Guoyu Li

The treatment of rheumatoid arthritis using Chinese medicinal plants: From pharmacology to potential molecular mechanisms.

ETHNOPHARMACOLOGICAL RELEVANCE Rheumatoid arthritis (RA) is a common worldwide public health problem. Traditional Chinese Medicine (TCM) achieved some results to some extent in the treatment of rheumatoid arthritis (RA). Especially in China, TCM formulas are used in the clinic because of their advantages. Some of these TCM formulas have been used for thousands of years in ancient China, they pays much attention to strengthening healthy qi, cleaning heat, and wet, activating blood, etc. So TCM in anti-RA drug is considered as a simple and effective method. In addition, TCM are also traditionally used as extracts and many Chinese herbs which are considered to be effective for RA. With the advancement of technologies and research methods, researchers have devoted themselves to exploring new therapeutic materials from troves of TCM. The components of TCM are identified and purified, which include alkaloids, coumarins, flavonoids, saponins and so on. However, little or no review works are found in the research literature on the anti-RA drugs from TCM. The present review aims to provide systematically reorganized information on the ethnopharmacology, phytochemistry and pharmacology of TCM used traditionally against RA. The information recorded in this review will provide new directions for researchers in the future. MATERIALS AND METHODS Relevant scientific literatures were collected from Chinese traditional books and Chinese Pharmacopoeia. Several important pharmacology data, clinical observations, animal experiments on effects of anti-RA drugs from TCM and their mechanisms were extracted from a library and electric search (Pubmed, PubChem Compound, Science Direct, Spring Link, Elsevier, Web of Science, CNKI, Wan Fang, Bai du, The Plant List, etc.). We collected information published between 2002 and 2015 on Chinese medicine in the treatment of RA. Information was also acquired from local classic herbal literature, conference papers, government reports, and PhD and MSc dissertations. RESULTS This review mainly introduces the current research on anti-RA TCM formulas, extracts and compounds from TCM, pharmacological data and potential mechanisms (inhibit osteoclast proliferation, suppress fibroblast-like synoviocytes (FLSs) growth, decrease the expression of inflammatory cytokines, blocking signal pathways, etc.). CONCLUSIONS TCM, as a multi-component and multi-target approach, which is a perfect match with the holistic concept of systems biology, is applicable in the treatment of RA. The synergistic connections of Chinese herbs and mechanisms of related active compounds on RA increase the trust for TCM. TCM as alternative remedies for RA not only has an important position in the world market, but also has an irreplaceable role in the treatment of RA in future.

Development and application of a rapid and efficient CZE method coupled with correction factors for determination of monosaccharide composition of acidic hetero-polysaccharides from Ephedra sinica

INTRODUCTION Ephedrine alkaloids cannot account for all the effects of Ephedra sinica and the polysaccharides are also demonstrated to be one of the main bioactive constituents of E. sinica. However, no work has been reported on the analysis of monosaccharide composition of purified polysaccharides isolated from the stem of E. sinica. OBJECTIVE To develop a rapid and efficient capillary zone electrophoresis (CZE) method based on pre-column derivatisation with 1-phenyl-3-methyl-5-pyrazolone for the simultaneous determination of neutral and acidic sugars of purified polysaccharides from E. sinica. METHODOLOGY Three polysaccharides (ESP-A3, ESP-A4 and ESP-B4) were isolated and purified by ion exchange and gel-filtration chromatography from the stem of E. sinica. The effects of background electrolyte pH and concentration, applied voltage and temperature on the separation were investigated. Meanwhile, factors affecting the hydrolysis of ESP-B4 with sulphuric acid were investigated by changing the hydrolysis time, acid concentration and hydrolytic temperature to achieve complete hydrolysis. The standard curves coupled with correction factors were used to calculate molar ratios. RESULTS The optimal CZE method coupled with correction factors was successfully applied to the determination of molar ratios of three purified polysaccharides and their corresponding partial acid hydrolysis products. ESP-A3, ESP-A4 and ESP-B4 were all typical acidic hetero-polysaccharides and consisted of xylose, arabinose, glucose, rhamnose, mannose, galactose, glucuronic acid and galacturonic acid, and their corresponding molar ratios were 6.8:7.5:1.0:14.0:13.7:22.3:10.2:3.8 for ESP-A3, 1.2:4.1:1.0:5.1:1.6:17.3:3.1:2.2 for ESP-A4, and 1.0:4.5:1.0:2.0:1.0:5.5:1.5:50.0 for ESP-B4. CONCLUSION The results provided scientific evidence for the further study of the structure and bioactivity of complex acidic E. sinica polysaccharides.

A strategy for characterization of triterpene saponins in Caulophyllum robustum hairy roots by liquid chromatography with electrospray ionization quadrupole time-of-flight mass spectrometry

Triterpene saponins are important bioactive constituents widely distributed in many plants. Saponins present in Caulophyllum (Berberidaceae) have not been fully characterized. In this study, we studied triterpene saponins from Caulophyllum robustum using liquid chromatography combined with electrospray ionization quadrupole time-of-flight mass spectrometry (LC-qTOF-MS). Rapid identification of Caulophyllum saponins was facilitated using low and high MS cone voltages to induce controlled fragmentation in positive mode. The full scan spectra at low cone voltage of 40V provided considerable structural information relating to aglycone skeletons, sugar types, and linked sequences for Caulophyllum saponins. Seven Caulophyllum aglycones were differentiated and identified by their diagnostic fragment ions combined with accurate mass measurements and characteristic fragmentation pathways. Peak intensity ratio of [aglycone+H-2H2O](+) to [aglycone+H-H2O](+) in full scan spectra acquired with low cone voltage is correlated with structural features of hederagenin and echinocystic acid and is useful for the discrimination of these positional isomers. However, at a high voltage of 200V, the saponin [M+H](+) ion and its fragmentation ions were not present; and the single saponin [M+Na](+) generated [Bα+Na](+) and [Y0α+Na](+) by in-source fragmentation, which provided structural information on the α- and β-sugar chains in the saponins. This approach enabled simultaneous acquisition of structural information on both aglycones and sugar chains from full scan spectra in one injection. Based on the developed strategy, 51 triterpene saponins of seven different classes were fully characterized or tentatively identified, of which 32 constituents were the first to be reported in genus Caulophyllum and 18 compounds were characterized as potentially new compounds.

A new phenolic glycoside from the aerial parts of Dryopteris fragrans

A new phenolic glycoside, 3,5-dimethyl-6-hydroxy-2-methoxy-4-O-D-glucopyranosyl-oxy-acetophenone (1), was isolated from the aerial parts of Dryopteris fragrans. The structure was elucidated on the basis of spectroscopic methods.

Genus Caulophyllum: An Overview of Chemistry and Bioactivity

Recently, some promising advances have been achieved in understanding the chemistry, pharmacology, and action mechanisms of constituents from genus Caulophyllum. Despite this, there is to date no systematic review of those of genus Caulophyllum. This review covers naturally occurring alkaloids and saponins and those resulting from synthetic novel taspine derivatives. The paper further discussed several aspects of this genus, including pharmacological properties, mechanisms of action, pharmacokinetics, and cell membrane chromatography for activity screening. The aim of this paper is to provide a point of reference for pharmaceutical researchers to develop new drugs from constituents of Caulophyllum plants.

Leiyemudanosides A-C, three new bidesmosidic triterpenoid saponins from the roots of Caulophyllum robustum.

Three new oleanane bidesmosidic triterpenoid saponins, named leiyemudanosides A-C (1-3) were isolated from the roots of Caulophyllum robustum Maxim. Their structures were established by chemical and detailed spectroscopic analysis as 3-O-alpha-L-arabinopyranosyl-caulophyllogenin-28-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester (1), 3-O-beta-D-glucopyranosyl-(1-->3)-alpha-L-arabinopyranosyl-caulophyllogenin-28-O-alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester (2), and 3-O-beta-D-glucopyranosyl-(1-->3)-alpha-L-arabinopyranosyl-echinocystic acid-28-O-alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester (3), respectively.

Energy‐resolved technique for discovery and identification of malonyl‐triterpene saponins in Caulophyllum robustum by UHPLC‐electrospray Fourier transform mass spectrometry

Malonyl-triterpene saponins (MTSs) attract scientific attentions because of their structural diversities and valuable bioactivities. However, its thermal instability brings a huge amount of challenges for isolation and purification of this class of compounds. To our best knowledge, there has been no report on isolation and analysis of MTSs from genus Caulophyllum. In this study, a strategy combining data acquisition using an energy-resolved technique and the narrow widow extracted ion chromatograms as data mining method was developed for discovery and identification of MTSs in Caulophyllum robustum hair roots by ultra high liquid chromatography coupled to electrospray ionization Fourier transform mass spectrometry. The method was performed at an independent MS full scan using our bottom-up energies by in-source collision induced dissociations with 0, 25, 50 and 100 eV in both positive and negative modes. Precursor ion as well as fragment ion information was simultaneously collected from four energy-resolved MS spectra in a single run of 18 min. The fragmentation pathways of intact deprotonated, protonated and sodium ions of MTSs were proposed for the structural elucidation of Caulophyllum MTSs. A flowchart involving a stepwise procedure based on key fragments from ESI- /ESI+ -FT-MS(1, 1) to MS(1, 4) spectra was constructed for the identification of structural elements in the MTSs. As a result, a total of 23 MTSs were discovered and tentatively identified, which had not been reported from Caulophyllum species before. All of these were potentially new compounds. This study provides an excellent example for discovery and identification of MTSs in herb medicines. Copyright

Analysis of oligosaccharide sequences of trace Caulophyllum robustum saponins by direct infusion multiple-stage tandem mass spectrometry.

The saponins in Caulophyllum robustum have not yet been fully characterized. Furthermore these saponins are often present in trace amounts and are structurally complex. Here, a simple direct infusion electrospray ion trap multiple-stage tandem mass spectrometry (DI-ESI-IT-MS(n)) method was described for the characterization of trace C. robustum saponins. Eight reference saponins from the C. robustum hairy root were investigated by DI-ESI-IT-MS(n) in positive ion mode. Some fragmentation approaches were proposed through analysis of the [M+Na](+) ions: (1) preferential cleavage of the C-28 ester glycosidic bond to provide complementary [Y0α+Na](+) and [Bα+Na](+) ions for bidesmosidic saponins; (2) diagnostically neutral loss of CO2 from free carboxyl groups at C-28 for monodesmosidic saponins; and (3) the ion intensity ratio between [C2β+Na](+) and [B2β+Na](+), which is sensitive to the structural differences between the two isomeric β-sugar chains (Glc → (2)Ara and Glc → (3)Ara). The DI-ESI-IT-MS(n) method was successfully used for the analysis of trace C. robustum saponins with [M+Na](+) ions at m/z 1745.6, 1729.5, 1583.7, 1567.7, 1421.7 and 1405.7. This article highlights the discovery and identification of complex α- and β-oligosaccharide moieties in Caulophyllum saponins by glycosidic product ions along with cross ring cleavage product ions. Five oligosaccharide moieties were unambiguously or tentatively identified as Rha → (4)Glc → (6)Glc → (4)Rha → (4)Glc → (6)Glc, Glc → (4)Glc → (6)Glc → (4)Rha → (4)Glc → (6)Glc, Rha → Glc → Glc (Glc) → (2,3)Ara, Glc → Glc (Glc) → (2,3)Ara and Glc (Glc) → (2,3)Ara. Accuracy of the analytical procedure was demonstrated by structural identification of two saponins isolated using 1D and 2D-NMR spectroscopy. The DI-ESI-IT-MS(n) method facilitates rapid discovery and analysis of trace Caulophyllum saponins and is a powerful and practical tool for structural characterization of complex oligosaccharide moieties in triterpene saponins.

Citri Reticulatae Pericarpium (Chenpi): Botany, ethnopharmacology, phytochemistry, and pharmacology of a frequently used traditional Chinese medicine

ETHNOPHARMACOLOGICAL RELEVANCE Citri Reticulatae Pericarpium (Rutaceae, CRP), commonly called as Chenpi () in Chinese, is most frequently used as a qi-regulating drug in thousands of Chinese medicine prescriptions. CRP is found mainly in major citrus-producing areas such as the Guangdong, Guangxi, Sichuan, Fujian, and Zhejiang Provinces of China. Since thousands of years in China, CRP has been used widely in clinical practice to treat nausea, vomiting, indigestion, anepithymia, diarrhea, cough, expectoration, and so on. Currently, CRP is listed in the Pharmacopoeia of the Peoples Republic of China. The present paper reviews the botany, ethnopharmacology, phytochemistry, pharmacology, quality control, and toxicology of CRP. MATERIALS AND METHODS Information on CRP was gathered from various sources including the books on traditional Chinese herbal medicine; scientific databases including Elsevier, PubMed, and ScienceDirect; Baidu Scholar; CNKI; and others and from different professional websites. RESULTS Approximately 140 chemical compounds have been isolated and identified from CRP. Among them, volatile oils and flavonoids are generally considered as the main bioactive and characteristic ingredients. CRP possesses wide pharmacological effects such as having a beneficial effect on the cardiovascular, digestive, and respiratory systems, antitumor, antioxidant, and anti-inflammatory properties; and a protective effect on the liver and nerve. Moreover, hesperidin is chosen as an indicator in the quantitative determination of CRP, and the quantity of aflatoxin in CRP must not exceed the standard limit mentioned in the pharmacopoeia. CONCLUSIONS In brief, CRP has a warming nature, and hence, it can be used in harmony with a lot of medicines. CRP not only exhibits its effects individually but also aids other medicines exhibit a better effect. CRP can be consumed with tea, food, alcohol, and medicine. Irrespective of the form it is being consumed, CRP not only shows a synergistic effect but also has strengths on its own. Modern pharmacological studies have demonstrated that CRP has marked bioactivities, especially on the diseases of the digestive and respiratory systems. The bioactivities of CRP are useful for its clinical application and provide prospects for the development of drugs as well as food and health products for people. Although CRP is a commonly used drug in the traditional Chinese herbal prescription, there is an urgent need for further research on its synergistic effect with other herbs based on the compatibility theory of TCM, which would further increase our understanding on the compatibility theory of TCM.

Four New Glycosides from the Rhizoma of Anemarrhena asphodeloides

Four new compounds, aneglycoside A–C (1–3) and timosaponin U (4), were isolated from the rhizomes of Anemarrhena asphodeloides. Their structures were determined through extensive spectroscopic analysis, chemical characteristics, and high-resolution mass spectrometry (HRMS). All the isolations were evaluated for cytotoxicity against HepG2, Hela, and SGC7901 human cancer lines. Compounds 1, 2, and 4 showed weak antiproliferative activities on HepG2, Hela, and SGC7901 cells.