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口服生物可利用乳香提取物卡斯珀罗米对脂多糖诱导的小鼠全身炎症的保护作用。

Protective Effect of Casperome, an Orally Bioavailable Frankincense Extract, on Lipopolysaccharide- Induced Systemic Inflammation in Mice.

作者信息

Loeser Konstantin, Seemann Semjon, König Stefanie, Lenhardt Isabell, Abdel-Tawab Mona, Koeberle Andreas, Werz Oliver, Lupp Amelie

机构信息

Institute of Pharmacology and Toxicology, Jena University Hospital, Jena, Germany.

Chair of Pharmaceutical Medicinal Chemistry, Institute of Pharmacy, Friedrich Schiller University Jena, Jena, Germany.

出版信息

Front Pharmacol. 2018 Apr 20;9:387. doi: 10.3389/fphar.2018.00387. eCollection 2018.

Abstract

Despite recent advances in critical care, sepsis remains a crucial cause of morbidity and mortality in intensive care units. Therefore, the identification of new therapeutic strategies is of great importance. Since ancient times, frankincense is used in traditional medicine for the treatment of chronic inflammatory disorders such as rheumatoid arthritis. Thus, the present study intends to evaluate if Casperome (Casp), an orally bioavailable soy lecithin-based formulation of standardized frankincense extract, is able to ameliorate systemic effects and organ damages induced by severe systemic inflammation using a murine model of sepsis, i.e., intraperitoneal administration of lipopolysaccharides (LPS). Male 60-day-old mice were assigned to six treatment groups: (1) control, (2) LPS, (3) soy lecithin (blank lecithin without frankincense extract), (4) Casp, (5) soy lecithin plus LPS, or (6) Casp plus LPS. Soy lecithin and Casp were given 3 h prior to LPS treatment; 24 h after LPS administration, animals were sacrificed and health status and serum cytokine levels were evaluated. Additionally, parameters representing liver damage or liver function and indicating oxidative stress in different organs were determined. Furthermore, markers for apoptosis and immune cell redistribution were assessed by immunohistochemistry in liver and spleen. LPS treatment caused a decrease in body temperature, blood glucose levels, liver glycogen content, and biotransformation capacity along with an increase in serum cytokine levels and oxidative stress in various organs. Additionally, apoptotic processes were increased in spleen besides a pronounced immune cell infiltration in both liver and spleen. Pretreatment with Casp significantly improved health status, blood glucose values, and body temperature of the animals, while serum levels of pro-inflammatory cytokines and oxidative stress in all organs tested were significantly diminished. Finally, apoptotic processes in spleen, liver glycogen loss, and immune cell infiltration in liver and spleen were distinctly reduced. Casp also appears to induce various cytochromeP450 isoforms, thus causing re-establishment of liver biotransformation capacity in LPS-treated mice. Casp displayed anti-inflammatory, anti-oxidative, and hepatoprotective effects. Thus, orally bioavailable frankincense extracts may serve as a new supportive treatment option in acute systemic inflammation and accompanied liver dysfunction.

摘要

尽管重症监护领域最近取得了进展,但脓毒症仍然是重症监护病房发病和死亡的重要原因。因此,确定新的治疗策略非常重要。自古以来,乳香就在传统医学中用于治疗类风湿性关节炎等慢性炎症性疾病。因此,本研究旨在评估卡斯珀罗(Casp),一种口服生物可利用的基于大豆卵磷脂的标准化乳香提取物制剂,是否能够使用脓毒症小鼠模型,即腹腔注射脂多糖(LPS),改善严重全身炎症引起的全身效应和器官损伤。60日龄雄性小鼠被分为六个治疗组:(1)对照组,(2)LPS组,(3)大豆卵磷脂组(不含乳香提取物的空白卵磷脂),(4)Casp组,(5)大豆卵磷脂加LPS组,或(6)Casp加LPS组。大豆卵磷脂和Casp在LPS治疗前3小时给予;LPS给药24小时后,处死动物并评估健康状况和血清细胞因子水平。此外,还测定了代表肝损伤或肝功能以及指示不同器官氧化应激的参数。此外,通过免疫组织化学评估肝和脾中凋亡和免疫细胞重新分布的标志物。LPS治疗导致体温、血糖水平、肝糖原含量和生物转化能力下降,同时血清细胞因子水平和各器官氧化应激增加。此外,除了肝和脾中明显的免疫细胞浸润外,脾中的凋亡过程也增加。用Casp预处理显著改善了动物的健康状况、血糖值和体温,而所有测试器官中的促炎细胞因子血清水平和氧化应激均显著降低。最后,脾中的凋亡过程、肝糖原损失以及肝和脾中的免疫细胞浸润明显减少。Casp似乎还能诱导各种细胞色素P450同工酶,从而使LPS处理的小鼠肝脏生物转化能力得以重建。Casp具有抗炎、抗氧化和肝保护作用。因此,口服生物可利用的乳香提取物可能成为急性全身炎症及伴随肝功能障碍的一种新的支持性治疗选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b534/5921439/22e766ab169f/fphar-09-00387-g001.jpg

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