Department of Pharmacology, Institute of Pharmaceutical Sciences, University of Tuebingen, Auf der Morgenstelle 8, 72076 Tuebingen, Germany.
Phytomedicine. 2011 Sep 15;18(12):1037-44. doi: 10.1016/j.phymed.2011.06.035. Epub 2011 Aug 9.
Type 1-diabetes is an autoimmune disease, where a chronic inflammatory process finally causes β-cell death and insulin deficiency. Extracts from gum resin of Boswellia serrata (BE) have been shown to posses anti-inflammatory properties especially by targeting factors/mediators related to autoimmune diseases. Multiple low dose-streptozotocin (MLD-STZ) treatment is a method to induce diabetes in animals similar to Type 1 diabetes in humans. It was aimed to study whether or not a BE could prevent hyperglycemia, inflammation of pancreatic islets and increase of proinflammatory cytokines in the blood in MLD-STZ treated mice. In BK+/+ wild type mice, 5 days of daily treatment with 40 mg/kg STZ i.p. produced permanent increase of blood glucose, infiltration of lymphocytes into pancreatic islets (CD3-stain), apoptosis of periinsular cells (staining for activated caspase 3) after 10 days as well as shrinking of islet tissue after 35 days (H&E staining). This was associated with an increase of granulocyte colony stimulating factor (G-CSF), granulocyte/macrophage colony stimulating factor (GM-CSF) and proinflammatory cytokines (IL-1A, IL-1B, IL-2, IL-6, IFN-γ, TNF-α) in the blood. Whereas BE alone did not affect blood glucose in non diabetic mice, in STZ treated mice simultaneous i.p. injection of 150 mg/kg of BE over 10 days prevented animals from increase of blood glucose levels. Histochemical studies showed, that i.p. injection of 150 mg/kg BE for 10 days starting with STZ treatment, avoided lymphocyte infiltration into islets, apoptosis of periinsular cells and shrinking of islet size 35 days after STZ. As far as the cytokines tested are concerned, there was a significant inhibition of the increase of G-CSF and GM-CSF. BE also significantly prevented the increase of IL-1A, IL-1B, IL-2, IL-6, IFN-γ and TNF-α. It is concluded that extracts from the gum resin of Boswellia serrata prevent islet destruction and consequent hyperglycemia in an animal model of type 1 diabetes probably by inhibition of the production/action of cytokines related to induction of islet inflammation in an autoimmune process.
1 型糖尿病是一种自身免疫性疾病，其中慢性炎症过程最终导致β细胞死亡和胰岛素缺乏。乳香（Boswellia serrata）树脂提取物已被证明具有抗炎特性，特别是通过针对与自身免疫性疾病相关的因子/介质。多次小剂量链脲佐菌素（MLD-STZ）处理是一种在动物中诱导类似于人类 1 型糖尿病的糖尿病的方法。目的是研究乳香是否可以预防 MLD-STZ 处理的小鼠中的高血糖、胰岛炎症和血液中促炎细胞因子的增加。在 BK+/+野生型小鼠中，每天腹腔注射 40mg/kg STZ 5 天可导致血糖永久性升高，10 天后淋巴细胞浸润胰岛（CD3 染色），胰岛周围细胞凋亡（活化 caspase 3 染色），35 天后胰岛组织缩小（H&E 染色）。这与血液中粒细胞集落刺激因子（G-CSF）、粒细胞/巨噬细胞集落刺激因子（GM-CSF）和促炎细胞因子（IL-1A、IL-1B、IL-2、IL-6、IFN-γ、TNF-α）的增加有关。虽然乳香单独使用不会影响非糖尿病小鼠的血糖，但在 STZ 处理的小鼠中，同时腹腔注射 150mg/kg 的乳香 10 天可防止动物血糖升高。组织化学研究表明，从 STZ 处理开始，腹腔注射 150mg/kg 的乳香 10 天可避免淋巴细胞浸润胰岛、胰岛周围细胞凋亡和 STZ 后 35 天胰岛缩小。就测试的细胞因子而言，G-CSF 和 GM-CSF 的增加受到显著抑制。乳香还显著预防了 IL-1A、IL-1B、IL-2、IL-6、IFN-γ和 TNF-α的增加。综上所述，乳香树脂提取物通过抑制与自身免疫过程中胰岛炎症诱导相关的细胞因子的产生/作用，防止 1 型糖尿病动物模型中的胰岛破坏和随之而来的高血糖。
