodium currents in dorsal root ganglion neurons were observed by using patch clamp technique. Results showed that loureirin B could modulate the above two types of the voltage-gated sodium currents in dorsal root ganglion neurons. It can be inferred that loureirin B could directly interfere with the transmission of nociceptive information in primary sensory neurons by modulating sodium channels. This viewpoint has been verified by the in vivo experimental results. Loureirin B could inhibit the discharge activities of wide dynamic range (WDR) neurons in spinal dorsal horn (SDH) of intact male Wistar rats evoked by electric stimulation at sciatic nerve. But the mechanism of the modulation of loureirin B on the voltage-gated sodium currents is still unclear. However, it is remarkable that the chemical structures of capsaicin and loureirin B are similar. It has been proved by experiments that capsaicin could inhibit the action potentials and voltage-gated sodium channels in capsaicin-sensitive trigeminal ganglion neurons. Moreover, the selective effect of capsaicin on voltage-gated sodium channels was reversed in transient receptor potential vanilloid subtype 1 (TRPV1) -/- mice, which suggested that this effect was dependent on TRPV1 receptor. TRPV1 is known as capsaicin receptor and activated by capsaicin. From the above, it can be seen that there are some similarities between the mechanism of capsaicin modulating sodium channels and that of loureirin B. To verify our conjecture, the effect of loureirin B on TRPV1 receptor and the modulation of the combination of loureirin B and capsaicin on the sodium channels in acutely isolated rat DR G neurons were observed by using patch clamp technique. Results showed that loureirin B could inhibit both the capsaicin-activated currents and the capsaicin-evoked depolarization in DRG neurons, which indicated that loureirin B could modulate TRPV1 receptor. Although the combination of loureirin B and capsaicin could inhibit the voltage-gated sodium currents in DRG neurons, the inhibition degree of the combination was lower than that of each component. If there is only additive interaction between the two components, the more inhibition degree on the voltage-gated sodium currents should be induced by the combination of capsaicin and loureirin B than each component used alone. It suggested that the effect of loureirin B on the voltage-gated sodium currents in DRG neurons was antagonized by capsaicin. The inhibition mechanism of loureirin B on the voltage-gated sodium currents should be consistent with that of capsaicin. Since loureirin B and capsaicin could competitive binding to the TRPV1 receptor, the inhibition degree of loureirin B on the voltage-gated sodium currents was weakened by capsaicin. Besides of capsaicin, loureirin B perhaps should become a novel chemical component which can modulate voltage-gated sodium currents through TRPV1 receptor.