The Novel Analogue of Hirsutine as an Anti-Hypertension and Vasodilatary Agent Both In Vitro and In Vivo

Abstract

In this paper, an analogue of hirsutine (compound 1) has been synthesized and evaluated as an anti-hypertension agent, which exhibits extraordinary effects on the contractile response of thoracic aorta rings from male SD rats in vitro (IC50 = 1.129×10-9±0.5025) and the abilities of reducing the systolic blood pressure (SBP) and heart rate (HR) of SHR in vivo. The mechanism investigation reveals that the vasodilatation induced by compound 1 is mediated by both endothelium-dependent and -independent manners. The relaxation in endothelium-intact aortic rings induced by compound 1 can be inhibited by L-NAME (1×10-6 mol•L-1) and ODQ (1×10-6 mol•L-1). Moreover, compound 1 can also block Ca2+ influx through L-type Ca2+ channels and inhibit intracellular Ca2+ release while no effect on K+ channel has been observed. All these data demonstrated that the NO/cyclic GMP pathway can be involved in endothelium-dependent manner induced by compound 1. Meanwhile the mechanism on the vasodilatation of compound 1 probably also related to blockade of Ca2+ influx through L-type Ca2+ channels and inhibition of intracellular Ca2+ release may have no relationship with K+ channels.

Hirsutine induces mPTP-dependent apoptosis through ROCK1/PTEN/PI3K/GSK3β pathway in human lung cancer cells

“…Hirsutine, a major indole alkaloid (Fig. 1a ), derived from U. rhynchophylla , has attracted a great deal of interest because of its wide range of biological activities such as cardioprotective, anti-hypertensive, and anti-arrhythmic activities 6 , 7 . It has recently been shown that hirsutine exhibits anticancer activities.…”

Uncaria tomentosa (Willd. ex Schult.) DC.: A Review on Chemical Constituents and Biological Activities

“…Hirsutine isolated from U. rhynchophylla extract was found to decrease intracellular calcium concentrations in rat aortas by inhibiting the calcium channels and effecting calcium stores [51]. Moreover, it showed a vasodilated, negative chronotropic, and antiarrhythmic effect.…”

Anti-hypertensive medicinal plants and their mode of action

“…Eugenol from the plant was isolated and was shown to be responsible for observed effects. Alkaloids such as; hirsutine, rhynchophylline and isorhynchophylline, isolated from the plant, Uncaria rhynchophylla, have been demonstrated to be the mediators of observed vasodilatory property (Zhu et al , 2015;Shi et al , 2003). In in vitro experiments, two cumarin glycosides coded as DC-2 and DC-3 isolated from D. carota, were tested for their inhibitory response against K + induced depolarization and contraction which suggested that the glycosides action is through blockade of calcium channels (Gilani et al , 2000).…”

“…Blockade of Calcium channel (Zhu, Yang, 2015;Wu et al , 1980;Shi, Yu, 2003;Horie, Yano, 1992) (Ojulari, Olatubosun, Ghayur and Gilani, 2005;Elkhishin and Awwad, 2009) Plasma Renin Activity Assay Elevated in patients with essential hypertension and suppressed in patients with hypertension due to primary aldosteronism (Gunnells Jr et al , 1967) 2…”