Lamiophlomis rotata, an orally available Tibetan herbal painkiller, specifically reduces pain hypersensitivity states through the activation of spinal glucagon-like peptide-1 receptors

Anesthesiology. 2014 Oct;121(4):835-51. doi: 10.1097/ALN.0000000000000320.


Background: Lamiophlomis rotata is an orally available Tibetan herb prescribed for the management of pain, with shanzhiside methylester (SM) and 8-O-acetyl-SM as quality control ingredients. This study aimed to evaluate the antinociceptive properties of L. rotata, determine whether SM and 8-O-acetyl-SM are principle effective ingredients, and explore whether L. rotata produces antinociception through activation of spinal glucagon-like peptide-1 receptors (GLP-1Rs).

Methods: Formalin test, neuropathic pain, and bone cancer pain models were used, and the animal sample size was 5 to 6 in each group. Hydrogen peroxide-induced oxidative damage was also assayed.

Results: The L. rotata aqueous extract blocked formalin-induced tonic hyperalgesia and peripheral nerve injury- and bone cancer-induced mechanical allodynia by 50 to 80%, with half-effective doses of 130 to 250 mg/kg, close to the human dosage. The herb was not effective in alleviating acute nociceptive pain. A 7-day gavage with L. rotata aqueous extract did not lead to antiallodynic tolerance. Total iridoid glycosides, rather than total flavonoids, were identified by the activity-tracking method as effective ingredients for antihyperalgesia, whereas both SM and 8-O-acetyl-SM were principal components. Further demonstrations using the GLP-1R antagonist and gene silencer against GLP-1R at both the spinal and the cellular levels indicated that L. rotata inhibited pain hyperactivity by activation of spinal GLP-1Rs, and SM and 8-O-acetyl-SM appeared to be orthosteric, reversible, and fully intrinsic agonists of both rat and human GLP-1Rs.

Conclusions: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Analgesics / administration & dosage*
  • Analgesics / isolation & purification
  • Animals
  • Drugs, Chinese Herbal / administration & dosage*
  • Drugs, Chinese Herbal / isolation & purification
  • Glucagon-Like Peptide-1 Receptor
  • HEK293 Cells
  • Hot Temperature / adverse effects
  • Humans
  • Hyperalgesia / drug therapy
  • Hyperalgesia / metabolism*
  • Male
  • Mice
  • Neuralgia / drug therapy
  • Neuralgia / metabolism*
  • PC12 Cells
  • Pain Measurement / drug effects
  • Pain Measurement / methods
  • Plant Preparations / administration & dosage
  • Plant Preparations / isolation & purification
  • Rats
  • Rats, Wistar
  • Receptors, Glucagon / metabolism*
  • Spinal Cord / drug effects
  • Spinal Cord / metabolism
  • Tibet


  • Analgesics
  • Drugs, Chinese Herbal
  • GLP1R protein, human
  • Glp1r protein, mouse
  • Glp1r protein, rat
  • Glucagon-Like Peptide-1 Receptor
  • Plant Preparations
  • Receptors, Glucagon