钩藤(Uncaria tomentosa(Willd. ex Schult.)DC.)水提物可降低哮喘小鼠模型的支气管高反应性和炎症。
Aqueous extracts from Uncaria tomentosa (Willd. ex Schult.) DC. reduce bronchial hyperresponsiveness and inflammation in a murine model of asthma.
机构信息
Departamento de Biotecnologia em Plantas Medicinais, Universidade de Ribeirão Preto, Av. Costábile Romano 2201, 14096-900 Ribeirão Preto, SP, Brazil.
Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Av. Bandeirantes 3900, Monte Alegre, 14049-900 Ribeirão Preto, SP, Brazil.
出版信息
J Ethnopharmacol. 2018 May 23;218:76-89. doi: 10.1016/j.jep.2018.02.013. Epub 2018 Feb 10.
ETHNOPHARMACOLOGICAL RELEVANCE
Uncaria tomentosa (Willd. Ex Schult) DC is used by indigenous tribes in the Amazonian region of Central and South America to treat inflammation, allergies and asthma. The therapeutic properties of U. tomentosa have been attributed to the presence of tetracyclic and pentacyclic oxindole alkaloids and to phenolic acids.
AIMS OF THE STUDY
To characterize aqueous bark extracts (ABE) and aqueous leaf extracts (ALE) of U. tomentosa and to compare their anti-inflammatory effects.
MATERIALS AND METHODS
Constituents of the extracts were identified by ultra performance liquid chromatography-mass spectrometry. Anti-inflammatory activities were assessed in vitro by exposing lipopolysaccharide-stimulated macrophage cells (RAW264.7-Luc) to ABE, ALE and standard mitraphylline. In vivo assays were performed using a murine model of ovalbumin (OVA)-induced asthma. OVA-sensitized animals were treated with ABE or ALE while controls received dexamethasone or saline solution. Bronchial hyperresponsiveness, production of Th1 and Th2 cytokines, total and differential counts of inflammatory cells in the bronchoalveolar lavage (BAL) and lung tissue were determined.
RESULTS
Mitraphylline, isomitraphylline, chlorogenic acid and quinic acid were detected in both extracts, while isorhyncophylline and rutin were detected only in ALE. ABE, ALE and mitraphylline inhibited the transcription of nuclear factor kappa-B in cell cultures, ALE and mitraphylline reduced the production of interleukin (IL)-6, and mitraphylline reduced production of tumor necrosis factor-alpha. Treatment with ABE and ALE at 50 and 200 mg kg, respectively, reduced respiratory elastance and tissue damping and elastance. ABE and ALE reduced the number of eosinophils in BAL, while ALE at 200 mg kg reduced the levels of IL-4 and IL-5 in the lung homogenate. Peribronchial inflammation was significantly reduced by treatment with ABE and ALE at 50 and 100 mg kg respectively.
CONCLUSION
The results clarify for the first time the anti-inflammatory activity of U. tomentosa in a murine model of asthma. Although ABE and ALE exhibited distinct chemical compositions, both extracts inhibited the production of pro-inflammatory cytokines in vitro. In vivo assays revealed that ABE was more effective in treating asthmatic inflammation while ALE was more successful in controlling respiratory mechanics. Both extracts may have promising applications in the phytotherapy of allergic asthma.
民族药理学相关性
在中美洲和南美洲的亚马逊地区,钩藤(Willd. Ex Schult)DC 被土著部落用于治疗炎症、过敏和哮喘。钩藤的治疗特性归因于四环和五环吲哚生物碱和酚酸的存在。
研究目的
对钩藤的水提树皮提取物(ABE)和水提叶提取物(ALE)进行表征,并比较它们的抗炎作用。
材料和方法
通过超高效液相色谱-质谱联用鉴定提取物中的成分。通过将脂多糖刺激的巨噬细胞(RAW264.7-Luc)暴露于 ABE、ALE 和标准麦角新碱来评估抗炎活性。使用卵清蛋白(OVA)诱导的哮喘小鼠模型进行体内试验。用 ABE 或 ALE 处理 OVA 致敏动物,而对照动物则接受地塞米松或生理盐水处理。测定支气管高反应性、Th1 和 Th2 细胞因子的产生、支气管肺泡灌洗液(BAL)和肺组织中炎症细胞的总计数和分类计数。
结果
在两种提取物中均检测到麦角新碱、异麦角新碱、绿原酸和奎宁酸,而异钩藤碱和芦丁仅在 ALE 中检测到。ABE、ALE 和麦角新碱抑制细胞培养物中核因子 kappa-B 的转录,ALE 和麦角新碱降低白细胞介素(IL)-6 的产生,麦角新碱降低肿瘤坏死因子-α的产生。ABE 和 ALE 以 50 和 200mg/kg 的剂量治疗可降低呼吸弹性和组织阻尼和弹性。ABE 和 ALE 减少 BAL 中的嗜酸性粒细胞数量,而 ALE 以 200mg/kg 的剂量降低肺匀浆中的 IL-4 和 IL-5 水平。ABE 和 ALE 以 50 和 100mg/kg 的剂量治疗可分别显著减轻支气管周围炎症。
结论
本研究首次阐明了钩藤在哮喘小鼠模型中的抗炎活性。尽管 ABE 和 ALE 表现出不同的化学成分,但两种提取物均抑制体外促炎细胞因子的产生。体内试验表明,ABE 治疗哮喘炎症更有效,而 ALE 更成功地控制呼吸力学。两种提取物在过敏性哮喘的植物疗法中可能具有广阔的应用前景。