从山竹子中分离得到的柚皮苷的抗炎和抗氧化活性：体外和体内证据。

Anti-inflammatory and antioxidant activities of naringin isolated from Carissa carandas L.: In vitro and in vivo evidence.

机构信息

Department of Pharmacognosy, National Research Centre, El-Tahrir St., Dokki, Giza 12622, Egypt.

Department of Pharmacology, National Research Centre, El-Tahrir St., Dokki, Giza 12622, Egypt.

出版信息

Phytomedicine. 2018 Mar 15;42:126-134. doi: 10.1016/j.phymed.2018.03.051. Epub 2018 Mar 19.

DOI:10.1016/j.phymed.2018.03.051

PMID:29655678

Abstract

BACKGROUND

Carissa carandas L. is known in folk medicine for its anti-inflammatory and hepatoprotective activities. Meanwhile it is an evergreen shrub that constitutes a continuous source of leaves throughout the year.

HYPOTHESIS/PURPOSE: The leaves of Carissa carandas L. may be rich in compounds that can be used as safe anti-inflammatory and antioxidant remedies. The combined antioxidant and anti-inflammatory activities provoked the study of the hepatoprotective effects.

STUDY DESIGN

To isolate major constituents from the leaves of Carissa carandas L. and test their anti-inflammatory and antioxidant activities in-vivo and in-vitro.

METHODS

The leaves of Carissa carandas L. were extracted with 80% MeOH and then defatted with CHCl to yield Carissa carandas defatted extract (CCDE). The extract was chemoprofiled using UPLC-MS/MS to stand for major constituents, then subjected to different chromatographic separation steps and naringin (NG) was isolated in a high yield. The anti-inflammatory activity of NG was investigated in-vivo by carrageenan induced hind rat paw edema model at two dose levels (50 and 25 mg/kg). The anti-inflammatory activity was also evaluated in-vitro by measuring its inhibitory effect on LPS induced release of NO from RAW 264.7 macrophages. The antioxidant activity was evaluated by superoxide and DPPH radical scavenging ability. The safety of NG was tested against primary rat hepatocytes. The hepatoprotective effect of CCDE was evaluated by detecting its effects on serum liver function markers and liver cell oxidative stress markers.

RESULTS

NG exhibited potent inhibition of inflammation as compared to indomethacin (20 mg/kg). NG inhibited LPS induced release of NO from macrophages (IC, 6.4 μM). NG showed significant antioxidant activity as it scavenged the superoxide radical (EC, 10.95 μM) and DPPH radical (EC, 11.2 μM). CCDE inhibited the elevation of the serum liver marker enzymes and increased GSH and decreased MDA contents in the liver homogenate. Liver histopathology supported the biochemical findings.

CONCLUSION

C. carandas has potent anti-inflammatory, antioxidant and hepatoprotective activities.

摘要

背景

作为民间医学的一部分，嘉兰被认为具有抗炎和保肝作用。同时，它也是一种常绿灌木，全年不断提供叶子。

假说/目的：嘉兰的叶子可能富含可用于安全抗炎和抗氧化治疗的化合物。抗氧化和抗炎的综合活性促使我们研究其保肝作用。

研究设计

从嘉兰的叶子中分离主要成分，并在体内和体外测试其抗炎和抗氧化活性。

方法

用 80%甲醇提取嘉兰的叶子，然后用 CHCl 脱脂得到嘉兰脱脂提取物（CCDE）。使用 UPLC-MS/MS 对提取物进行化学分析，以代表主要成分，然后进行不同的色谱分离步骤，以高产率分离得到柚皮苷（NG）。通过角叉菜胶诱导的大鼠后爪水肿模型在两个剂量水平（50 和 25mg/kg）体内研究 NG 的抗炎活性。还通过测量其对 LPS 诱导 RAW 264.7 巨噬细胞释放 NO 的抑制作用来评估 NG 的抗炎活性。通过超氧化物和 DPPH 自由基清除能力评估抗氧化活性。使用原代大鼠肝细胞测试 NG 的安全性。通过检测对血清肝功能标志物和肝细胞氧化应激标志物的影响来评估 CCDE 的保肝作用。

结果

与吲哚美辛（20mg/kg）相比，NG 表现出强烈的抗炎抑制作用。NG 抑制 LPS 诱导的巨噬细胞释放 NO（IC，6.4μM）。NG 表现出显著的抗氧化活性，因为它清除了超氧自由基（EC，10.95μM）和 DPPH 自由基（EC，11.2μM）。CCDE 抑制血清肝标志物酶的升高，并增加肝匀浆中的 GSH 含量，降低 MDA 含量。肝组织病理学支持生化发现。