Rutaecarpine prevents Ang II -induced vascular smooth muscle cell senescence through TRPV1/ SIRT1 pathway / 中国药理学通报

Aim To evaluate the effects of Rutaecarpine(Rut)on the expression of SIRT1 and the senescence of vascular smooth muscle cells(VSMCs)induced by angiotensin Ⅱ.Methods VSMC senescencewas induced by exposure to AngⅡ(1 μmol·L-1)for 72 h.VSMCs were treated with different concentrations of Rut(0.3, 1, 3 μmol·L-1).TRPV1 competitive antagonist CAPZ(10 μmol·L-1)and AMPK inhibitor Compound C(1 μmol·L-1)were used to explore whether TRPV1/AMPK mediated the protective effect of Rut.The quantity of senescent cells were determined by senescence-associated SA-β-Gal staining, and the intracellular ROS level was measured by(DCFH-DA)fluorescent probe.The migration ability of VSMCs was evaluated by Wound-healing assay combined with Transwell assay.The protein level of longevity protein SIRT1 and senescence-related proteins p53, p21 and AMPK phosphorylation level were detected by Western blot.Results Rut significantly inhibited Ang Ⅱ-induced VSMC senescence and ROS production and prevented VSMCs migration.Preprocessing of TRPV1 antagonist CAPZ could abolish the protective effect of Rut.Ang Ⅱ inhibited the expression of longevity protein SIRT1.Rut recovered SIRT1 expression in a dose-dependent manner, while prevented the up-regulation of senescence-related proteins p53 and p21.Ang Ⅱ inhibited AMPK phosphorylation, pre-treatment with Rut restored AMPK phosphorylation level.CAPZ and Compound C eliminated the up-regulating function of Rut on SIRT1 expression.Conclusions Rut up-regulates the expression of SIRT1 and prevents the senescence and migration of VSMCs induced by Angiotensin Ⅱ, which is related to activation of the TRPV1/AMPK signaling pathway.

Study on Liver Injury of Different Components of Evodia Fructus in Vivo and in Vitro / 中国实验方剂学杂志

ObjectiveTo evaluate the in vivo and in vitro toxicity of Evodia Fructus water extraction and its index components， and provide a basis for basic research on the toxic substances of Evodia Fructus. MethodInstitute of Cancer Research（ICR） mice were divided into high， medium and low dose groups of water extraction of Evodia Fructus and a blank control group. The administration groups were respectively given 80，60，40 g·kg-1 water extraction of Evodia Fructus， the blank control group was given distilled water in equal volume， blood was taken 24 hours later to determine the serum alanine aminotransferase（ALT）and aspartate aminotransferase（AST）values， the liver was weighed and histopathological examination was performed. Evodia Fructus water extract， evodiamine， rutaecarpine and limonin were respectively acted on HepG2 cells for 24 h， and cell counting kit-8（CCK-8） method was used to investigate the cytotoxicity. The ICR Mice were divided into two groups， one group was given by oral gavage and the other group was given intraperitoneal injection. The two routes of administration were separately given 3 index components of Evodia Fructus， and the dosage was 200 mg·kg-1. Take blood 24 hours after administration to determine the activity of ALT and AST in serum， and take liver to calculate liver index. ResultCompared with the blank group， the high and medium dose groups of Evodia Fructus water extract were depressed 24 hours after administration， and the behavior of the low dose group was not significantly abnormal. The serum biochemical results showed that the activities of serum ALT and AST in the high and medium dose groups were significantly increased （P<0.01）， the activities of serum ALT and AST in the low dose group were significantly increased， and the histopathological results showed that the high and medium dose groups were significantly increased Punctate necrosis and vacuolar degeneration appeared in the liver of the medium dose group， and there was no obvious abnormality in the low dose group. Compared with the blank group， evodiamine and rutaecarpine had a certain inhibitory effect on the proliferation of HepG2 cells， but the inhibitory effect was not strong. Limonin had no significant inhibitory effect on the proliferation of HepG2 cells. Compared with the control group， the 3 index components of Evodia Fructus have no effect after oral administration. There was no significant difference in the activity of ALT and AST in serum of mice， and there was no significant difference in liver index. Intraperitoneal injection of evodiamine and rutaecarpine can cause the activity of serum ALT and AST to increase， and limonin can cause ALT activity was significantly increased （P<0.01）， and the liver index was significantly increased （P<0.05）. ConclusionEvodia Fructus water extract can cause acute liver injury in mice， Oral administration of evodiamine， rutaecarpine and limonin had no damage to the liver of mice. Intraperitoneal administration of evodiamine and rutaecarpine had no effect on liver injury in mice， and intraperitoneal administration of limonin could cause acute liver injury in mice.

Rutaecarpine exerted anti-osteroporosis / 药学学报

Osteoprotegerin (OPG), secreted by osteoblasts, is a marker of bone turnover. OPG can inhibit osteoclastic differentiation by binding receptor activator of nuclear factor-κB ligand (RANKL). In this study, we found that rutaecarpine (RUT) had the up-regulating OPG activity, and it could significantly increase OPG protein levels in both mouse embryonic osteogenic precursor MC3T3-E1 and human osteosarcoma U-2OS cells. Osteoblastogenic differentiation calcified nodules staining results showed that RUT significantly promoted the osteogenic differentiation of MC3T3-E1 cells. Osteoclastic differentiation tartrate resistant acid phosphatase (TRAP) staining results showed that RUT obviously inhibited the osteoclast differentiation of mouse macrophages RAW264.7 induced by RANKL. In vivo studies showed that low-dose RUT group (5 mg·kg-1·day-1) and high-dose RUT group (45 mg·kg-1·day-1) treatments for 3 months significantly increased bone density in ovariectomized (OVX) rats; calcein double labeling experiment and toluidine blue staining results indicated that low-dose RUT group promoted bone formation and decreased bone loss in vivo; immunohistochemistry results showed that low-dose RUT group increased the expression of OPG in rat femur. All animal procedures were performed in accordance with the regulations of the Institutional Animal Care and Use Committee of Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences. In summary, this study demonstrated that RUT could up-regulate OPG expression and had promoting osteoblastic differentiation and inhibiting osteoclastic differentiation effects in vitro and in vivo.

UPLC-MS/MS determination of active components from Wuzhuyu Decoction in plasma and brain tissues of nitroglycerin-induced migraine rats / 中国中药杂志

A sensitive and specific ultra-performance liquid chromatography-mass spectrometry(UPLC-MS/MS) method was deve-loped for analysis of rutaecarpine(Ru), evodiamine(Ev), rutaevine(Rv), limonin(Li), ginsendside Rb_1(Rb_1), ginsendside Re(Re) in rat plasma and brain tissues of nitroglycerin-induced migraine rats. Male healthy Sprague-Dawley(SD) rats were orally given multiple dose of optimized(OS) and un-optimized Wuzhuyu Decoction(UNOS), and their blood samples and brainstem were collected at different time points after injection of nitroglycerin(10 mg·kg~(-1)) into the frontal region. The drug concentrations of the 6 analytes in plasma and brainstem were determined by UPLC-MS/MS method. Subsequently, the main pharmacokinetics parameters of plasma were calculated by using Phoenix WinNolin 5.2.1 software. The methodological test showed that all of analytes in both plasma and brainstem homogenate exhibited a good linearity within the concentration range(r>0.994 7). The intra-day and inter-day accuracy, precision, matrix effect, stability of the investigated components meet the requirements for biopharmaceutical analysis. The developed method was successfully applied in pharmacokinetic studies on abovementioned ingredients in rat plasma and brain stem. The plasma pharmacokinetic parameters of active ingredients in two different Wuzhuyu Decoction group were compared, it was found that Rb_1 had higher t_(1/2), T_(max), C_(max), AUC_(0-24 h) and AUC_(0-∞ )in OS group. Meanwhile, Ev had higher t_(1/2) and T_(max) but lower C_(max), AUC_(0-24 h) and AUC_(0-∞), Ru has higher t_(1/2 )but lower C_(max), AUC_(0-24 h) and AUC_(0-∞ )in OS group. The brain tissue distribution of each component were compared between the two groups, the component with higher content in OS, such as Ru at 30 min and 2 h after administration, Ev at 30 min, Rb_1 at 30 min and Rb_1 at 2 h after administration have lower brain tissue distribution than those in UNOS group, while the component with higher content in UNOS, such as Rv at 30 min, 2 h and 12 h after administration had higher brain tissue distribution than those in OS group.

Quality control of eight substances in Changwei San based on quantitative analysis of multi-components by single-marker / 国际药学研究杂志

Objective: To establish a quantitative analysis of multi-components by single marker(QAMS)method for the simultaneous determination of jaceosidin, eupatilin, limoni, evodiamine, rutaecarpine, cinnamyl alcohol, cinnamic acid and cinnamal-dehyde in Changwei San. Methods: The Waters Symmetry C18 column(250 mm×4.6 mm, 5 μm)was used for the separation, and the mobile phase was the acetonitrile(A)and 0.1% phosphoric acid(B)solution in a gradient elution at a flow rate of 1.0 ml/min. The detection wavelengths were set at 345 nm for jaceosidin and eupatilin, 215 nm for limoni, evodiamine and rutaecarpine, and 275 nm for cinnamyl alcohol, cinnamic acid and cinnamaldehyde. With evodiamine as an internal reference standard, the relative correction factors for the other 7 components were established and their contents were calculated with the relative correction factors to achieve the QAMS, and then the differences between the calculated values by QAMS and measured values by the external standard method(ESM) were compared to validate the accuracy and feasibility of the QAMS method. Results: Jaceosidin, eupatilin, limoni, evodiamine, rutaecarpine, cinnamyl alcohol, cinnamic acid and cinnamaldehyde showed good linear relationships within the ranges of 0.98-19.60, 2.67-53.40, 4.06-81.20, 1.98-39.60, 2.69-53.80, 0.56-11.20, 1.49-29.80, and 8.77-175.40 μg/ml(r≥0.9992), whose average recoveries(RSD) were 98.77%(0.96%), 99.38%(1.01%), 100.02%(0.83%), 97.80%(1.40%), 98.91%(1.18%), 96.99% (1.13%), 98.09%(1. 24%)and 99.10%(0.67%), respectively. No significant difference was observed between the calculated values by QAMS and the measured values by ESM. Conclusion: The established QAMS method is simple and accurate, which might be used to evaluate the quality of Changwei San.

Determination of rutaecarpine in Fuzhengpingxiao capsule by HPLC method / 药学实践杂志

Objective To develop a new method to determine the contents of rutaecarpine in Fuzhengpingxiao capsule by HPLC method.Methods Samples were handled by ethanol and extraction with ethyl acetate.The separation was achieved on an Agilent TC-C18column using a mobile phase system of acetonitrile-water(2% Tetrahydrofuran and 0.2 % formic acid)at a flow rate of 1.0 ml/min.The temperature of column was 40 ℃ and the detection wavelength was 240 nm.Results The cali-bration curves of rutaecarpine showed good linearity in the ranges of 1.18-118 μg/ml,r=0.999 9.The results of intra-day and inter-day precisions were both within 2%,the average additional recovery rate was 94.20%.Conclusion The HPLC method was accurate,specific,sensitive and reproducible,which could be used for quality control of rutaecarpine in the preparation of Fuzhengpingxiao capsule.

Inhibitory Effect of Rutaecarpine on Left Ventricular Hypertrophy Rat Model Induced by Abdominal Aorta Coarctation / 医药导报

Objective To investigate the inhibition of rutaecarpine (Rut) on left ventricular hypertrophy rat induced by abdominal aorta coarctation (AAC) and further explore the potential mechanisms. Methods Left ventricular hypertrophy was induced by AAC in male Sprague-Dawley rats.Fifty rats were randomly divided into five groups:model control group,sham operation group,low-,middle- and high-dose (10,20,40 mg?kg-1?d-1 ) Rut group,with 10 rats of each group.Rut was administrated by gavage once daily from the first day after operation for consecutive 4 weeks.The sham operation and model groups were administrated with equal volume of 0.9％ sodium chloride solution.The hemodynamics parameters were detected by BL-420 E biology function laboratory system,and the left ventricular hypertrophy index (LVHI,left ventricular weight/ body weight) was measured at 8 h after administration of the last dose.The pathological changes of left ventricular hypertrophy were evaluated by HE staining.To elucidate the mechanism of protection,the mRNA expressions of atrial natriuretic factor ( ANF),extracellular signal-regulated kinase 2 (ERK2) and MAPK phosphatase-1 (MKP-1) were analyzed by real time RT-PCR,and the protein expressions of MKP-1 and phosphorylated ERK2 (p-ERK2) were examined by Western blotting. Results Left ventricular hypertrophy induced by AAC was evidenced by the increased left ventricular weight (LVW) and LVHI (P<0.01),the decreased± dp/ dt max (P<0.01),and the elevated expression of ANF (P<0.01).Compared with model control,Rut (20,40 mg?kg-1?d-1 ) treatment significantly attenuated AAC-induced rat left ventricular hypertrophy,decreased the LVHI (P<0.05),left ventricular systole pressure (LVSP),and left ventricular end diastolic pressure ( LVEDP ) ( P < 0. 05), and increased ± dp/ dtmax ( P < 0. 01). In addition, Rut ( 20, 40 mg?kg-1?d-1 ) downregulated the expression of ANF,ERK2 mRNA,and ERK2 protein,but upregulated the MKP-1 mRNA and protein expression.However,Rut low-dose (10 mg?kg-1 ?d-1 ) was ineffective (P> 0.05). Conclusion Rut alleviates left ventricular hypertrophy induced by abdominal aorta coarctation,and the protection appears to be due,at least in part,to its inhibitory effects on the MAPK/ ERK signal pathway.

Rutaecarpine protects against bleomycin-induced pulmonary fibrosis through inhibiting Notch1/eIF3a signaling pathway in rats / 中国中药杂志

To investigate whether the protection of rutaecarpine against bleomycin-induced pulmonary fibrosis is mediated by inhibiting Notch1/eukaryotic initiation factor 3a (eIF3a) signaling pathway, and whether these effects are related to the synthesis and release of calcitonin gene-related peptide (CGRP) and inhibition of epithelial-mesenchymal transition (EMT) of alveolar epithelial cells, male Sprague-Dawley rats were randomly divided into five groups (=12), respectively, Control group, bleomycin group, rutaecarpine (100, 300 mg·kg⁻¹) group and capsaicin plus rutaecarpine (300 mg·kg⁻¹) group. Bleomycin (5 mg·kg⁻¹) was used to induce pulmonary fibrosis rat model. Rats were given capsaicin (50 mg·kg⁻¹) by subcutaneous injections 1 days before and 7, 14, 21 days after induce pulmonary fibrosis rat model to deplete endogenous CGRP. At the end of experiments, blood was collected from carotid artery to determinate the plasma levels of CGRP by ELISA. Pulmonary tissue change was observed by HE staining. Masson's trichrome stain was used to demonstration collagen deposition. The collagen I expression in pulmonary tissue was measured by immunohistochemisty. The expression of CGRP, Notch1, eIF3a, collagen I, vimentin, alpha-smooth muscle actin (α-SMA), E-cadherin and zonula occludens-1 (ZO-1) was detected by qPCR or Western blot. Compared with the control group, the pulmonary tissue of the bleomycin group showed significant fibrosis, including significant disturbed alveolar structure, marked thickening of the interalveolar septa and dense interstitial infiltration by inflammatory cells and fibroblasts, and concomitantly with the decrease in plasma CGRP and expression of CGRP. Importantly the expression of E-cadherin and ZO-1 was decreased and expression of Notch1, eIF3a, collagen I, vimentin and α-SMA was increased in bleomycin group (<0.05 or <0.01). Compared with the bleomycin group, rutaecarpine (100, 300 mg·kg⁻¹) group significantly reduced bleomycin-induced pulmonary injury concomitantly with the increase in plasma CGRP and expression of CGRP. Importantly the expression of E-cadherin and ZO-1 was increased and expression of Notch1, eIF3a, collagen I, vimentin and α-SMA was decreased by rutaecarpine treatment (<0.05 or <0.01). All these effects of rutaecarpine were abolished by capsaicin.These results suggest that rutaecarpine protects against bleomycin-induced pulmonary fibrosis by inhibiting Notch1/eIF3a signaling pathway, alleviating EMT process, which is related to the increased synthesis and release of CGRP.

Formulation optimization of rutaecarpine lipid liquid crystalline nanoparticles by Box-Behnken design-response surface methodology / 中草药

Objective To optimize the formulation of rutaecarpine lipid liquid crystalline nanoparticles (Rut-LLCN) by Box-Behnken design-response surface methodology. Methods Rut-LLCN were prepared by precursor injection-high pressure homogenization method. A three factor and three-level Box-Behnken design was employed with the glyceryl monoolein quality, percentage of poloxamer in glyceryl monoolein and the rutaecarpine quality as independent variables, the entrapment efficiency, drug loading, mean particle size and polydispersity index as the dependent variables to sereen the optimal formaula. Results Optimized prescription was GMO 450 mg, F127-GMO 12%, and Rut 20 mg. All items of optimized prescription were similar to target values. According to the optimized prescription, the entrapment efficiency, drug loading, average particle size, and PDI of Rut-LLCN were (84.02 ± 7.99)%, (3.24 ± 0.30)%, (186.90 ± 13.50) nm, and 0.313 ± 0.020, respectively. Conclusion The prescription optimization model of Rut-LLCN was optimized by Box-Behnken designs-response surface methodology, and entrapment efficiency, drug loading, mean particle size, and PDI of Rut-LLCN are measured to investigate the model.

Rutaecarpine Inhibits Intimal Hyperplasia in A Balloon-Injured Rat Artery Model / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the effect and potential mechanisms of rutaecarpine (Rut) in a rat artery balloon-injury model.</p><p><b>METHODS</b>The intimal hyperplasia model was established by rubbing the endothelia with a balloon catheter in the common carotid artery (CCA) of rats. Fifty rats were randomly divided into five groups, ie. sham, model, Rut (25, 50 and 75 mg/kg) with 10 rats of each group. The rats were treated with or without Rut (25, 50, 75 mg/kg) by intragastric administration for 14 consecutive days following injury. The morphological changes of the intima were evaluated by hematoxylin-eosin staining. The expressions of proliferating cell nuclear antigen (PCNA) and smooth muscle (SM) α-actin in the ateries were assayed by immunohistochemical staining. The mRNA expressions of c-myc, extracellular signal-regulated kinase 2 (ERK2), MAPK phosphatase-1 (MKP-1) and endothelial nitric oxide synthase (eNOS) were determined by real-time reverse transcription-polymerase chain reaction. The protein expressions of MKP-1 and phosphorylated ERK2 (p-ERK2) were examined by Western blotting. The plasma contents of nitric oxide (NO) and cyclic guanosine 3',5'-monophosphate (cGMP) were also determined.</p><p><b>RESULTS</b>Compared with the model group, Rut treatment significantly decreased intimal thickening and ameliorated endothelial injury (P<0.05 or P<0.01). The positive expression rate of PCNA was decreased, while the expression rate of SM α-actin obviously increased in the vascular wall after Rut (50 and 75 mg/kg) administration (P<0.05 or P<0.01). Furthermore, the mRNA expressions of c-myc, ERK2 and PCNA were downregulated while the expressions of eNOS and MKP-1 were upregulated (P<0.05 or P<0.01). The protein expressions of MKP-1 and the phosphorylation of ERK2 were upregulated and downregulated after Rut (50 and 75 mg/kg) administration (P<0.05 or P<0.01), respectively. In addition, Rut dramatically reversed balloon injury-induced decrease of NO and cGMP in the plasma (P<0.05 or P<0.01).</p><p><b>CONCLUSION</b>Rut could inhibit the balloon injury-induced carotid intimal hyperplasia in rats, possibly mediated by promotion of NO production and inhibiting ERK2 signal transduction pathways.</p>

Chemical constituents of Euodia rutaecarpa var. officinalis and their antifungal activities / 中草药

Objective: To study the chemical constituents from the fruits of Evodia rutaecarpa var. officinalis. Methods: The constituents were isolated and purified by chromatographic methods. The structures were elucidated by physicochemical properties and spectroscopic methods. The antifungal activities were tested with mycelium growth method. Results: Fifteen compounds were obtained from the 70% ethanol extract of E. rutaecarpa var. officinalis, and were identified as evodiamine (1), rutaecarpine (2), dehydroevodiamine (3), dihydroevocarpine (4), evocarpine (5), 1-methyl-2-undecyl-4 (1H)-quinolone (6), 1-methyl-2-[(4Z,7Z)- 4,7-tridecadienyl]-4 (1H)-quinolone (7), 1-methyl-2-[(6Z,9Z)-6,9-pentadecadienyl-4 (1H)-quinolone (8), limonin (9), shihulimonin A (10), isolimonexic acid (11), wuzhuyurutine B (12), stigmasterol (13), β-sitosterol (14), and β-daucosterin. (15). Conclusion: Compounds 5-8 and 11-13 are isolated from E. rutaecarpa var. officinalis for the first time. Different types of compounds show diverse antimicrobial activities against plant-pathogenic fungi.

Pharmacological effects of drugs mediated by calcitonin gene-related peptide:a review / 中国药理学与毒理学杂志

Calcitonin gene-related peptide (CGRP), a predominant neurotransmitter in sensory nerves, is widely distributed in central and peripheral tissues. In the cardiovascular system, besides relaxing vascular smooth muscle, CGRP protects against ischemic myocardium while inhibiting cardiac remodeling. The pharmacological effects of nitroglycerin and rutaecarpine have proved to be associated with the increase in the synthesis and release of CGRP. In gastrointestinal tissues, CGRP participates in the regulation of gastrointestinal function and has protective effects on the gastric mucosa. Rutaecar?pine, capsaicin and its derivatives can reduce gastric mucosa damage induced by a variety of factors by increasing synthesis and release of CGRP.

Rutaecarpine protects against myocardial ischemia / reperfusion injury through inhibiting Toll-like receptor 4 / NF-κB signaling pathway in rats / 中国药理学通报

Aim To investigate whether the protection of rutaecarpine against myocardial ischemia / reperfusion (I/ R ) injury is mediated by Toll-like receptor 4 (TLR4)/ NF-κB pathway,and whether these effects are related to the release of calcitonin gene-related peptide(CGRP)in plasma. Methods Sprague-Daw-ley rats were subjected to 60 min of ligation of the left anterior descending coronary followed by 3h of reperfu-sion to induce I/ R injury. Rats were pretreated with rutaecarpine 10 min before the ligation,and some rats were pretreated with capsazepine 2 min before rutae-carpine administration. Myocardial infarct size,CGRP concentration in plasma and creatine kinase (CK)ac-tivity in serum were measured. The expression of TLR4 mRNA in myocardial tissue was determined by RT-PCR. The protein expression of TLR4 and NF-κB in myocardial tissue was analyzed by immunohistochemis-try. Results Rutaecarpine (100,300 μg · kg - 1 , iv)significantly reduced the infarct size and the serum CK activity concomitantly with the increase in plasma CGRP concentration (P < 0. 05). Importantly,the ex-pression of TLR4 (both mRNA and protein)and NF-κB (protein)was increased by myocardial I/ R injury, and dramatically inhibited by rutaecarpine pretreatment (P < 0. 05). All these effects of rutaecarpine were a-bolished by capsazepine (1. 5 mg·kg - 1 ,iv),a spe-cific antagonist for vanilloid receptor-1. Conclusion Rutaecarpine protects against myocardial I/ R injury by inhibiting TLR4 / NF-κB pathway,which is related to the increased release of CGRP.

Chemical constituents of fruits from Evodia delavayi / 中国药学杂志

OBJECTIVE: To study the chemical constituents from Evodia delavayi. METHODS: The constituents of Evodia delavayi were isolated by silica gel and Sephadex LH-20 column chromatography. RESULTS: Their structures were elucidated by anlalyzing their spectral data and compared with previously reported literatures. Thirteen compounds were identified as evodiamine (1), rutaecarpine (2), skimmiamine (3), 7β-hydroxyrutaecrpine (4), goshuyuamide 1(5), goshuyuamide II (6), negunfurol (7), schensianol(8), rutaecine(9), isorhamnetin(10), 7-ketositosterol(11), evodol(12), and β-sitosterol(13). CONCLUSION: All compounds are isolated from this plant for the first time, and compounds 7, 8, and 11 are isolated from the genus Evodia for the first time.

Optimization of rutaecarpine solid lipid nanoparticles by central composite design and response surface methodology / 中草药

Objective: To optimize the prescription of rutaecarpine solid lipid nanoparticles (Rut-SLN). Methods: Using the film-ultrasound method to lining-up the Rut-SLN, with the entrapment efficiency (EE), Zeta potential, and the average particle size as the evaluation indexes, using central composite design to inspect the effects of glycerol monostearate/drug quality ratio (A), soybean lecithin for injection/glycerol monostearate mass ratio (B), Poloxamer 188 (C) on three factors of the EE, Zeta potential, and average particle size. Prediction and analysis for selecting the best prescription condition were carried out by using the response surface method. Results: According to the optimized prescription, the EE, Zeta potential, and the average particle size of Rut-SLN was respectively 84.27%, 122.6 nm, and -20.7 mV. Conclusion: The optimal prescription of Rut-SLN has better stability, feasibility, and high EE, which is suitable for the production.

Inhibition of rutaecarpine on in vitro hepatic metabolism of five Coptis alkaloids in rats / 中草药

Objective: To investigate the inhibition of rutaecarpine, a main component in Evodiae Fructus, on the hepatic metabolism of five Coptis alkaloids, and to provide the basis for further study of compatibility mechanism between Coptidis Rhizoma and Evodiae Fructus. Methods: Using rat liver microsome incubation method, the inhibition of rutaecarpine on hepatic metabolism of five Coptis alkaloids in vitro was investigated. Results: Rutaecarpine could inhibit the in vitro hepatic metabolisms of coptisine, epiberberine, berberine, palmatine, and jatrorrhizine. The half inhibitory concentration (IC50) was all greater than 50 μmol/L which showed rutaecarpine had a weak inhibition on Coptis alkaloids. The differences of inhibition constant (Ki) were statistically significant (P jatrorrhizine > palmatine > epiberberine > coptisine. Conclusion: The results could provide the basis to learn the major role on the links that Evodiae Fructus acted on Coptis alkaloids and reveal the compatibility mechanism between Coptidis Rhizoma and Evodiae Fructus.

Chemical constituents from fruits of Euodia rutaecarpa / 中草药

Objective: To study the chemical constituents from the fruits of Euodia rutaecarpa. Methods: The chemical constituents of ethanol extract from E. rutaecarpa were isolated and purified by chromatography over silica gel, Sephadex LH-20 columns, and semipreparative reversed-phase HPLC. The structures were elucidated on the basis of physicochemical properties and spectral data analyses. Results: Eleven compounds were isolated and identified as evodiamine (1), rutaecarpine (2), 3-hydroxyacetylindole (3), N-(trans-p-coumaroyl)-tyramine (4), N-(cis-p-coumaroyl)-tyramine (5), dictamnine (6), evolitrine (7), 6-methoxydictamnine (8), skimmiamine (9), 7-hydroxyrutaecarpine (10), and atanine I (11). Conclusion: Compound 3 is reported for the first time from the plants of genus Euodia J. R. et G. Forst. and compounds 4-11 are reported for the first time from E. rutaecarpa.

Simultaneous determination of evodiamine and rutaecarpine of compound Wuzhuyu ointment by HPLC / 国际中医中药杂志

Objective To establish a method for the determination of evodiamine and rutaecarpine of compound wuzhuyu ointment.Methods HPLC method was used with Agilent HC-C18(250 mm× 4.6 mm,5 μm) column and the mobile phase being acetonitrile-0.08％ ocane sutfonic acid sodium(41:59).The flow rate was 0.8 ml/min,the column temperature was 30℃,and the UV detector was set at 225 nm.Results The linear ranges of evodiamine and rutaecarpine were 0.62～ 12.40 μg/ml (r=0.9997) and 0.24～4.8 0 μg/ml (r=0.9996),respectively.The average recovery of evodiamine and rutaecarpine was 97.9％ and 98.0％,respectively.Conclusion The method is simple,repeatable and accurate.It can be applied in quantitative determination of evodiamine and rutaecarpine in compound Wuzhuyu ointment.

Determination of five components in Fuzheng Pingxiao Capsula by HPLC-MS / 中草药

Objective: To simultaneously determine the contents of five components (amygdalin, paeoniflorin, peimine, astragaloside IV and rutaecarpine) in Fuzheng Pingxiao Capsula by LC-MS. Methods: Chromatographic separation was achieved with gradient elution by Agilent Eclipse plus C18 column (250 mm x 4.6 mm, 5 μm) and an Agilent 1100 Mass Spectrometer system was operated under the SIM mode with electrospray positive ionization (ESI). The mobile phase is acetonitrile-0.1% methanoic acid. Results: The LOQ of amygdalin, paeoniflorin, peimine, astragaloside IV, and rutaecarpine in Fuzheng Pingxiao Capsula were 12.9, 32.2, 1.00, 1.21, and 0.40 ng/mL, and the LOD were 6.46, 6.44, 0.25, 0.61, and 0.16 ng/mL, respectively. Within the linear range, r > 0.999 0. Both intra-day and inter-day precision with RSD was less than 2%. The average recovery rates of the five components were in the range of 98%-102%. Conclusion: This method is fast, sensitive, and reproducible. It could be used to determine amygdalin, paeoniflorin, peimine, astragaloside IV, and rutaecarpine in Fuzheng Pingxiao Capsula under the same chromatogram condition.

Simultaneous Analysis of Thirteen Bioactive Components in Evodia rutaecarpa and Its Varieties by HPLC-DAD-MS / 中草药·英文版

Objective To control the quality of Evodia rutaecarpa better. Methods An HPLC-DAD-MS/MS method was established for the rapid and efficient identification of bioactive constituents and for simultaneous quantitative analysis of four bioactive ingredients including evodiamine, rutaecarpine, dehydroevodiamine, and evodin in E.rutaecarpa, which was applied to evaluating eight samples of E. rutaecarpa and its varieties from different areas.Results Thirteen potentially bioactive constituents including one flavonoid glycoside, one limonin, four indoloquinazoline alkaloids, and seven quinolone alkaloids were identified in all samples and the contents of dehydroevodiamine, evodine, evodiamine, and rutaecarpine varied widely from 0.10% to 0.51%, 0.49% to 3.12%,0.07% to 1.56%, and 0.10% to 0.69%, respectively. Conclusion This method is found to be convenient, fast,accurate, and it is facilitated to improve the quality control standard of E. rutaecarpa and related products.