Andrographolide exhibits antinociceptive effects in neuropathic rats via inhibiting class Ⅱ MHC associated response and regulating synaptic plasticity

作者：Le Ma, Ying Sun, Bingxun Liu, Yu Shi, Chao Luo, Ying Cheng, Weidi Wang, Fang Yu, Lixuan Huang, Usman Ali, Jianming Zhang, Jianhua Chen, Peijun Ju · 发表于：Phytomedicine · 年份：2024 · DOI：10.1016/j.phymed.2024.155823 · 被引用次数：7 · 研究领域：Andrographolide Research and Applications、Pain Mechanisms and Treatments、Magnolia and Illicium research

BACKGROUND: Neuropathic pain (NP) due to nerve injury, disrupts neural plasticity by triggering the release of inflammatory mediators. Alongside the hypothesis that neuro-inflammation contributes to this disruption, Andrographolide (Andro), a traditional bioactive compound derived from Andrographis paniculata, has garnered attention for its potent anti-inflammatory properties. However, whether Andro could ameliorate NP by regulating neuroinflammation remains unknown. PURPOSE: This study aimed to investigate whether and how Andro regulates neuroinflammation and alleviates NP. METHODS: The analgesic effects of Andro on NP were evaluated using both the spinal nerve ligation (SNL) and formalin rat models. A combination of network pharmacology, RNA sequencing, and experimental validation was employed to elucidate the underlying mechanism behind Andro's analgesic effects. Additionally, various techniques such as functional ultrasound, immunohistochemistry, quantitative real-time polymerase chain reaction (qPCR), patch clamp, and electron microscopy were employed to investigate the specific neural cell types, neural functions, and changes in neural plasticity influenced by Andro. RESULTS: Network pharmacology analysis unveiled the crucial roles played by shared targets of Andro and pain in regulating pain-related inflammation, including microglia activation, neuroinflammation, immune modulation, and synaptic transmission. Furthermore, we confirmed Andro's superior efficacy in pain r...