Vasorelaxant and hypotensive effects of a hydroalcoholic extract from the fruits of Nitraria sibirica Pall. (Nitrariaceae).

ETHNOPHARMACOLOGICAL RELEVANCE: Fruits of Nitraria sibirica Pall. are traditionally used in Uighur medicine to treat hypertension. This study aimed to support that folk use by defining their vasoactive and hypotensive properties. MATERIALS AND METHODS: The vasorelaxant activity and the underlying mechanisms of a hydroalcoholic extract from the fruits of Nitraria sibirica Pall. (NSHE) were evaluated on thoracic aortic rings isolated from Wistar rats. In addition, the acute hypotensive effect of NSHE was assessed in anesthetized spontaneously hypertensive rats (SHR) and in their normotensive control Wistar Kyoto (WKY) rats. RESULTS: NSHE (0.1-10 g/l) was clearly more effective to induce vasodilation of phenylephrine- (PE, 1 µM) than high KCl- (60mM) pre-contracted aortic rings with respective E(max) values of 82.9±2.2% and 34.8±3.6%. The removal of endothelium almost abolished the relaxant effect of the extract. In addition, pre-treatment with N(w)-nitro-L-arginine-methyl ester (L-NAME, 100 µM), atropine (1 µM) or charybdotoxin (30 nM) plus apamin (30 nM), respective blockers of nitric oxide (NO) synthase, muscarinic receptors and endothelium-derived hyperpolarizing factor (EDHF), significantly reduced the observed effect of NSHE. By contrast, the cyclooxygenase (COX) inhibitor indomethacin (10 µM) or the K(+) channels blockers glibenclamide (10 µM), iberiotoxin (30 nM) and 4-amino-pyridine (4-AP, 1 mM) failed to modify the vasodilation. Finally, the acute intravenous injection of NSHE (1, 5, 10, 20 mg/kg) induced an immediate and transient hypotensive effect in anesthetized SHR and in WKY rats. CONCLUSIONS: This experimental animal study suggests that hydroalcoholic extract from the fruits of Nitraria sibirica Pall. induces vasorelaxation through an endothelium-dependent pathway involving NO synthase (NOS) activation, EDHF production and muscarinic receptor stimulation. Additionally, our results determine that this vasorelaxant effect is translated by a significant hypotensive effect.

The aqueous extract of Terminalia superba (Combretaceae) prevents glucose-induced hypertension in rats.

AIM OF THE STUDY: The stem bark of Terminalia superba (Combretaceae) (TS) is used in traditional Cameroonian medicine as antihypertensive remedy. The aim of this study was to investigate the hypotensive and the antihypertensive effects of the aqueous extract of the stem bark of Terminalia superba. MATERIALS AND METHODS: Hypertension was obtained in rats by oral administration of 10% D-glucose for 3 weeks. The acute effects of Terminalia superba were studied on blood pressure (BP) and heart rate (HR) after intravenous administration in normotensive rats (NTR) and glucose hypertensive rats (GHR). The antihypertensive effects were studied after oral administration of the extract (50 and 100 mg/kg/day) or nifedipine (10 mg/kg/day) for 3 weeks. At the end of the experiment, BP and HR were measured and reduced glutathione (GSH), malondialdehyde (MDA) and superoxide dismutase (SOD) activity levels were measured in heart, aorta, liver and kidney. RESULTS: Intravenous administration of the aqueous extract of Terminalia superba induced a significant hypotensive response without any change in HR. The hypotensive effect of the extract was unaffected by atropine or propranolol but decreased by reserpine (5 mg/kg) and yohimbine (0.1 mg/kg). In addition, the oral administration of the extract significantly prevented the rise in BP in glucose-hypertensive rats. Finally, the treatment with plant extract significantly blunted the decrease in GSH and the increase in MDA levels associated with hypertension, and significantly prevents the increase in aortic SOD activity. CONCLUSIONS: The present study demonstrates that the aqueous extract of the stem bark of Terminalia superba exhibits hypotensive and anti-hypertensive properties that are, at least in part, related to a withdrawal of sympathetic tone and to an improvement of the antioxidant status, respectively. Overall data validate the use of Terminalia superba as antihypertensive therapy in traditional medicine.

Mechanisms of vasorelaxation induced by Ziziphora clinopodioides Lam. (Lamiaceae) extract in rat thoracic aorta.

AIM OF THE STUDY: Ziziphora clinopodioides Lam. (ZC) is widely used in Uyghur folk medicine for the treatment of hypertension diseases in Xinjiang, an autonomous region of China. To provide pharmacological basis for this traditional use, we explored the vasodilating effects of ZC and investigated the underlying mechanisms. MATERIALS AND METHODS: Activity of hexane (ZCHE), dichloromethane (ZCDE) and aqueous (ZCAE) extracts of ZC were evaluated on isolated rat aortic rings pre-contracted with phenylephrine (PE) or high KCl. The mechanisms were evaluated on ZCDE, the most potent extract. RESULTS: ZCDE-induced relaxation in endothelium-intact aortic rings pre-contracted with phenylephrine (PE, 10(-6) M) or high KCl (6×10(-2) M), with respective EC(50) values of 0.27±0.03 and 0.34±0.04 g/l. Mechanic removal of the endothelium did not significantly modify ZCDE-induced relaxation. In endothelium-denuded aorta pre-contracted with PE (10(-6) M), the vasorelaxant effect of ZCDE was significantly decreased by 4-amino-pyridine (10(-3) M), but not by glibenclamide (10(-4) M), iberiotoxin (3×10(-8) M) and thapsigargin (10(-7) M). In Ca(2+) free solution, ZCDE significantly inhibited extracellular Ca(2+)-induced contraction in high KCl and PE pre-contracted rings. Additionally ZDCE inhibited the intracellular Ca(2+) release sensitive to PE (10(-6) M). CONCLUSIONS: The results demonstrate that ZDCE exhibits endothelium-independent vasodilating properties that are mediated by inhibition of extracellular Ca(2+) influx through voltage- and receptor-operated Ca(2+) channels (VDDCs and ROCCs), by inhibition of Ca(2+) release from intracellular stores, and also by the opening of voltage-dependent K(+) channels.

Vasorelaxant effects of extracts of the stem bark of Terminalia superba Engler & Diels (Combretaceae).

AIM OF THE STUDY: The stem bark of Terminalia superba (Combretaceae) (TS) is used in traditional Cameroonian medicine as antihypertensive remedy. In the present study, we investigated the vasorelaxant properties of different extracts of TS and their underlying mechanisms. MATERIALS AND METHODS: Activities of aqueous (AQU), methanolic (MET), methylene chloride (MC), and methylene chloride-methanol (MCM) extracts of TS were evaluated on isolated rat aortic rings precontracted with phenylephrine (PE) or high KCl. RESULTS: All extracts induced a vasodilating effect both on KCl- and PE-induced contractions. The effects of MC and MCM extracts were greater than those of AQU or MET extracts (P<0.05). MC had an endothelium-independent effect and reduced Ca(++)-induced contraction following PE or KCl challenge (P<0.05). After incubation with verapamil, MC induced a relaxation in rings precontracted by PE (P<0.001). By contrast, the effect of MCM was endothelium-dependent and decreased by the nitric oxide synthase inhibitor N(W)-nitro-L-arginine methyl ester (P<0.05). CONCLUSIONS: These data demonstrate that the MC extract exhibits vasorelaxant effects that are partly due to inhibition of extracellular Ca(++) influx and/or inhibition of intracellular Ca(++) release in vascular smooth muscle cells. By contrast, the effect of the MCM extract was found to be endothelium- and nitric oxide dependent.

Effect of 7-O-beta-D-glucopyranosylchrysin and its aglycone chrysin isolated from Podocytisus caramanicus on estrogen receptor alpha transcriptional activity.

A screening of Greek Fabaceae extracts identified the methanolic extract of Podocytisus caramanicus Boiss. & Heldr. as having proliferative activity on human breast cancer cells (MCF-7). Using transient transfection experiments, we have first used three compounds described for their estrogen-like properties, E (2), genistein (Gen) and biochanin A (Bch), as controls to evaluate our cellular model. Secondly, we have demonstrated that the 7- O-beta- D-glucopyranosylchrysin (Glc-chr), the most abundant flavone of the extract, and its aglycone chrysin were able to increase estrogen receptor alpha transcriptional activity in MCF-7 cells. We have also shown that the estrogenic activity of Glc-chr could be completely suppressed by the pure estrogen antagonist ICI 182,780 suggesting that the effect of Glc-chr is mediated by ERalpha.

Effect of chrysin and natural coumarins on UGT1A1 and 1A6 activities in rat and human hepatocytes in primary culture.

Flavonoids and coumarins are naturally occurring compounds that are widely distributed in vegetables and have a broad pharmacological activity. Inducibility of UDP-glucuronosyltransferases (UGTs) by xenobiotics is well documented and can be considered beneficial for health. In particular, UGT1A1-dependent bilirubin conjugation plays a critical role in the detoxification of neurotoxic bilirubin and phenobarbital-mediated UGT1A1 induction therapy is commonly used in the treatment of unconjugated hyperbilirubinemic diseases such as Crigler-Najjar type II disease. In the present study, the effects of the flavone chrysin and six natural coumarins isolated from various Rutaceous plants on UGT1A6-dependent P-nitrophenol and/or UGT1A1-dependent bilirubin glucuronoconjugation activities were evaluated in cultured rat and human hepatocytes and compared to those of the prototypical UGT1A inducers beta-naphthoflavone, phenobarbital and clofibric acid. After 3 days of treatment at a concentration of 25 microM, the pyranocoumarins avicennin and CIS-avicennol, and the furocoumarins bergapten and imperatorin, increased by 2-fold UGT1A1-dependent activity, equivalent to the increases obtained with chrysin at 25 microM, whereas in the presence of the simple coumarins such as coumarin or umbelliferone, UGT1A1-dependent activity was not modified. In terms of structural requirements for UGT1A1 induction, the present study suggests that the B-ring (phenyl) for chrysin and the furan or pyran rings for coumarins are essential for the biological activity.

Phebaclavin I, a novel 3-prenylated coumarin, and trichoclin acetate, a new natural furocoumarin, from the aerial parts of Phebalium aff. tuberculosum (Rutaceae).

Phebaclavin I, a novel 3-prenylated coumarin, was isolated from the aerial parts of Phebalium aff. tuberculosum (Rutaceae) together with five known related compounds, Phebaclavin A, B, D, G, H. The structure of phebaclavin I was established by spectroscopic methods. Several other known coumarins were obtained, including trichoclin acetate, a furocoumarin isolated for the first time from a natural source, but previously described from acetylation of trichoclin.

Synthesis of 4-hydroxycoumarin and 2,4-quinolinediol derivatives and evaluation of their effects on the viability of HepG2 cells and human hepatocytes culture.

We report here the synthesis of aromatic coumarins and aromatic alpha-quinolones which were evaluated in vitro for their protective potentialities against tert-butyl hydroperoxide (t-BHP)-induced oxidative damage on human liver cell death, i.e., human hepatoma HepG2 cell line and human hepatocytes in primary culture. We found that the presence of a benzylidene at the 3-position or a heterocycle with N and S heteroatoms on the benzopyrone or quinolone system was essential for the protective effect of these compounds against t-BHP-induced decrease in viability of cells. We found also that a methoxy group on the aromatic ring systems decreased this potential. t-BHP-induced cytotoxicity in primary cultures of human hepatocytes could be therefore prevented by these compounds suggesting that they could display hepatoprotective effects in humans.

Prenylated p-coumarates from the twigs of Phebalium rude subsp. amblycarpum (Rutaceae).

Phebarudol, a novel prenylated p-coumarate, was isolated from the twigs of Phebalium rude Bartl. subsp. amblycarpum (F. Muell.) P. G. Wilson (Rutaceae) together with the two already known related compounds, werneria chromene and methyl demethoxywutaiensate. The structure of phebarudol was established by spectroscopic methods.

Eight new prenylcoumarins from Phebalium clavatum.

The aerial parts of Phebalium clavatum yielded eight new 3-prenylated coumarins, phebaclavin A-H (1-8). Their structures were established on the basis of their NMR and mass spectral data. In addition, seven known compounds were also isolated, including two 8-geranyloxy linear furocoumarins previously obtained from Phebalium tuberculosum ssp. megaphyllum, included in the same section of the genus.