Yuerong Wang

Development of a Method to Extract and Purify Target Compounds from Medicinal Plants in a Single Step: Online Hyphenation of Expanded Bed Adsorption Chromatography and Countercurrent Chromatography

Pure compounds extracted and purified from natural sources are crucial to lead discovery and drug screening. This study presents a novel two-dimensional hyphenation of expanded bed adsorption chromatography (EBAC) and high-speed countercurrent chromatography (HSCCC) for extraction and purification of target compounds from medicinal plants in a single step. The EBAC and HSCCC were hyphenated via a six-port injection valve as an interface. Fractionation of ingredients of Salvia miltiorrhiza and Rhizoma coptidis was performed on the hyphenated system to verify its efficacy. Two compounds were harvested from Salvia miltiorrhiza, one was 52.9 mg of salvianolic acid B with an over 95% purity and the other was 2.1 mg of rosmarinic acid with a 74% purity. Another two components were purified from Rhizoma coptidis, one was 4.6 mg of coptisine with a 98% purity and one was 4.1 mg of berberine with a 82% purity. The processing time was nearly 50% that of the multistep method. The results indicate that the present method is a rapid and green way to harvest targets from medicinal plants in a single step.

Development of a Process for Separation of Mogroside V from Siraitia grosvenorii by Macroporous Resins

A separation method was developed for the preparative separation and enrichment of the non-caloric sweetener mogroside V from Siraitia grosvenorii. The adsorption properties of six macroporous resins were evaluated. Results showed that HZ 806 resin offered the best adsorption and desorption capacities. Based on the adsorption experiments on HZ 806, the adsorption data were found to fit the Freundlich model well. The pseudo-second-order kinetic model showed the highest correlation with the experimental results. Separation was performed with deionized water and 40% aqueous ethanol solution as mobile phases. In a typical run, 100 g of herb was processed and 3.38 g of mogroside V with a purity of 10.7% was harvested. This separation method provided a 15.1-fold increase in the purification factor from 0.5% to 10.7%. The present study showed that HZ 806 resins were effective for the separation and enrichment of mogroside V from S. grosvenorii.

Coupling of ultrasound‐assisted extraction and expanded bed adsorption for simplified medicinal plant processing and its theoretical model: Extraction and enrichment of ginsenosides from Radix Ginseng as a case study

A high-efficient and environmental-friendly method for the preparation of ginsenosides from Radix Ginseng using the method of coupling of ultrasound-assisted extraction with expanded bed adsorption is described. Based on the optimal extraction conditions screened by surface response methodology, ginsenosides were extracted and adsorbed, then eluted by the two-step elution protocol. The comparison results between the coupling of ultrasound-assisted extraction with expanded bed adsorption method and conventional method showed that the former was better than the latter in both process efficiency and greenness. The process efficiency and energy efficiency of the coupling of ultrasound-assisted extraction with expanded bed adsorption method rapidly increased by 1.4-fold and 18.5-fold of the conventional method, while the environmental cost and CO(2) emission of the conventional method were 12.9-fold and 17.0-fold of the new method. Furthermore, the theoretical model for the extraction of targets was derived. The results revealed that the theoretical model suitably described the process of preparing ginsenosides by the coupling of ultrasound-assisted extraction with expanded bed adsorption system.

Combination of integrated expanded bed adsorption chromatography and countercurrent chromatography for the direct extraction and purification of pseudohypericin and hypericin from St. John's wort (Hypericum perforatum L.).

St. Johns wort has attracted particular attention because of its beneficial effects as an antidepressant, antiviral, and anticancer agent. A method for the combination of integrated expanded bed adsorption chromatography and countercurrent chromatography for the simultaneous extraction and purification of pseudohypericin and hypericin from the herb is presented in this paper. Firstly, the constituents were extracted and directly adsorbed by expanded bed adsorption chromatography under optimal conditions. The stepwise elution was then performed by expanded bed adsorption chromatography that enriched the targets with higher purities and recoveries compared to other methods. Secondly, the eluent fractions from expanded bed adsorption chromatography were further separated by two-step high-speed countercurrent chromatography. A two-step high-speed countercurrent chromatography method with a biphasic solvent system composed of n-hexane/ethyl acetate/methanol/water with a volume ratio of 1:2:1:2 was performed by stepwise changing the flow rate of the mobile phase. Consequently, 5.6 mg of pseudohypericin and 2.2 mg of hypericin with purities of 95.5 and 95.0%, respectively, were successfully obtained from 40 mg of crude sample.

Organs-on-chips and Its Applications

Abstract Microfluidic chips have been proven to be attractive platforms for cell culture in vitro. Microfluidic chip-based organs-on-chips technology has received more attention because it can mimic the complex structures and functions of human organs. In this review, the recent advances of organs-on-chips technology in different organs are introduced, including the build of human physiological models, drug discovery, and toxicology research. The development trend of this technology is also proposed.

Two-stage fractionation of polar alkaloids from Rhizoma coptidis by countercurrent chromatography considering the strategy of reactive extraction.

Separation of polar alkaloids by countercurrent chromatography (CCC) is challengeable due to their close partition behaviors in solvent system. In this paper, a two-stage method for isolation of epiberberine, jatrorrhizine, palmatine, coptisine, and berberine from Rhizoma coptidis was presented. The first stage separation performed on CCC was based on the principle of reactive extraction. Trifluoroacetic acid was acted as a modulator to selectively react with alkaloids, which changed their partition coefficients in solvent system. Purified epiberberine and other partially separated targets were eluted by ammonium adjusted mobile phase. In the second stage, four alkaloids were purified in pH-zone-refining CCC mode. All the targets collected were over 97% pure determined by HPLC. The method developed demonstrates performing of reactive extraction on standard CCC as an option for separation of polar alkaloids from medicinal plants.

Serum Metabolomic Characterization of Liver Fibrosis in Rats and Anti-Fibrotic Effects of Yin-Chen-Hao-Tang.

Yin-Chen-Hao-Tang (YCHT) is a famous Chinese medicine formula which has long been used in clinical practice for treating various liver diseases, such as liver fibrosis. However, to date, the mechanism for its anti-fibrotic effects remains unclear. In this paper, an ultra-performance liquid chromatography-time-of-flight mass spectrometry (UPLC-TOF-MS)-based metabolomic study was performed to characterize dimethylnitrosamine (DMN)-induced liver fibrosis in rats and evaluate the therapeutic effects of YCHT. Partial least squares-discriminant analysis (PLS-DA) showed that the model group was well separated from the control group, whereas the YCHT-treated group exhibited a tendency to restore to the controls. Seven significantly changed fibrosis-related metabolites, including unsaturated fatty acids and lysophosphatidylcholines (Lyso-PCs), were identified. Moreover, statistical analysis demonstrated that YCHT treatment could reverse the levels of most metabolites close to the normal levels. These results, along with histological and biochemical examinations, indicate that YCHT has anti-fibrotic effects, which may be due to the suppression of oxidative stress and resulting lipid peroxidation involved in hepatic fibrogenesis. This study offers new opportunities to improve our understanding of liver fibrosis and the anti-fibrotic mechanisms of YCHT.

Integrated Expanded-Bed Ion Exchange Chromatography as a Tool for Direct Recovery of Shikimic Acid from Illicium verum

Shikimic acid (SA) is the drug lead of oseltamivir phosphate (Tamiflu®). The pharmaceutical industry has great demand for SA to match the production of the drug. This article describes the development of an integrated expanded-bed adsorption chromatography (EBAC) system and its application in SA extraction and separation. The hydrodynamic behavior of an expanded-bed ion exchange resin, D293, was investigated to show that D293 resin is able to act as an adsorbent for recovery of SA from Illicium verum. SA was extracted from 8 g of I. verum in 150 mL of deionized water at an expansion ratio of 1.4 via integrated EBAC at 40°C. The SA was then eluted in 200 mL of a 2% NaCl solution. The recovery rate of SA was 96.7% and its purity was 59.6%. Different methods were compared, and the results indicated that the method developed in this article is promising for the recovery of SA from I. verum. The process efficiency of the integrated method was 2.6 times higher than that of the conventional method, while its energy efficiency was about 6 times of that of the conventional method.

Tartaric acid induced conversion of protopanaxadiol to ginsenosides Rg3 and Rg5 and their in situ recoveries by integrated expanded bed adsorption chromatography.

Panax ginseng has been applied in traditional Chinese medicine for over 2000 years. It is still one of the most popular herbs in recent decades. The prescribed ginseng-containing medicines consist of protopanaxadiol and protopanaxatriol ginsenosides, which are the major constituents of the herb. Minor ginsenosides at low levels in the herb, such as Rg3 and Rg5 , have attracted more rising attention than the major ones. The existing approaches to prepare Rg3 and Rg5 usually rely on either steamed red ginseng as the source or chemical/enzymatic conversion of protopanaxadiol to the targets. It is still highly desirable to effectively achieve such minor components. In this paper, a method integrated extraction of protopanaxadiol and conversion of it to Rg3 and Rg5 has been proposed. Protopanaxadiol was extracted and simultaneously converted to Rg3 and Rg5 by d,l-tartaric acid. The targets were absorbed by resins on expanded bed adsorption chromatography and were then separated from other ginsenosides in different stages. Compared with conventional methods, the developed process has advantages in shortening time consumption and improving the conversion ratio of protopanaxadiol, which is promising in directly achieving Rg3 and Rg5 from P. ginseng.

Determination of glyphosate in heart blood of corpse by ion chromatography

A method for the determination of glyphosate in human blood by ion chromatography was established. The protein in heart blood from a corpse was precipitated with acetonitrile. The large molecules and Cl(-) in the supernatant were removed by a Dionex OnGuard II RP column and a Dionex OnGuard II Ag column, respectively. The filtrate was separated on an IonPac AS-19 column with KOH solution as eluent produced online by an eluent generator (EG). A suppressor with external water mode and a conductivity detector for the detection were used. The linear range of this method was 10 - 100 mg/L with a correlation coefficient (r2) of 0.9999. The limits of detection (LOD, S/N = 3) and quantification (LOQ, S/N = 10) of glyphosate in blood were 0.12 mg/L and 0.39 mg/L, respectively. The recoveries ranged between 95.2% -109.1% with the relative standard deviations (RSDs, n = 5) of 1.2% - 3.7%. The glyphosate content in a heart blood sample from a corpse in an actual case was 508 mg/L detected by this method. This method is simple, sensitive, accurate, and can rapidly provided reliable clues and evidences for glyphosate poisoning cases. This method can meet the needs of public security work.