Department of Pharmacy, International Islamic University Chittagong, Chittagong 4318, Bangladesh.
Department of Bio-Health Convergence, College of Biomedical Science, Kangwon National University, Chuncheon 24341, Republic of Korea.
J Ethnopharmacol. 2021 Aug 10;276:114182. doi: 10.1016/j.jep.2021.114182. Epub 2021 May 5.
Ophiorrhiza rugosa var. prostrata is a traditional medicinal plant used by the indigenous and local tribes (Chakma, Marma and Tanchangya) of Bangladesh for the management of chest pain, body ache, and earache. However, the knowledge of anti-nociceptive and anti-inflammatory potentials of this plant is scarce.
Therefore, we scrutinized the anti-nociceptive and anti-inflammatory properties of O. rugosa leaves along with its possible mechanism(s) of action using chemical and heat-induced pain models.
O. rugosa was extracted using 100% ethanol (EEOR) followed by exploring phytochemicals and assessing acute toxicity. To determine anti-nociceptive potentials, chemical-induced (acetic acid and formalin) and heat-induced (hot plate and tail immersion) nociceptive models were followed. To investigate the possible involvement of opioid receptors during formalin, hot plate, and tail immersion tests, naltrexone was administered whereas methylene blue and glibenclamide were used to explore cGMP involvement and ATP-sensitive K channel pathways, respectively. Moreover, the anti-inflammatory potential was assessed using the carrageenan-induced paw edema test model. Motor behaviours of EEOR were assessed by the open-field test. Finally, bioactive constituents (identified by GC-MS) from O. rugosa were subjected to molecular docking and ADME/t analysis to evaluate its potency and safety.
During chemical-induced and heat-induced pain models, EEOR exhibited significant and effective nociception suppression at all experimental doses (200 and 400 mg/kg). Also, the administration of naltrexone corroborated the association of opioid receptors with the anti-nociceptive activity by EEOR. Similarly, cGMP and ATP-sensitive K channel pathways were also found to be involved in the anti-nociceptive mechanism. Furthermore, significant and dose-dependent inhibition of inflammation induced by carrageenan was recorded for EEOR. Both doses of EEOR did not affect the animal's locomotor capacity in the open-field test. Besides, in silico test identified the key compounds (loliolide, harman, squalene, vitamin E, and gamma-sitosterol) that inhibited some particular receptors regarding pain and inflammation.
This research exposes central and peripheral pain intervention as well as anti-inflammatory activity of O. rugosa. Also, the identified compounds from this plant support its activities by effectively inhibiting anti-nociceptive and anti-inflammatory receptors. Overall, these outcomes valorize the ethnomedicinal efficacy of O. rugosa in managing various painful conditions.
平卧延胡索 var. prostrata 是孟加拉国土着和当地部落（Chakma、Marma 和 Tanchangya）用于治疗胸痛、身体疼痛和耳痛的传统药用植物。然而，关于这种植物的镇痛和抗炎潜力的知识却很少。
因此，我们使用化学和热诱导疼痛模型研究了平卧延胡索叶的镇痛和抗炎特性及其可能的作用机制。
使用 100%乙醇（EEOR）提取平卧延胡索，然后探索其植物化学物质并评估急性毒性。为了确定镇痛潜力，我们使用化学诱导（乙酸和甲醛）和热诱导（热板和尾浸）疼痛模型进行了研究。为了研究阿片受体在甲醛、热板和尾浸试验中的可能参与，给予纳曲酮，而使用亚甲蓝和格列本脲分别研究 cGMP 参与和 ATP 敏感性 K 通道途径。此外，使用角叉菜胶诱导的爪肿胀试验模型评估抗炎潜力。通过旷场试验评估 EEOR 的运动行为。最后，通过 GC-MS 鉴定平卧延胡索的生物活性成分，并进行分子对接和 ADME/t 分析，以评估其效力和安全性。
在化学诱导和热诱导疼痛模型中，EEOR 在所有实验剂量（200 和 400mg/kg）下均表现出显著有效的镇痛抑制作用。此外，纳曲酮的给药证实了 EEOR 的镇痛活性与阿片受体的关联。同样，cGMP 和 ATP 敏感性 K 通道途径也被发现参与了镇痛机制。此外，EEOR 对角叉菜胶诱导的炎症有显著的、剂量依赖性的抑制作用。EEOR 的两个剂量均未影响动物在旷场试验中的运动能力。此外，在计算机测试中，鉴定出一些特定的疼痛和炎症受体的关键化合物（螺旋内酯、哈尔曼、角鲨烯、维生素 E 和γ-谷甾醇），它们可有效抑制这些受体。
本研究揭示了平卧延胡索对中枢和外周疼痛的干预作用以及抗炎活性。此外，从这种植物中鉴定出的化合物通过有效抑制镇痛和抗炎受体，支持其活性。总的来说，这些结果提升了平卧延胡索在治疗各种疼痛疾病方面的民族医学功效。
