PKC-Mediated Potentiation of Morphine Analgesia by St. John’s Wort in Rodents and Humans

Journal of Pharmacological Sciences

Nicoletta Galeotti³  Enrica Bianchi²  Mersedeh Farzad¹  Carla Ghelardini³ 

[1] Oncology Department, CORAT, Italy;Department of Medicine, Surgery and Neuroscience, University of Siena, Italy;Department of Neurosciences, Psychology, Drug Area and Child Health, NEUROFARBA, Pharmacology Unit, University of Florence, Italy

关键词: morphine;    St. John’s wort;    protein kinase C;    thermal nociception;   

DOI  :  10.1254/jphs.13226FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(24)Cited-By(2)Our purpose was to combine the use of morphine with clinically available inhibitors of protein kinase C (PKC), finally potentiating morphine analgesia in humans. Thermal tests were performed in rodents and humans previously administered with acute or chronic morphine combined or not with increasing doses of the PKC-blocker St. John’s Wort (SJW) or its main component hypericin. Phosphorylation of the γ subunit of PKC enzyme was assayed by western blotting in the periaqueductal grey matter (PAG) from rodents co-administered with morphine and hypericin and was prevented in rodent PAG by SJW or hypericin co-administration with morphine, inducing a potentiation of morphine analgesia in thermal pain. The score of pain assessment in healthy volunteers were decreased by 40% when morphine was co-administered with SJW at a dose largely below those used to obtain an antidepressant or analgesic effect in both rodents and humans. The SJW/hypericin potentiating effect lasted in time and preserved morphine analgesia in tolerant mice. Our findings indicate that, in clinical practice, SJW could reduce the dose of morphine obtaining the same analgesic effect. Therefore, SJW and one of its main components, hypericin, appear ideal to potentiate morphine-induced analgesia.

【 授权许可】

Unknown