Gui-Lin Jin1, Li-Mian Hong2, Hai-Ping Liu3, Rong-Cai Yue3, Zu-Cheng Shen3, Jian Yang4, Ying Xu4, Hui-Hui Huang4, Yi Li3, Bo-Jun Xiong3, Yan-Ping Su4, Chang-Xi Yu5. 1. Department of Pharmacology, College of Pharmacy, Fujian Medical University, Fuzhou, Fujian, P.R. China; Fujian Key Laboratory of Natural Medicine Pharmacology, College of Pharmacy, Fujian Medical University, Fuzhou, Fujian, P.R. China. Electronic address: jinguilin0611@163.com. 2. Department of Pharmacology, College of Pharmacy, Fujian Medical University, Fuzhou, Fujian, P.R. China; Department of Pharmacy, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, Fujian 362000, P.R. China. 3. Department of Pharmacology, College of Pharmacy, Fujian Medical University, Fuzhou, Fujian, P.R. China. 4. Department of Pharmacology, College of Pharmacy, Fujian Medical University, Fuzhou, Fujian, P.R. China; Fujian Key Laboratory of Natural Medicine Pharmacology, College of Pharmacy, Fujian Medical University, Fuzhou, Fujian, P.R. China. 5. Department of Pharmacology, College of Pharmacy, Fujian Medical University, Fuzhou, Fujian, P.R. China; Fujian Key Laboratory of Natural Medicine Pharmacology, College of Pharmacy, Fujian Medical University, Fuzhou, Fujian, P.R. China. Electronic address: changxiyu@mail.fjmu.edu.cn.
Abstract
BACKGROUND: Diabetic neuropathic pain (DNP), a complication of diabetes, has serious impacts on human health. As the pathogenesis of DNP is very complex, clinical treatments for DNP is limited. Koumine (KM) is an active ingredient extracted from Gelsemium elegans Benth. that exerts an inhibitory effect on neuropathic pain (NP) in several animal models. PURPOSE: To clarify the anti-NP effect of KM on rats with DNP and the molecular mechanisms involving the Notch- Jκ recombination signal binding protein (RBP-Jκ) signaling pathway. METHODS: Male Sprague-Dawley rats were administered streptozocin (STZ) by intraperitoneal injection to induce DNP. The effect of KM on mechanical hyperalgesia in rats with DNP was evaluated using the Von Frey test. Microglial polarization in the spinal cord was examined using western blotting and quantitative real-time PCR. The Notch-RBP-Jκ signaling pathway was analysed using western blotting. RESULTS: KM attenuated DNP during the observation period. In addition, KM alleviated M1 microglial polarization in STZ-induced rats. Subsequent experiments revealed that Notch-RBP-Jκ signaling pathway was activated in the spinal cord of rats with DNP, and the activation of this pathways was decreased by KM. Additionally, KM-mediated analgesia and deactivation of the Notch-RBP-Jκ signaling pathway were inhibited by the Notch signaling agonist jagged 1, indicating that the anti-DNP effect of KM may be regulated by the Notch-RBP-Jκ signaling pathway. CONCLUSIONS: KM is a potentially desirable candidate treatment for DNP that may inhibit microglial M1 polarization through the Notch-RBP-Jκ signaling pathway.
BACKGROUND:Diabetic neuropathic pain (DNP), a complication of diabetes, has serious impacts on human health. As the pathogenesis of DNP is very complex, clinical treatments for DNP is limited. Koumine (KM) is an active ingredient extracted from Gelsemium elegans Benth. that exerts an inhibitory effect on neuropathic pain (NP) in several animal models. PURPOSE: To clarify the anti-NP effect of KM on rats with DNP and the molecular mechanisms involving the Notch- Jκ recombination signal binding protein (RBP-Jκ) signaling pathway. METHODS: Male Sprague-Dawley rats were administered streptozocin (STZ) by intraperitoneal injection to induce DNP. The effect of KM on mechanical hyperalgesia in rats with DNP was evaluated using the Von Frey test. Microglial polarization in the spinal cord was examined using western blotting and quantitative real-time PCR. The Notch-RBP-Jκ signaling pathway was analysed using western blotting. RESULTS:KM attenuated DNP during the observation period. In addition, KM alleviated M1 microglial polarization in STZ-induced rats. Subsequent experiments revealed that Notch-RBP-Jκ signaling pathway was activated in the spinal cord of rats with DNP, and the activation of this pathways was decreased by KM. Additionally, KM-mediated analgesia and deactivation of the Notch-RBP-Jκ signaling pathway were inhibited by the Notch signaling agonist jagged 1, indicating that the anti-DNP effect of KM may be regulated by the Notch-RBP-Jκ signaling pathway. CONCLUSIONS:KM is a potentially desirable candidate treatment for DNP that may inhibit microglial M1 polarization through the Notch-RBP-Jκ signaling pathway.