PMID- 32014501
OWN - NLM
STAT- MEDLINE
DCOM- 20210618
LR  - 20210618
IS  - 1873-4596 (Electronic)
IS  - 0891-5849 (Linking)
VI  - 152
DP  - 2020 May 20
TI  - Echinacoside attenuates inflammatory response in a rat model of cervical 
      spondylotic myelopathy via inhibition of excessive mitochondrial fission.
PG  - 697-714
LID - S0891-5849(19)31255-9 [pii]
LID - 10.1016/j.freeradbiomed.2020.01.014 [doi]
AB  - 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.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Zhou, Longyun
AU  - Zhou L
AD  - Spine Disease Institute, Longhua Hospital, Shanghai University of Traditional 
      Chinese Medicine, Shanghai, 200032, China; Key Laboratory of Theory and Therapy 
      of Muscles and Bones, Ministry of Education, Shanghai University of Traditional 
      Chinese Medicine, Shanghai, 200032, China; Rehabilitation Medicine College, 
      Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
FAU - Yao, Min
AU  - Yao M
AD  - Spine Disease Institute, Longhua Hospital, Shanghai University of Traditional 
      Chinese Medicine, Shanghai, 200032, China; Key Laboratory of Theory and Therapy 
      of Muscles and Bones, Ministry of Education, Shanghai University of Traditional 
      Chinese Medicine, Shanghai, 200032, China.
FAU - Tian, Zirui
AU  - Tian Z
AD  - Spine Disease Institute, Longhua Hospital, Shanghai University of Traditional 
      Chinese Medicine, Shanghai, 200032, China; Key Laboratory of Theory and Therapy 
      of Muscles and Bones, Ministry of Education, Shanghai University of Traditional 
      Chinese Medicine, Shanghai, 200032, China.
FAU - Song, Yongjia
AU  - Song Y
AD  - Spine Disease Institute, Longhua Hospital, Shanghai University of Traditional 
      Chinese Medicine, Shanghai, 200032, China; Key Laboratory of Theory and Therapy 
      of Muscles and Bones, Ministry of Education, Shanghai University of Traditional 
      Chinese Medicine, Shanghai, 200032, China.
FAU - Sun, Yueli
AU  - Sun Y
AD  - Spine Disease Institute, Longhua Hospital, Shanghai University of Traditional 
      Chinese Medicine, Shanghai, 200032, China; Key Laboratory of Theory and Therapy 
      of Muscles and Bones, Ministry of Education, Shanghai University of Traditional 
      Chinese Medicine, Shanghai, 200032, China.
FAU - Ye, Jie
AU  - Ye J
AD  - Department of Orthopedics and Traumatology, Longhua Hospital, Shanghai University 
      of Traditional Chinese Medicine, Shanghai, 200032, China.
FAU - Li, Gan
AU  - Li G
AD  - Spine Disease Institute, Longhua Hospital, Shanghai University of Traditional 
      Chinese Medicine, Shanghai, 200032, China; Key Laboratory of Theory and Therapy 
      of Muscles and Bones, Ministry of Education, Shanghai University of Traditional 
      Chinese Medicine, Shanghai, 200032, China.
FAU - Sng, Kim Sia
AU  - Sng KS
AD  - Spine Disease Institute, Longhua Hospital, Shanghai University of Traditional 
      Chinese Medicine, Shanghai, 200032, China; Key Laboratory of Theory and Therapy 
      of Muscles and Bones, Ministry of Education, Shanghai University of Traditional 
      Chinese Medicine, Shanghai, 200032, China.
FAU - Xu, Leqin
AU  - Xu L
AD  - Xiamen Hospital of Traditional Chinese Medicine, Fujian, 361009, China.
FAU - Cui, Xuejun
AU  - Cui X
AD  - Spine Disease Institute, Longhua Hospital, Shanghai University of Traditional 
      Chinese Medicine, Shanghai, 200032, China; Key Laboratory of Theory and Therapy 
      of Muscles and Bones, Ministry of Education, Shanghai University of Traditional 
      Chinese Medicine, Shanghai, 200032, China. Electronic address: 
      13917715524@139.com.
FAU - Wang, Yongjun
AU  - Wang Y
AD  - Spine Disease Institute, Longhua Hospital, Shanghai University of Traditional 
      Chinese Medicine, Shanghai, 200032, China; Key Laboratory of Theory and Therapy 
      of Muscles and Bones, Ministry of Education, Shanghai University of Traditional 
      Chinese Medicine, Shanghai, 200032, China. Electronic address: 
      yjwang8888@126.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200131
PL  - United States
TA  - Free Radic Biol Med
JT  - Free radical biology & medicine
JID - 8709159
RN  - 0 (Glycosides)
RN  - 0 (Inflammasomes)
RN  - EC 3.6.5.5 (Dynamins)
RN  - I04O1DT48T (echinacoside)
SB  - IM
MH  - Animals
MH  - Dynamins/genetics
MH  - Glycosides
MH  - Inflammasomes
MH  - *Mitochondrial Dynamics
MH  - Rats
MH  - *Spinal Cord Diseases
OTO - NOTNLM
OT  - Cervical spondylotic myelopathy
OT  - Drp1
OT  - ECH
OT  - Mdivi-1
OT  - Mitochondrial dynamics
OT  - NLRP3 inflammasome
COIS- Declaration of competing interest We declare that we have no conflicts of 
      interest.
EDAT- 2020/02/06 06:00
MHDA- 2021/06/22 06:00
CRDT- 2020/02/05 06:00
PHST- 2019/07/28 00:00 [received]
PHST- 2019/12/27 00:00 [revised]
PHST- 2020/01/14 00:00 [accepted]
PHST- 2020/02/06 06:00 [pubmed]
PHST- 2021/06/22 06:00 [medline]
PHST- 2020/02/05 06:00 [entrez]
AID - S0891-5849(19)31255-9 [pii]
AID - 10.1016/j.freeradbiomed.2020.01.014 [doi]
PST - ppublish
SO  - Free Radic Biol Med. 2020 May 20;152:697-714. doi: 
      10.1016/j.freeradbiomed.2020.01.014. Epub 2020 Jan 31.