Phytomedicine

Editorial Board

2010-08-01

Antiasthmatic effect of Nigella sativa in airways of asthmatic patients

M.H. Boskabady, N. Mohsenpoor, L. Takaloo — 2010-02-11

Abstract: In the present study, the antiasthmatic (bronchodilatory) effect of the boiled extract of Nigella sativa in the airways of asthmatic patients was examined.The bronchodilatory effects of 50 and 100mg/kg of boiled extract in comparison with 6mg/kg theophylline were studied on 15 asthmatic patients. Pulmonary function tests (PFTs) including forced expiratory volume in one second (FEV1), peak expiratory flow (PEF), maximal mid expiratory flow (MMEF), maximal expiratory flow at 75, 50 and 25% of the FVC (MEF75, MEF50, and MEF25, respectively) and specific airway conductance (sGaw) were measured before administration and repeated , 30, 60, 90 120, 150, and 180min after administration of the oral extract and theophylline.The results showed that the extract caused significant increases in all measured pulmonary function tests (PFTs), in most time intervals, (p<0.05 to p<0.001). However, the increase in FEV1, MMEF and MEF50 due to both doses of boiled extract and increase in MEF75 and MEF25 due to its lower doses were significantly lower than those of theophylline (p<0.05 to p<0.001). The onset of brochodilatory effect of extract was similar to that of theophylline beginning 30min, and the effect of extract decline after 150min following administration similar to the effect of theophylline. The effect of both doses of the extract was also significantly less than that of salbutamol at 30 minutes post administration (p<0.001 for all cases).The results of the present study showed that Nigella sativa has a relatively potent antiasthmatic effect on asthmatic airways. However, the effects of boiled extract of this plant on most measured PFTs was less than those of theophylline at concentrations used.

Thymoquinone, a potential therapeutic agent of Nigella sativa, binds to site I of human serum albumin

2010-02-19

Abstract: Thymoquinone (TQ) is the main constituent of Nigella sativa essential oil which shows promising in vitro and in vivo antineoplastic growth inhibition against various tumor cell lines. Because of the increasing interest to test it in pre-clinical and clinical researches for assessing its health benefits, we here evaluate the interactions between TQ and human serum albumin (HSA), a possible carrier of this drug in vivo. Binding to HSA was studied using different spectroscopic techniques. Fourier transform infrared (FT-IR) and circular dichroism (CD) spectroscopies suggest that the association between TQ and HSA does not affect the secondary structure of HSA. Using fluorescence spectroscopy, one mole of TQ was found to bind one mole of HSA with a binding constant of 2.39 ± 0.2 104M−1. At 25°C (pH 7.4), van’t Hoff’s enthalpy and entropy that accompany the binding were found to be −10.24kJ/mol−1 and 45J/mol−1K−1 respectively. The thermodynamic analysis of the TQ-HSA complex formation shows that the binding process is enthalpy driven and spontaneous, and that hydrophobic interactions are the predominant intermolecular forces stabilizing the complex. Furthermore, displacement experiments using warfarin and ibuprofen indicate that TQ could bind to site I of HSA, which is also in agreement with the results of the molecular modeling study.

Croton sonderianus essential oil samples distinctly affect rat airway smooth muscle

2010-02-22

Abstract: Plants of the genus Croton have been used extensively in the northeast of Brazil for treating various clinical conditions. Previous studies have demonstrated that the essential oil of some specimens of Croton sp. have a relaxing effect on tracheal smooth muscle. Our study aimed to characterize the effects of Croton sonderianus essential oil samples, collected at 1:00pm (EO-13) and 9:00pm (EO-21), on rat tracheal smooth muscle. The two samples were submitted to gas chromatography (GC) and mass spectrometry (MS) analysis to identify their components. Rat tracheal smooth muscle strips were used to assess the biological activity.The major constituents of EO-21 were: spathulenol (18.32%), β-caryophyllene (14.58%) and caryophyllene oxide (8.54%) and the major constituents of EO-13 were bicyclogermacrene (16.29%), β-phellandrene (15.42%) and β-caryophyllene (13.82%). These samples showed an antispasmodic effect on tracheal smooth muscle strips pre-contracted with high K+ concentration (80mM) or with acetylcholine. EO-21 increased baseline tonus while EO-13 provoked a decrease.These results demonstrated that EO-13 and EO-21 have different chemical composition and showed myorelaxant activity. In conclusion, EO-13 and EO-21 may have potential therapeutic use in the treatment of bronchospasm.

Therapeutic effect of norisoboldine, an alkaloid isolated from Radix Linderae, on collagen-induced arthritis in mice

Y. Luo, M. Liu, Y. Xia, Y. Dai, G. Chou, Z. Wang — 2010-04-05

Abstract: The alkaloid fraction of Radix Linderae, the main active component of this herb drug, has been proven to exhibit anti-inflammatory, analgestic and antimicrobial activities. The present study was undertaken to investigate the therapeutic potential of norisoboldine, the major isoquinoline alkaloid present in Radix Linderae, in collagen II -induced arthritis (CIA) of mice as well as the possible mechanisms. CIA was induced in mice by immunization with chicken type II collagen (II). After boosted on day 21, mice were treated with norisoboldine (10, 20, 40mg/kg) for twenty consecutive days. The clinical scores, body weight changes and joint histopathology were evaluated. Norisoboldine treatment significantly alleviated the severity of the disease, based on the reduced clinical scores and elevated the lowered body weights of model mice. Meanwhile, this alkaloid dose-dependently reduced the infiltration of inflammatory cells, synovial hyperplasia and protected joint from destruction. Additionally, the serum level of anti-CII IgG and the CII-stimulated lymphocyte proliferation were remarkably decreased in the groups administered with norisoboldine. An assessment of Th1 function using the delayed-type hypersensitivity model confirmed that norisoboldine also significantly suppressed the enhanced T cell responses in vivo. These findings suggest that norisoboldine might be a potential therapeutic agent for rheumatoid arthritis, and it functions through protecting joint destruction as well as regulating the abnormal immune responses.

Atrovirinone inhibits proinflammatory mediator synthesis through disruption of NF-κB nuclear translocation and MAPK phosphorylation in the murine monocytic macrophage RAW 264.7

2010-04-08

Abstract: In a previous communication we showed that atrovirinone, a 1,4-benzoquinone isolated from the roots of Garcinia atroviridis, was able to inhibit several major proinflammatory mediators of inflammation. In this report we show that atrovirinone inhibits NO and PGE2 synthesis through inhibition of iNOS and COX-2 expression. We also show that atrovirinone inhibits the secretion of IL-1β and IL-6 in a dose dependent fashion whereas the secretion of IL-10, the anti-inflammatory cytokine, was enhanced. Subsequently we determined that the inhibition of proinflammatory cytokine synthesis and inducible enzyme expression was due to a dose-dependent inhibition of phosphorylation of p38 and ERK1/2. We also showed that atrovirinone prevented phosphorylation of I-κBα, which resulted in a reduction of p65NF-κB nuclear translocation as demonstrated by expression analysis. We conclude that atrovirinone is a potential anti-inflammatory drug lead that targets both the MAPK and NF-κB pathway.

Topical anti-inflammatory potential of Physalin E from Physalis angulata on experimental dermatitis in mice

2010-02-11

Abstract: The anti-inflammatory effect of physalin E, a seco-steroid isolated from Physalis angulata L. was evaluated on acute and chronic models of dermatitis induced by 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and oxazolone, respectively, in mouse ear. The changes in ear edema/thickness, production of pro-inflammatory cytokines (TNF-α and IFN-γ), myeloperoxidase (MPO) activity, and histological and immunohistochemical findings were analysed, as indicators of dermal inflammation. Similar to dexamethasone, topically applied Physalin E (0.125; 0.25 and 0.5mg/ear) potently inhibited the TPA and oxazolone-induced dermatitis, leading to substantial reductions in ear edema/thickness, pro-inflammatory cytokines, and MPO activity. These effects were reversed by mifepristone, a steroid antagonist and confirmed by immunohistochemical and histopathological analysis. The data suggest that physalin E may be a potent and topically effective anti-inflammatory agent useful to treat the acute and chronic skin inflammatory conditions.

Cardioprotective properties of Crataegus oxycantha extract against ischemia-reperfusion injury

2010-02-19

Abstract: The aim of the study was to investigate the cardioprotective effect and mechanism of Crataegus oxycantha (COC) extract, a well-known natural antioxidant-based cardiotonic, against ischemia/reperfusion (I/R) injury. Electron paramagnetic resonance studies showed that COC extract was capable of scavenging superoxide, hydroxyl, and peroxyl radicals, in vitro. The cardioprotective efficacy of the extract was studied in a crystalloid perfused heart model of I/R injury. Hearts were subjected to 30min of global ischemia followed by 45min of reperfusion. During reperfusion, COC extract was infused at a dose rate of 1mg/ml/min for 10min. Hearts treated with COC extract showed a significant recovery in cardiac contractile function, reduction in infarct size, and decrease in creatine kinase and lactate dehydrogenase activities. The expressions of xanthine oxidase and NADPH oxidase were significantly reduced in the treated group. A significant upregulation of the anti-apoptotic proteins Bcl-2 and Hsp70 with simultaneous downregulation of the pro-apoptotic proteins cytochrome c and cleaved caspase-3 was observed. The molecular signaling cascade including phospho-Akt (ser-473) and HIF-1α that lead to the activation or suppression of apoptotic pathway also showed a significant protective role in the treatment group. No significant change in phospho-p38 levels was observed. The results suggested that the COC extract may reduce the oxidative stress in the reperfused myocardium, and play a significant role in the inhibition of apoptotic pathways leading to cardioprotection.

Leonurine improves ischemia-induced myocardial injury through antioxidative activity

X.H. Liu, L.L. Pan, P.F. Chen, Y.Z. Zhu — 2010-02-25

Abstract: The present study was designed to investigate the protective effects of 4-guanidino-n-butyl syringate (leonurine), a compound in Herba Leonuri (HL) on ischemic rat heart to determine the protective mechanisms associated with ischemic rat hearts. Rat heart ischemia was induced by ligation of the left coronary artery. Creatine kinase (CK) and lactate dehydrogenase (LDH) in plasma and superoxide dismutase (SOD) activity in heart homogenates were measured. We found leonurine significantly decreased levels of LDH and CK activities in plasma. This observation corresponded with decreased infarct size of ischemic rat heart induced by ligation of the left coronary artery. Moreover, the mRNA expression of the pro-apoptotic gene Bax was significantly down-regulated by 0.68-fold (p<0.05) and the anti-apoptotic gene Bcl-2 was up-regulated by 1.41–fold (p<0.05) in the leonurine treated groups as compared with acute myocardium ischemia (MI) controls measured by RT-PCR. Correspondingly, Bcl-2 and Bax protein levels detected by Western blotting coincided with gene expression levels. In addition, the mRNA expression level of the antioxidant enzyme Mn-SOD was significantly increased 1.23-fold (p<0.05) and this finding corresponded with an observed increase in SOD activity and also with a committed decrease in lipid peroxidation. Taken together, our results demonstrated that leonurine attenuated myocardium injury during MI via antioxidative and anti-apoptotic effects and leonurine might become a useful adjuvant cardioprotective agent.

Baicalin, a flavonoid from Scutellaria baicalensis Georgi, activates large-conductance Ca2+-activated K+ channels via cyclic nucleotide-dependent protein kinases in mesenteric artery

2010-02-19

Abstract: Baicalin isolated from Scutellaria baicalensis is a traditional Chinese herbal medicine used for cardiovascular dysfunction. The ionic mechanism of the vasorelaxant effects of baicalin remains unclear. We investigated whether baicalin relaxes mesenteric arteries (MAs) via large-conductance Ca2+-activated K+ (BKCa) channel activation and voltage-dependent Ca2+ channel (VDCC) inhibition. The contractility of MA was determined by dual wire myograph. BKCa channels and VDCCs were measured using whole-cell recordings in single myocytes, enzymatically dispersed from rat MAs. Baicalin (10-100μM) attenuated 80mM KCl-contracted MA in a concentration-related manner. L-NAME (30μM) and indomethacin (10μM) little affected baicalin (100μM)-induced vasorelaxations. Contractions induced by iberiotoxin (IbTX, 0.1μM), Bay K8644 (0.1μM) or PMA (10μM) were abolished by baicalin 100μM. In MA myocytes, baicalin (0.3-30μM) enhanced BKCa channel activity in a concentration-dependent manner. Increased BKCa currents were abolished by IbTX (0.1μM). Baicalin-mediated (30μM) BKCa current activation was significantly attenuated by an adenylate cyclase inhibitor (SQ 22536, 10μM), a soluble guanylate cyclase inhibitor (ODQ, 10μM), competitive antagonists of cAMP and cGMP (Rp-cAMP, 100μM and Rp-cGMP, 100μM), and cAMP- and cGMP-dependent protein kinase inhibitors (KT5720, 0.3μM and KT5823, 0.3μM). Perfusate with PMA (0.1μM) abolished baicalin-enhanced BKCa currents. Additionally, baicalin (0.3-30μM) reduced the amplitude of VDCC currents in a concentration-dependent manner and abolished VDCC activator Bay K8644-enhanced (0.1μM) currents. Baicalin produced MA relaxation by activating BKCa and inhibiting VDCC channels by endothelium-independent mechanisms and by stimulating the cGMP/PKG and cAMP/PKA pathways.

In vitro synergistic efficacy of combination of amphotericin B with Myrtus communis essential oil against clinical isolates of Candida albicans

M. Mahboubi, F. Ghazian Bidgoli — 2010-03-02

Abstract: In this study, we evaluated the antifungal activity of the essential oil from Myrtus communis (myrtle) leaves against Candida albicans (eight clinical isolates and one ATCC type strains) and different species of Aspergillus sp (A. niger, A. parasiticus, six isolates of Aspergillus flavus) using broth micro dilution assay. In addition, we evaluated the synergistic effect between the essential oil and the antifungal compound amphotericin B by checkboard micro titer assay. The essential oil was obtained from myrtle leaves by hydrodistillation method and the oil was analyzed by GC and GC-MS methods. Chemical analysis of oil revealed the presence of 70 components, representing 99.23% of the total oil. 1,8-cineole (36.1%), α-pinene (22.5%), linalool (8.4%), bornyl acetate (5.2%), α-terpineol (4.4%), linalyl acetate (4.2%) and limonene (3.8%) were found to be the major components of the oil. The antifungal evaluating showed that myrtle oil exhibited good antifungal activity against fungi. Myrtle oil showed significant antifungal activity when combined with amphotericin B.

First isolation and characterization of a novel lectin with potent antitumor activity from a Russula mushroom

G. Zhang, J. Sun, H. Wang, T.B. Ng — 2010-04-08

Abstract: To date only a ribonuclease and a protein with anti-HIV-1 reverse transcriptase activity have been isolated from mushrooms of the genus Russula. In this study a novel lectin, with a molecular weight of 32kDa, and a unique N-terminal sequence different from other lectins, was isolated from the mushroom Russula lepida. It represents the first lectin isolated from Russula mushrooms. The purification scheme involved (NH4)2SO4 precipitation, ion exchange chromatography on diethylaminoethyl DEAE-cellulose and SP-Sepharose, and fast protein liquid chromatography-gel filtration on Superdex 75. The hemagglutinating activity of the lectin (RLL) was inhibited by inulin and O-nitrophenyl-β-D-galacto-pyranoside. The lectin was stable at temperatures up to 70°C (half of the activity was preserved at 80°C), and in the presence of NaOH or HCl solutions up to a concentration of 12.5mM. Its hemagglutinating activity was reduced in the presence of Mn2+, Co2+, and Hg2+ ions, and enhanced by Cu2+ ions. It exhibited antiproliferative activity toward hepatoma Hep G2 cells and human breast cancer MCF-7 cells with an IC50 of 1.6μM and 0.9μM, respectively. Daily intraperitoneal injections of RLL (5.0mg/kg body weight/day for 20 days) brought about 67.6% reduction in the weight of S-180 tumor. RLL was devoid of antifungal, ribonuclease, and HIV-1 reverse transcriptase inhibitory activities.

Pisiferdiol and pisiferic acid isolated from Chamaecyparis pisifera activate protein phosphatase 2C in vitro and induce caspase-3/7-dependent apoptosis via dephosphorylation of Bad in HL60 cells

N. Aburai, M. Yoshida, M. Ohnishi, K. Kimura — 2010-02-15

Abstract: Protein phosphatase 2C (PP2C) dephosphorylates a broad range of substrates and regulates apoptosis, stress response and growth-related pathways. In the course of screening for PP2C activators from natural sources, we isolated abietane-type diterpenes, pisiferdiol and pisiferic acid from Chamaecyparis pisifera. Pisiferdiol having a unique seven-membered ring showed more specific PP2C activation activity (1.3-fold at 100μM) than pisiferic acid having a normal six-membered ring and oleic acid, which is known to activate PP2C. Pisiferdiol and pisiferic acid showed mixed-type activation with respect to α-casein, and this differed from the non-competitive activation of oleic acid in vitro. In vivo, the cytotoxicity of pisiferdiol toward human promyelocytic leukemia cell line HL60 with an IC50 value of 18.3μM was 2-fold and 7-fold stronger than those of pisiferic acid and oleic acid, and pisiferdiol induced apoptosis through a caspase 3/7-dependent mechanism involving the dephosphorylation of Bad, which is a PP2C substrate. We thus conclude that pisiferdiol and pisiferic acid are novel PP2C activators, and the more specific activator, pisiferdiol, may be a useful chemical probe to study PP2C-mediated signaling pathways, and a lead compound for pharmaceutical agents.

Apoptosis inducing activity of steroidal constituents from Solanum xanthocarpum and Asparagus racemosus

K.K. Bhutani, A.T. Paul, W. Fayad, S. Linder — 2010-02-22

Abstract: A series of Sarsapogenin and Diosgenin derived steroidal constituents (1-12), isolated from Solanum xanthocarpum and Asparagus racemosus were screened for their ability to induce cell death and apoptosis of colon carcinoma cells. The carbohydrate moieties linked to the steroid backbones were found to strongly influence cytotoxic activity and cell death mode (apoptosis or necrosis). Compound 10, from A. racemosus was found to be a potent inducer of apoptosis.

Potential antidepressant properties of Radix Polygalae (Yuan Zhi)

P. Liu, Y. Hu, D.-H. Guo, D.-X. Wang, H.-H. Tu, L. Ma, T.-T. Xie, L-Y. Kong — 2010-06-14

Abstract: Radix Polygalae (“Yuan Zhi”, the roots of Polygala tenuifolia Willd., YZ) is an important herb used in traditional Chinese medicine to mediate depression. The present study was designed to verify the antidepressant effects of the standardized YZ ethanol extract (YZE) and its four fractions YZ-30, YZ-50, YZ-70 and YZ-90 on the tail suspension (TST) and forced swimming test (FST). Furthermore, the standardization of the fractions obtained from the separation procedures was carried out by high-performance liquid chromatography (HPLC)-fingerprint. The YZ-50 fraction (Oligosaccharide esters –enriched, oral (200mg/kg) showed a significant anti-immobility like effects. The data of YZ-50 on the corticosterone-induced injure of SH-SY5Y human neuroblastoma cell indicated that YZ-50 may have biological effects on neuroprotection. Proliferation of cell lines was assessed by dimethylthiazoldiphenyltetrazoliumbromide (MTT) and 5-bromo-2′-deoxyuridine (BrdU) incorporation assays. It was found that YZ-50 and its two bioactive compounds, 3,6′-di-o-sinapoyl-sucrose (DISS) and tenuifoliside A(TEA) showed protection activities in SY5Y cells from the lesion. By using bioassay-screening methods, our results indicate that the presence of oligosaccharide esters such as DISS and TEA in this herb may be responsible for the cytoprotective activity effects.

Roasted licorice extracts dampen high glucose-induced mesangial hyperplasia and matrix deposition through blocking Akt activation and TGF-β signaling

J. Li, Y.S. Lee, J.-S. Choi, H.-Y. Sung, J.-K. Kim, S.S. Lim, Y.-H. Kang — 2010-04-12

Abstract: Diabetic nephropathy (DN) characterized as nephrotic syndrome and diffuse glomerulosclerosis can cause renal failure and end-stage kidney disease. Expansion of mesangial matrix around capillaries in the kidney glomeruli is a prominent feature of DN. This study investigated whether licorice extracts inhibited mesangial cell (MC) proliferation and matrix accumulation induced by high glucose (HG). Human renal MC were cultured in media containing 5.5mM glucose plus 27.5mM mannitol as an osmotic control or 33mM glucose for 3 d in the presence of water or ethanol extracts from raw licorice (LW, LE) or roasted licorice (RLW, RLE). Non-polar components including glycyrrhetic acid were elevated during licorice roasting, whereas polar components soluble in water extracts were diminished. Exposure of cells to HG caused significant increases in collagen IV secretion and connective tissue growth factor (CTGF) expression, which was appeased by RLW and RLE at transcriptional levels. The inhibitory potency was high in the order of RLE ≥ RLW ≥ LE >>LW. Non-polar glycyrrhetic acid but not glycyrrhizin retarded HG-stimulated mesangial matrix deposition through diminishing CTGF expression. In addition, RLW and RLE but not LW modulated membrane type matrix metalloproteinase-1 (MT-1 MMP) expression, MMP-2 activity and tissue inhibitor of MMP-2 (TIMP-2), which facilitated the degradation of mesangial matrix. Furthermore, the augmented expression of CTGF and TIMP-2 in HG-exposed cells was mediated by Akt activation and TGF-β/Smad signaling through PKCβ2-responsive signaling pathways. However, HG-down-regulated MT-1 MMP expression was independent of activation of ERK1/2 and Akt when using their inhibitors of DB98059 (ERK1/2) and LY294002 (Akt) alone or in combination. These results demonstrate that extracts from roasted licorice may be highly potent therapeutic agents for the prevention and treatment of mesangial fibrosis and glomerulosclerosis leading to diabetes nephropathy due to longstanding diabetes mellitus.

Protective effects of Asiaticoside on acute liver injury induced by lipopolysaccharide/D-galactosamine in mice

2010-02-22

Abstract: Asiaticoside (AS), a triterpenoid product isolated from Centella asiatica, has been described to exhibit anti-inﬂammatory activities in several inflammatory models. However, the effects of AS on liver injury are poorly understood. The present study was undertaken to investigate whether AS is efficacious against Lipopolysaccharide (LPS) /D-galactosamine (D-GalN)-induced acute liver injury in mice and its potential mechanisms. AS (5, 10 and 20 mg/kg/d) was pretreated orally once daily for 3 days before LPS/D-GalN injected in mice. The mortality, hepatic tissue histology, plasma levels of Tumor necrosis factor-alpha (TNF-α) and alanine aminotransferase (ALT) and aspartate aminotransferase (AST), hepatic tissue TNF-α and caspase-3 activity were measured. Besides, western blotting analysis of phospho-p38 mitogen-activated protein kinase (phospho-p38 MAPK), phospho-c-jun N-terminal kinase (phospho-JNK) and phospho-extracellular signal regulated kinase (phospho-ERK) were determined. As a result, AS showed significant protection as evidenced by the decrease of elevated aminotransferases, hepatocytes apoptosis and caspase-3, alleviation of mortality and improvement of liver pathological injury in a dose-dependent manner. Further, we found that AS dose-dependently reduced the elevation of phospho-p38 MAPK, phospho-JNK, phospho-ERK protein and TNF-α mRNA expression in liver tissues and plasma TNF-α. These results suggest that AS has remarkable hepatoprotective effects on LPS/D-GalN-induced liver injury and the possible mechanism is related to inhibition of TNF-α and MAPKs.

Enhancing effects of a chromone glycoside, eucryphin, isolated from Astilbe rhizomes on burn wound repair and its mechanism

Maho Sumiyoshi, Yoshiyuki Kimura — 2010-02-10

Abstract: We previously reported that three compounds isolated from Astilbe thunbergii rhizomes accelerated burn wound healing. Among the three substances, eucryphin enhanced burn wound healing most strongly; however, the biological mechanisms of eucryphin are not yet well understood and here we examined the effects on chemokine, growth factor, and cytokine productions in in vivo and in vitro experiments. We have set burn wounds on the backs of mice and topically applied either vehicle alone or vehicle containing low doses of eucryphin to the burn wound. We examined the effects of eucryphin on chemokine, cytokine, and growth factor production at the wound site and in various cells. Eucryphin (10−4 to 10−8% ointment) facilitated burn wound repair compared to the vehicle control. Eucryphin (100ng per wound) increased IL-1β, MCP-1, VEGF, and TGF-β1 levels in the exudates from the wound area. Eucryphin increased VEGF, TGF-β1, and HIF-1α expression levels in keratinocytes. These findings suggest that the enhancement of burn wound healing by eucryphin might be due to promotional angiogenesis during skin wound repair as a result of the stimulation of VEGF and TGF-β1 production caused by the increase in HIF-1α expression in keratinocytes.

The effect of standardized Echinacea purpurea extract on rat cytochrome P450 expression level

2010-04-08

Abstract: It is claimed that application of botanical supplements or herbal medicinal products with synthetic drugs that are cytochrome P450 enzymes substrates may induce significant herb-drug interactions and may alter pharmacotherapy. Echinacea preparations are one of the best selling products in the Europe and their medicinal use is still increasing but data about interactions of Echinacea extract with CYP enzymes are limited. In this study, we have investigated potential influence of standardized Echinacea purpurea extract containing 3,7% polyphenolic compounds on the mRNA expression level of major CYP450 enzymes using animal model. Total RNA was isolated from the rat liver tissue according to the manufacturer’s protocol. Complementary DNA was synthesized from a mature mRNA template using reverse transcription. The level of mRNA expression in liver was analyzed by real-time quantitative PCR using specific target primers for CYP450 genes. In this study, it was demonstrated a significant increase of rat CYP2D1 and CYP1A1 expression level by 40% (p=0,007) and 80% (p=0,01), respectively. A weak inductory effect of the extract was observed for CYP1A2 by 16% (p>0,05) compared with the control group. The levels of rat CYP3A1 and CYP3A2 mRNA were reduced by 41% (p<0,05) and 25% (p=0,001), respectively. A weak inhibitory effect was observed for CYP2D2 by 15% (p=0,008) and CYP2C6 by 18% (p=0,004) after long application of the Echinacea ethanolic extract. CYP2D2 and CYP2C6 activities were also inhibited by extract but in a lesser degree than CYP3A1 activity. Moreover, very little or no inhibition was noted for CYP2E1 both after 3 and 10 days of treatment. Our in vivo data indicate that the Echinacea ethanolic extract can potently inhibit the expression of CYP3A1/2 and can also induce of CYP1A1, CYP2D1. These findings suggest that Echinacea extract may influence the P450-mediated metabolism of different drugs and may initiate chemical carcinogenesis by activation of some compounds to their carcinogenic metabolites.