Molecular Signaling Pathways Behind the Biological Effects of Salvia Species Diterpenes in Neuropharmacology and Cardiology.

This review examines the molecular signaling pathways of bioactive diterpenes from the genus Salvia, focusing on their therapeutic potential for nervous and cardiovascular diseases. The authors describe mechanisms including effects on apoptosis, oxidative stress, amyloid beta accumulation, and tau phosphorylation that may underlie anti-Alzheimer properties. They note neuropharmacological actions via benzodiazepine and kappa opioid receptors, and neuroprotective effects of specific diterpenes such as tanshinone IIA, salvinorin A, cryptotanshinone, and miltirone. Tanshinone IIA is highlighted for cardioprotective effects, including antiarrhythmic activity and benefits in myocardial infarction, attributed to free radical scavenging and modulation of NF-κB and MAPKs. The authors call for comprehensive clinical trials to evaluate these compounds as leads.

Study at a glance

Abstract

The genus Salvia, from the Lamiaceae family, has diverse biological properties that are primarily attributable to their diterpene contents. There is no comprehensive review on the molecular signaling pathways of these active components. In this review, we investigated the molecular targets of bioactive Salvia diterpenes responsible for the treatment of nervous and cardiovascular diseases. The effects on different pathways, including apoptosis signaling, oxidative stress phenomena, the accumulation of amyloid beta plaques, and tau phosphorylation, have all been considered to be mechanisms of the anti-Alzheimer properties of Salvia diterpenes. Additionally, effects on the benzodiazepine and kappa opioid receptors and neuroprotective effects are noted as neuropharmacological properties of Salvia diterpenes, including tanshinone IIA, salvinorin A, cryptotanshinone, and miltirone. Tanshinone IIA, as the primary diterpene of Salvia miltiorrhiza, has beneficial activities in heart diseases because of its ability to scavenge free radicals and its effects on transcription factors, such as nuclear transcription factor-kappa B (NF-κB) and the mitogen-activated protein kinases (MAPKs). Additionally, tanshinone IIA has also been proposed to have cardioprotective properties including antiarrhythmic activities and effects on myocardial infarction. With respect to the potential therapeutic effects of Salvia diterpenes, comprehensive clinical trials are warranted to evaluate these valuable molecules as lead compounds. Copyright © 2016 John Wiley & Sons, Ltd.