State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, People's Republic of China; University of Chinese Academy of Sciences, Beijing, 100049, People's Republic of China.
Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education and Yunnan Province, School of Chemical Science and Technology, Yunnan University, Kunming, 650091, People's Republic of China.
J Ethnopharmacol. 2022 Mar 1;285:114848. doi: 10.1016/j.jep.2021.114848. Epub 2021 Nov 17.
"Ya gai", an important part of Dai medical theory, is traditionally recognized as an antidote. Kopsia officinalis Tsiang et P. T. Li is a "Ya gai" related medicine and has been widely used by Dai people for the treatment of pain and inflammation. Previous literature on title species suggested that monoterpenoid indole alkaloids (MIAs) could be its main bioactive components. However, the specific bioactive ingredients for inflammation-related treatment are still unrevealed, which inspired us to conduct a phytochemical and pharmacological investigation related to its traditional use.
To support the traditional use of K. officinalis by assessing the anti-inflammatory and analgesic effects of its purified MIAs.
Compounds were isolated and purified from the barks and leaves of K. officinalis using diverse chromatographic methods. The structures were established by means of extensive spectroscopic analyses and quantum computational technique. The anti-inflammatory activities of the purified MIAs were evaluated in vitro based on the suppression of lipopolysaccharide-activated inflammatory mediators (COX-2, IL-1β, and TNF-α) in RAW 264.7 macrophage cells. Anti-inflammatory and analgesic activities in vivo were assessed with carrageenan-induced paw edema and acetic acid-stimulated writhing in mice models.
23 MIAs including four new compounds were obtained and structurally established. Most of isolates showed significant anti-inflammatory effects in vitro by inhibiting inflammatory mediators (COX-2, IL-1β, and TNF-α). Further pharmacological evaluation in vivo revealed that 12-hydroxy-19(R)-hydroxy-ibophyllidine (1) and 11,12-methylenedioxykopsinaline N-oxide (5) remarkably decreased the number of writhing, while kopsinic acid (8), (-)-kopsinilam (12), and normavacurine-21-one (20) significantly relieved paw edema, respectively, even better than the positive control aspirin.
The in vitro and in vivo findings supported the traditional use of K. officinalis with respect to its anti-inflammatory and analgesic effect, as well as provided potent bioactive MIAs for further chemical modification and pharmacological investigation.
“雅该”是傣医学理论的重要组成部分，传统上被认为是一种解毒剂。黄堇属植物是一种“雅该”相关药物，被傣族人广泛用于治疗疼痛和炎症。关于标题种的先前文献表明，单萜吲哚生物碱（MIAs）可能是其主要的生物活性成分。然而，用于炎症相关治疗的特定生物活性成分仍未被揭示，这激发了我们对其传统用途进行植物化学和药理学研究。
通过评估其纯化的 MIA 对炎症的抗炎和镇痛作用，支持黄堇属植物的传统用途。
使用多种色谱方法从黄堇属植物的树皮和叶子中分离和纯化化合物。通过广泛的光谱分析和量子计算技术确定结构。根据对脂多糖激活的炎症介质（COX-2、IL-1β 和 TNF-α）在 RAW 264.7 巨噬细胞中的抑制作用，在体外评估纯化 MIA 的抗炎活性。在角叉菜胶诱导的爪肿胀和醋酸刺激的扭体小鼠模型中评估体内抗炎和镇痛活性。
从黄堇属植物中获得并结构确证了 23 种 MIA，包括 4 种新化合物。大多数分离物在体外通过抑制炎症介质（COX-2、IL-1β 和 TNF-α）显示出显著的抗炎作用。体内进一步的药理评价表明，12-羟基-19(R)-羟基-异波林定（1）和 11,12-亚甲二氧基考斯那林 N-氧化物（5）显著减少扭体次数，而黄堇酸（8）、（-）-考斯宁拉明（12）和去甲野罂粟碱-21-酮（20）分别显著缓解爪肿胀，甚至优于阳性对照阿司匹林。
体内外研究结果支持黄堇属植物在抗炎和镇痛方面的传统用途，并为进一步的化学修饰和药理学研究提供了有效的生物活性 MIA。
