Secoisolariciresinol diglycoside, a flaxseed lignan, exerts analgesic effects in a mouse model of type 1 diabetes: Engagement of antioxidant mechanism.
Peripheral painful neuropathy is one of the most common complications in diabetes and necessitates improved treatment. Secoisolariciresinol diglycoside (SDG), a predominant lignan in flaxseed, has been shown in our previous studies to exert antidepressant-like effect. As antidepressant drugs are clinically used to treat chronic neuropathic pain, this work aimed to investigate the potential analgesic efficacy of SDG against diabetic neuropathic pain in a mouse model of type 1 diabetes. We subjected mice to diabetes by a single intraperitoneal (i.p.) injection of streptozotocin (STZ, 200 mg/kg), and Hargreaves test or von Frey test was used to assess thermal hyperalgesia or mechanical allodynia, respectively. Chronic instead of acute SDG treatment (3, 10 or 30 mg/kg, p.o., twice per day for three weeks) ameliorated thermal hyperalgesia and mechanical allodynia in diabetic mice, and these analgesic actions persisted about three days when SDG treatment was terminated. Although chronic treatment of SDG to diabetic mice did not impact on the symptom of hyperglycemia, it greatly attenuated excessive oxidative stress in sciatic nerve and spinal cord tissues, and partially counteracted the condition of weight decrease. Furthermore, the analgesic actions of SDG were abolished by co-treatment with the reactive oxygen species donor tert-butyl hydroperoxide (t-BOOH), but potentiated by the reactive oxygen species scavenger phenyl-N-tert-butylnitrone (PBN). These findings indicate that chronic SDG treatment can correct neuropathic hyperalgesia and allodynia in mice with type 1 diabetes. Mechanistically, the analgesic actions of SDG in diabetic mice may be associated with its antioxidant activity.
Department of Vasculocardiology, Jingzhou Central Hospital, Jingzhou, Hubei Province 434020, China.
Pei
P
Hu
Department of Neurosurgery, Shanghai Changzheng Hospital, The Second Military Medical University, Shanghai 200003, China.
Qi-Yong
QY
Mei
Department of Neurology, Jingzhou Central Hospital, Jingzhou, Hubei Province 434020, China.
Li
L
Ma
Department of Pharmacology, Ningbo University, School of Medical Science, Ningbo, Zhejiang Province 315211, China.
Wu-Geng
WG
Cui
Department of Pharmacology, Ningbo University, School of Medical Science, Ningbo, Zhejiang Province 315211, China.
Wen-Hua
WH
Zhou
Department of Psychiatry, Ningbo Kangning Hospital, Ningbo, Zhejiang Province 315201, China.
Dong-Sheng
DS
Zhou
Department of Neurology, Putuo District Center Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China.
Qing
Q
Zhao
Department of Obstetrics and Gynecology, TongRen Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China.
Dong-Ying
DY
Xu
Department of Pharmacology, Ningbo University, School of Medical Science, Ningbo, Zhejiang Province 315211, China. Electronic address: zhaoxin@nbu.edu.cn.
Xin
X
Zhao
Department of Obstetrics and Gynecology, TongRen Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China. Electronic address: luqin118@163.com.
Qin
Q
Lu
Department of Pharmacology, Ningbo University, School of Medical Science, Ningbo, Zhejiang Province 315211, China; Department of Psychiatry, Ningbo Kangning Hospital, Ningbo, Zhejiang Province 315201, China. Electronic address: hzy86690952@163.com.
Zhen-Yu
ZY
Hu
D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D002072:Butylene Glycols / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D003497:Cyclic N-Oxides / Q000494:pharmacology; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism; D003929:Diabetic Neuropathies / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D019597:Flax / Q000737:chemistry*; D006027:Glycosides / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006930:Hyperalgesia / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D017705:Lignans / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D009437:Neuralgia / Q000150:complications / Q000188:drug therapy; D012584:Sciatic Nerve / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism; D020122:tert-Butylhydroperoxide / Q000494:pharmacology
D000700:Analgesics; D000975:Antioxidants; D002072:Butylene Glycols; D003497:Cyclic N-Oxides; D006027:Glycosides; D017705:Lignans; C029217:phenyl-N-tert-butylnitrone; D020122:tert-Butylhydroperoxide; C060283:secoisolariciresinol
Analgesic effects; Antioxidant; Diabetes; Secoisolariciresinol diglycoside