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毛叶枣通过下调 LPS 刺激的 RAW264.7 巨噬细胞和 OVA 诱导的气道炎症模型中的 NFκB 通路来减轻炎症。

Ziziphus mauritiana Lam attenuates inflammation via downregulating NFκB pathway in LPS-stimulated RAW 264.7 macrophages & OVA-induced airway inflammation in mice models.

机构信息

Laboratory of Pulmonary Research, National Facility for Drug Development (NFDD), Department of Pharmaceutical Technology, Bharathidasan Institute of Technology, Anna University, Tiruchirappalli, 620024, Tamil Nadu, India.

Department of Biotechnology, Bharathidasan Institute of Technology, Anna University, Tiruchirappalli, 620024, Tamil Nadu, India.

出版信息

J Ethnopharmacol. 2022 Sep 15;295:115445. doi: 10.1016/j.jep.2022.115445. Epub 2022 Jun 9.

DOI:10.1016/j.jep.2022.115445
PMID:35690340
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Ziziphus mauritiana Lam leaves were utilized in treating asthma, diabetes, inflammation, and hepatic diseases in Indian traditional medicine. The leaves were used as an edible vegetables in rural parts of India.

AIM OF THE STUDY

The aim is to prove the anti-inflammatory activity of Ziziphus mauritiana Lam leaves against LPS-stimulated RAW 264.7 macrophages and OVA-induced airway inflammation in mice through its attenuation mechanism in the NFκB signalling pathway.

MATERIALS AND METHODS

Terpenoids present in MEZ were quantified using U(H)PLC analysis. MEZ at 50 and 100 μg/mL were tested against LPS stimulated RAW 264.7 macrophages. The concentration of NO, ROS, and cytokines was quantified from the cell culture supernatants. OVA-induced asthma in mice was adopted for screening airway inflammation. MEZ at 250 and 500 mg/kg was tested for airway hyperresponsiveness, leukocyte counting, pro-inflammatory cytokines (IL-4, IL-5, IL-13 and TNF-α), lung histopathology, and various inflammatory gene expressions in lungs for NFκB signalling pathway in asthma.

RESULTS

Terpenoids like betulin, betulinic acid, oleanolic acid, and ursolic acid were quantified from U(H)PLC analysis. MEZ at higher doses reduced the NO, ROS, and pro-inflammatory cytokines in LPS stimulated RAW 264.7 macrophages. MEZ at 500 mg/kg significantly reduced AHR and also decreased total and differential leukocytes. MEZ also reduced the expressions of ICAM, VCAM, and Muc5C genes. Histopathological analysis revealed MEZ significantly reduced the leukocyte infiltration and mucus hypersecretion in the lungs. MEZ suppressed lung inflammation by inhibition of p65 mediated IκB-α translocation in the NFκB signalling pathway.

CONCLUSION

From these findings, MEZ significantly reduced airway inflammation by inhibiting NFκB mediated inflammatory pathway. Hence, this study proved that Ziziphus mauritiana Lam has anti-asthmatic potential in Indian traditional medicine.

摘要

民族药理学相关性

印度传统医学中,酸枣仁叶被用于治疗哮喘、糖尿病、炎症和肝脏疾病。在印度农村地区,这种叶子也被用作食用蔬菜。

目的

本研究旨在通过其在 NFκB 信号通路中的衰减机制,证明酸枣仁叶对 LPS 刺激的 RAW 264.7 巨噬细胞和 OVA 诱导的小鼠气道炎症的抗炎活性。

材料和方法

使用 U(H)PLC 分析定量 MEZ 中的萜类化合物。在 50 和 100μg/mL 下测试 MEZ 对 LPS 刺激的 RAW 264.7 巨噬细胞的作用。从细胞培养上清液中定量测定 NO、ROS 和细胞因子的浓度。采用 OVA 诱导的哮喘小鼠筛选气道炎症。在哮喘中,测试 MEZ (250 和 500mg/kg)对气道高反应性、白细胞计数、促炎细胞因子(IL-4、IL-5、IL-13 和 TNF-α)、肺组织病理学以及 NFκB 信号通路中肺部各种炎症基因的表达。

结果

使用 U(H)PLC 分析定量萜类化合物,如白桦脂醇、白桦脂酸、齐墩果酸和熊果酸。MEZ 在高剂量下可减少 LPS 刺激的 RAW 264.7 巨噬细胞中的 NO、ROS 和促炎细胞因子。MEZ(500mg/kg)可显著降低 AHR,还可降低总白细胞和白细胞分类计数。MEZ 还降低了 ICAM、VCAM 和 Muc5C 基因的表达。组织病理学分析表明,MEZ 可显著减少肺部白细胞浸润和粘液分泌过度。MEZ 通过抑制 NFκB 介导的炎症通路抑制 p65 介导的 IκB-α易位,从而抑制肺炎症。

结论

从这些发现可以看出,MEZ 通过抑制 NFκB 介导的炎症通路显著减轻气道炎症。因此,本研究证明了酸枣仁在印度传统医学中具有抗哮喘的潜力。

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