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Antidepressant effects of apocynum venetum leaves in a forced swimming test.

An extract of the leaves of Apocynum venetum L. (Apocynaceae) markedly shortened the immobility time of male rats in a forced swimming test (FST) in a dose range of 30-125 mg/kg, indicating a possible antidepressant activity. This effect was comparable to that of the tricyclic antidepressant imipramine (20 mg/kg). Neither imipramine (20 mg/kg) nor the Apocynum extract in various doses (30, 60, 125 mg/kg) produced any overt behavioural change or motor dysfunction in the open field test. This result confirms the assumption that the antidepressant effect of an Apocynum extract in the FST is specific. Further, it can be speculated that this effect might be related to hyperoside and isoquercitrin which are major flavonoids in the extract.

Animals↗

[Study on flavonoids in leaves of Apocynum ventum].

OBJECTIVE: To study the flavonoids in the leaves of Apocynum ventum. METHOD: Compounds were separated by repeated polyacrylamide column chromatgraphy combined with Sephadex LH-20 column chromatgraphy, their structures were confirmed by the analysis of spectral data and physicochemical properties. RESULT: Six compounds were isolated from A. ventum. They were elucidated as quercetin (1), kaempferol (2), kaempferol-3-O-(6"-O-acetyl)-beta-D-glucopyranoside (3), quercetin-3-O-(6"-O-acetyl )-beta-D-glucopyranoside (4), quercetin-3-O-(6"-O-acetyl)-beta-D-galactopyranoside (5), kaempferol-7-O-alpha-L-rhamnopyranoside (6). CONCLUSION: Compound 5 and 6 were isolated from the genus Apocynum for the first time.

Apocynum↗

[Observations on the anti-aging, antihypertensive and antihyperlipemic effect of Apocynum venetum leaf extract].

The effect of Apocynum venetum leaf extract on hypertension, hyperlipemia, SOD content of erythrocyte, platelet aggregation rate, pulse wave transmission time (RP interval) and human diploid cell was studied to evaluate if it has some anti-aging effects. The mean BP in 60 cases of the treated group decreased from 171 +/- 19/98 +/- 11 mmHg to 154 +/- 22/91 +/- 10 mmHg and 148 +/- 17/89 +/- 10 mmHg after treatment for 4 and 8 weeks (P less than 0.01). The HDL-C in 40 cases of hyperlipemia increased from 47.5 +/- 13 mg% to 63.9 +/- 18 mg% (P less than 0.01). These results were better than those in the control groups. delta RPF was lengthened from 10.1 +/- 6.0 ms to 15.3 +/- 7.3 ms, which indicated that the cardiac performance was improved. No significant change of platelet aggregation rate was obtained after 5-8 weeks treatment. The retarding effect on cell aging was observed by the morphologic changes of nucleus and the increase of subcultivation from 77 to 80 generations. SOD content of erythrocyte was significantly increased from 546.1 +/- 51 micrograms/gHb to 574.6 +/- 42 micrograms/gHb in 20 cases. So Apocynum venetum leaf extract might have some anti-aging effects.

Aged↗

Anti-anxiety effects of Apocynum venetum L. in the elevated plus maze test.

The purpose of this study was to characterize the putative anxiolytic-like activity of an ethanolic extract prepared from the leaves of Apocynum venetum (AV) using the elevated plus maze (EPM) in mice. Male C75BL/6 mice were either treated orally with the AV extract or the positive controls diazepam and buspirone, respectively, 1h before behavioral evaluation in the EPM. A single treatment of AV extract markedly increased the percentage time spent on and the number of entries into the open arms of the EPM in doses of 30 and 125 mg/kg p.o., respectively. This effect was comparable to that of the benzodiazepine diazepam (1.5 mg/kg p.o.) and the 5-HT(1A) agonist buspirone (10 mg/kg p.o.). The effects of AV in 125 mg/kg were effectively antagonized by the benzodiazepine antagonist flumazenil (3 mg/kg i.p.). However, the effects of AV extract could only partially be blocked by the unspecific 5-HT(1A) receptor antagonist WAY-100635 (0.5 mg/kg i.p.). Neither diazepam and buspirone nor the AV extract produced any overt behavioral change or motor dysfunction in the open field test. These results indicate that AV extract is an effective anxiolytic agent, and suggest that the anxiolytic-like activities of this plant are mainly mediated via the GABAergic system.

Animals↗

Long-term effects of an Apocynum venetum extract on brain monoamine levels and beta-AR density in rats.

The present study was designed to get further insight into the mode of antidepressant action of an extract prepared of the leaves of Apocynum venetum L. (AV). To evaluate biochemical changes, we used a high-performance liquid chromatography system to examine the effects of short-term (2 weeks) and long-term (8 weeks) administration of imipramine (15 mg/kg po) and an AV-extract (15, 60 and 250 mg/kg) on regional levels of serotonin (5-HT), norepinephrine (NE), dopamine (DA) and their metabolites in the rat hypothalamus, striatum and hippocampus. Pronounced changes in 5-HT, NE and DA levels were detected mainly after 8 weeks of daily imipramine treatment. Similar to imipramine, AV-extract reduced NE and DA concentrations after 8 weeks, whereas it failed to affect 5-HT levels. We speculate that the decrease in NE levels after chronic AV treatment might be based partly on the subsensitivity of presynaptic alpha(2)-receptors. In addition to the determination of central monoamine concentrations, quantitative radioligand receptor-binding studies were used to examine the effects of long-term administration of imipramine and AV-extract on beta-adrenergic binding in rat frontal cortex. [125I]CYP binding to beta-adrenergic receptors was found to be decreased after 8 weeks treatment with imipramine, whereas AV-extract had no effect on beta-receptor binding.

Animals↗

Seasonal, spatial, and interspecific variation in quercetin in Apocynum venetum and Poacynum hendersonii, Chinese traditional herbal teas.

Quercetin is of particular importance as it has been found to have functions of suppressing tumors, reducing blood pressure, and scavenging free radicals. It is one of the major flavonoids in Apocynum venetum and Poacynum hendersonii, whose leaves have long been used as traditional herbal teas in China and Japan. Both species are also cultivated as fiber plants because of their outstanding quality of phloem fiber in stems. To obtain high output of both quercetin and fiber, it is necessary to optimize harvesting time for their leaves. Thus, understanding the developmental patterns of quercetin in leaves and fiber in stems is crucial to achieving this goal. In the present study, temporal and interspecific variations in quercetin in the leaves between A. venetum and P. hendersonii and spatial variation among P. hendersonii populations were studied by HPLC during the period from April to October in 1999. The results show that the content of quercetin in both species reached its highest level in summer and its lowest in autumn. The quercetin content in the leaves of P. hendersonii was generally higher than that of A. venetum no matter when their leaves were harvested. There was significant difference in quercetin content among three geographical populations of P. hendersonii, which might be the result of climatic difference-cooler climate might favor accumulation of quercetin in the leaves of P. hendersonii. Furthermore, the developmental patterns of total phenolics in the leaves of the two species were the same as that of the quercetin, that is, summer is an optimal harvesting season for both quercetin and other phenolics. The results obtained here suggest that P. herdersonii is a better material for herbal tea or pharmaceutical purposes, and that the best harvest time of its leaves should be summer.

Apocynum↗

A novel in vitro endothelium-dependent vascular relaxant effect of Apocynum venetum leaf extract.

1. In the present study, a novel in vitro vascular relaxant effect of Apocynum venetum leaf extract (AVLE; also called 'Luobuma'), obtained from a traditional Chinese medicinal herb with known antihypertensive effects, is reported in isometric contraction studies of rat aorta and superior mesenteric artery. At low concentrations (0.3-10 microg/mL), AVLE had no effect on the resting tension of either blood vessel and caused relaxation in agonist-precontracted vessels with functionally intact endothelium. 2. We demonstrated pharmacologically that the AVLE-induced vasorelaxation was mediated selectively by the endothelial cells in both blood vessels. Using NG-nitro-L-arginine methyl ester (L-NAME) and a low concentration of KCl (15 mmol/L), we also demonstrated that AVLE acted by releasing endothelium-derived relaxation factors; nitric oxide (NO) in the rat aorta and NO plus endothelium-derived hyperpolarizing factor in the rat mesenteric artery. 3. The vascular relaxation following brief exposure to AVLE appeared to persist even after subsequent prolonged washout; this was manifested as an attenuated contraction to subsequent application of phenylephrine (PE) compared with the PE-induced contraction after exposure to carbachol (CCh) and subsequent similar washout. The addition of L-NAME at this point in the absence of AVLE totally restored the contraction to PE, suggesting that enzymatic generation of endothelial NO persisted even after brief exposure to AVLE. 4. Unlike the endothelium-dependent NO-mediated relaxation induced by CCh, which is mediated by endothelial muscarinic receptors (and inhibited by atropine), the relaxation induced by AVLE was not inhibited by atropine and, thus, was not mediated by muscarinic receptors. However, similar to CCh-induced relaxation, AVLE-induced relaxation was associated with the activation of K+ channels. 5. These results provide a strong scientific basis for the folk use of AVLE decoction for antihypertensive therapy in traditional Chinese medicine.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Apocynum venetum extract does not induce CYP3A and P-glycoprotein in rats.

We investigated the effect of Apocynum venetum L. extract (AV) on the activity of cytochrome P450 (CYP) 3A and P-glycoprotein (P-gp). The plasma concentration of nifedipine (NF), which is a substrate for CYP3A, did not change after oral administration with AV (3.3 mg/kg). Also, AV (3.3 and 33 mg/kg) did not affect the intestinal absorption of NF. In the rats treated with multiple administrations (15 mg/kg/d) of St. John's wort extract (SJW) for 2 weeks, the plasma concentration of NF after oral administration was significantly decreased. On the other hand, there was no significant differences in the pharmacokinetic parameters of NF between AV-treated (3.3 mg/kg/d) and none-treated rats. Furthermore, the intestinal absorption of methylprednisolone, which is a substrate for P-gp, was not affected by AV treatment for 2 weeks. These results suggest that, unlike SJW, the recommended dose of AV (3.3 mg/kg/d) would not influence hepatic CYP3A and intestinal P-gp in rats.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[Studies on antihypertensive effect of Luobuma (Apocynum venetum L.) leaf extract (3)].

To clarify the mechanisms underlying the antihypertensive effect of Luobuma (Apocynum venetum L. (Apocynaceae)) leaf extract (LLE), we investigated the vasodilator effect of LLE in the rat mesenteric vascular bed, which plays an important role in changes in peripheral resistance and thus the regulation of blood pressure. In the perfused mesenteric vascular bed with active tone and intact endothelium, perfusion of LLE (0.1 ng to 100 mg/ml for 15 min) caused dose-dependent vasodilation, which was abolished by chemical removal of the endothelial layer with perfusion of sodium deoxycholate, but not by N(G)-nitro-L-arginine-methyl ester (L-NAME), a competitive inhibitor of nitric oxide (NO), which instead increased the effect. The LLE-induced vasodilation was partially inhibited by high K(+)-containing Krebs solution and tetraethylammonium (a K(+) channel blocker) and completely by the combination of L-NAME and high K(+)-Krebs solution. However, atropine (a muscarinic acetylcholine receptor antagonist) did not affect the vasodilation. These results suggest that the vasodilation induced by LLE is endothelium-dependent and mediated by endothelium-derived hyperpolarizing factor, which involves the activation of K(+)-channels. The higher concentrations of LLE may enhance NO production/release to cause vasodilation.

Animals↗

[Studies on chemical constituents from flowers of Apocynum venetum].

OBJECTIVE: To study the chemical constituents of the flowers of Apocynum venetum. METHOD: Chromatographic methods were used to isolate compounds from the flowers of A. venetum and spectral methods were used to identify the structures of the isolated compounds. RESULT: Seven compounds, kaempferol (I), quercetin (II), quercetin-3-O-beta-D-glucoside (III), kaempferol-3-O-beta-D-glucoside (IV), vanillic acid (V), baimaside (VI), daucosterol (III), were isolated from the flowers of A. venetum. CONCLUSION: Compound I, V, VI, VII were obtained from this plant for the first time.

Apocynum↗

Inhibitory effects of an aqueous extract of Apocynum venetum leaves and its constituents on Cu(2+)-induced oxidative modification of low density lipoprotein.

An aqueous extract of Apocynum venetum leaves and its constituents inhibited thiobarbituric acid reactive substances (TBARS) and conjugated-diene formation in the Cu(2+)-induced oxidation of low density lipoprotein (LDL) in vitro. The TBARS formation was most strongly inhibited by chlorogenic acid with an IC(50) value of 1.9 microM, but other constituents were in a range of 2.3-23.3 microM. On the other hand, the lag time in the conjugated-diene formation was dose-dependently prolonged by addition of the aqueous extract. Catechin prolonged the lag time more than 300 min and other constituents such as chlorogenic acid, epicatechin, epigallocatechin, hyperoside and isoquercitrin led to no conjugated-diene formation within 700 min under the experimental conditions.

Cholesterol, LDL↗

Inhibition of flowering and reproductive success in spreading dogbane (Apocynum androsaemifolium) by exposure to ambient ozone.

Ground-level ozone continues to be a cause for concern in terrestrial ecosystems in the northeastern United States and Canada. Spreading dogbane (Apocynum androsaemifolium L.) is one of many indigenous herbaceous plant species exhibiting foliar injury that are commonly monitored in ecosystem assessment programs. Details about possible effects of ambient ozone on reproductive components of these species are lacking. For 103 days, from 31 May to 10 September, A. androsaemifolium plants were grown in open-top chambers in either carbon-filtered air (CF), non-filtered air (NF) (approximately 1xambient), or chamberless ambient air plots (AA). Aspects of sexual reproduction were measured to determine whether impairment occurs in polluted air. Additionally, the ozone protectant chemical ethylenediurea (EDU) was applied to foliage to determine its effect on foliar injury. By the end of the experiment visible foliar injury was absent in CF air and nominal in the NF and AA treatments. Plants grown in CF-chamber air produced significantly more flowers and fruits than those grown in either NF-chamber air or AA plots. Flowers produced by plants grown in CF air also survived to mature fruits at a rate 1.7x greater than plants in NF air and 1.5x greater than plants in AA plots. We were unable to conclude whether EDU protected plants from foliar ozone injury due to the general lack of foliar injury in ozone-exposed plants. The results demonstrate that foliar injury is not necessarily required to elicit negative effects on sexual reproduction in A. androsaemifolium. Implications for the population biology of A. androsaemifolium related to adverse effects of chronic ozone exposure on sexual reproduction are discussed.

Journal Article↗

Effects of aqueous extracts of Apocynum venetum leaves on spontaneously hypertensive, renal hypertensive and NaCl-fed-hypertensive rats.

Effects of aqueous extracts of Apocynum venetum leaves (Luobuma extracts) on the blood pressure were evaluated in hypertensive animal models, such as spontaneously hypertensive rats (SHR), renal hypertensive rats and NaCl-induced hypertensive rats. In SHR, administration of Luobuma (heat-processed and unprocessed leaves) extracts at a dose of 70 mg/rat per day significantly decreased the systolic blood pressure value, but their decreasing effects were weaker than that of captopril. The urine volume, and the urinary Na(+), K(+) and protein excretions were not significantly different between Luobuma-treated and untreated groups. In 3/4 nephrectomized rats, the Luobuma extracts significantly decreased the systolic blood pressure value, accompanied by significant increases of the urine volume and the urinary Na(+) and K(+) excretions. Furthermore, they decreased the blood urea nitrogen (BUN) level. In NaCl-induced hypertensive rats, the Luobuma extract decreased the systolic blood pressure value. However, it did not change the urinary excretions of Na(+), K(+) and protein. The BUN level was lower than that of control rats, but the serum total cholesterol (TC) level did not changed. From these findings, the Luobuma extracts have an anti-hypertensive effect, possibly due to amelioration of the kidney functions in the three experimental animal models.

Animals↗

Hepatoprotective effect of Apocynum venetum and its active constituents.

The leaves of Apocynum venetum L. are used as a tea material in north China and Japan. A water extract (500 mg/kg/day, one week administration) of the leaves of A. venetum showed protective effects against carbon tetrachloride (CCl4, 30 microliters/mouse) or D-galactosamine (D-GalN, 700 mg/kg)/lipopolysaccharide (LPS, 20 micrograms/kg)-induced liver injury in mice. Tumor necrosis factor-alpha (TNF-alpha) secreted from LPS-stimulated macrophages is the most crucial mediator in the D-GalN/LPS-induced liver injury model. The extract had no significant inhibition on the increase of serum TNF-alpha (1169 +/- 132 pg/ml vs. 1595 +/- 314 pg/ml of control), but exhibited a complete inhibition at the concentration of 100 micrograms/ml on TNF-alpha (100 ng/ml)-induced cell death in D-GalN (0.5 mM)-sensitized mouse hepatocytes. Further activity-guided fractionation resulted in the isolation of fifteen flavonoids viz. (-)-epicatechin (1), (-)-epigallocatechin (2), isoquercetin (3), hyperin (4), (+)-catechin (5), (+)-gallocatechin (6), kaempferol-6'-O-acetate (7), isoquercetin-6'-O-acetate (8), catechin-[8,7-e]-4 alpha-(3,4-dihydroxpyhenyl)-dihydro-2(3H)-pyranone (9), apocynin B (10), apocynin A (11), cinchonain Ia (12), apocynin C (13), apocynin D (14) and quercetin (15). All the compounds showed inhibitory effects on TNF-alpha-induced cell death with different intensities. The flavonol glycosides 3, 4, 7 and 8 and the phenylpropanoid-substituted flavan-3-ols 11 and 12 showed potent inhibitory effects on TNF-alpha-induced cell death with IC50 values of 37.5, 14.5, 31.2, 55.1, 71.9 and 41.2 microM, respectively. In contrast, the clinically used 5 and its analogues 1, 2 and 6 showed apparent activity only at 80 microM. These flavonoids appeared to be the hepatoprotective principles of the leaves of A. venetum. The hepatoprotective effects exhibited by the extract and its constituents suggest a validation of the leaves as a tea material.

Animals↗

Medicinal foodstuffs. XXIV. Chemical constituents of the processed leaves of Apocynum venetum L.: absolute stereostructures of apocynosides I and II.

Two new ionone glucosides, named apocynosides I and II, were isolated from the roasted leaves of Apocynum venetum L. together with nine known compounds. The absolute stereostructures of apocynosides I and II were determined by chemical and physicochemical evidence, which included the application of a modified Mosher's method and the circular dichroism helicity rule.

Apocynaceae↗

[Sedative chemical constituents of leaves of Apocynum venetum Linn].

Eight constituents were isolated from the ether solvent fraction of leaves of Apocynum venetum and identified as triacontanol, beta-sitosterol, quercetin, hyperin, long-chain fatty acids (C28-C34), lupeol, scopoletin and isofraxidin. Isofraxidin and hyperin were effective sedative components.

Alkaloids↗