Research Progress on Mechanisms Underlying Aconitines Analgesia

doi:10.3969/j.issn.2095-1396.2017.03.004

Abstract

Abstract: Aconitum has abundant resources and has been prescribed in China and other eastern Asia countries for analgesic，anti-rheumatic and neurological indications for centuries. As the principal active constituents present in Aconitum，diterpenoid alkaloids possess therapeutic activities against inflammation，nociception and tumors，and can be divided into four skeletal categories：C18-，C19-，C20- and bis-diterpenoid alkaloid. In this review，we summarized the research progress on the analgesic effects and the underlying mechanisms of several clinically effective diterpenoid alkaloids in Aconitum including bulleyaconitine （C19-diterpenoid alkaloid），bullatine A （C20-diterpenoid alkaloid） and lappaconitine （C18-diterpenoid alkaloid），as well as aconitine （C19-diterpenoid alkaloid）. We also explored the scientific rationale for the Aconitum processing.Bulleyaconitine，bullatine A，lappaconitine and aconitine exhibit potent analgesic effects in a variety of animal models of pain hypersensitivity as well as in clinic. Their antinociception is
entirely mediated by stimulation of spinal microglial dynorphin A expression via a Gs/cAMP/ PKA/p38β/CREB signal transduction pathway，which then activates the post-synaptic neuronal κ-opioid receptors. Processing of aconitine induces the increase of benzoylaconine，which has lower toxicity and higher therapeutic index. In addition，aconitines or the Aconitum extracts produce antinociception without induction of tolerance and inhibit morphine antinociceptive tolerance，which is also through stimulation expression of spinal dynorphin A.

Key words: conitines, bulleyaconitine, bullatine A, lappaconitine, analgesia, dynorphin A, microglia

CLC Number:

R964

HUANG Qian，SUN Ming-li，LI Teng-fei，WANG Yong-xiang. Research Progress on Mechanisms Underlying Aconitines Analgesia[J]. Acta Neuropharmacologica, 2017, 7(3): 21-32.

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