Lipidomics study of Liujunzi decoction in hyperlipidemia rats with spleen deficiency based on UPLC-Q-TOF/MS.

Hyperlipidemia refers to the abnormal levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL-C) and high-density lipoprotein (HDL-C) in peripheral blood circulation. It is a predominant risk factor underlying cardiovascular and cerebrovascular diseases, including coronary heart disease and atherosclerosis. Furthermore, it is also one of the most prevalent chronic diseases globally. Liujunzi Decoction is the basic prescription for the treatment of spleen and stomach diseases. It can tonify the spleen and qi, remove dampness, and reduce turbidity. Moreover, it is also clinically used for the treatment of spleen deficiency hyperlipidemia. However, its metabolites and therapeutic effect on spleen deficiency hyperlipidemia have not been comprehensively determined in vitro and in vivo. This study established a rat model of spleen deficiency hyperlipidemia by inducing starvation and satiety disorders, exhaustion swimming, and intragastric administration of the fat emulsion. To identify related metabolite changes and serum lipid composition, UPLC-Q-TOF-MS, PCA, and OPLS-DA lipidological methods were performed. The results demonstrated significant changes in rat's signs during the modeling process, which were consistent with the criteria for the syndrome differentiation of spleen deficiency in traditional Chinese medicine. Furthermore, this study identified 100 potential biomarkers in rat serum, of which 52 were associated with lipid synthesis, such as LPC, PC, PI, PE, PA, Cer, SM, etc. The pathways involved were glycerol phospholipid, sphingomyelin, and glycerol ester metabolisms. After the Liujunzi decoction intervention, 56 potential biomarkers were observed in the high-dose group, alleviating the metabolic spectrum imbalance by reducing metabolite levels. In addition, metabolic pathway disturbances were markedly improved. This study provides references for future studies on Liujunzi decoction and furnishes essential data for assessing the relationships between chemical constituents and pharmacological activities of Liujunzi decoction.

The First Discovery of a Microstructure in Black Plaster and Its Performance Characterization.

Background: Black plaster is one of the classic dosage forms of traditional Chinese medicine for external use and has been widely utilized since the Tang and Song Dynasties. In this paper, we take Goupi Gao as the research object and discuss the scientific characteristics of the black plaster dosage form. Goupi Gao ointment is a plaster for external use of traditional Chinese medicine. Methods: Methods for the morphological and quantitative characterization of black plaster's microstructure, based on FESEM-IPP (Field Emission Scanning Electron Microscope IPP Image Processing) technology, were established. According to the actual operating temperature of Goupi Gao, three temperatures were selected: 28°C, 35°C, and 45°C. A UPLC analysis method was applied to the cinnamaldehyde and eugenol in Goupi Gao, and the release behavior of Goupi Gao from three samples at three temperatures was investigated using the paddle over disk method. Preparation of rabbit model of knee osteoarthritis of cold blood stasis type by cold stimulation combined with drug induction. Results: In terms of morphology, Goupi Gao and the blank black plaster matrix both formed a double continuous phase system with a thicker vegetable oil phase and crossed "branched" soap crystal fibers. Based on the IPP image quantification parameters, the pore area (A) was highly positively correlated with temperature. After the 28 °C treatment, A1 = (216.8±59.5) µm2; after the 35 °C treatment, A2 = (259.7±52.8) µm2; after the 45 °C treatment, A3 = (408.0±57.7) µm2, and there were no significant differences in other pore parameters. Conclusion: The black plaster matrix's unique structure makes it highly applicable in numerous medications; it exhibits slow-release and performs well in extreme temperatures, with good adhesion and peeling properties.

Content Determination and Release Characteristics of Six Components in the Different Phases of "Glycyrrhizaglabra-Nux vomica" Decoction by UPLC-MS/MS.

The decoction turns into a complex multiphase system following exposure to high temperature and a complex chemical environment. However, the differences in the concentration of key active ingredients in different phase states and the release of drugs in sedimentary phase have yet to be elucidated. A simple ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the simultaneous quantitative determination of brucine, strychnine, liquiritin, isoliquiritin, isoliquiritigenin and glycyrrhizic acid concentrations and it was applied to compare the content of different phases and measure the release characteristics of the sedimentary phase in "Glycyrrhiza glabra-Nux vomica" decoction (NGD). The results show that the method's selectivity, precision (intraday and interday ≤ 2%), matrix effect (101-108%), recovery and stability results were acceptable according to the guidelines. The method is sensitive and reliable. The content determination results show that the most toxic strychnine in the sedimentary phase accounted for 75.70% of the total components. The different components exhibited differential release in different media, and its components were released in the artificial intestinal fluid up to 81.02% in 12 h. Several components conformed to the primary kinetic model and the Ritger-Peppas model, and the most toxic compound exhibited slow release, thus conforming to the Ritger-Peppas model. This study provides a standard of reference for studies investigating reduction in toxicity of the combination of Glycyrrhiza glabra (Glycyrrhiza glabra L.) and Nux vomica (Strychnos nux-vomica L.).

Detoxification mechanisms of a combination of Semen Strychni and Radix Glycyrrhizae: A comparative analyses of differences in toxicokinetics and tissue distribution after oral administration of Semen Strychni-Radix Glycyrrhizae decoction.

To evaluate the detoxification effect of a combination of Radix Glycyrrhizae (GU) and Semen Strychni (SN) from toxicokinetics and drug tissue distribution perspectives, decoctions of processed SN and codecoction of SN and GU (SGN) were prepared, and an HPLC-ESI-MS/MS method was developed to monitor the severe exposure level in 1-month toxicokinetics and tissue distribution experiments to detect brucine and strychnine in rats. The toxicokinetic characteristics and tissue distribution before and after the addition of GU were analyzed. The method was successfully applied to evaluate the toxicokinetics and tissue distribution before and after the combination of SN and GU. The results show that GU decreased the blood concentration of toxic components in SN, and a double peak was observed in the drug time curve. The results of tissue distribution show that a combination of GU and SN significantly decreased the accumulation of toxic substances in metabolic organs and accelerated the clearance of toxic substances in the brain. These results provide a reference for the toxicity reduction mechanism of GU combined with SN.

Metabolomic Analysis of the Urine from Rats with Collagen-Induced Arthritis with the Effective Part of Caulophyllum robustum Maxim.

Rheumatoid arthritis (RA) is a chronic autoimmune disease with high incidence and high disability and recurrence rates. Caulophyllum robustum Maxim (C. robustum) is a traditional Chinese medicine (TCM) with main effective parts (CRME) commonly used for RA treatment. To explore the mechanism of CRME in RA, we used metabolomics to investigate the effect of CRME intervention on urine metabolism in rats with collagen-induced arthritis (CIA). CIA rats were randomly divided into normal control, CIA model, and CRME groups. A metabolomics approach, using Ultra-Performance Liquid Chromatography-Quadrupole-Time-of-Flight/Mass Spectrometry, was developed to perform urinary metabolic profiling. Differential metabolites were identified by comparing the CIA model and CRME groups. Preliminarily, 56 significant differential metabolites were identified in urine, and 20 metabolic pathways were disturbed by the CIA. The amount of 16 different metabolites changed in urine after CRME intervention. The production of these metabolites involves tryptophan, tyrosine, energy, cholesterol, and vitamin metabolism. CRME has anti-inflammatory and immunosuppressive effects in CIA model rats. By examining the endogenous metabolite levels, we identified potential CRME targets and pathways involved in the treatment of RA. The results of our metabolic studies indicate that CRME regulates amino acid, vitamin, energy, and lipid metabolism pathways to treat RA and may provide a new explanation for the anti-RA mechanism of CRME.

Analysis of bioactive components and pharmacokinetics of Caulophyllum robustum in rat plasma after oral administration by UPLC-ESI-MS/MS.

A UPLC-MS/MS method was developed and validated the determination and pharmacokinetic study of magnoflorine, cauloside C, hederagenin, and oleanolic acid from Caulophyllum robustum. Digoxin was used as the internal standard. The pretreated plasma samples were carried out on a Waters ACQUITYUPLC HSS T3 column at 35 °C with a mobile phase of acetonitrile-water (90:10, v/v) at a flow rate of 0.2 mL/min. This article describes the most simple, sensitive, and validated UPLC-MS/MS method to date for the simultaneous successful determination of four compounds in rat plasma after oral administration of the extract of C. robustum and their pharmacokinetic studies.

HPLC-MS/MS method for the determination and pharmacokinetic study of six compounds against rheumatoid arthritis in rat plasma after oral administration of the extract of Caulophyllum robustum Maxim.

Caulophyllum robustum Maxim (CRM) is a well-known traditional Chinese medicine (TCM) mainly present in the northeast, northwest and southwest regions of China, which is belong to the family Berberidaceae. The roots and rhizomes of CRM have been used as a famous TCM for the treatment of rheumatoid arthritis (RA). The selective, sensitive and accurate high-performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) method for the determination and pharmacokinetic study cauloside H, leonticin D, cauloside G, cauloside D, cauloside C and magnoflorine in rat plasma was developed and validated in this paper. Chromatographic separation was achieved by using a Waters ACQUITY UPLC HSS T3 (100 mm × 2.1 mm, 1.7 µm) with gradient elution using a mobile phase consisting of acetonitrile and 0.1 % formic acid in water at a flow rate of 0.4 mL/min. The detection was performed in multiple reaction monitoring (MRM) mode and electrospray ionization (ESI) in positive and negative modes. The linearity, precision, accuracy, extraction recovery, matrix effects and stability were assessed to validate the current high-performance liquid chromatography/mass spectrometry (HPLC-MS) assay. Good linearity was achieved for each analyte with a correlation coefficient (r2) > 0.99). All the precision (RSD) data were less than 12.20 %, the accuracies ranged from -12.39 % to 10.55 %, the recovery rates from the rat plasma ranged from 85.48%-98.69 %, and the matrix effects ranged from 80.96 % to 91.35 %. The validated approach was successfully applied to study the pharmacokinetic characteristics of saponins and alkaloids in plasma after administering CRME to rats, and this assay provides a platform for studying the active components of multicomponent traditional Chinese medicines and provides useful information for further clinical studies.

A study of nanometre aggregates formation mechanism and antipyretic effect in Bai-Hu-Tang, an ancient Chinese herbal decoction.

BACKGROUND: Bai-Hu-Tang (BHT), a Chinese herbal decoction used as an antipyretic agent, results from the combination of Anemarrhena asphodeloides Bunge, Glycyrrhizae, Japonica rice, and Gypsum. In our previous study, we identified nanoaggregates in BHT. However, the present study aimed to analyze and elucidate the mechanism of nanoaggregate formation and to investigate its antipyretic effect. METHODS: A BHT decoction extract was split into 15 groups, and in each group, the extract was further separated into two solutions: Nano-phase and Decoction. The physicochemical properties of these solutions, such as particle size, salinity, conductivity, and surface tension were investigated, and analyzed the 15 groups of by transmission electron microscopy (TEM) and fingerprint chromatography. Furthermore, the antipyretic effect of nanoaggregates was evaluated through enzyme-linked immunosorbent assays, HE staining, Western Blot, and Real-time PCR. RESULTS: In the 15 groups, the salinity and conductivity results showed a promoting and stabilizing effect towards the Nano-phase formation. Analysis of the surface tension indicated good solubilization of Radix Glycyrrhizae. The TEM analysis of the BHT separated extracts revealed that only in the presence of Japonica rice the Nano-phase is formed. Sixteen common peaks were identified in the BHT fingerprint chromatogram, and the main chemical components were Neomangiferin, Mangiferin, Liquiritin, and Ammonium glycyrrhizinate. Furthermore, BHT and nanoaggregates from Bai-Hu-Tang (N-BHT) groups did not differ in the main chemical components. Additionally, the N-BHT group had the same antipyretic effect compared with the BHT group. However, the pathological analysis indicated that treatment with N-BHT could ameliorate the lung damage in the rat. At the same time, N-BHT group inhibited expression of several proteins, specifically IL-1ß, TRPV4, NF-κB, and TNF-α, which agreed with the Real-time PCR results. CONCLUSION: We identified the key factors that are involved in the nano-phase formation. Also, by Western blot and Real-time PCR methods, we investigated the N-BHT mechanism of antipyretic action. The discovery of the N-BHT formation would provide a new idea of studying traditional Chinese medicine decoction.

Mechanism of Caulophyllum robustum Maxim against rheumatoid arthritis using LncRNA-mRNA chip analysis.

BACKGROUND: Caulophyllum robustum Maxim (CRM) is a medicinal compound of the Northeast and is commonly used in China for the treatment of rheumatic pain and rheumatoid arthritis (RA). A preliminary study found that CRM has good anti-inflammatory, analgesic and immunosuppressive effects. However, the specific links and targets for its function remain unclear. Our study aimed to provide a mechanism for the action of Caulophyllum robustum Maxim extraction (CRME) against RA and to establish a method for studying disease treatment using Chinese medicine. METHODS: The 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) method was used to detect the toxicity of CRME in L929 cells, and the concentration ranges of the blank, model, and CRME drug groups were determined. Differentially expressed long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) were identified between the three groups. Gene Ontology (GO) and pathway enrichment analyses were performed to analyze the biological functions and pathways of the differentially expressed genes. Expression of Hist1h2bj, Hist1h2ba, Zfp36, Ccl3, Cxcl2 and Egr1 in the blank, model and drug groups was detected by quantitative real-time PCR (qRT-PCR), and the role of CRME on the above factors was determined to ensure consistency with the chip data. RESULTS: A total of 329 significantly upregulated genes and 141 downregulated genes were identified between the blank and model groups. A total of 218 significantly upregulated genes and 191 downregulated genes were identified between the CRME drug group and model group. CRME has a significant role in multiple pathways involved in the occurrence and development of RA. Additionally, Hist1h2bj, Hist1h2ba, Zfp36, Ccl3, Cxcl2, and Egr1 were observed in modules of the lncRNA-mRNA weighted co-expression network, consistent with the chip data. CONCLUSIONS: CRME has regulatory effects on inflammatory factors, the histone family, chemokines and their ligands that are related to RA-related cytokines, the RA pathway, the TNF signaling pathway, the Toll receptor-like signaling pathway, the chemokine signaling pathways and other pathways are related to the course of RA.

Systematic screening and characterization of prototype constituents and metabolites of triterpenoid saponins of Caulopphyllum robustum Maxim using UPLC-LTQ Orbitrap MS after oral administration in rats.

Triterpenoid saponins are the main bioactive components in Caulopphyllum Robustum Maxim (CRM), and they have been reported to have extensive pharmacological properties, such as anti-inflammatory, immunomodulatory, and anti-tumor effects. Cauloside C, Cauloside D, Leonticin D and Cauloside H are the main active chemical constituents of CRM in the treatment of rheumatoid arthritis (RA). However, their metabolic processes and products remain unclear. Therefore, the purpose of this study was to analyze the metabolic components and metabolic pathways of total saponins after oral administration of CRM effective part (CRME) in rats. In this work, we collected plasma, bile, urine and feces of rats at different sampling time points after intragastric administration. The saponins and reference substances were separated from CRME and analyzed via Thermo Scientific™ Ultra Performance Liquid Chromatography-Orbitrap Elite Combined High resolution Mass Spectrometry. According to the structural characteristics of the compounds in CRM, the pyrolysis behavior of various components was inferred in the negative ion mode. Twenty-two components were found in rat plasma, bile, urine and stool; among these components, there were 8 prototypes and 14 metabolites. Seven prototypes and 8 metabolites were found in rat plasma; no prototype and 6 metabolites were found in bile; 5 prototypes and 8 metabolites were found in urine; and 4 prototypes and 9 metabolites were found in stool. The metabolites include deglycosylation products, sapogenin products, sulfides, and glucuronide conjugates. The same metabolites were also found in biological samples, and these products may be important metabolic pathways of triterpene saponins in rats. The current findings clarified the metabolic pathways of the main active ingredients in CRME and further elucidated the anti-RA drug-responsive substance basis of CRM.

Isolation and characterization of nanometre aggregates from a Bai-Hu-Tang decoction and their antipyretic effect.

In China, a decoction is one of the most common clinical dosage forms. Nanometre aggregates (NAs), which often consist of circular or irregular nanoparticles, have been observed in previous research on decoctions. A Bai-Hu-Tang (BHT) decoction is an ancient clinical dosage form in China. The purpose of this work was to isolate and characterize NAs from BHT and to investigate their antipyretic effect. A BHT decoction was prepared by the traditional method. The mechanism and active components of the aggregates in BHT were investigated by high-speed centrifugation, transmission electron microscopy (TEM), and HPLC (high-performance liquid chromatography). In addition to the aggregation, therapeutic activities were evaluated through temperature measurements, enzyme-linked immunosorbent assays, cellular uptake measurements and fluorescence imaging. The majority of the NAs in BHT had diameters of 100 nm, and the spherical structures contained C, O, Mg, Al, Si, Ca, Zn et al. Antipyretic bioactive compounds, such as neomangiferin, mangiferin, glycyrrhizic acid and ammonium glycyrrhizinate, existed in the aggregates. In addition, the NAs in BHT had a better antipyretic effect than the other dispersion phases of BHT. In particular, the nanometre aggregates of Bai-Hu-Tang (N-BHT) were easily taken up by cells, and the fluorescein isothiocyanate (FITC) signals of NAs were more enriched in the lungs and brain than in other organs over time. These results revealed that the antipyretic effect was associated with the NAs in BHT. The discovery of NAs might present a new perspective for understanding BHT decoctions and even lead to the development of a new nanomedicine approach in traditional Chinese medicine (TCMs). Therefore, this topic deserves further study.

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 People's 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.

Spectrum-Effect Relationships between Fingerprints of Caulophyllum robustum Maxim and Inhabited Pro-Inflammation Cytokine Effects.

Caulophyllum robustum Maxim (CRM) is a Chinese folk medicine with significant effect on treatment of rheumatoid arthritis (RA). This study was designed to explore the spectrum-effect relationships between high-performance liquid chromatography (HPLC) fingerprints and the anti-inflammatory effects of CRM. Seventeen common peaks were detected by fingerprint similarity evaluation software. Among them, 15 peaks were identified by Liquid Chromatography-Mass Spectrometry (LC-MS). Pharmacodynamics experiments were conducted in collagen-induced arthritis (CIA) mice to obtain the anti-inflammatory effects of different batches of CRM with four pro-inflammation cytokines (TNF-α, IL-ß, IL-6, and IL-17) as indicators. These cytokines were suppressed at different levels according to the different batches of CRM treatment. The spectrum-effect relationships between chemical fingerprints and the pro-inflammation effects of CRM were established by multiple linear regression (MLR) and gray relational analysis (GRA). The spectrum-effect relationships revealed that the alkaloids (N-methylcytisine, magnoflorine), saponins (leiyemudanoside C, leiyemudanoside D, leiyemudanoside G, leiyemudanoside B, cauloside H, leonticin D, cauloside G, cauloside D, cauloside B, cauloside C, and cauloside A), sapogenins (oleanolic acid), ß-sitosterols, and unknown compounds (X3, X17) together showed anti-inflammatory efficacy. The results also showed that the correlation between saponins and inflammatory factors was significantly closer than that of alkaloids, and saponins linked with less sugar may have higher inhibition effect on pro-inflammatory cytokines in CIA mice. This work provided a general model of the combination of HPLC and anti-inflammatory effects to study the spectrum-effect relationships of CRM, which can be used to discover the active substance and to control the quality of this treatment.

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.

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.

Preparation, characterization and in vivo distribution of solid lipid nanoparticles loaded with syringopicroside.

A solvent emulsification evaporation method was employed to prepare solid lipid nanoparticles (SLN) loaded with syringopicroside. The conventional broad-spectrum antibacterial and antiviral drug syringopicroside was incorporated into SLN to improve drug targeting. The SYR-SLNs were spherical and uniform in transmission electron microscopy (TEM). The mean particle size and potential were 180.31 +/- 10 nm, and -41.9 +/- 10.3 mV, respectively. Also, a sephadex column chromatography was adopted to investigate the encapsulation efficiency (EE %) of the SLN. This method is based on the principle of molecular sieve effect, and the EE% of the optimal formulation was 42.35 %. Drug-loading capacity was 5.33 %. The in vitro release profile revealed that syringopicroside was released from SLN efficiently and completely in normal saline (NS) compared with other release media. A HPLC method was established for in vivo assay of syringopicroside. A tissue distribution study was conducted in rats after iv administration of 15 mg/kg SYR-SLN and syringopicroside NS, and it was found that SYR-SLN has improved delivery to the liver compared with any other organizations. These results indicated that solvent emulsification evaporation is a simple, easy, available and effective method for preparing SYR-SLN.

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.

Lignan constituents from Chloranthus japonicus Sieb.

A new coumarinolignan glucoside named yinxiancaoside C, along with five known benzofuran lignans, have been isolated from the whole plant of Chloranthus japonicus Sieb. The structures of compounds 1-6 were elucidated by chemical and spectroscopic methods including 1D-NMR, 2D-NMR, ESI-MS and HR-ESI-MS. Five known benzofuran lignans were firstly discovered in the Chloranthaceae. In addition, the cytotoxic activity of the isolated compounds against human hepatoma (Hepg-2), ovarian carcinoma (OV420), and breast cancer (MCF-7) cells was investigated by MTT method.

Sesquiterpene Glucosides from Chloranthus japonicus Sieb.

A new lindenane sesquiterpene glucoside named yinxiancaoside A (1), a new, rare bidesmosidic megastigmane sesquiterpene glucoside named yinxiancaoside B (5), and three known sesquiterpene glucosides, chloranoside A (2), pisumionoside (3), and sarcaglaboside A (4), were isolated from the whole plant of Chloranthus japonicus Sieb. The structures of the new compounds were established by an extensive study of their spectral data, especially 1D- and 2D-NMR. The cytotoxic activity of the isolated compounds against human hepatoma (Hepg-2), human ovarian carcinoma (OV420), and human breast cancer (MCF-7) cells was investigated.