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Planta medica [journal]
- Antiplasmodial and Antioxidant Isoquinoline Alkaloids from Dehaasia longipedicellata. [JOURNAL ARTICLE]
- Planta Med 2014 Apr 10.
The crude extract of the bark of Dehaasia longipedicellata exhibited antiplasmodial activity against the growth of Plasmodium falciparum K1 isolate (resistant strain). Phytochemical studies of the extract led to the isolation of six alkaloids: two morphinandienones, (+)-sebiferine (1) and (-)-milonine (2); two aporphines, (-)-boldine (3) and (-)-norboldine (4); one benzlyisoquinoline, (-)-reticuline (5); and one bisbenzylisoquinoline, (-)-O-O-dimethylgrisabine (6). Their structures were determined on the basis of 1D and 2D NMR, IR, UV, and LCMS spectroscopic techniques and upon comparison with literature values. Antiplasmodial activity was determined for all of the isolated compounds. They showed potent to moderate activity with IC50 values ranging from 0.031 to 30.40 µM. (-)-O-O-dimethylgrisabine (6) and (-)-milonine (2) were the two most potent compounds, with IC50 values of 0.031 and 0.097 µM, respectively, that were comparable to the standard, chloroquine (0.090 µM). The compounds were also assessed for their antioxidant activities with di(phenyl)-(2,4,6-trinitrophenyl)iminoazanium (IC50 = 18.40-107.31 µg/mL), reducing power (27.40-87.40 %), and metal chelating (IC50 = 64.30 to 257.22 µg/mL) having good to low activity. (-)-O-O-dimethylgrisabine (6) exhibited a potent antioxidant activity of 44.3 % reducing power, while di(phenyl)-(2,4,6-trinitrophenyl)iminoazanium and metal chelating activities had IC50 values of 18.38 and 64.30 µg/mL, respectively. Thus it may be considered as a good reductant with the ability to chelate metal and prevent pro-oxidant activity. In addition to the antiplasmodial and antioxidant activities, the isolated compounds were also tested for their cytotoxicity against a few cancer and normal cell lines. (-)-Norboldine (4) exhibited potent cytotoxicity towards pancreatic cancer cell line BxPC-3 with an IC50 value of 27.060 ± 1.037 µM, and all alkaloids showed no toxicity towards the normal pancreatic cell line (hTERT-HPNE).
- Preclinical Evidence for the Pharmacological Actions of Naringin: A Review. [JOURNAL ARTICLE]
- Planta Med 2014 Apr 7.
Naringin, chemically 4',5,7- trihydroxyflavanone-7-rhamnoglucoside, is a major flavanone glycoside obtained from tomatoes, grapefruits, and many other citrus fruits. It has been experimentally documented to possess numerous biological properties such as antioxidant, anti-inflammatory, and antiapoptotic activities. In vitro and in vivo studies have further established the usefulness of naringin in various preclinical models of atherosclerosis, cardiovascular disorders, diabetes mellitus, neurodegenerative disorders, osteoporosis, and rheumatological disorders. Apart from this, naringin has also exerted chemopreventive and anticancer attributes in various models of oral, breast, colon, liver, lung, and ovarian cancer. This wide spectrum of biological expediency has been documented to be a result of either the upregulation of various cell survival proteins or the inhibition of inflammatory processes, or a combination of both. Due to the scarcity of human studies on naringin, this review focuses on the various established activities of naringin in in vitro and in vivo preclinical models, and its potential therapeutic applications using the available knowledge in the literature. Additionally, it also encompasses the pharmacokinetic properties of naringin and its inhibition of CYP isoenzymes, and the subsequent drug interactions. Moreover, further clinical research is evidently needed to provide significant insights into the mechanisms underlying the effects of naringin in humans.
- Simultaneous Determination of Eight Active Components in the Traditional Chinese Medicine Dan Deng Tong Nao Capsules by HPLC-MS/MS. [JOURNAL ARTICLE]
- Planta Med 2014 Apr 7.
An high-performance liquid chromatography-tandem mass spectrometry method has been optimised and established for the quality evaluation of the traditional Chinese medicine Dan Deng Tong Nao capsules through simultaneous determination of the following eight active components: danshensu, salvianolic acid A, salvianolic acid C, puerarin, scutellarin, apigenin, 3,4-dihydroxybenzaldehyde, and ferulic acid. All of the analytes were separated on a Waters Xbridge™ C18 column (4.6 × 150 mm, 3.5 µm particle size) with a mobile phase consisting of methanol/acetonitrile (50 : 50, v/v) and water containing 0.1 % formic acid. All of the compounds showed good linearity (R2 > 0.997). The recoveries, measured at three concentration levels, varied from 94.94 to 107.3 %. The validated method was successfully applied to evaluate the eight active components in Dan Deng Tong Nao capsules collected from different production batches. The results suggested that the method established in this study could be considered a good approach to controlling the quality of Dan Deng Tong Nao capsules and other related botanical drugs.
- Anti-inflammatory Terpenes from Flowers of Inula japonica. [JOURNAL ARTICLE]
- Planta Med 2014 Apr 7.
Five new terpenes (1-5) and ten known compounds (6-15) were isolated from Inula japonica, and their structures were identified by spectroscopic analysis. Compounds 3 and 14 showed positive inhibitory effects on nitric oxide production. Furthermore, compound 14 suppressed both leukotriene C4 synthesis and degranulation in c-kit ligand-induced bone marrow-derived mast cells.
- In Vitro and In Vivo Antiplasmodial Activity of Three Rwandan Medicinal Plants and Identification of Their Active Compounds. [JOURNAL ARTICLE]
- Planta Med 2014 Apr 7.
In our previous study, we reported the interesting in vitro antiplasmodial activity of some Rwandan plant extracts. This gave rise to the need for these extracts to also be evaluated in vivo and to identify the compounds responsible for their antiplasmodial activity. The aim of our study was, on the one hand, to evaluate the antiplasmodial activity in vivo and the safety of the selected Rwandan medicinal plants used in the treatment of malaria, with the objective of promoting the development of improved traditional medicines and, on the other hand, to identify the active ingredients in the plants. Plant extracts were selected according to their selectivity index. The in vivo antiplasmodial activity of aqueous, methanolic, and dichloromethane extracts was then evaluated using the classical 4-day suppressive test on Plasmodium berghei infected mice. The activity of the plant extracts was estimated by measuring the percentage of parasitemia reduction, and the survival of the experimental animals was recorded. A bioguided fractionation was performed for the most promising plants, in terms of antiplasmodial activity, in order to isolate active compounds identified by means of spectroscopic and spectrometric methods. The highest level of antiplasmodial activity was observed with the methanolic extract of Fuerstia africana (> 70 %) on days 4 and 7 post-treatment after intraperitoneal injection and on day 7 using oral administration. After oral administration, the level of parasitemia reduction observed on day 4 post-infection was 44 % and 37 % with the aqueous extract of Terminalia mollis and Zanthoxylum chalybeum, respectively. However, the Z. chalybeum extract presented a high level of toxicity after intraperitoneal injection, with no animals surviving on day 1 post-treatment. F. africana, on the other hand, was safer with 40 % mouse survival on day 20 post-treatment. Ferruginol is already known as the active ingredient in F. Africana, and ellagic acid (IC50 = 175 ng/mL) and nitidine (IC50 = 77.5 ng/mL) were identified as the main active constituents of T. mollis and Z. chalybeum, respectively. F. africana presented very promising antiplasmodial activity in vivo. Although most of the plants tested showed some level of antiplasmodial activity, some of these plants may be toxic. This study revealed for the first time the role of ellagic acid and nitidine as the main antimalarial compounds in T. mollis and Z. chalybeum, respectively.
- In Vitro and In Vivo Evaluation of the Effect of Puerarin on Hepatic Cytochrome P450-Mediated Drug Metabolism. [JOURNAL ARTICLE]
- Planta Med 2014 Apr 7.
Puerarin (8-β-D-glucopyranosyl-7-hydroxy-3-(4-hydroxyphenyl)-4H-1-benzopyran-4-one) is a major pharmacological component of Puerariae Radix, the root of Pueraria lobata. We investigated the effect of puerarin on hepatic cytochrome P450-mediated drug metabolism in rats and humans. The in vitro cytochrome P450 inhibitory effect of puerarin in human and rat liver microsomes was evaluated using the following model cytochrome P450 substrates: phenacetin for CYP1A, diclofenac for CYP2C, dextromethorphan for CYP2D, and testosterone for CYP3A. The in vivo pharmacokinetics of intravenous and oral buspirone, a probe substrate for CYP3A, was studied with single simultaneous intravenous coadministration of puerarin in rats. In the in vitro cytochrome P450 inhibition study, the rate of disappearance of testosterone was significantly reduced in the presence of 10 µM PU, while that of other cytochrome P450 substrates was not significantly affected in both human and rat liver microsomes, suggesting that puerarin inhibits the in vitro hepatic CYP3A-mediated metabolism in the human and rat systems (IC50 = 15.5 ± 3.9 µM). After intravenous administration of buspirone with single simultaneous coadministration of intravenous puerarin at a dose of 10 mg/kg in rats, the total area under the plasma concentration-time curve from time zero to time infinity was increased while time-averaged total body clearance decreased. When buspirone was orally administered in rats with the 10 mg/kg intravenous puerarin coadministration, both total area under the plasma concentration-time curve from time zero to time infinity and the extent of absolute oral bioavailability were significantly increased. Therefore, results of the in vitro microsomal and in vivo pharmacokinetic studies suggest the possible inhibition of hepatic CYP3A-mediated drug metabolism by puerarin administration, potentially leading to metabolism-mediated herb-drug interactions with clinical significance.
- Enhancement of Voltage-Gated K+ Channels and Depression of Voltage-Gated Ca2+ Channels Are Involved in Quercetin-Induced Vasorelaxation in Rat Coronary Artery. [JOURNAL ARTICLE]
- Planta Med 2014 Apr 7.
Quercetin is one of the most common flavonoids in the human daily diet. Its affects the coronary artery, especially L-type voltage-gated Ca2+ channels and voltage-gated K+ channels in the arterial smooth muscle cells, which are poorly understood. The present experiments were designed to study the myogenic effect of quercetin and its possible underlying mechanisms in the rat coronary artery. A wire myograph was used to observe the myogenic effects. Arterial smooth muscle cells were freshly isolated from the rat coronary artery and the intracellular free Ca2+ concentration was measured with molecular probe fluo-4-AM. The effects of quercetin on L-type voltage-gated Ca2+ channels and voltage-gated K+ channels were studied using a whole-cell patch clamp. Quercetin (3-30 µM) produced a depression and relaxation on the contraction induced by KCl or the thromboxane A2 analog 9,11-Dideoxy-9α,11α-methanoepoxy prostaglandin F 2α . The vasorelaxation was attenuated by 4-aminopyridine, a specific voltage-gated K+ channel inhibitor, but was not affected by the NG-nitro-L-arginine methylester ester (a nitric oxide synthesis inhibitor), glibenclamide (a ATP-activated K+ channel inhibitor), iberiotoxin (a Ca2+-activated K+ channel inhibitor), BaCl2 (an inward rectifier K+ channel inhibitor), or by endothelium denudation. At the same concentrations, quercetin reduced the KCl-induced elevation of the intracellular free Ca2+ concentration, inhibited the inward Ca2+ currents through L-type voltage-gated Ca2+ channels, and increased the outward K+ currents through voltage-gated K+ channels in the rat coronary artery smooth muscle cells. Collectively, our results demonstrate that quercetin possesses vasospasmolytic effects in RCA and suggest that depression of the Ca2+ influx through L-type voltage-gated Ca2+ channels and augmentation of voltage-gated K+ channel activity in the myocytes may underlie coronary relaxation.
- The Anti-Promyelocytic Leukemia Mode of Action of Two Endophytic Secondary Metabolites Unveiled by a Proteomic Approach. [JOURNAL ARTICLE]
- Planta Med 2014 Apr 7.
As a result of a program to find antitumor compounds of endophytes from medicinal Asteraceae, the steroid (22E,24R)-8,14-epoxyergosta-4,22-diene-3,6-dione (a) and the diterpene aphidicolin (b) were isolated from the filamentous fungi Papulaspora immersa and Nigrospora sphaerica, respectively, and exhibited strong cytotoxicity against HL-60 cells. A proteomic approach was used in an attempt to identify the drugs' molecular targets and their respective antiproliferative mode of action. Results suggested that the (a) growth inhibition effect occurs by G2/M cell cycle arrest via reduction of tubulin alpha and beta isomers and 14-3-3 protein gamma expression, followed by a decrease of apoptotic and inflammatory proteins, culminating in mitochondrial oxidative damage that triggered autophagy-associated cell death. Moreover, the decrease observed in the expression levels of several types of histones indicated that (a) might be disarming oncogenic pathways via direct modulation of the epigenetic machinery. Effects on cell cycle progression and induction of apoptosis caused by (b) were confirmed. In addition, protein expression profiles also revealed that aphidicolin is able to influence microtubule dynamics, modulate proteasome activator complex expression, and control the inflammatory cascade through overexpression of thymosin beta 4, RhoGDI2, and 14-3-3 proteins. Transmission electron micrographs of (b)-treated cells unveiled dose-dependent morphological characteristics of autophagy- or oncosis-like cell death.
- Effect of Icariin on UDP-Glucuronosyltransferases in Mouse Liver. [Journal Article]
- Planta Med 2014 Mar; 80(5):387-92.
Icariin is a flavonol glycoside isolated from Epimedium genus and has been used in the treatment of sexual dysfunction and osteoporosis. Our laboratory has shown that icariin is beneficial in brain disorders and cardiovascular diseases. Since icariin is widely used with other herbs and drugs, to understand its potential herb-drug interactions is of importance. Recently, icariin was shown to inhibit UDP-glucuronosyltransferases, particularly the Ugt1 family enzymes in vitro, but little is known about such effects in vivo. This study investigated the effects of icariin on the expression of UDP-glucuronosyltransferases and cytochrome P450 enzymes in the livers of mice. Adult mice were treated with icariin at doses of 0, 40, 80, 160, and 320 mg/kg, p. o., for 7 days. Phenobarbital (120 mg/kg, p. o.) and rifampin (360 mg/kg, p. o.) were given twice daily for 3 days as positive controls. The livers were removed to determine UDP-glucuronosyltransferase activity and total RNA isolation. The UDP-glucuronosyltransferase activities towards 2-aminophenol were basically unaltered by the treatments. The expression of Cyp2b10 was increased 35-fold by phenobarbital, and Cyp3a11 was increased 4.5-fold by rifampin. Icariin did not affect Cyp2b10 and Cyp3a11 expression, but unexpectedly increased Cyp4a14 expression. Both phenobarbital and rifampin increased Ugt1a1, Ugt1a6, Ugt1a9, and icariin but did not show any suppressive effects on the Ugt1 family genes. Icariin at the highest dose (320 mg/kg) slightly increased Ugt2b1, Ugt2b5, and Ugt2b36. These findings indicate that icariin did not suppress UDP-glucuronosyltransferase expression, instead, it increased the mRNA of Cyp4a14 and slightly increased Ugt2b isoforms in mouse livers.
- Editorial - planta medica abstract issue. [Journal Article]
- Planta Med 2014 Mar; 80(5):353.