Honokiol alleviates monosodium urate-induced gouty pain by inhibiting voltage-gated proton channels in mice.

IF 4.6 2区医学 Q2 IMMUNOLOGY Inflammopharmacology Pub Date : 2024-08-01 Epub Date: 2024-06-03 DOI:10.1007/s10787-024-01498-9

Lurong Miao, Ziqi Yuan, Shijia Zhang, Guangqin Zhang

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Abstract

Objective: To investigate whether honokiol (HNK) acted as an analgesic in connection with inhibiting the voltage-gated proton channel (Hv1).

Methods: 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.

Results: HNK (10, 20, 40 mg/kg) alleviated inflammatory response and mechanical allodynia in a dose-dependent manner. In normal DRG neurons, 50 µM Zn²⁺ 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_tail) but did not alter the neuronal excitability of DRG neurons in gouty mice.

Conclusion: HNK may be a potential analgesic by inhibiting Hv1 current.

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红没药醇通过抑制电压门控质子通道减轻小鼠尿酸单钠诱发的痛风痛。

摘要研究霍诺克醇（HNK）的镇痛作用是否与抑制电压门控质子通道（Hv1）有关：方法：向小鼠后踝关节注射尿酸单钠（MSU）结晶，诱导痛风性关节炎模型。胃内注射 HNK。踝关节肿胀程度和机械异感分别通过踝关节周长测量和 von Frey 灯丝进行评估。采用膜片钳技术记录背根神经节（DRG）神经元的 Hv1 电流、尾电流和动作电位：结果：HNK（10、20、40 毫克/千克）以剂量依赖的方式减轻了炎症反应和机械异感。在正常 DRG 神经元中，50 µM Zn2+ 或 2-GBI 能显著抑制 Hv1 电流，且 Hv1 电流密度随 pH 梯度的增加而增加。HNK剂量依赖性地逆转了Hv1电流的上调。与 MSU 组相比，40 毫克/千克 HNK 使激活曲线向电压更正值的方向移动，并使反转电位升至正常水平。此外，40 毫克/千克 HNK 可逆转尾电流失活时间常数（τtail）的下调，但不会改变痛风小鼠 DRG 神经元的兴奋性：结论：HNK可抑制Hv1电流，是一种潜在的镇痛药。

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来源期刊

Inflammopharmacology IMMUNOLOGYTOXICOLOGY-TOXICOLOGY

CiteScore

8.00

自引率

3.40%

发文量

200

期刊介绍： Inflammopharmacology is the official publication of the Gastrointestinal Section of the International Union of Basic and Clinical Pharmacology (IUPHAR) and the Hungarian Experimental and Clinical Pharmacology Society (HECPS). Inflammopharmacology publishes papers on all aspects of inflammation and its pharmacological control emphasizing comparisons of (a) different inflammatory states, and (b) the actions, therapeutic efficacy and safety of drugs employed in the treatment of inflammatory conditions. The comparative aspects of the types of inflammatory conditions include gastrointestinal disease (e.g. ulcerative colitis, Crohn''s disease), parasitic diseases, toxicological manifestations of the effects of drugs and environmental agents, arthritic conditions, and inflammatory effects of injury or aging on skeletal muscle. The journal has seven main interest areas: -Drug-Disease Interactions - Conditional Pharmacology - i.e. where the condition (disease or stress state) influences the therapeutic response and side (adverse) effects from anti-inflammatory drugs. Mechanisms of drug-disease and drug disease interactions and the role of different stress states -Rheumatology - particular emphasis on methods of measurement of clinical response effects of new agents, adverse effects from anti-rheumatic drugs -Gastroenterology - with particular emphasis on animal and human models, mechanisms of mucosal inflammation and ulceration and effects of novel and established anti-ulcer, anti-inflammatory agents, or antiparasitic agents -Neuro-Inflammation and Pain - model systems, pharmacology of new analgesic agents and mechanisms of neuro-inflammation and pain -Novel drugs, natural products and nutraceuticals - and their effects on inflammatory processes, especially where there are indications of novel modes action compared with conventional drugs e.g. NSAIDs -Muscle-immune interactions during inflammation [...]