da Fonsêca Diogo Vilar, Rocha Juliana Sousa, da Silva Pablo R, de Sá Novaes Pereira Hugo Natan, Dos Santos Lucas Vinicius Novaes, de Santana Melquisedec Abiaré Dantas, Alves Alan F, Pontes Adiel H O, de Souza Gomes Joás, Felipe Cícero F Bezerra, de Sousa Damião Pergentino, Scotti Marcus T, Scotti Luciana
Postgraduate Program in Biosciences, Federal University of the São Francisco Valley (UNIVASF), Pernambuco 56304-917, PE, Brazil.
Postgraduate Program of Dentistry (PPGO), Health Sciences Center, Federal University of Paraíba, João Pessoa 58051-900, PB, Brazil.
Int J Mol Sci. 2025 Mar 19;26(6):2788. doi: 10.3390/ijms26062788.
Chronic pain significantly impacts quality of life and is often accompanied by inflammation, a natural bodily response that can become harmful when excessive. The orofacial region is commonly affected, making effective treatment crucial. However, current drugs often cause undesirable side effects, highlighting the need for new pharmacological alternatives. 4-hydroxycoumarin (4-HC), a natural compound, has shown promising antinociceptive and anti-inflammatory effects, but studies confirming its specific properties are limited. In silico analyses suggest that 4-HC exhibits favorable pharmacokinetic characteristics, not interacting with P-glycoprotein and successfully crossing the blood-brain barrier. Molecular docking studies indicate that its effects may be mediated through NMDA or by inhibiting iNOS. Our study assessed the antinociceptive and anti-inflammatory effects of 4-HC in animal models at doses of 25, 50, and 75 mg/kg. 4-HC significantly reduced abdominal contortions induced by acetic acid and decreased nociceptive rubbing in orofacial pain models induced by formalin, glutamate, and capsaicin. Interactions with opioid receptors were not observed, suggesting that 4-HC's antinociceptive effect does not involve this pathway. Additionally, 4-HC reduced paw edema induced by carrageenan and significantly decreased leukocyte migration and TNF-α levels. These findings highlight the therapeutic potential of 4-HC and warrant further investigation into its mechanisms.
慢性疼痛会显著影响生活质量，且常伴有炎症，炎症是一种自然的身体反应，过度时可能会变得有害。口腔面部区域常受影响，因此有效治疗至关重要。然而，目前的药物往往会引起不良副作用，这凸显了对新的药理学替代方案的需求。4-羟基香豆素（4-HC）是一种天然化合物，已显示出有前景的镇痛和抗炎作用，但证实其具体特性的研究有限。计算机模拟分析表明，4-HC具有良好的药代动力学特性，不与P-糖蛋白相互作用，并能成功穿过血脑屏障。分子对接研究表明，其作用可能通过NMDA介导或通过抑制诱导型一氧化氮合酶来实现。我们的研究评估了25、50和75mg/kg剂量的4-HC在动物模型中的镇痛和抗炎作用。4-HC显著减少了乙酸诱导的腹部扭体，并减少了福尔马林、谷氨酸和辣椒素诱导的口腔面部疼痛模型中的伤害性摩擦。未观察到与阿片受体的相互作用，这表明4-HC的镇痛作用不涉及该途径。此外，4-HC减少了角叉菜胶诱导的爪部水肿，并显著降低了白细胞迁移和肿瘤坏死因子-α水平。这些发现突出了4-HC的治疗潜力，并值得对其作用机制进行进一步研究。
