Lie-Chwen Lin1, Lin-Chien Lee2, Cheng Huang3, Chiung-Tong Chen4, Jen-Shin Song4, Young-Ji Shiao5, Hui-Kang Liu6. 1. Division of Chinese Medicine Literature and Informatics, National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei, Taiwan, ROC. 2. Department of Physical Medicine and Rehabilitation, Cheng Hsin General Hospital, Taipei, Taiwan, ROC. 3. Department of Biotechnology and Laboratory Science in Medicine, National YangMing University, Taipei, Taiwan, ROC; Department of Earth and Life Sciences, University of Taipei, Taipei, Taiwan, ROC. 4. Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli, Taiwan, ROC. 5. Division of Basic Chinese Medicine,National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei, Taiwan, ROC; Institute of Biopharmaceutical Science, National Yang-Ming University, Taipei, Taiwan, ROC. 6. Division of Basic Chinese Medicine,National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei, Taiwan, ROC; Ph.D Program for the Clinical Drug Discovery from Herbal Medicine, College of Pharmacy, Taipei Medical University, Taipei, Taiwan, ROC. Electronic address: hk.liu@nricm.edu.tw.
Abstract
BACKGROUND: Boschniakia rossica is a well-known traditional Chinese medicine for tonifying kidney and improving impotence. Boschnaloside is the major iridoid glycoside in this herb but therapeutic benefits for diabetes remained to be evaluated. HYPOTHESIS/ PURPOSE: The current investigation aims to study the antidiabetic effect and the underlying pharmacological mechanisms. STUDY DESIGN AND METHODS: Receptor binding, cAMP production, Ins secretion, glucagon-like peptide 1 (GLP-1) secretion, and dipeptidyl peptidase-4 activity assays were performed. Therapeutic benefits of orally administrated boschnaloside (150 and 300 mg/kg/day) were evaluated using severely 12-week old female diabetic db/db mice (Hemoglobin A1c >10%). RESULTS: Oral treatment of boschnaloside for 4 weeks improved diabetic symptoms including fasting blood sugar, hemoglobin A1c, glucose intolerance, and Homeostatic Model Assessment of Ins Resistance, accompanied by circulating GLP-1active and adiponectin levels. In addition, bochnaloside treatment improved islet/β cell function associated with an alteration of the pancreatic and duodenal homeobox 1 level. It was shown that boschnaloside interacted with the extracellular domain of GLP-1 receptor and enhanced glucose stimulated Ins secretion. Boschnaloside also augmented the insulinotropic effect of GLP-1. Finally, the presence of boschnaloside caused a reduction of dipeptidyl peptidase-4 activity while enhanced GLP-1 secretion from STC-1 cells. CONCLUSION: It appears that bochnaloside at oral dosage greater than 150 mg/kg/day exerts antidiabetic effects in vivo through modulating the action of GLP-1.
BACKGROUND: Boschniakia rossica is a well-known traditional Chinese medicine for tonifying kidney and improving impotence. Boschnaloside is the major iridoid glycoside in this herb but therapeutic benefits for diabetes remained to be evaluated. HYPOTHESIS/ PURPOSE: The current investigation aims to study the antidiabetic effect and the underlying pharmacological mechanisms. STUDY DESIGN AND METHODS: Receptor binding, cAMP production, Ins secretion, glucagon-like peptide 1 (GLP-1) secretion, and dipeptidyl peptidase-4 activity assays were performed. Therapeutic benefits of orally administrated boschnaloside (150 and 300 mg/kg/day) were evaluated using severely 12-week old female diabetic db/db mice (Hemoglobin A1c >10%). RESULTS: Oral treatment of boschnaloside for 4 weeks improved diabetic symptoms including fasting blood sugar, hemoglobin A1c, glucose intolerance, and Homeostatic Model Assessment of Ins Resistance, accompanied by circulating GLP-1active and adiponectin levels. In addition, bochnaloside treatment improved islet/β cell function associated with an alteration of the pancreatic and duodenal homeobox 1 level. It was shown that boschnaloside interacted with the extracellular domain of GLP-1 receptor and enhanced glucose stimulated Ins secretion. Boschnaloside also augmented the insulinotropic effect of GLP-1. Finally, the presence of boschnaloside caused a reduction of dipeptidyl peptidase-4 activity while enhanced GLP-1 secretion from STC-1 cells. CONCLUSION: It appears that bochnaloside at oral dosage greater than 150 mg/kg/day exerts antidiabetic effects in vivo through modulating the action of GLP-1.