Key Laboratory of Chemistry in Ethnic Medicinal Resources, State Ethnic Affairs Commission & Ministry of Education, School of Ethnic Medicine, Yunnan Minzu University, Kunming, China.
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Pharm Biol. 2023 Dec;61(1):201-212. doi: 10.1080/13880209.2022.2163407.
Linn (Leguminosae) is often used in Yi ethnic medicine to treat pain, fracture, and rheumatism.
To explore the therapeutic potential of doliroside B (DB) from and its disodium salt (DBDS) and the underlying mechanism in pain.
In the writhing test, Kunming mice were orally treated with DB and DBDS at doses of 0.31, 0.62, 1.25, 2.5, and 5 mg/kg. Vehicle, morphine, indomethacin, and acetylsalicylic acid were used as negative and positive control on the nociception-induced models, respectively. In the hot plate test, mice were orally treated with DB and DBDS at doses of 2.5, 5, 10, and 20 mg/kg. In the formalin test, mice were orally treated with DB and DBDS at doses of 2.5, 5, 10, and 20 mg/kg. In the meanwhile, lipopolysaccharide-induced inflammatory model in RAW264.7 macrophages was adopted to study the mechanism of pain alleviation for DBDS.
DBDS (5 mg/kg) inhibited the writhing number by 80.2%, which exhibited the highest antinociceptive activity in pain models. DBDS could selectively inhibite the activity of COX-1. Meanwhile, it also reduced the production of NO, iNOS, and IL-6 by 55.8%, 69.0%, and 49.9% inhibition, respectively. It was found that DBDS also positively modulated the function of GABA receptor.
DBDS displayed antinociceptive activity by acting on both the peripheral and central nervous systems, which may act on multitargets. Further work is warranted for developing DBDS into a potential drug for the treatment of pain.
Linn（豆科）常用于彝族医学治疗疼痛、骨折和风湿病。
探索来自 Linn 的地奥司明 B（DB）及其二钠盐（DBDS）的治疗潜力及其在疼痛中的潜在机制。
在扭体试验中，昆明小鼠口服给予 DB 和 DBDS 剂量为 0.31、0.62、1.25、2.5 和 5mg/kg。车辆、吗啡、吲哚美辛和乙酰水杨酸分别用作致痛模型的阴性和阳性对照。在热板试验中，小鼠口服给予 DB 和 DBDS 剂量为 2.5、5、10 和 20mg/kg。在福尔马林试验中，小鼠口服给予 DB 和 DBDS 剂量为 2.5、5、10 和 20mg/kg。同时，采用脂多糖诱导 RAW264.7 巨噬细胞炎症模型研究 DBDS 缓解疼痛的机制。
DBDS（5mg/kg）抑制扭体数 80.2%，在疼痛模型中表现出最高的镇痛活性。DBDS 可选择性抑制 COX-1 的活性。同时，它还分别降低了 NO、iNOS 和 IL-6 的产生，抑制率为 55.8%、69.0%和 49.9%。研究发现 DBDS 还能正向调节 GABA 受体的功能。
DBDS 通过作用于外周和中枢神经系统表现出镇痛活性，可能作用于多个靶点。进一步的工作是将 DBDS 开发成治疗疼痛的潜在药物。
