Diterpenes: A Therapeutic Promise for Cardiovascular Diseases

Abstract

The research, development and use of natural products as therapeutic agents, especially those derived from plants, have been increasing in recent years. There has been great deal of focus on the naturally occurring antispasmodic phytochemicals as potential therapy for cardiovascular diseases. Naturally occurring diterpenes exert several biological activities such as anti-inflammatory action, antimicrobial and antispasmodic activities. Several diterpenes have been shown to have pronounced cardiovascular effects, for example, grayanotoxin I produces positive inotropic responses, forskolin is a well-known activator of adenylate cyclase, eleganolone and 14-deoxyandrographolide exhibit vasorelaxant properties and marrubenol inhibits smooth muscle contraction by blocking L-type calcium channels. In the last few years, we have investigated the biological activity of kaurane and pimarane-type diterpenes, which are the main secondary metabolites isolated from the roots of Viguiera robusta and V. arenaria, respectively. These diterpenoids exhibit vasorelaxant action and inhibit the vascular contractility mainly by blocking extracellular Ca 2+ influx. Moreover, kaurane and pimarane-type diterpenes decreased mean arterial blood pressure in normotensive rats. Diterpenes likely fulfil the definition of a pharmacological preconditioning class of compounds and give hope for the therapeutic use in cardiovascular diseases. This article will review patents, structure-activity relationship, pharmacology, antihypertensive efficiency, and the vascular mechanisms underlying the effects of diterpenes. Careful examination of the cardiovascular effects exhibited by kaurane and pimarane-type diterpenes will be provided.

Antispasmodic effects of a new kaurene diterpene isolated from Croton argyrophylloides on rat airway smooth muscle

“…Some studies have shown that kaurenoic acid inhibits the contractions induced by KCl and phenylephrine on rat carotid artery [15] . The aforementioned studies and others indicate the potential use of this diverse class of compounds in pharmacological therapies related to smooth muscle [16,17] …”

“…[15] The aforementioned studies and others indicate the potential use of this diverse class of compounds in pharmacological therapies related to smooth muscle. [16,17] Owing to their importance in asthma physiopathology, respiratory smooth muscle contraction and airway inflammation constitute potential targets for therapeutic approaches but existing pharmacological interventions are limited by numerous problems such as tachyphylaxis, loss of efficacy and treatment side-effects. [18,19] Accordingly, identifying new bronchorelaxant agents and determining their mechanisms of action may lead to significant advances in asthma therapy.…”

Terpenoides com atividade antifúngica para Candida Berkhout, causadoras de infecções hospitalares

“…Os terpenoides constituem um vasto grupo de substâncias químicas biossintetizadas a partir da via do mevalonato, extraídas de produtos naturais. Possuem diversas atividades biológicas bem definidas, dentre as quais a antifúngica 8,9,10 .…”

“…Atualmente, uma tendência multidisciplinar vem contribuindo cada vez mais para o desenvolvimento de novas drogas. Tal estratégia inicia-se pela bioprospecção de substâncias naturais bioativas, extraídas principalmente de plantas ou de microrganismos, seguida pela tentativa de obtenção de seus análogos estruturais, o que pode ser realizado por métodos sintéticos ou biotecnológicos, que culminam com a avaliação de suas atividades farmacológicas, toxicológicas e determinação do mecanismo de ação 9,10 .…”

“…O desenvolvimento de novos fármacos de origem natural envolve um longo, caro e multidisciplinar processo, sendo necessários investimentos variando entre 100 e 360 milhões de dólares e mínimo de 10 anos de trabalho 10 .…”