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Fulltext Vasorelaxant effect of diterpenoid lactones from Andrographis paniculata chloroform extract on rat aortic rings

Sriramaneni RN, Omar AZ, Ibrahim SM, Amirin S, Mohd Zaini A

Pharmacognosy Res, 2010 Jul;2(4):242-6.
PMID: 21808575 DOI: 10.4103/0974-8490.69125

BACKGROUND: The aim of the present study is to evaluate the possible mechanism of the vasorelaxant effect of the Andrographis paniculata chloroform extract (APCE) and diterpenoids, such as, 14-deoxyandrographolide (DA) and 14-deoxy-11, 12-didehydroandrographolide (DDA), on rat aortic rings.
METHODS: DA and DDA (10 μM to 40 μM) induce relaxation in the aortic rings pre-contracted with KCl (80 mM).
RESULTS: The IC(50) values are 40.47 ± 1.44 and 37.43 ± 1.41%, respectively, and this inhibition is antagonized by increasing the Ca(2+) concentration in the Kreb's medium. The results indicate that APCE, DA, and DDA may have a calcium anatgonist property. APCE, DA, and DDA also relax norepinephrene (NE)-induced sustained contractions with IC(50) values 41.63 ± 1.19, 49.22 ± 2.76, and 37.46 ± 1.41% and this relaxant effect is unaffected by the removal of the endothelium or by the presence of indomethacin and Nω-nitro-L-arginine (L-NAME). Moreover, DA and DDA inhibit the phasic and tonic contractions induced by NE in a concentration-dependent manner and show the most potent inhibition on phasic contraction (P < 0.01).
CONCLUSION: This study shows that APCE, DA, and DDA pre-treatment presents a more potent inhibition compared to post-treatment, after the tension has reached a steady state. These results suggest that the vasorelaxation of APCE, DA, and DDA direct the inhibition of the calcium influx. The vasorelaxant effect is more active in the calcium independent pathway and more sensitive in the intial stage of contraction.
Fulltext In vitro cholinomimetic effect of Loranthus ferrugineus in isolated guinea pig ileum

Ameer OZ, Salman IM, Siddiqui MJ, Yam MF, Sriramaneni RN, Sadikun A, et al.

J Acupunct Meridian Stud, 2009 Dec;2(4):288-93.
PMID: 20633504 DOI: 10.1016/S2005-2901(09)60070-4

This study aimed to elucidate the mechanism(s) of the spasmogenic action of Loranthus ferrugineus in isolated guinea pig ileum. Thus the contractile responses of guinea pig ileum to graded additions of either L. ferrugineus methanol extract or its n-butanol fraction were tested in the presence and absence of various pharmacological interventions. The data showed that L. ferrugineus methanol extract and the n-butanol fraction produced a concentration-dependent spasmogenic effect in isolated guinea pig ileum segments. These effects were significantly inhibited in the presence of 1 microM atropine. In contrast, the response to the lowest concentrations of L. ferrugineus methanol extract (0.25, 0.5 and 1 mg/mL) and n-butanol fraction of L. ferrugineus (0.125, 0.25 and 0.5 mg/mL) were considerably enhanced in the presence of 0.05 microM neostigmine. Neither L. ferrugineus methanol extract nor n-butanol fraction contractile responses were affected upon the incubation of the ileal segments with 100 microM hexamethonium. The results of this study show that the spasmogenic effect of L. ferrugineus is possibly mediated through a direct action on intestinal muscarinic receptors. It is suggested that the bioactive constituents of L. ferrugineus serve as a substrate for acetylcholinesterase.
Cardiovascular activity of the n-butanol fraction of the methanol extract of Loranthus ferrugineus Roxb

Ameer OZ, Salman IM, Siddiqui MJ, Yam MF, Sriramaneni RN, Sadikun A, et al.

Braz. J. Med. Biol. Res., 2010 Feb;43(2):186-94.
PMID: 20084331

We investigated the vascular responses and the blood pressure reducing effects of different fractions obtained from the methanol extract of Loranthus ferrugineus Roxb. (F. Loranthaceae). By means of solvent-solvent extraction, L. ferrugineus methanol extract (LFME) was successively fractionated with chloroform, ethyl acetate and n-butanol. The ability of these LFME fractions to relax vascular smooth muscle against phenylephrine (PE)- and KCl-induced contractions in isolated rat aortic rings was determined. In another set of experiments, LFME fractions were tested for blood pressure lowering activity in anesthetized adult male Sprague-Dawley rats (250-300 g, 14-18 weeks). The n-butanol fraction of LFME (NBF-LFME) produced a significant concentration-dependent inhibition of PE- and KCl-induced aortic ring contractions compared to other fractions. Moreover, NBF-LFME had a significantly higher relaxant effect against PE- than against high K+-induced contractions. In anesthetized Sprague-Dawley rats, NBF-LFME significantly lowered blood pressure in a dose-dependent manner and with a relatively longer duration of action compared to the other fractions. HPLC, UV and IR spectra suggested the presence of terpenoid constituents in both LFME and NBF-LFME. Accordingly, we conclude that NBF-LFME is the most potent fraction producing a concentration-dependent relaxation in vascular smooth muscle in vitro and a dose-dependent blood pressure lowering activity in vivo. The cardiovascular effects of NBF-LFME are most likely attributable to its terpenoid content.
Characterization of the possible mechanisms underlying the hypotensive and spasmogenic effects of Loranthus ferrugineus methanolic extract

Ameer OZ, Salman IM, Siddiqui MJ, Yam MF, Sriramaneni RN, Sadikun A, et al.

Am J Chin Med, 2009;37(5):991-1008.
PMID: 19885958

In the present study, L. ferrugineus methanol extract (LFME) was evaluated for its blood pressure lowering effect in anesthetized normotensive Sprague Dawley (SD) rats and its spasmogenic effect in isolated guinea pig ileum. The possible mechanism(s) of action were also investigated. LFME was obtained by Soxhlet extraction. The rats were fasted overnight and anesthetized with sodium pentobarbitone (60 mg/kg i.p.). LFME was administered in i.v. boluses in the concentrations of 25, 50, 100 and 200 mg/kg respectively, with concomitant monitoring of mean arterial pressure (MAP). It was found that LFME dose-dependently reduced MAP. An i.v. bolus injection of atropine significantly decreased the blood pressure lowering effect of LFME. Similarly, L-NAME (Nomega-nitro-L-arginine methyl ester) significantly lowered both the MAP and the action duration. Conversely, no significant change in MAP was seen following i.v. injections of neostigmine, hexamethonium, prazosin and propranolol. LFME also produced a dose-dependent contractile effect in guinea pig ileum. This contraction was significantly reduced in atropine pre-incubated tissue segments, yet it was significantly enhanced in the presence of neostigmine. No appreciable change in the ability of LFME to contract guinea pig ileum was seen in the presence of hexamethonium. Accordingly, it can be postulated that LFME possesses a marked hypotensive effect that can be attributed to stimulation of muscarinic receptors and/or stimulation of nitric oxide (NO) release. Moreover, LFME retains a considerable spasmogenic action due to its cholinergic properties. The hypotensive and spasmogenic effects of LFME justify its traditional uses.
Pharmacological mechanisms underlying the vascular activities of Loranthus ferrugineus Roxb. in rat thoracic aorta

Ameer OZ, Salman IM, Siddiqui MJ, Yam MF, Sriramaneni RN, Mohamed AJ, et al.

J Ethnopharmacol, 2010 Jan 8;127(1):19-25.
PMID: 19808083 DOI: 10.1016/j.jep.2009.09.057

The present study was aimed to investigate the pharmacological basis for the use of Loranthus ferrugineus in hypertension.