The Anxiolytic, Antinociceptive, Anti-inflammatory, Cardioprotective, Cytostatic, and Proliferative Effects of Songorine. Receptor and Signaling Mechanisms
Introduction: Extracts of the Aconite genus are used for medicinal purposes in China, Korea, Japan, and India. Extracts of the Aconite genus contain the highly toxic alkaloid aconitine and a number of low-toxicity alkaloids with medicinal properties. One of these alkaloids is songorine. The objective of the review is an analysis of data on the anxiolytic, antinociceptive, antiinflammatory, anticancer, cardioprotective, and proliferative effects of songorine. Methods: The information was retrieved from PubMed between from 1835 and 2026. Results: It was demonstrated that songorine has anxiolytic, antinociceptive, anti-inflammatory, anticancer, cardioprotective, and proliferative properties. The anti-inflammatory effect of songorine is accompanied by a decrease in pro-inflammatory cytokine production and a reduction of neutrophil invasion in injured tissue. The role of the GABAA, dopamine D2, peripheral κ-opioid, cannabinoid CB1, and other receptors in the effects of songorine is discussed. The involvement of protein kinases in the proliferative effect of songorine is demonstrated. The role of transcription factors NF-κB, Nrf2, STAT3, and protein synthesis in the effects of songorine is discussed. Discussion: Despite accumulated experimental data demonstrating a broad spectrum of pharmacological effects of songorine, including anxiolytic, analgesic, anti-inflammatory, and cardioprotective effects, a number of unresolved questions remain related to an incomplete understanding of the molecular targets and signaling pathways. Furthermore, most results were obtained in preclinical models, limiting their direct extrapolation to clinical practice. Conclusion: Songorine is discussed for use in the treatment of depression, chronic pain, chronic inflammation, and cancer. It can be used to accelerate wound healing, in the treatment of sepsis, doxorubicin-induced cardiomyopathy, and stress-induced cardiac injury.