Hypotensive and endothelium-independent vasorelaxant effects of methanolic extract from Curcuma longa L. in rats

Laboratório de Tecnologia Farmacêutica, Universidade Federal da Paraíba, Brazil.
Journal of ethnopharmacology (Impact Factor: 3). 06/2009; 124(3):457-62. DOI: 10.1016/j.jep.2009.05.021
Source: PubMed


Curcuma longa L. (CL) is a yellow rhizome that is used in African traditional medicine to treat palpitation, hypertension or other related blood circulation disorders.
To justify the use of CL in ethnomedicine, we investigated the vasorelaxant effect of methanolic extract of CL (CLME) and its underlying mechanisms in isolated rat mesenteric artery.
The effect of CLME on the mean arterial pressure (MAP) and heart rate (HR) (pulse interval) were determined in vivo in non-anaesthetized rats. Superior mesenteric rings were isolated, suspended in organ baths containing Tyrode solution at 37 degrees C and gassed with 95% O(2)+5% CO(2), under a resting tension of 0.75 g. The vasorelaxant effects of CLME were studied by means of isometric tension recording experiments.
In normotensive rats, CLME (10, 20 and 30 mg/kg, i.v.) induced dose-dependent hypotension (2.0+/-0.5%; 27.1+/-5.0% and 26.7+/-4.6%, respectively), and pronounced bradycardia (5.8+/-1.2%, 19.3+/-3.2% and 22.9+/-4.6%, respectively). CLME (1-1000 microg/mL) induced concentration-dependent relaxation of tonic contractions evoked by phenylephrine (Phe) (10 microM) and KCl (80 mM) in rings with intact-endothelium (E(max)=82.3+/-3.2% and 97.7+/-0.7%) or denuded-endothelium (E(max)=91.4+/-1.0% and 97.8+/-1.1%). Also, in a depolarized, Ca(2+) free medium, CLME inhibited CaCl(2) (1 microM-30 mM)-induced contractions and caused a concentration-dependent rightward shift of the response curves, indicating that CLME inhibited the contractile mechanisms involving extracellular Ca(2+) influx. In addition, in Ca(2+) free media containing EGTA (1 mM), CLME inhibited the transient contraction of denuded rings constricted with Phe, but not those evoked by caffeine (20 mM). In contrast, neither glibenclamide, BaCl(2), tetraethylammonium nor 4-aminopyridine affected CLME-induced relaxation.
These results demonstrate the hypotensive and bradycardic effects of CLME, as well as its potent vasodilation of rat mesenteric arteries. These effects, may in part, be due to the inhibition of extracellular Ca(2+) influx and/or inhibition of intracellular Ca(2+) mobilization from Phe-sensitive stores.

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    • "By contrast, caffeine-induced contractions, which release Ca2+ from intracellular stores by IP3-independence, were not altered. Thus, it seems likely that the vascular effects of oligopeptides involved a reduction of IP3-dependent Ca2+ releases form SR sensitive to phenylephrine [27, 28]. "
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    ABSTRACT: Sericin-derived oligopeptides obtained from silk cocoons were investigated for the in vivo hypotensive effect and investigated for the underlying mechanism involved in vasodilation in isolated rat thoracic aorta. In normotensive anesthetized rats, oligopeptides induced an immediate and transient hypotensive activity. In rat aortic rings, oligopeptides induced a concentration-dependent vasorelaxation in vessels precontracted with both KCl and phenylephrine (PE) with endothelium-intact or endothelium-denuded rings. In endothelium-intact rings, pretreatment with N ω -Nitro-L-arginine methyl ester hydrochloride (L-NAME, 100 µM), an inhibitor of the NO synthase (NOS) or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 1 µM), a selective inhibitor of the guanylyl cyclase enzyme, significantly reduced the relaxant effect of oligopeptides. However, indomethacin, an inhibitor of the cyclooxygenase, had no effect on oligopeptides-induced relaxation. In addition, pretreatment with tetraethylammonium (TEA, 5 mM) reduced the maximal relaxant effect induced by oligopeptides. By contrast, relaxation was not affected by 4-aminopyridine (4-AP, 1 mM), glibenclamide (10 µM), or barium chloride (BaCl2, 1 mM). In depolarization Ca(2+)-free solution, oligopeptides inhibited calcium chloride- (CaCl2-) induced contraction in endothelium-denuded rings in a concentration-dependent manner. Nevertheless, oligopeptides attenuated transient contractions in Ca(2+)-free medium containing EGTA (1 mM) induced by 1 µM PE, but they were not affected by 20 mM caffeine. It is obvious that potent vasodilation effect of oligopeptides is mediated through both the endothelium and the vascular smooth muscle.
    11/2013; 2013:717529. DOI:10.1155/2013/717529
    • "Interestingly, treatment with KV or CL offered remarkable protection against oxidative stress induced by L- NAME by normalizing the values of biochemical markers of oxidative stress. Several lines of evidence previously reported support the superb cardiac, renal and hepatic protective capabilities of KV and CL.[161726] "
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    ABSTRACT: Kolaviron (KV) (biflavonoid from Garcinia kola) and extract of Curcuma longa (CL) are frequently used in folk medicine for treatment of hypertension. One of their mechanisms of action is to enhance antioxidant properties in animals. N(G)- nitro- l- arginine methyl- ester (L- NAME) is L- arginine analogue, which by binding to Nitric Oxide Synthase (NOS) may induce hypertension partly due to increase in tissues oxidative stress. To investigate the effect of L- NAME on some biochemical indices and the possible protective effect of KV or CL. Four groups consisting of 6 rats each were used. One group served as control, second group received L- NAME (40 mg/kg/day). Third and fourth groups were treated with KV and CL, respectively and also received L- NAME. KV and CL were given at a dose of 200 mg/kg/day. L- NAME caused a significant (P <0.05) increase in the levels of serum urea, creatine kinase and alanine aminotransferase relative to controls. L- NAME treated rats had markedly decreased hepatic catalase (CAT), superoxide dismutase (SOD), glutathione- S- transferase (GST) and reduced glutathione (GSH) levels. Precisely, L- NAME decreased CAT, SOD, GST and GSH by 48, 52, 76 and 40%, respectively. L- NAME intoxication significantly decreased (P <0.05) renal GSH and SOD levels. Also, L- NAME caused a significant (P <0.05) induction of lipid peroxidation (LPO) in the animals. Administration of KV or CL with L- NAME caused significant (P <0.05) inhibition of LPO and augments tissue antioxidant indices. These results confirm the adverse effect of L- NAME on biochemical indices and, the ability of kolaviron or Curcuma longa to ameliorate the alterations.
    Pharmacognosy Research 07/2012; 4(3):127-33. DOI:10.4103/0974-8490.99071
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    • "Medicinal plants contain several classes of bioactive compounds such as polyphenols, alkaloids and terpenes (Oliveira et al., 1996; Barbosa-Filho et al., 2000; Adaramoye et al., 2009). Among the pharmacological activities of compounds isolated from medicinal drugs on the cardiovascular system are calcium antagonism, NO release, antioxidant and others (Guedes et al., 2004; Ribeiro et al., 2010). "
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    ABSTRACT: The cardiovascular effects elicited by the ethanolic extract obtained from the roots of Erythroxylum pungens O.E. Schulz, Erythroxylaceae (EEEP) and the vasorelaxant effect induced by its main tropane alkaloid (pungencine) were investigated. In normotensive rats, administration of EEEP (1, 10, 30 and 60 mg/kg i.v., randomly) produced dose-dependent hypotension (-2±1, -7±0.5 -17.6±1, -24±1 Δ mmHg, n=5) followed by tachycardia (3±0.5, 7±2, 7.1±1, 10±5 Δ bpm, n=5). In intact phenylephrine (Phe, 10 µM)-pre-contracted rings, EEEP (0.01-500 µg/mL) induced concentration-dependent vasorelaxation (EC50 13.7±5.5 µg/mL, Maximal Response= 92±2.6%), and this effect was unchanged after the removal of the vascular endothelium (EC50 27.2±4.7 µg/ml, Maximal Response= 88.3±3.3 %). In KCl (80 mM)-pre-contracted-endothelium-denuded rings, EEEP elicited concentration-dependent relaxation (EC50= 128.2±11.2 µg/mL, Maximal Response 76.8±3.4%). Vasorelaxation has also been achieved with tonic contractions evoked by the L-type Ca2+ channel agonist Bay K 8644 (EC50 80.2±9.1 µg/mL, Maximal Response 86.3±8.3%). In addition, in a depolarizing medium, EEEP inhibited CaCl2 (30-500 µg/mL) induced contractions and caused a concentration-dependent rightward shift of the relaxation curves. Lastly, the tropane alkaloid pungencine caused vasorelaxation in mesenteric arteries resembling to the EEEP responses. These results suggests that EEEP induces hypotension and vasorelaxation, at least in part, due to the reduction in [Ca2+]i in vascular smooth muscle cells.
    Revista Brasileira de Farmacognosia 03/2012; 0102-695X(22):436. DOI:10.1590/s0102-695x2012005000005 · 0.83 Impact Factor
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