4.7 Article

Proteomic and metabolomic approaches elucidate the molecular mechanism of emodin against neuropathic pain through modulating the gamma-aminobutyric acid (GABA)-ergic pathway and PI3K/AKT/NF-κB pathway

期刊

PHYTOTHERAPY RESEARCH
卷 37, 期 5, 页码 1883-1899

出版社

WILEY
DOI: 10.1002/ptr.7704

关键词

emodin; GABAergic pathway; metabolomics; neuropathic pain; PI3K; AKT; NF-kappa B pathway; proteomics

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In this study, the mechanisms underlying the pain-relief effects of emodin in the cerebral cortex were investigated using proteomic and metabolomic approaches. The results showed that emodin treatment could reverse chronic constriction injury-induced hyperalgesia and alleviate neuropathic pain mainly through regulating the GABAergic pathway and PI3K/AKT/NF-kappa B pathway.
Neuropathic pain (NeP) is a major health concern. Due to the complex pathological mechanisms, management of NeP is challenging. Emodin, a natural anthraquinone derivative, exerts excellent analgesic effects. However, its mechanisms of action are still poorly understood. In this study, we investigated the mechanisms underlying pain-relief effects of emodin in the cerebral cortex using proteomic and metabolomic approaches. After 15 days of emodin administration, the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) values in the emodin groups were significantly higher than those in the chronic constriction injury (CCI) group (p < .05), suggesting emodin treatment could reverse CCI-induced hyperalgesia. Emodin treatment evoked the expression alteration of 402 proteins (153 up-regulated and 249 down-regulated) in the CCI models, which were primarily involved in PI3K/AKT signaling pathway, gamma-aminobutyric acid (GABA) receptor signaling, complement and coagulation cascades, cGMP/PKG signaling pathway, MAPK signaling pathway, and calcium signaling pathway. In parallel, emodin intervention regulated the abundance alteration of 27 brain metabolites (20 up-regulated and 7 down-regulated) in the CCI rats, which were primarily implicated in carbon metabolism, biosynthesis of amino acids, pentose phosphate pathway, and glucagon signaling pathway. After a comprehensive analysis and western blot validation, we demonstrated that emodin alleviated NeP mainly through regulating GABAergic pathway and PI3K/AKT/NF-kappa B pathway.

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