查找使用阿拉丁产品的科研文献

Preparative enantioseparation of synephrine by conventional and pH-zone-refining counter-current chromatography

Yang Zhang,Shanshan Wang,Jianguang Luo,Yaolan Lin,Xiao Xu,Chao Han,Lingyi Kong

Synephrine, a chiral adrenergic agonist, exists as R - (more active) and S -enantiomers (less active) that are difficult to separate because of their alkalinity and high polarity. Herein, we show that although this enantioseparation can hardly be achieved by high-performance liquid chromatography, acceptable preparative separation can be realized using high-speed counter-current chromatography (HSCCC) and pH-zone-refining counter-current chromatography (CCC) under optimal conditions. Specifically, 23.0 mg of S -synephrine and 25.0 mg of R -synephrine were isolated from 60.0 mg of racemic synephrine by conventional HSCCC, while 70.0 mg of S -synephrine and 69.0 mg of R -synephrine were obtained from 200.0 mg of racemic synephrine by pH-zone-refining CCC. The pH-zone-refining CCC was identified as the most efficient enantioseparation technique for synephrine and can be applied for the preparative enantioseparation of other β-amino alcohols.

Establishing an Artificial Pathway for the Biosynthesis of Octopamine and Synephrine

Jiao Feng,Runyuan Jin,Shasha Cheng,Hui Li,Xin Wang,Kequan Chen

In this study, we designed an artificial pathway composed of tyramine β-hydroxylase (TBH) and phenylethanolamine N-methyltransferase (PNMT) for the biosynthesis of both octopamine and synephrine. As most TBH and PNMT originate from eukaryotic animals and plants, the heterologous expression and identification of functional TBH and PNMT are critical for establishing the pathway in mode microorganisms like Escherichia coli. Here, three TBHs were evaluated, and only TBH from Drosophila melanogaster was successfully expressed in the soluble form in E. coli. Its expression was promoted by evaluating the effects of different expression strategies. The specific enzyme activity of TBH was optimized up to 229.50 U·g–1, and the first step in the biosynthetic pathway was successfully established and converted tyramine to synthesize 0.10 g/L of octopamine. Furthermore, the second step to produce synephrine from octopamine was developed by screening PNMT, enhancing enzyme activity, and optimizing reaction conditions, with a maximum synephrine production of 2.02 g/L. Finally, based on the optimization of the reaction conditions for each individual reaction, the one-pot cascade reaction for synthesizing synephrine from tyramine was constructed by combining the TBH and PNMT. The synthetic synephrine reached 30.05 mg/L with tyramine as substrate in the two-step enzyme cascade system. With further optimization and amplification, the titers of octopamine and synephrine were increased to 0.45 and 0.20 g/L, respectively, with tyramine as substrate. This work was the first achievement of the biosynthesis of octopamine and synephrine to date.

Molecularly imprinted polymers for selective extraction of synephrine from Aurantii Fructus Immaturus

Fan Jie-Ping,Zhang Lu,Zhang Xue-Hong,Huang Jun-zhong,Tong Sheng,Kong Tao,Tian Zhe-You,Zhu Jian-Hang

In this work, molecularly imprinted solid-phase extraction (MISPE) has been used to selectively enrich, purify, or remove synephrine from Aurantii Fructus Immaturus . To this end, a molecularly imprinted polymer (MIP) was prepared by self-assembly from the template synephrine, the functional monomer methacrylic acid, and the crosslinker ethylene glycol dimethacrylate in 1:4:20 molar ratio. Subsequent molecular interrogation of the MIP binding sites revealed preferential structural selectivity for synephrine relative to other structurally related naturally occurring compounds (i.e. octopamine and tyramine ). This selectivity was subsequently exploited to achieve substantial sample clean-up of extracts of crude Aurantii Fructus Immaturus and Aurantii Fructus Immaturus stir-baked with bran. The purity of synephrine in the extracts after MISPE represented approximately 24.21-fold enrichment of the synephrine in the untreated extracts of Aurantii Fructus Immaturus stir-baked with bran. High recoveries (85–90%) from the samples proved that the method was valid for selective enrichment, purification, or removal of synephrine from Aurantii Fructus Immaturus . The Molecularly imprinted polymers for the selective extraction of synephrine

Stachydrine, a Bioactive Equilibrist for Synephrine, Identified from Four Citrus Chinese Herbs

Yifei Sun,Xuexue Xia,Ganjun Yuan,Tongke Zhang,Beibei Deng,Xinyu Feng,Qixuan Wang

Four Chinese herbs from theCitrusgenus, namely Aurantii Fructus Immaturus (Zhishi), Aurantii Fructus (Zhiqiao), Citri Reticulatae Pericarpium Viride (Qingpi) and Citri Reticulatae Pericarpium (Chenpi), are widely used for treating various cardiovascular and gastrointestinal diseases. Many ingredients have already been identified from these herbs, and their various bioactivities provide some interpretations for the pharmacological functions of these herbs. However, the complex functions of these herbs imply undisclosed cholinergic activity. To discover some ingredients with cholinergic activity and further clarify possible reasons for the complex pharmacological functions presented by these herbs, depending on the extended structure–activity relationships of cholinergic and anti-cholinergic agents, a simple method was established here for quickly discovering possible choline analogs using a specific TLC method, and then stachydrine and choline were first identified from theseCitrusherb decoctions based on their NMR and HRMS data. After this, two TLC scanning (TLCS) methods were first established for the quantitative analyses of stachydrine and choline, and the contents of the two ingredients and synephrine in 39 samples were determined using the valid TLCS and HPLC methods, respectively. The results showed that the contents of stachydrine (3.04‰) were 2.4 times greater than those of synephrine (1.25‰) inZhiqiaoand about one-third to two-thirds of those ofZhishi,QingpiandChenpi. Simultaneously, the contents of stachydrine, choline and synephrine in these herbs present similar decreasing trends with the delay of harvest time; e.g., those of stachydrine decrease from 5.16‰ (Zhishi) to 3.04‰ (Zhike) and from 1.98‰ (Qingpi) to 1.68‰ (Chenpi). Differently, the contents of synephrine decrease the fastest, while those of stachydrine decrease the slowest. Based on these results, compared with the pharmacological activities and pharmacokinetics reported for stachydrine and synephrine, it is indicated that stachydrine can be considered as a bioactive equilibrist for synephrine, especially in the cardio-cerebrovascular protection from these citrus herbs. Additionally, the results confirmed that stachydrine plays an important role in the pharmacological functions of these citrus herbs, especially in dual-directionally regulating the uterus, and in various beneficial effects on the cardio-cerebrovascular system, kidneys and liver.Keywords:choline;Citrus;method;analysis;decoction;Aurantii Fructus Immaturus;Aurantii Fructus;effect;cardiovascular protection;uterus

Preparation, quality evaluation and preliminary pharmacokinetic-pharmacodynamic studies of synephrine dry powder inhaler

Jiming Ke,Shenao Li,Miaomiao Zi,Jing Zhang,Shan Huang,Wenhui Luo,Hailun Han,Jiwen Zhang,Can Peng

Acute lung injury (ALI) is a lung disease characterized by pulmonary edema caused by an excessive inflammatory response within the lungs and disruption of the alveolar capillary barrier, with a high morbidity and mortality rate in critically ill patients. Dry powder inhalers (DPI) are an effective way of administering medication to improve efficacy, and inhalation administration not only improves efficacy but also increases the bioavailability of the drug. Synephrine, a natural ingredient derived from the fruit of the citrus plant in the Brassicaceae family, has anti-inflammatory and antioxidant properties. In the present study, we prepared a synephrine dry powder inhaler (SYN-DPI) by anti-solvent precipitation method and evaluated it in vivo and in vitro. The in vitro results show that SYN-DPI has low hygroscopicity and good aerodynamic properties. The in vitro and in vivo efficacy results showed that SYN-DPI not only had low toxicity but also possessed good anti-inflammatory and antioxidant capacity, which could significantly reduce inflammation, oxidative stress, and lung injury. Pharmacokinetic results showed that inhalation administration significantly increased SYN bioavailability. In conclusion, this study provides inhalation administration of synephrine as an inhalable formulation that can be used to improve ALI.

Synthesis and Evaluation of Uniformly Sized Synephrine-Imprinted Microparticles Prepared by Precipitation Polymerization

Jie-Ping Fan,Lie Li,Ze-You Tian,Chun-Fang Xie,Yuan Xue,Yan-Long Xie,Rui Xu,Yu Qin,Xue-Hong Zhang,Jian-Hang Zhu

Uniformly sized synephrine molecularly imprinted polymer (MIP) microparticles were prepared via precipitation polymerization. The presence of the template, the amount of monomer, crosslinker, and porogenic solvent could affect the size distribution and morphology of the polymers. The pseudo-second-order kinetic model could provide a better correlation for the adsorption than the pseudo-first-order model. The intraparticle diffusion study showed that the sorption involved intraparticle diffusion, but that was not the only rate-controlling step. The equilibrium data better fit the Freundlich model than the Langmuir model. The Scatchard plot of MIPs revealed MIPs had two groups of sites with different affinities. Subsequent recognition selectivity experiments demonstrated preferential structural selectivity for synephrine with respect to other structurally similar compounds (i.e., octopamine and tyramine). Compared with the bulk MIP of SYN, the SYN MIP microparticles in this work had higher adsorption selectivity and capacity due to their smaller particle sizes; moreover, the precipitation polymerization was time-saving due to not using a crash-and-sieve process.

Ultrasound-assisted aqueous two-phase extraction of synephrine, naringin, and neohesperidin from Citrus aurantium L. fruitlets

Yang Yan,Hui Zhou,Chuanhai Wu,Xiaoye Feng,Chenggang Han,Hao Chen,Yan Liu,Yanfang Li

Alleviation of pericarp browning in harvested litchi fruit by synephrine hydrochloride in relation to membrane lipids metabolism

Mingyang He,Zhixing Ge,Min Hong,Qu Hongxia,Xuewu Duan,Yun Ze,Taotao Li,Yueming Jiang

This study investigated the effect of synephrine hydrochloride (Syn-HCl) on litchi pericarp browning and the potential regulating mechanism. Results showed that 0.5 g L −1 Syn-HCl significantly inhibited the development of pericarp browning. Compared to control, Syn-HCl treatment reduced malondialdehyde and H 2 O 2 content and inhibited activities of polyphenol oxidase (PPO) and peroxidase (POD). Meanwhile, Syn-HCl-treated litchi fruit exhibited higher amounts of USFA (unsaturated fatty acids) as well as lower amounts of SFA (saturated fatty acids) through regulating activities of membrane lipids-degrading enzymes: lipase and lipoxygenase. Additionally, higher ratio of USFA to SFA and double bond index were shown in Syn-HCl-treated fruit. Further analysis showed that key genes involved in fatty acid synthesis were also regulated by Syn-HCl treatment. Taken together, these findings indicated that Syn-HCl alleviated litchi pericarp browning resulting from regulation of fatty acid metabolism and maintenance of membrane integrity, which inhibited the enzymatic browning caused by PPO and POD.

A novel free-standing flexible molecularly imprinted membrane for selective separation of synephrine in methanol–water media

Jie-Ping Fan,Lie Li,Ze-You Tian,Chun-Fang Xie,Fa-tian Song,Xue-Hong Zhang,Jian-Hang Zhu

Flexibility was very important for molecularly imprinted membrane (MIM) to apply to practical use. A novel free-standing flexible MIM was prepared using methacrylic acid (MAA) and 2-hydroxyethyl acrylate (HEA) as co-functional monomer , and ionic liquid as porogen. HEA was able to effectively improve the flexibility of MIM. Ionic liquid, 1-butyl-3-methylimidazolium bromide, was able to accelerate the synthesis process and improve the selectivity and adsorption of the MIM. The properties of MIM were characterized by scanning electron microscopy (SEM), Fourier transform infrared (FT-IR), thermo gravimetric analysis (TGA), differential thermal analysis (DTA) and X-ray photoelectron spectroscopy (XPS). Two structurally similar compounds (octopamine and tyramine) were selected as competitors to examine the selective recognition of MIM to synephrine (SYN). The competitive adsorption and permeation selectivity experiments showed that the MIM could selectively recognize SYN, and was able to be used to selectively separate SYN from the standard mixtures or the extract of stir-baked Aurantii Fructus Immaturus in methanol/water (4:1, v / v ) media.

A highly sensitive sensor for synephrine detection based on multi-walled carbon nanotubes modified glass carbon electrodes

Jie Liu,Wei Zhang,Yinfeng Li,Lingxi Yang,Baoxian Ye

A sensitive, fast and cheap sensor, based on a glassy carbon electrode (GCE) modified with a multiwalled carbon nanotubes (MWCNTs)/Nafion film, is reported for the quantitative determination of synephrine in the Chinese traditional herbal drug Pericarpium citri reticulatae using . The electrochemical behavior of synephrine at this sensor was explored in Britton–Robinson buffer solution using cyclic voltammetry. An oxidation peak at 1027 mV was observed for synephrine when a bare GCE was used, whereas an oxidation peak at 998 mV with greatly enhanced peak current was obtained at the MWCNTs/Nafion/GCE, showing the electrocatalytic nature of the modified electrode. Moreover, cyclic voltammetric studies indicated that the oxidation of synephrine at the modified electrode was irreversible, adsorption controlled and involved two electrons. A calibration plot of oxidation peak current versus synephrine concentration was linear in the range of 1 × 10−8 to 1 × 10−5 mol L−1. The detection limit of synephrine was found to be 8 × 10−9 mol L−1 by linear sweep voltammetry . The effect of pH and scan rate of synephrine were studied. This is currently the first report on the determination of trace synephrine by a purely electroanalytical method. The analytical performance of this sensor was also evaluated for the detection of synephrine in real samples.

Load mechanism and release behaviour of synephrine-loaded calcium pectinate beads: Experiments characterizations, theoretical calculations and mathematical modeling

Peng Zhou,Min Zheng,Xiangzhou Li,Jun Zhou,Wensheng Li,Yanhong Yang

It is an appropriate strategy to construct the carrier material with polysaccharide pectin, which is the characteristics of good bio-compatible, safe and non-toxic, avoiding the functional loss of bioactive ingredients and achieve sustained release . However, the loading mechanism of the active ingredient and the release behaviour of the active ingredient from the carrier material is still at the stage of conjecture. In this study, a kind of synephrine-loaded calcium pectinate beads (SCPB) with high encapsulation efficiency (95.6 %), loading capacity (11.5 %) and excellent controlled release behaviour was constructed. The interaction between synephrine (SYN) and quaternary ammonium fructus aurantii immaturus pectin (QFAIP) was revealed by FTIR, NMR and density functional theory (DFT) calculation. An inter-molecular hydrogen bond and Van der Waals forces between 7-OH, 11-OH and 10-NH of SYN and -OH, -C=O and N + (CH 3 ) 3 of QFAIP were formed. The release experiment in vitro showed that the QFAIP could effectively avoid the release of SYN in gastric fluid, and also realized the slow and full release of SYN in intestinal tract. Moreover, the release mechanism of SCPB in simulated gastric fluid (SGF) was Fickian diffusion, while in simulated intestinal fluid (SIF) was a non-Fickian diffusion controlled by both diffusion and skeleton dissolution.

A novel molecularly imprinted polymer of the specific ionic liquid monomer for selective separation of synephrine from methanol–water media

Jie-Ping Fan,Ze-You Tian,Sheng Tong,Xue-Hong Zhang,Yan-Long Xie,Rui Xu,Yu Qin,Lie Li,Jian-Hang Zhu,Xiao-Kun Ouyang

A novel molecularly imprinted polymer (MIP) using the specific ionic liquid (i.e. 1-vinyl-3-carboxymethylimidazolium bromide, 1-vinyl-3-carboxyethylimidazolium bromide, 1-viny-3-carboxybutylimidazolium bromide, or 1-vinyl-3-carboxypentylimidazolium bromide) as functional monomer was prepared via precipitation polymerization, which can be used to selectively separate synephrine (SYN) from methanol–water media. Ionic liquids are facile to be designed with varying the cation or anion, which enables the specific ionic liquid to be effectively designed to be a functional monomer for the preparation of MIP. The MIP showed a good selectivity and high adsorption capacity for SYN in methanol–water media. The adsorption process could be described by the pseudo-first-order model, which meant that the adsorption kinetics described a diffusion-controlled process. The equilibrium data fitted well to the Freundlich model, indicating multilayer adsorption . Finally, the MIP were successfully applied as sorbent to selectively enrich and separate SYN from the extracts of Aurantii Fructus Immaturus with a relatively high recovery (80–90%).