Mechanism of Mongolian drug Naru-3 in initiation of neuroinflammation of neuropathic pain from MMP9/IL-1β signaling pathway.
10.19540/j.cnki.cjcmm.20230216.401
- Author:
Fang-Ting ZHOU
1
;
Ying ZONG
2
;
Yuan-Bin LI
3
;
Ren-Li CAO
4
;
Wu-Qiong HOU
2
;
Li-Ting XU
1
;
Fei YANG
2
;
Yan-Li GU
4
;
Xiao-Hui SU
2
;
Qiu-Yan GUO
5
;
Wei-Jie LI
2
;
Hui XIONG
6
;
Chao WANG
2
;
Na LIN
1
Author Information
1. School of Traditional Chinese Medicine, Guangzhou University of Traditional Chinese Medicine Guangzhou 510405, China Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences Beijing 100700, China.
2. Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences Beijing 100700, China.
3. Dongzhimen Hospital, Beijing University of Chinese Medicine Beijing 100700, China.
4. Inner Mongolia Medical University Hohhot 010110, China.
5. Artemisinin Research Center, China Academy of Chinese Medical Sciences Beijing 100700, China.
6. School of Pharmaceutical Sciences, South-Central Minzu University Wuhan 430074, China.
- Publication Type:Journal Article
- Keywords:
MMP9/IL-1β signaling pathway;
Mongolian drug Naru-3;
initiation of neuroinflammation in neuropathic pain;
mechanism;
microglia activation
- MeSH:
Rats;
Mice;
Animals;
Matrix Metalloproteinase 9/metabolism*;
Rats, Sprague-Dawley;
Neuroinflammatory Diseases;
Interleukin-1beta/metabolism*;
Spinal Cord/metabolism*;
Signal Transduction;
Hyperalgesia/metabolism*;
Neuralgia/metabolism*
- From:
China Journal of Chinese Materia Medica
2023;48(15):4173-4186
- CountryChina
- Language:Chinese
-
Abstract:
Neuropathic pain(NP) has similar phenotypes but different sequential neuroinflammatory mechanisms in the pathological process. It is of great significance to inhibit the initiation of neuroinflammation, which has become a new direction of NP treatment and drug development in recent years. Mongolian drug Naru-3 is clinically effective in the treatment of trigeminal neuralgia, sciatica, and other NPs in a short time, but its pharmacodynamic characteristics and mechanism of analgesia are still unclear. In this study, a spinal nerve ligation(SNL) model simulating clinical peripheral nerve injury was established and the efficacy and mechanism of Naru-3 in the treatment of NPs was discussed by means of behavioral detection, side effect evaluation, network analysis, and experimental verification. Pharmacodynamic results showed that Naru-3 increased the basic pain sensitivity threshold(mechanical hyperalgesia and thermal radiation hyperalgesia) in the initiation of SNL in animals and relieved spontaneous pain, however, there was no significant effect on the basic pain sensitivity threshold and motor coordination function of normal animals under physiological and pathological conditions. Meanwhile, the results of primary screening of target tissues showed that Naru-3 inhibited the second phase of injury-induced nociceptive response of formalin test in mice and reduced the expression of inflammatory factors in the spinal cord. Network analysis discovered that Naru-3 had synergy in the treatment of NP, and its mechanism was associated with core targets such as matrix metalloproteinase-9(MMP9) and interleukin-1β(IL-1β). The experiment further took the dorsal root ganglion(DRG) and the stage of patho-logical spinal cord as the research objects, focusing on the core targets of inducing microglial neuroinflammation. By means of Western blot, immunofluorescence, agonists, antagonists, behavior, etc., the mechanism of Naru-3 in exerting NP analgesia may be related to the negative regulation of the MMP9/IL-1β signaling pathway-mediated microglia p38/IL-1β inflammatory loop in the activation phase. The relevant research enriches the biological connotation of Naru-3 in the treatment of NP and provides references for clinical rational drug use.
