Pharmacological comparison of the vasorelaxant action displayed by kaurenoic acid and pimaradienoic acid

Abstract

The vascular effects of two natural occurring diterpenes from the kaurane and pimarane classes were compared. The diterpenes ent-kaur-16-en-19-oic acid (kaurenoic acid; KA) and ent-pimara-8(14), 15-dien-19-oic acid (pimaradienoic acid; PA) were tested for their antispasmodic activity on isolated rat aorta. Vascular reactivity experiments, using standard muscle bath procedures, showed that KA and PA (both at 50 and 100 microM) inhibited phenylephrine and KCl-induced contraction in both endothelium-intact and endothelium-denuded rat aortic rings, with PA being more effective than KA. These compounds also reduced CaCl(2)-induced contraction in Ca(2+)-free solution containing KCl (30 mm). Again, PA produced a greater reduction in CaCl(2)-induced contraction than KA. PA (1-300 microM) and KA (1-450 microM) concentration dependently relaxed endothelium-denuded aortic rings pre-contracted with KCl (maximum relaxation 102.31+/-6.94% and 82.71+/-1.40%, respectively). Similarly, the relaxation induced by KA on aortic rings pre-contracted with phenylephrine (73.06+/-3.68%) was less pronounced than that found for PA (102.21+/-3.64%). Incubation of endothelium-denuded rings for different periods showed that at 50 microM, KA and PA achieved maximum inhibitory activity on KCl-induced contraction after incubation for 60 (53.48+/-5.83%) and 30 min (83.89+/-2.12%), respectively. At 100 microM, KA and PA inhibited KCl-induced contraction, with a maximum after incubation for 30 min (73.58+/-5.30% and 92.07+/-1.20%, respectively). The maximum inhibition induced by PA at both concentrations tested was greater than that induced by KA. The results provide evidence that structural differences between diterpenes, independent of the C-19 carboxylic acid site, influence selectivity for voltage-operated Ca2+ channels and rate of equilibrium with the target site for their vasorelaxant action in rat aortic rings.

Kaurane and pimarane-type diterpenes from the Viguiera species inhibit vascular smooth muscle contractility

“…On the other hand, pimaradienoic acid possesses a double bond between C-15 and C-16 that is not present in kaurenoic acid. A pharmacological comparison of the vascular effects of these two natural occurring diterpenes showed that that pimaradienoic acid is more effective than kaurenoic acid at inhibiting phenylephrine, KCl and CaCl 2 -induced aorta contraction (Tirapelli et al, 2005). Moreover, the equilibrium period for pimaradienoic acid to achieve its maximal inhibitory response, which is more pronounced than that found for kaurenoic acid, is shorter than that observed for kaurenoic acid.…”

Anti-inflammatory activity of the constituents of the roots of Aralia continentalis

“…Importantly, A. cordata extract protected cartilage degradation and inhibited apoptosis, suggesting the potential to inhibit Correspondence to: Hyun Pyo Kim, College of Pharmacy, Kangwon National University,-9271 E-mail: hpkim@kangwon.ac.kr osteoarthritis (Bae et al, 2006). Among its constituents, pimaradienoic acid and kaurenoic acid have been shown to exert vasorelaxant action (Tirapelli et al, 2005). When the inhibitory activities against COX-1 and COX-2 were measured, several compounds, including pimaradienoic acid and kaurenoic acid, moderately inhibited COX-1, while only kaurenoic acid inhibited COX-2 weakly (Dang et al, 2005).…”

Cholinesterase and BACE1 inhibitory diterpenoids from Aralia cordata

“…In previous phytochemical investigations, various diterpenes, flavonoids, saponins, and essential oils were isolated from the roots and leaves of this plant (Kang, 1997). Considering the biological studies of these isolated compounds, ent-pimara-8 (14), 15-diene-19-oic acid and ent-kaur-16-en-19-oicacid as major constituents were reported to possess analgesic (Okuyama et al, 1991), anti-tumor (Ryu et al, 1996), anti-inflammatory (Han et al, 1983;1985), vasorelaxant (Ambrosio et al, 2006;Tirapelli et al, 2005), and antimicrobial activities (Porto et al, 2009;Ambrosio et al, 2008). Recent studies on the aerial parts of this plant showed ent- pimara-8(14),15-diene-19-oic acid to be a potent antibacterial constituent (Jeong et al, 2006).…”