Lee Jee Youn, Choi Hye Young, Baik Hyung Hwan, Ju Bong G, Kim Won-Ki, Yune Tae Young
Age-Related and Brain Diseases Research Center, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea.
Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea.
J Ethnopharmacol. 2017 May 5;203:90-100. doi: 10.1016/j.jep.2017.03.047. Epub 2017 Mar 30.
Cordyceps militaris is an ingredient of traditional Chinese medicine and have been widely used for inflammatory diseases and cancer. Cordycepin is one of the major bioactive components of Cordyceps militaris, and has been known to have anti-inflammatory and anti-oxidant effects.
In the present study, we examined whether WIB-801C, a standardized and cordycepin-enriched extract of caterpillar fungus (Cordyceps militaris), would attenuate blood-spinal cord barrier (BSCB) disruption by inhibiting matrix metalloprotease (MMP)-9 activity, leading to improvement of functional outcomes after spinal cord injury (SCI).
Male Sprague-Dawley rats were subjected to contusive SCI using a New York University (NYU) impactor, and WIB-801C (50mg/kg) was administered at 2h and 8h after injury orally and further treated once a day for indicated time points. BSCB disruption, MMP-9 activity, blood infiltration, inflammation, neuronal apoptosis, axonal loss, demyelination, and neurological deficit were evaluated.
We found that WIB-801C significantly attenuated BSCB disruption by inhibiting MMP-9 expression and activation after injury. The infiltration of neutrophils at 1 d and macrophage at 5 d after SCI was also ameliorated by WIB-801C as compared with vehicle control. In addition, the expression of inflammatory cytokines and mediators such as Tnf-α, IL-1β, IL-6, Cox-2, and inos as well as chemokines such as Gro-α and Mip-2α was significantly inhibited by WIB-801C. Furthermore, WIB-801C inhibits p38MAPK activation and proNGF production in microglia after injury. These events eventually led to the inhibition of apoptotic cell death of neurons and oligodendrocytes, improved functional recovery and attenuated demyelination and axon loss after SCI.
Our results suggest that WIB-801C can be used as a therapeutic agent after SCI by attenuating BSCB disruption followed inflammation.
蛹虫草是一种中药成分，已被广泛用于治疗炎症性疾病和癌症。虫草素是蛹虫草的主要生物活性成分之一，已知具有抗炎和抗氧化作用。
在本研究中，我们检测了WIB - 801C，一种标准化且富含虫草素的蛹虫草提取物，是否会通过抑制基质金属蛋白酶（MMP）- 9活性来减轻血脊髓屏障（BSCB）破坏，从而改善脊髓损伤（SCI）后的功能结局。
雄性Sprague - Dawley大鼠使用纽约大学（NYU）撞击器造成挫伤性脊髓损伤，在损伤后2小时和8小时口服给予WIB - 801C（剂量为50mg/kg），并在指定时间点每天进一步给药一次。评估血脊髓屏障破坏、MMP - 9活性、血液浸润、炎症、神经元凋亡、轴突损失、脱髓鞘和神经功能缺损情况。
我们发现WIB - 801C通过抑制损伤后MMP - 9的表达和激活，显著减轻了血脊髓屏障破坏。与溶剂对照组相比，WIB - 801C还改善了脊髓损伤后1天中性粒细胞和5天巨噬细胞的浸润情况。此外，WIB - 801C显著抑制了炎性细胞因子和介质如肿瘤坏死因子-α（Tnf-α）、白细胞介素-1β（IL - 1β）、白细胞介素-6（IL - 6）、环氧化酶-2（Cox - 2）和诱导型一氧化氮合酶（inos）以及趋化因子如生长调节致癌基因-α（Gro-α）和巨噬细胞炎性蛋白-2α（Mip - 2α）的表达。此外，WIB - 801C抑制损伤后小胶质细胞中p38丝裂原活化蛋白激酶（p38MAPK）的激活和前神经生长因子（proNGF）的产生。这些事件最终导致神经元和少突胶质细胞凋亡性细胞死亡受到抑制，功能恢复得到改善，脊髓损伤后的脱髓鞘和轴突损失减轻。
我们的结果表明，WIB - 801C可通过减轻血脊髓屏障破坏及随后的炎症反应，用作脊髓损伤后的治疗药物。
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