Department of Clinical Pharmacy, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009, China.
School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China.
Inflammopharmacology. 2024 Aug;32(4):2413-2425. doi: 10.1007/s10787-024-01498-9. Epub 2024 Jun 3.
To investigate whether honokiol (HNK) acted as an analgesic in connection with inhibiting the voltage-gated proton channel (Hv1).
The model of gouty arthritis was induced by injecting monosodium urate (MSU) crystals into the hind ankle joint of mice. HNK was given by intragastric administration. Ankle swelling degree and mechanical allodynia were evaluated using ankle joint circumference measurement and von Frey filaments, respectively. Hv1 current, tail current, and action potential in dorsal root ganglion (DRG) neurons were recorded with patch-clamp techniques.
HNK (10, 20, 40 mg/kg) alleviated inflammatory response and mechanical allodynia in a dose-dependent manner. In normal DRG neurons, 50 µM Zn or 2-GBI significantly inhibited the Hv1 current and the current density of Hv1 increased with increasing pH gradient. The amplitude of Hv1 current significantly increased on the 3rd after MSU treatment, and HNK dose-dependently reversed the upregulation of Hv1 current. Compared with MSU group, 40 mg/kg HNK shifted the activation curve to the direction of more positive voltage and increased reversal potential to the normal level. In addition, 40 mg/kg HNK reversed the down-regulation of tail current deactivation time constant (τ) but did not alter the neuronal excitability of DRG neurons in gouty mice.
HNK may be a potential analgesic by inhibiting Hv1 current.
研究霍诺内酯（HNK）是否通过抑制电压门控质子通道（Hv1）发挥镇痛作用。
向小鼠后踝关节注射单钠尿酸盐（MSU）晶体诱导痛风性关节炎模型。通过灌胃给予 HNK。通过测量踝关节周长和 von Frey 纤维分别评估踝关节肿胀程度和机械性痛觉过敏。采用膜片钳技术记录背根神经节（DRG）神经元中的 Hv1 电流、尾电流和动作电位。
HNK（10、20、40mg/kg）呈剂量依赖性缓解炎症反应和机械性痛觉过敏。在正常 DRG 神经元中，50µM Zn 或 2-GBI 显著抑制 Hv1 电流，随着 pH 梯度的增加，Hv1 电流密度增加。MSU 处理后第 3 天，Hv1 电流的幅度显著增加，HNK 呈剂量依赖性逆转 Hv1 电流的上调。与 MSU 组相比，40mg/kg HNK 使激活曲线向更正电压方向移动，并将反转电位提高至正常水平。此外，40mg/kg HNK 逆转了痛风小鼠 DRG 神经元尾电流失活时间常数（τ）的下调，但不改变神经元兴奋性。
HNK 可能通过抑制 Hv1 电流成为一种潜在的镇痛剂。
