Student Research Committee.
Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah.
Behav Pharmacol. 2024 Oct 1;35(7):399-407. doi: 10.1097/FBP.0000000000000792. Epub 2024 Sep 2.
The l -arginine ( l -Arg)/nitric oxide/cyclic GMP/potassium channel (K ATP ) pathway and opioid receptors are known to play critical roles in pain perception and the antinociceptive effects of various compounds. While there is evidence suggesting that the analgesic effects of rutin may involve nitric oxide modulation, the direct link between rutin and the l -Arg/nitric oxide/cyclic GMP/K ATP pathway in the context of pain modulation requires further investigation. The antinociceptive effect of rutin was studied in male NMRI mice using the formalin test. To investigate the role of the l -Arg/nitric oxide/cyclic GMP/K ATP pathway and opioid receptors, the mice were pretreated intraperitoneally with different substances. These substances included l -Arg (a precursor of nitric oxide), S-nitroso- N -acetylpenicillamine (SNAP, a nitric oxide donor), N(gamma)-nitro- l -arginine methyl ester (L-NAME, an inhibitor of nitric oxide synthase), sildenafil (an inhibitor of phosphodiesterase enzyme), glibenclamide (a K ATP channel blocker), and naloxone (an opioid receptor antagonist). All pretreatments were administered 20 min before the administration of the most effective dose of rutin. Based on our investigation, it was found that rutin exhibited a dose-dependent antinociceptive effect. The administration of SNAP enhanced the analgesic effects of rutin during both the initial and secondary phases. Moreover, L-NAME, naloxone, and glibenclamide reduced the analgesic effects of rutin in both the primary and secondary phases. In conclusion, rutin holds significant value as a flavonoid with analgesic properties, and its analgesic effect is directly mediated through the nitric oxide/cyclic GMP/K ATP channel pathway.
左旋精氨酸（L-Arg）/一氧化氮/环鸟苷酸/钾通道（KATP）途径和阿片受体已知在疼痛感知和各种化合物的镇痛作用中发挥关键作用。虽然有证据表明芦丁的镇痛作用可能涉及一氧化氮的调节，但在疼痛调节的背景下，芦丁与 L-Arg/一氧化氮/环鸟苷酸/KATP 途径之间的直接联系需要进一步研究。本研究采用福尔马林试验，在雄性 NMRI 小鼠中研究了芦丁的镇痛作用。为了研究 L-Arg/一氧化氮/环鸟苷酸/KATP 途径和阿片受体的作用，将小鼠预先腹膜内给予不同的物质。这些物质包括 L-Arg（一氧化氮的前体）、S-亚硝基-N-乙酰青霉胺（SNAP，一氧化氮供体）、N（γ）-硝基-L-精氨酸甲酯（L-NAME，一氧化氮合酶抑制剂）、西地那非（磷酸二酯酶抑制剂）、格列本脲（KATP 通道阻滞剂）和纳洛酮（阿片受体拮抗剂）。所有预处理均在给予芦丁最有效剂量前 20 分钟进行。根据我们的研究，发现芦丁表现出剂量依赖性的镇痛作用。SNAP 的给予增强了芦丁在初始和次级阶段的镇痛作用。此外，L-NAME、纳洛酮和格列本脲在初级和次级阶段均降低了芦丁的镇痛作用。总之，芦丁作为一种具有镇痛特性的黄酮类化合物具有重要价值，其镇痛作用是通过一氧化氮/环鸟苷酸/KATP 通道途径直接介导的。
