圆叶筋骨草变种宽叶变种中的筋骨草 A 具有抗炎活性，可作用于脂多糖激活的 RAW264.7 巨噬细胞和急性炎症动物模型。
Ajudecumin A from Ajuga ovalifolia var. calantha exhibits anti-inflammatory activity in lipopolysaccharide-activated RAW264.7 murine macrophages and animal models of acute inflammation.
机构信息
a State Key Laboratory Breeding Base of Systematic Research Development and Utilization of Chinese Medicine Resources, Sichuan Province and Ministry of Science and Technology, College of Pharmacy and College of Ethnic Medicine , Chengdu University of Traditional Chinese Medicine , Chengdu , China.
b Department of Traditional Chinese Medicine, College of Pharmacy , Southwest Minzu University , Chengdu , China.
出版信息
Pharm Biol. 2018 Dec;56(1):649-657. doi: 10.1080/13880209.2018.1543331.
CONTEXT
Ajuga ovalifolia Bur. et Franch. var. calantha (Diels) C. Y. Wu et C. Chen (Labiatae), a traditional Chinese medicine, has been used to treat several inflammatory diseases.
OBJECTIVE
To assess the anti-inflammatory activity of ajudecumin A isolated from Ajuga ovalifolia var. calantha, and its possible mechanisms.
MATERIALS AND METHODS
Lipopolysaccharide (LPS, 0.5 μg/mL)-stimulated RAW264.7 macrophages were used to assess the anti-inflammatory activity of ajudecumin A (1-40 μM) in vitro. Nitric oxide levels were evaluated by Griess reagent. The mRNA levels of iNOS, COX-2, TNF-α, IL-1β and IL-6 were determined using qRT-PCR. Phosphorylation of ERK, JNK, p38 MAPK and IκBα were detected by western Blot. To further assess the anti-inflammatory of ajudecumin A in vivo, mice were oral treated with ajudecumin A (10 mg/kg) or dexamethasone (0.25 mg/kg, positive control) for 5 days before administration of carrageenan or xylene. Paw and ear edema were then measured, respectively.
RESULTS
Ajudecumin A (10-40 μM) decreased LPS-induced nitric oxide production with an IC value of 16.19 μM. Ajudecumin A (20 and 40 μM) also attenuated cell spreading and formation of pseudopodia-like structures, and decreased the mRNA levels of iNOS (55.23-67.04%, p < 0.001), COX-2 (57.58-70.25%, p < 0.001), TNF-α (53.75-58.94%, p < 0.01-0.001), IL-1β (79.41-87.85%, p < 0.001) and IL-6 (54.26-80.52%, p < 0.01-0.001) in LPS-activated RAW264.7 cells. Furthermore, ajudecumin A suppressed LPS-induced phosphorylation of ERK, p38 MAPK, and IκBα, as well as IκBα degradation (p < 0.05-0.001). Finally, ajudecumin A (10 mg/kg) attenuated carrageenan- and xylene-induced inflammation in mice by about 28 and 24%, respectively.
DISCUSSION AND CONCLUSIONS
Ajudecumin A exhibited a potent anti-inflammatory activity in vitro and in vivo through inhibition on NF-κB and ERK/p38 MAPK pathways, suggesting that ajudecumin A may be potentially developed as a lead compound in anti-inflammatory drug discovery.
背景
筋骨草 Ajuga ovalifolia Bur. et Franch. 变种 calantha (Diels) C. Y. Wu et C. Chen（唇形科）是一种传统中药，已被用于治疗多种炎症性疾病。
目的
评估筋骨草变种 calantha 中的 ajugacumin A 分离物的抗炎活性及其可能的机制。
材料和方法
使用脂多糖（LPS，0.5μg/mL）刺激的 RAW264.7 巨噬细胞在体外评估 ajugacumin A（1-40μM）的抗炎活性。通过格里斯试剂评估一氧化氮水平。使用 qRT-PCR 测定诱导型一氧化氮合酶（iNOS）、环氧化酶-2（COX-2）、肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和白细胞介素-6（IL-6）的 mRNA 水平。通过 Western Blot 检测 ERK、JNK、p38 MAPK 和 IκBα的磷酸化。为了进一步评估 ajugacumin A 的体内抗炎作用，在给予角叉菜胶或二甲苯前，小鼠连续 5 天经口给予 ajugacumin A（10mg/kg）或地塞米松（0.25mg/kg，阳性对照）。然后分别测量爪和耳肿胀。
结果
ajugacumin A（10-40μM）降低 LPS 诱导的一氧化氮产生，IC 值为 16.19μM。ajugacumin A（20 和 40μM）还减弱了细胞铺展和伪足样结构的形成，并降低了 iNOS（55.23-67.04%，p<0.001）、COX-2（57.58-70.25%，p<0.001）、TNF-α（53.75-58.94%，p<0.01-0.001）、IL-1β（79.41-87.85%，p<0.001）和 IL-6（54.26-80.52%，p<0.01-0.001）的 mRNA 水平。此外，ajugacumin A 抑制了 LPS 诱导的 ERK、p38 MAPK 和 IκBα的磷酸化以及 IκBα 的降解（p<0.05-0.001）。最后，ajugacumin A（10mg/kg）分别减轻了角叉菜胶和二甲苯诱导的小鼠炎症约 28%和 24%。
讨论与结论
ajugacumin A 在体外和体内均表现出强大的抗炎活性，通过抑制 NF-κB 和 ERK/p38 MAPK 通路，提示 ajugacumin A 可能作为抗炎药物发现的潜在先导化合物。
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