Gelsemium, a small genus of flowering plant from the family Loganiaceae, comprises five species including the popular Gelsemium sempervirens Ait. and Gelsemium elegans Benth., which are indigenous to North America and China/East Asia, respectively. Approximately 120
alkaloids have been isolated and identified from Gelsemium, with the predominant
indole alkaloids including
gelsemine,
koumine, gelsemicine,
gelsenicine,
gelsedine,
sempervirine, koumidine, koumicine and
humantenine.
Gelsemine is the principal active
alkaloid in G. sempervirens Ait., and
koumine and
gelsemine are the most and second-most dominant
alkaloids in G. elegans Benth. Gelsemium extract and its active
alkaloids serve a variety of
biological functions, including neurobiological, immunosuppressive and antitumor effects, and have traditionally been used to treat
pain,
neuralgia, anxiety,
insomnia,
asthma, respiratory ailments and
cancers. This review focuses on animal-based studies of Gelsemium as a
pain treatment and its mechanism of action. In contrast to
morphine, when administered intrathecally and systemically,
koumine,
gelsemine and
gelsenicine have marked antinociception in inflammatory, neuropathic and
bone cancer pains without inducing antinociceptive tolerance. Gelsemium and its active
alkaloids may produce antinociception by activating the spinal α3
glycine/
allopregnanolone pathway. The results of this review support the clinical use of Gelsemium and suggest that its active
alkaloids may be developed to treat intractable and other types of
pain, preferably after chemical modification. However, Gelsemium is a known toxic plant, and its toxicity limits its appropriate dosage and clinical use. To avoid or decrease the side/toxic effects of Gelsemium, an individual monomer of highly potent
alkaloids must be selected, or
alkaloids that exhibit greater α3
glycine receptor selectivity may be discovered or modified.