Medicinal plants from
traditional chinese medicine are used increasingly worldwide for their benefits to health and quality of life for the relevant clinical symptoms related to
pain. Among them, Salvia miltiorrhiza Bunge is traditionally used in asian countries as
antioxidant, anticancer, anti-inflammatory and
analgesic agent. In this context, several evidences support the hypothesis that some tanshinones, in particular
cryptotanshinone (CRY), extracted from the roots (Danshen) of this plant exhibit
analgesic actions. However, it is surprisingly noted that no pharmacological studies have been carried out to explore the possible
analgesic action of this compound in terms of modulation of peripheral and/or central
pain. Therefore, in the present study, by using peripheral and central
pain models of nociception, such as tail flick and hot plate test, the
analgesic effect of CRY in mice was evaluated. Successively, by the aim of a computational approach, we have evaluated the interaction mode of this
diterpenoid on
opioid and
cannabinoid system. Finally, CRY was dosed in mice serum by an HPLC method validated according to European Medicines Agency guidelines validation rules. Here, we report that CRY displayed anti-nociceptive activity on both hot plate and tail flick test, with a prominent long-lasting peripheral
analgesic effect. These evidences were indirectly confirmed after the daily administration of the
tanshinone for 7 and 14 days. In addition, the
analgesic effect of CRY was reverted by
naloxone and
cannabinoid antagonists and amplified by
arginine administration. These findings were finally supported by HPLC and docking studies, that revealed a noteworthy presence of CRY on mice serum 1 h after its intraperitoneal administration and a possible interaction of tested compound on μ and k receptors. Taken together, these results provide a new line of evidences showing that CRY can produce
analgesia against various phenotypes of nociception with a mechanism that seems to be related to an agonistic activity on
opioid system.