Evidence for the Mechanisms Underlying the Effects of Pimaradienoic Acid Isolated from the Roots of <i>Viguiera arenaria </i>on Rat Aorta

Abstract

The present study examines the effects of the diterpene ent-pimara-8(14),15-dien-19-oic acid (PA) on rat thoracic aorta. PA (10^–5, 3 × 10^–5 and 10^–4 mol/l) caused concentration-dependent inhibition of phenylephrine (Phe)-induced contraction in either endothelium-intact or endothelium-denuded aortic rings. PA attenuated the contraction induced by CaCl₂ in Ca²⁺-free solution containing Phe (10^–7 mol/l) or KCl (30 mmol/l). This diterpene did not interfere with Ca²⁺ release from intracellular stores mediated by either Phe (10^–6 mol/l) or caffeine (30 mmol/l). PA (10^–6 to 3 × 10^–4 mol/l) concentration dependently relaxed Phe-pre-contracted rings with intact (92.64 ± 7.60%) or denuded endothelium (98.82 ± 1.56%). Pre-incubation of denuded aortic rings with N^G-nitro-L-arginine methyl ester (10^–4 mol/l), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (10^–6 mol/l) or indomethacin (10^–5 mol/l) reduced PA-induced relaxation (percentage of relaxation: 77.50 ± 3.95, 78.56 ± 2.81, 77.11 ± 6.22, respectively). However, the relaxant responses induced by PA on Phe-pre-contracted rings were unaffected by tetraethylammonium (1 and 5 mmol/l). PA also relaxed KCl-pre-contracted rings with intact (97.44 ± 3.66%) or denuded endothelium (95.95 ± 3.72%). Collectively, these results support the notion that the effects elicited by PA on vascular smooth muscle are endothelium-independent and involve extracellular Ca²⁺ influx blocked. In addition, PA effects are partly dependent on the release of nitric oxide from the vascular smooth muscle through an activation of guanylyl cyclase-dependent mechanism and are related to the release of metabolites derived from the arachidonic acid pathway. Finally, our results demonstrated that the PA relaxant action is not related with the opening of potassium (K⁺) channels.

Aralia cordata Protects Against Amyloid β Protein (25–35)–Induced Neurotoxicity in Cultured Neurons and Has Antidementia Activities in Mice

“…A. cordata has been reported to possess antioxidant principles such as those of diterpenes and triterpenes (35,36), suggesting that inhibition of Aβ(25-35)-induced neuronal death by A. cordata might be due to their ROS-scavenging activity. Furthermore, diterpenes and triterpenes have been demonstrated to inhibit Ca 2+ entry through Ca 2+ channels (37,38), indicating that these compounds, including oleanolic acid, may contribute to the inhibitory activity of A. cordata on Ca 2+ entry through VDCC-and/or NMDA-receptor-coupled channels to inhibit Aβ(25-35)-induced neuronal death. Further study to elucidate the precise mechanism should be performed.…”

Comparative pharmacognostical studies on three different plant sources of Pashanbhed

“…[23] Many reports have extensively shown that terpenoids exert significant cardiovascular effects. [242526] It has also been reported that some classes of diterpenes showed significant systemic hypotensive and coronary vasodilatory effects accompanied by gradual decrease in heart rate. [2728] Saponins are also known to have several physiologic activities, depending on their chemical structures, such as hemolytic properties, alteration of membrane permeability, particularly the modulation of renal sodium excretion.…”

Assessment of the in vitro and in vivo genotoxic and antigenotoxic effects of pimaradienoic acid in mammalian cells

“…PA exerts anti-inflammatory activity, inhibiting cyclooxygenase-2 [4,5], and has been shown to inhibit contraction induced by potassium chloride (KCl) and phenylephrine in rat thoracic aorta [6]. PA can also block Ca 2+ influx through interference with both voltage-and receptor-operated channels, but is more selective in inhibiting extracellular Ca 2+ influx through voltage-dependent channels [7]. More recently, significant …”