Lamiophlomis rotata, an Orally Available Tibetan Herbal Painkiller, Specifically Reduces Pain Hypersensitivity States through the Activation of Spinal Glucagon-like Peptide-1 Receptors

Abstract

Results support the notion that the activation of spinal GLP-1Rs leads to specific antinociception in pain hypersensitivity and further suggest that GLP-1R is a human-validated target molecule for the treatment of chronic pain.

Analgesic effects and possible mechanisms of iridoid glycosides from Lamiophlomis rotata (Benth.) Kudo in rats with spared nerve injury

“…Iridoid glycosides of L. rotata (IGLR) have been revealed as the active ingredients of analgesics (Li et al, 2010). Furthermore, a recent study showed that both shanzhiside methylester (SM) and 8-O-acetyl-SM of iridoid glycosides are the foundation for relieving pain hypersensitivity through the activation of the spinal glucagon-like peptide-1 receptor (GLP-1Rs) (Zhu et al, 2014). The mounting evidence shows that glia cells within the dorsal horn of the spinal cord create and maintain sensitization of pathological pain by releasing potent neuromodulators, such as proinflammatory cytokines (e.g.…”

Morroniside, a secoiridoid glycoside from Cornus officinalis, attenuates neuropathic pain by activation of spinal glucagon‐like peptide‐1 receptors

“…Beside its clinical utility against diabetes mellitus, activation of GLP‐1 receptors also exhibits neuroprotection in several animal models of neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, peripheral neuropathy, multiple sclerosis, ischaemia and stroke (Kim et al ., ; Harkavyi and Whitton, ; Holscher, ; Hansen et al ., ; Jia et al ., ). Moreover, activation of spinal GLP‐1 receptors by the peptide agonists GLP‐1(7‐37) and exenatide and the non‐peptide agonist WB4‐24 was shown to produce antinociception in a variety of rodent models of pain hypersensitivity, including neuropathic pain, inflammatory pain, bone cancer pain and diabetic neuropathic pain, through spinal β‐endorphin expression and secretion (Zhu et al ., ; Gong et al ., ; Gong et al ., ; Fan et al ., ; Fan et al ., ).…”

“…The therapeutic success of peptide agonists of GLP‐1 receptors against type 2 diabetes mellitus and identification of GLP‐1 receptors as a potential target in the treatment of pain have inspired efforts to develop orally available low MW GLP‐1 receptor agonists (Wang et al ., ; Willard et al ., ). Iridoid glycosides are compounds that have a scaffold of cyclopentapyran with double bond between C7 and C8, and the iridoid glycosides, including geniposide, geniposidic acid, loganin, catalpol, shanzhiside methylester and 8‐ O ‐acetyl shanzhiside methylester, are reversible and orthosteric agonists of GLP‐1 receptors, presumably acting at the same binding site as exendin(9‐39) (Liu et al ., ; Zhu et al ., ; Gong et al ., ; Jia et al ., ; Fan et al ., ). However, it is not clear whether secoiridoids with the broken double bond at the C7 and C8 in the five‐membered carbon ring have the same activity.…”

Pharmacological Inhibition of the Temperature-Sensitive and Ca2+-Permeable Transient Receptor Potential Vanilloid TRPV3 Channel by Natural Forsythoside B Attenuates Pruritus and Cytotoxicity of Keratinocytes

“…Lamiophlomis rotata, also known as Tibetan Duyiwei, is grown in Tibet and Southwestern areas of China and is commonly used as a traditional Chinese herbal medicine to alleviate detumescence, inflammation, and pain (Jiang et al, 2010a;Zhu et al, 2014). As an active ingredient of L. rotata leaves, forsythoside B is a phenylethanoid glycoside that suppresses inflammatory responses via inhibition of nuclear factor kB (NF-kB) signaling (Jiang et al, 2010a(Jiang et al, ,b, 2012.…”