ReferenceID 1791
Echinacoside attenuates inflammatory response in a rat model of cervical spondylotic myelopathy via inhibition of excessive mitochondrial fission
Free Radic Biol Med
Cervical spondylotic myelopathy (CSM) is a leading cause of spinal cord dysfunction with few treatment options. Although mitochondrial dynamics are linked to a wide range of pathological changes in neurodegenerative dise
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- Reference Id
- 1791
- Evidence Id
- 18381
- Core Evidence Id
- 18381
- Source Reference Id
- 3574
- Herb2 Reference Id
- HBREF004371
- Subject Paper Key
- HBIN024794_32014501
- Pubmed Id
- 32014501
- Doi
- 10.1016/j.freeradbiomed.2020.01.014
- Paper Title
- Echinacoside attenuates inflammatory response in a rat model of cervical spondylotic myelopathy via inhibition of excessive mitochondrial fission
- Paper Abstract
- Cervical spondylotic myelopathy (CSM) is a leading cause of spinal cord dysfunction with few treatment options. Although mitochondrial dynamics are linked to a wide range of pathological changes in neurodegenerative diseases, a connection between aberrant mitochondrial dynamics and CSM remains to be illuminated. In addition, mechanisms underlying the emerging anti-inflammatory and neuroprotective effects of echinacoside (ECH), the main active ingredient of Cistanche salsa, are poorly understood. We hypothesized that excessive mitochondrial fission plays a critical role in regulating inflammatory responses in CSM, and ECH might alleviate such responses by regulating mitochondrial dynamics. To this end, we assessed the effects of ECH and Mdivi-1, a selective inhibitor of dynamin-related protein (Drp1), in a rat model of chronic cervical cord compression and activated BV2 cells. Our results showed that rats with Mdivi-1 intervention had improved motor function compared with vehicle-treated rats. Indeed, Mdivi-1 treatment attenuated pro-inflammatory cytokine expression, as well as activation of the nod-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, nuclear transcription factor-kappaB (NF-kappaB), and Drp1 in lesions. Compared with vehicle-treated rats, compression sites of Mdivi-1-treated animals exhibited elongated mitochondrial morphologies and reduced reactive oxygen species (ROS). Similarly, ECH-treated rats exhibited neurological recovery and suppression of inflammatory response or related signals in the lesion area after treatment. Interestingly, ECH treatment partly reversed aberrant mitochondrial fragmentation and oxidative stress within the lesion area. In vitro data suggested that ECH suppressed activated microglia by modulating activation of the NLRP3 inflammasome and NF-kappaB signaling. Furthermore, we observed that ECH markedly inhibited Drp1 translocation onto mitochondria, whereby it regulated mitochondrial dynamics and ROS production, which act as regulators of NLRP3 inflammasome activation and NF-kappaB signaling. Thus, our findings reveal that mitochondrial dynamics modulate inflammatory responses during CSM. Moreover, ECH may attenuate neuroinflammation in rats subjected to chronic cervical cord compression by regulating Drp1-dependent mitochondrial fission and activation of downstream signaling.
- Journal
- Free Radic Biol Med
- Publish Year
- 2020
- Experiment Subject
- rat; bv2 cells
- Experiment Type
- Animal & Cell Experiment
- Phenotype Related
- Cervical Spondylotic Myelopathy; Chronic Cervical Cord Compression; Neurodegenerative Diseases; Spinal Cord Dysfunction
- Paper Title Cn
- Paper Title En
- Echinacoside attenuates inflammatory response in a rat model of cervical spondylotic myelopathy via inhibition of excessive mitochondrial fission
- Bilingual Status
- semi_complete