Flexibilide Obtained from Cultured Soft Coral HasAnti-Neuroinflammatory and Analgesic Effects through the Upregulation of Spinal Transforming Growth Factor-β1 in Neuropathic Rats

Marine Drugs

Chun-Sung Sung¹  Hui-Min David Wang²  Han-Chun Hung³  Chun-Hong Chen³  Yen-You Lin³  Jyh-Horng Sheu³  Zhi-Hong Wen³  Nan-Fu Chen³  Shi-Ying Huang³  Chien-Wei Feng³  Wu-Fu Chen⁴  Ching-Hsiang Lu⁵  Chun-Lin Chen⁵  Yu-Chia Chang⁶  Ping-Jyun Sung⁷  San-Nan Yang⁸ 

[1] Department of Anesthesiology, Taipei Veterans General Hospital, Taipei 11217, Taiwan;Department of Fragrance and Cosmetic Science, Kaohsiung Medical University, Kaohsiung 80708, Taiwan;Department of Marine Biotechnology and Resources, Asia-Pacific Ocean Research Center,National Sun Yat-sen University, Kaohsiung 80424, Taiwan;Department of Neurosurgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan;Division of Neurosurgery, Department of Surgery, Kaohsiung Armed Forces General Hospital, Kaohsiung 80284, Taiwan;Doctoral Degree Program in Marine Biotechnology, National Sun Yat-sen University and Academia Sinica, Kaohsiung 80424, Taiwan;National Museum of Marine Biology and Aquarium, Pingtung 944, Taiwan;School of Medicine, College of Medicine and Department of Pediatrics, E-DA Hospital, I-Shou University, Kaohsiung 84001, Taiwan;

关键词: flexibilide;    chronic constriction injury;    neuropathic pain;    spinal neuroinflammation;    microglial activation;    transforming growth factor-β1;    natural marine compound;   

DOI  :  10.3390/md12073792

来源: DOAJ

【 摘 要 】

Chronic neuroinflammation plays an important role in the development and maintenance of neuropathic pain. The compound flexibilide, which can be obtained from cultured soft coral, possesses anti-inflammatory and analgesic effects in the rat carrageenan peripheral inflammation model. In the present study, we investigated the antinociceptive properties of flexibilide in the rat chronic constriction injury (CCI) model of neuropathic pain. First, we found that a single intrathecal (i.t.) administration of flexibilide significantly attenuated CCI-induced thermal hyperalgesia at 14 days after surgery. Second, i.t. administration of 10-μg flexibilide twice daily was able to prevent the development of thermal hyperalgesia and weight-bearing deficits in CCI rats. Third, i.t. flexibilide significantly inhibited CCI-induced activation of microglia and astrocytes, as well as the upregulated proinflammatory enzyme, inducible nitric oxide synthase, in the ipsilateral spinal dorsal horn. Furthermore, flexibilide attenuated the CCI-induced downregulation of spinal transforming growth factor-β1 (TGF-β1) at 14 days after surgery. Finally, i.t. SB431542, a selective inhibitor of TGF-β type I receptor, blocked the analgesic effectsof flexibilide in CCI rats. Our results suggest that flexibilide may serve as a therapeutic agent for neuropathic pain. In addition, spinal TGF-β1 may be involved in theanti-neuroinflammatory and analgesic effects of flexibilide.

【 授权许可】

Unknown