Shanzhiside methylester, the principle effective iridoid glycoside from the analgesic herb Lamiophlomis rotata, reduces neuropathic pain by stimulating spinal microglial β-endorphin expression. (February 2016)

• Record Type: Journal Article
• Authors: Fan, Hui; Li, Teng-Fei; Gong, Nian; Wang, Yong-Xiang
• Is Part Of: Neuropharmacology. Volume 101(2016)
• Page Start: 98
• Page End: 109
• Publication Date: 2016-02
• Subjects: Shanzhiside methylester (SM) -- Anti-allodynia -- β-endorphin -- Microglia -- p38 mitogen-activated protein kinase (MAPK) -- Glucagon-like peptide-1 (GLP-1) receptor; L. rotata Lamiophlomis rotata -- SM shanzhiside methylester -- POMC proopiomelanocortin -- GLP-1 glucagon-like peptide-1 -- MAPKs mitogen-activated protein kinases -- ERK1/2 extracellular signal regulated kinase -- JNK c-Jun N-terminal kinase -- IL-1 interlukin-1β -- IL-6 interlukin-6 -- TNF-α tumor necrosis factor-α -- CFA Complete Freund's adjuvant -- LPS lipopolysaccharides -- % MPE % maximal possible effect -- ANOVA analysis of variance -- Emax maximum effect -- ED50 half-effective dose; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2015.09.010
• Languages: English
• ISSNs: 0028-3908

Abstract

Abstract: Lamiophlomis rotata ( L. rotata, Duyiwei ) is an orally available Tibetan analgesic herb widely prescribed in China. Shanzhiside methylester (SM) is a principle effective iridoid glycoside of L. rotata and serves as a small molecule glucagon-like peptide-1 (GLP-1) receptor agonist. This study aims to evaluate the signal mechanisms underlying SM anti-allodynia, determine the ability of SM to induce anti-allodynic tolerance, and illustrate the interactions between SM and morphine, or SM and β-endorphin, in anti-allodynia and anti-allodynic tolerance. Intrathecal SM exerted dose-dependent and long-lasting (>4 h) anti-allodynic effects in spinal nerve injury-induced neuropathic rats, with a maximal inhibition of 49% and a projected ED50 of 40.4 μg. SM and the peptidic GLP-1 receptor agonist exenatide treatments over 7 days did not induce self-tolerance to anti-allodynia or cross-tolerance to morphine or β-endorphin. In contrast, morphine and β-endorphin induced self-tolerance and cross-tolerance to SM and exenatide. In the spinal dorsal horn and primary microglia, SM significantly evoked β-endorphin expression, which was completely prevented by the microglial inhibitor minocycline and p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580. SM anti-allodynia was totally inhibited by the GLP-1 receptor antagonist exendin(9–39), minocycline, β-endorphin antiserum, μ-opioid receptor antagonist CTAP, and SB203580. SM and exenatide specifically activated spinal p38 MAPK phosphorylation. These results indicate that SM reduces neuropathic pain by activating spinal GLP-1 receptors and subsequently stimulating microglial β-endorphin expression via the p38 MAPK signaling. Stimulation of the endogenous β-endorphin expression may be a novel and effective strategy for the discovery and development of analgesics for the long-term treatment of chronic pain. Highlights: Lamiophlomis rotata is an analgesic herb, and SM is its principle effective iridoid glycoside. Intrathecal SM produced anti-allodynia in neuropathic rats without inducing tolerance. SM stimulated β-endorphin expression in spinal microglia and produced anti-allodynia. p38 MAPK mediated SM-induced β-endorphin expression and anti-allodynia.