Castranova V, Kang J H, Ma J K, Mo C G, Malanga C J, Moore M D, Schwegler-Berry D, Ma J Y
Division of Respiratory Disease Studies, National Institute for Occupational Safety and Health, Morgantown, West Virginia.
Toxicol Appl Pharmacol. 1991 Apr;108(2):242-52. doi: 10.1016/0041-008x(91)90115-u.
The Chinese have conducted extensive studies concerning the medicinal properties of plant products. In this investigation the ability of three bisbenzylisoquinoline alkaloids to inhibit particle-induced activation of alveolar macrophages was evaluated and this inhibitory potential was correlated with the ability of those drugs to bind to membrane components. Tetrandrine, i.e., an herbal medicine used as an antifibrotic agent in China, was a potent inhibitor of particle-stimulated oxygen consumption, superoxide release, and hydrogen peroxide secretion by alveolar macrophages. Tetrandrine also exhibited substantial binding affinity for membrane lipids and alveolar macrophages. In contrast, tubocurine, an analogue with little antifibrotic potential, exhibited low binding affinity and had little effect on macrophage activation. Methoxyadiantifoline, an alkaloid of unknown antifibrotic potential, exhibited inhibitory and binding properties similar to those of tetrandrine. The data indicate that a strong relationship exists between the antifibrotic potential of these alkaloids and their ability to bind to alveolar macrophages and inhibit particle-induced activation of these phagocytes. These drugs should serve as useful probes to evaluate the role of alveolar macrophages in pulmonary fibrosis.
中国人对植物制品的药用特性进行了广泛研究。在这项研究中，评估了三种双苄基异喹啉生物碱抑制颗粒诱导的肺泡巨噬细胞活化的能力，并将这种抑制潜力与这些药物结合膜成分的能力相关联。汉防己甲素，即中国用作抗纤维化剂的一种草药，是颗粒刺激的肺泡巨噬细胞耗氧量、超氧化物释放和过氧化氢分泌的有效抑制剂。汉防己甲素对膜脂质和肺泡巨噬细胞也表现出显著的结合亲和力。相比之下，箭毒碱，一种几乎没有抗纤维化潜力的类似物，表现出低结合亲和力，对巨噬细胞活化影响很小。甲氧基蝙蝠葛碱，一种抗纤维化潜力未知的生物碱，表现出与汉防己甲素相似的抑制和结合特性。数据表明，这些生物碱的抗纤维化潜力与其结合肺泡巨噬细胞并抑制颗粒诱导的这些吞噬细胞活化的能力之间存在密切关系。这些药物应作为评估肺泡巨噬细胞在肺纤维化中作用的有用探针。
