Pharmacology of boldine: summary of the field and update on recent advances

Abstract

Over the past decade, boldine, a naturally occurring alkaloid found in several plant species including the Chilean Boldo tree, has garnered attention for its efficacy in rodent models of human disease. Some of the properties that have been attributed to boldine include antioxidant activities, neuroprotective and analgesic actions, hepatoprotective effects, anti-inflammatory actions, cardioprotective effects and anticancer potential. Compelling data now indicates that boldine blocks connexin (Cx) hemichannels (HCs) and that many if not all of its effects in rodent models of injury and disease are due to CxHC blockade. Here we provide an overview of boldine's pharmacological properties, including its efficacy in rodent models of common human injuries and diseases, and of its absorption, distribution, pharmacokinetics, and metabolism.

Keywords: boldine; connexin (Cx); hemichannels; pharmacology; phramacokinetics.

FIGURE 1

The chemical structure of Boldine and its semisynthetic derivatives.

FIGURE 2

Molecular targets of boldine. Boldine inhibits connexin hemichannels (Cx HCs), pannexin 1 hemichannels (Panx1 HCs), and the purinergic receptor P2X7 (P2X7R). This channel blockade significantly reduces Ca2+ influx and K+ efflux, both of which are key activators of the inflammasome. As a result, boldine reduces the activation of caspase-1, leading to decreased production of IL-1β, a key outcome of inflammasome activation. Importantly, boldine does not inhibit gap junction channels formed by connexins.