Zhenli Liu

Prospects of Boswellic Acids as Potential Pharmaceutics

Boswellic acids have long been considered the main bioactive components of frankincense, and many studies in vitro and in animals as well as several clinical studies have confirmed their various bioactivities. In particular, a large number of mechanistic studies have confirmed their anti-inflammatory and antitumor activities. However, not every boswellic acid exhibits a satisfactory pharmacological performance, which depends on the chemical structure and functional groups of the acid. To enhance the pharmacological values of boswellic acids, derivatization has been specifically applied with the aim of discovering more active derivatives of BAs. In addition, the preliminary pharmacokinetic studies of these compounds using various standard methods show their poor bioavailability in humans and rodents, which has led to questions of their pharmacological relevance and potentially limits their use in clinical practice and pharmaceutical development. To improve these effects, some approaches have shown some improvements in effectiveness, and the new formula compatibility approach is considered a very reasonable method for improving the bioavailability of boswellic acids.

Maillard reaction involved in the steaming process of the root of Polygonum multiflorum.

The steaming process is one of traditional Chinese medicines processing approaches for many herbs. A new HPLC peak was found in the root of Polygonum multiflorum Thunb. (PM) after steaming. 2,3-dihydro-3,5-dihydroxy-6-methyl-4(H)-pyran-4-one (DDMP) and 5-hydroxymethyl furfural (5-HMF) were confirmed in the new peak. Additionally, two other compounds, butanedioic acid and 3,5-dihydroxy-2-methyl- 4(H)-pyran-4-one (hydroxymaltol), were isolated in the processed root of PM. An increase in DDMP concentration was observed during the first 24 h of steaming, followed by a constant decrease until 64 h of steaming. The amount of 5-HMF increased gradually throughout the steaming process. Changes to 16 kinds of amino acid were found after the steaming process. Drastic changes in the concentration of D-glucose, D-fructose, and sucrose were observed during the first 16 h, followed by steady value changes to 64 h of steaming using HPLC-ELSD. The pH values decreased from 6.28 to 5.61 during the 64-h steaming process. The production of DDMP, 5-HMF, butanedioic acid, and hydroxymaltol and the changes in amino acid, sugar, and pH values suggest that the Maillard reaction was involved in the steaming process of the root of PM, which may contribute to the activity differences between the root of PM and the processed root.

The chemotaxonomic classification of Rhodiola plants and its correlation with morphological characteristics and genetic taxonomy.

BackgroundRhodiola plants are used as a natural remedy in the western world and as a traditional herbal medicine in China, and are valued for their ability to enhance human resistance to stress or fatigue and to promote longevity. Due to the morphological similarities among different species, the identification of the genus remains somewhat controversial, which may affect their safety and effectiveness in clinical use.ResultsIn this paper, 47 Rhodiola samples of seven species were collected from thirteen local provinces of China. They were identified by their morphological characteristics and genetic and phytochemical taxonomies. Eight bioactive chemotaxonomic markers from four chemical classes (phenylpropanoids, phenylethanol derivatives, flavonoids and phenolic acids) were determined to evaluate and distinguish the chemotaxonomy of Rhodiola samples using an HPLC-DAD/UV method. Hierarchical cluster analysis (HCA) and principal component analysis (PCA) were applied to compare the two classification methods between genetic and phytochemical taxonomy.ConclusionsThe established chemotaxonomic classification could be effectively used for Rhodiola species identification.

Integrated and global pseudotargeted metabolomics strategy applied to screening for quality control markers of Citrus TCMs

Traditional Chinese medicine (TCM) exerts its therapeutic effect in a holistic fashion with the synergistic function of multiple characteristic constituents. The holism philosophy of TCM is coincident with global and systematic theories of metabolomics. The proposed pseudotargeted metabolomics methodologies were employed for the establishment of reliable quality control markers for use in the screening strategy of TCMs. Pseudotargeted metabolomics integrates the advantages of both targeted and untargeted methods. In the present study, targeted metabolomics equipped with the gold standard RRLC-QqQ-MS method was employed for in vivo quantitative plasma pharmacochemistry study of characteristic prototypic constituents. Meanwhile, untargeted metabolomics using UHPLC-QE Orbitrap HRMS with better specificity and selectivity was employed for identification of untargeted metabolites in the complex plasma matrix. In all, 32 prototypic metabolites were quantitatively determined, and 66 biotransformed metabolites were convincingly identified after being orally administered with standard extracts of four labeled Citrus TCMs. The global absorption and metabolism process of complex TCMs was depicted in a systematic manner.

Comparison of the roots of Salvia miltiorrhiza Bunge (Danshen) and its variety S. miltiorrhiza Bge f. Alba (Baihua Danshen) based on multi-wavelength HPLC-fingerprinting and contents of nine active components

The dried root of Salvia miltiorrhiza Bunge (Danshen in Chinese, ZHDS) is a very commonly used herbal medicine with purple flowers, and the dried root of S. miltiorrhiza Bge f. Alba (Baihua Danshen in Chinese, BHDS) with white flowers is a variety of ZHDS that is also used in clinics in some areas of China. Their authentication has always been a challenging task due to their similar morphological characteristics and ingredients. In the present study, an effective method for identifying BHDS and ZHDS based on multi-wavelength HPLC-fingerprinting chromatographic analysis and chemometric methodology was established. Peak-rich wavelengths (203, 270 and 281 nm) were combined to build a multi-wavelength fingerprint for each sample. Simultaneously, single-wavelength fingerprinting at 281 nm and content determination of nine active compounds were carried out. The results showed that a classification model between ZHDS and BHDS based on multi-wavelength fingerprint profiling was better than that on single-wavelength, and their discrimination became more feasible. The difference in components was not directly revealed, but latent information was revealed by PCA and PLS-DA. There were no significant differences in the contents of the nine main components (danshensu, caffeic acid, rosmarinic acid, lithospermic acid, salvianolic acid B, dihydrotanshinone I, cryptotanshinone, tanshinone I and tanshinone IIA). The results suggest that BHDS and ZHDS are chemically distinct and need to be evaluated for clinical applications.

Preparation and quantification of the total phenolic products in Citrus fruit using solid‐phase extraction coupled with high‐performance liquid chromatography with diode array and UV detection

Citrus fruit is an important health-promoting food that is rich in dietary phenolic metabolites. Traditional Chinese medicines, such as Zhishi and Zhiqiao, come from young and immature fruits of Citrus cultivars. The preparation of diversified bioactive phenolic products and establishment of the corresponding quality control methodology are challenging and necessary. In the current study, four types of solid-phase extraction sorbents for the enrichment and clean-up of the phenolic matrix were evaluated. A solid-phase extraction column coated with Strata-X was finally used in the procedure. Twenty phenolic compounds were selected to evaluate the extraction performances of the sorbents using high-performance liquid chromatography analysis. Under the optimized conditions, good linearities were obtained with R2 more than 0.9996 for all analytes with LODs of 0.04-1.012 μg/g. Intra- and interday relative standard deviation values were less than 3%, and the recovery was equal to or higher than 90.02%. Compared to non-solid-phase extraction process, the content of total phenolic products was elevated 35.55-68.48% with solid-phase extraction. Finally, the developed and validated method was successfully applied to the discrimination of Zhishi samples from different species as well as Zhishi and Zhiqiao samples in different development stages.

A single marker choice strategy in simultaneous characterization and quantification of multiple components by rapid resolution liquid chromatography coupled with triple quadrupole tandem mass spectrometry (RRLC-QqQ-MS)

Single standard to determine multi-components (SSDMC) method has been accepted as an efficient technique for the quality control of Traditional Chinese medicines (TCMs), especially for overcoming the shortage of reference standards. HPLC-UV methods have been applied to establish SSDMC method for quantitative analysis in several plant medicines and Chinese patent medicines, however, no LC-MS methods have been used. The purpose of this study is to put forward an improved strategy for the choice of single marker in SSDMC using rapid resolution liquid chromatography coupled with triple quadrupole tandem mass spectrometry (RRLC-QqQ-MS). Five different Panax genus plants, recorded in the Chinese Pharmacopeia 2015 edition, were used as research subjects. An improved SSDMC strategy for simultaneous characterization and determination of 18 bioactive saponins in five Panax plants was put forward, and which was validated to be more superior. Then, it was fully investigated with respect to linearity, LODs, LOQs, precision and accuracy. Coupling with multivariate statistical analysis, the established and validated SSDMC strategy could be successively used in discrimination of the five Panax genus plants.

Study on essential oils from four species of Zhishi with gas chromatography–mass spectrometry

BackgroundCitrus fruits are widely used as food and or for medicinal purposes, and they contain a host of active substances that contribute to health. The immature fruits of Citrus sinensis Osbeck and its cultivars (CS), C. junos Sieb. ex Tanaka (CJ), C. aurantium L. and its cultivars (CA) and Poncirus trifoliate Raf. (PT) are the most commonly used medicinal herbs in Traditional Chinese Medicine, called Zhishi. And their mature fruits can be used as food.ResultsIn this study, the essential oils of four different Zhishi species were extracted by steam distillation and detected using gas chromatography- mass spectrometry (GC-MS). A total of 39 volatiles from the four species were tentatively identified. The limonene was the most abundant amongst the four species. Principal component analysis (PCA) of essential oils showed a clear separation of volatiles among CS, CJ and PT. However, CA could not be separated from these three species. Additionally, the volatiles accounting for the variations among the widely separated species were characterized through their corresponding loading weight.ConclusionSesquiterpenes were identified as characteristic markers for PT. The content of some monoterpenes could be as taxonomic markers between CS and CJ. This work is of great importance for the evaluation and authentication of Zhishi samples through essential oils.

Chemotaxonomic Classification Applied to the Identification of Two Closely-Related Citrus TCMs Using UPLC-Q-TOF-MS-Based Metabolomics

This manuscript elaborates on the establishment of a chemotaxonomic classification strategy for closely-related Citrus fruits in Traditional Chinese Medicines (TCMs). UPLC-Q-TOF-MS-based metabolomics was applied to depict the variable chemotaxonomic markers and elucidate the metabolic mechanism of Citrus TCMs from different species and at different ripening stages. Metabolomics can capture a comprehensive analysis of small molecule metabolites and can provide a powerful approach to establish metabolic profiling, creating a bridge between genotype and phenotype. To further investigate the different metabolites in four closely-related Citrus TCMs, non-targeted metabolite profiling analysis was employed as an efficient technique to profile the primary and secondary metabolites. The results presented in this manuscript indicate that primary metabolites enable the discrimination of species, whereas secondary metabolites are associated with species and the ripening process. In addition, analysis of the biosynthetic pathway highlighted that the syntheses of flavone and flavone glycosides are deeply affected in Citrus ripening stages. Ultimately, this work might provide a feasible strategy for the authentication of Citrus fruits from different species and ripening stages and facilitate a better understanding of their different medicinal uses.

Comprehensive identification of active triterpenoid metabolites in frankincense using a coupling strategy.

Frankincense resins are extensively used as natural remedies in regions ranging from North Africa to China. Triterpenoid metabolites from frankincense exhibit notable anti-inflammatory and anti-tumor properties. In the present paper, without the use of an isolation process, the fragmentation rules and NMR spectral characteristics of triterpenoid metabolites in frankincense are summarized through a coupling method using high performance liquid chromatography-diode array detection/electrospray ionization tandem mass spectrometry (HPLC-DAD/ESI-MS(n)) combined with HPLC-nuclear magnetic resonance (NMR) experiments. Based on this groundwork, a coupling strategy for the comprehensive metabolic profiling of active triterpenoid metabolites from enriched fractions of frankincense was developed. The proposed strategy may serve as a method for the holistic screening of bioactive metabolites in complex TCM samples.