The combination of Schisandrin C and Luteolin synergistically attenuates hepatitis B virus infection via repressing HBV replication and promoting cGAS-STING pathway activation in macrophages.

BACKGROUND: HBV infection can result in severe liver diseases and is one of the primary causes of liver cell carcinoma-related mortality. Liuwei Wuling tablet (LWWL) is a traditional Chinese medicine formula, with a protecting liver and decreasing enzyme activity, usually used to treat chronic hepatitis B with NAs in clinic. However, its main active ingredients and mechanism of action have not been fully investigated. Hence, we aimed to screen the active ingredient and effective ingredient combinations from Liuwei Wuling tablet to explore the anti-herpatitis B virus activity and mechanism. METHODS: Analysis and screening of effective antiviral components in LWWL by network pharmacology, luteolin (Lut) may be a compound with significant antiviral activity. The mechanism of antiviral action of Lut was also found by real-time PCR detection and western blotting. Meanwhile, we established a co-culture model to investigate the antiviral mechanism of Schisandrin C (SC), one of the main active components of Schisandra chinensis fructus (the sovereign drug of LWWL). Next, HBV-infected mice were established by tail vein injection of pAAV-HBV1.2 plasmid and administered continuously for 20 days. And their antiviral capacity was evaluated by checking serum levels of HBsAg, HBeAg, levels of HBV DNA, and liver levels of HBcAg. RESULTS: In this study, we conducted network pharmacology analysis on LWWL, and through in vitro experimental validation and data analysis, we found that luteolin (Lut) possessed obviously anti-HBV activity, inhibiting HBV replication by downregulating hepatocyte nuclear factor 4α (HNF4α) via the ERK pathway. Additionally, we established a co-culture system and proved that SC promoted activation of cGAS-STINIG pathway and IFN-ß production in THP-1 cells to inhibit HBV replication in HepG2.2.15 cells. Moreover, we found the combination of SC and Lut shows a greater effect in inhibiting HBV compared to SC or Lut alone in HBV-infected mice. CONCLUSION: Taken together, our study suggests that combination of SC and Lut may be potential candidate drug for the prevention and treatment of chronic hepatitis B.

Flavonoid extracted from Epimedium attenuate cGAS-STING-mediated diseases by targeting the formation of functional STING signalosome.

Hyperactivation of the cyclic-GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signalling pathway has been shown to be associated with the development of a variety of inflammatory diseases, and the discovery of an inhibitor of the cGAS-STING signalling pathway holds great promise in the therapeutic interventions. Epimedium flavonoid (EF), a major active ingredient isolated from the medicinal plant Epimedium, has been reported to have good anti-inflammatory activity, but its exact mechanism of action remains unclear. In the present study, we found that EF in mouse bone marrow-derived macrophages (BMDMs), THP-1 (Tohoku Hospital Pediatrics-1) as well as in human peripheral blood mononuclear cells (hPBMC) inhibited the activation of the cGAS-STING signalling pathway, which subsequently led to a decrease in the expression of type I interferon (IFN-ß, CXCL10 and ISG15) and pro-inflammatory cytokines (IL-6 and TNF-α). Mechanistically, EF does not affect STING oligomerization, but inhibits the formation of functional STING signalosome by attenuating the interaction of interferon regulatory factor 3 (IRF3) with STING and TANK-binding kinase 1 (TBK1). Importantly, in vivo experiments, EF has shown promising therapeutic effects on inflammatory diseases mediated by the cGAS-STING pathway, which include the agonist model induced by DMXAA stimulation, the autoimmune inflammatory disease model induced by three prime repair exonuclease 1 (Trex1) deficiency, and the non-alcoholic steatohepatitis (NASH) model induced by a pathogenic amino acid and choline deficiency diet (MCD). To summarize, our study suggests that EF is a potent potential inhibitor component of the cGAS-STING signalling pathway for the treatment of inflammatory diseases mediated by the cGAS-STING signalling pathway.

Sambucus williamsii Hance: A comprehensive review of traditional uses, processing specifications, botany, phytochemistry, pharmacology, toxicology, and pharmacokinetics.

OBJECTIVE: Sambucus williamsii Hance, belonging to the Sambucus L. family (Viburnaceae), possesses medicinal properties in its roots, stems, leaves, flowers, and fruits. It is recognized for its ability to facilitate bone reunion, enhance blood circulation, remove stasis, and dispel wind and dampness. This traditional Chinese medicine holds significant potential for development and practical use. Hence, this paper offers an in-depth review of S. williamsii, covering traditional uses, processing guidelines, botany, phytochemistry, pharmacology, toxicology, and pharmacokinetics, aiming to serve as a reference for its further development and utilization. MATERIALS AND METHODS: Information for this study was gathered from various books, bibliographic databases, and literature sources such as Google Scholar, Web of Science, PubMed, Chinese National Knowledge Infrastructure, Baidu Scholar, VIP Database for Chinese Technical Periodicals, and Wanfang Data. RESULTS: Phytochemical investigations have identified approximately 238 compounds within the root bark, stem branches, leaves, and fruits of S. williamsii. These compounds encompass flavonoids, sugars, glycosides, terpenoids, phenylpropanoids, alkaloids, phenols, phenolic glycosides, and other chemical constituents, with phenylpropanoids being the most prevalent. S. williamsii exhibits a wide range of pharmacological effects, particularly in promoting osteogenesis and fracture healing. CONCLUSION: This comprehensive review delves into the traditional uses, processing guidelines, botany, phytochemistry, pharmacology, toxicology, and pharmacokinetics of S. williamsii. It provides valuable insights into this plant, which will prove beneficial for future research involving S. williamsii.

Polygonum ciliinerve (Nakai) Ohwi: a review of its botany, traditional uses, phytochemistry, pharmacology, pharmacokinetics and toxicology.

Polygonum ciliinerve (Nakai) Ohwi is a perennial twining vine plant from the Polygonaceae family, which is a Chinese herbal medicine with great value for development and utilization. The purpose of this paper is to provide a systematic review of the botany, traditional uses, phytochemistry, pharmacology, pharmacokinetics, and toxicology of Polygonum ciliinerve (Nakai) Ohwi, as well as an outlook on the future research directions and development prospects of the plant. Data on Polygonum ciliinerve (Nakai) Ohwi were obtained from different databases, including China National Knowledge Infrastructure, Baidu Academic, Wanfang Database, Google Academic, PubMed, Web of Science, SpringerLink, Wiley; books; standards; and Ph.D. and MSc theses. So far, 86 compounds have been identified from Polygonum ciliinerve (Nakai) Ohwi, including anthraquinones, stilbenes, flavonoids, tannins, chromogenic ketones, organic acids and esters, lignans, isobenzofurans, alkaloids, naphthols, and others. Studies have found that Polygonum ciliinerve (Nakai) Ohwi has a wide range of pharmacological effects, including antiviral, antibacterial, anti-inflammatory and analgesic, antitumor, immunomodulatory, hypoglycemic, and antioxidant effects. Clinically, Polygonum ciliinerve (Nakai) Ohwi is very effective in the treatment of gastritis and chronic gastritis. Based on its traditional use, chemical composition, and pharmacological activity, Polygonum ciliinerve (Nakai) Ohwi is a promising source of natural medicine in drug development.

Liuweiwuling Tablet relieves the inflammatory transformation of hepatocellular carcinoma by inhibiting the PI3K/AKT/NF-κB signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Liuweiwuling Tablet (LWWL) is a patented Chinese medicine approved by the Chinese National Medical Products Administration (NMPA). Clinically, it is used to treat a range of liver diseases that precede hepatocellular carcinoma (HCC), including hepatitis, liver fibrosis and cirrhosis. LWWL is hypothesized to inhibit the inflammatory transformation of HCC, which may have a positive impact on the prevention and treatment of HCC. However, its exact mechanism of action remains unknown. AIM OF THE STUDY: To investigate how LWWL is effective in the treatment of HCC and to validate the pathways involved in this process. MATERIALS AND METHODS: An in vivo model of HCC induced by diethylnitrosamine (DEN) was established to study the effect of LWWL on the development of HCC. The rat serum was analyzed for aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and gamma-glutamyl transpeptidase (γ-GT). The rat liver tissues were stained with hematoxylin and eosin (HE) and Masson's trichrome for pathological analysis. Rat liver tissue was subjected to transcriptome sequencing. Expression of inflammatory and liver fibrosis-related factors in bone marrow-derived macrophages (BMDMs) and LX-2 cells was detected by QRT-PCR, ELISA and Western blot (WB). The expression of apoptosis and stemness genes in HepG2 and Huh7 cells was assessed through flow cytometry and QRT-PCR. Transcriptomics, network pharmacology, WB, and QRT-PCR were employed to validate the mechanisms associated with the amelioration of HCC development by LWWL. RESULTS: LWWL significantly reduced the severity of hepatitis and liver fibrosis, the expression of tumor stemness genes, and the incidence of HCC. In addition, LWWL inhibited the release of inflammatory substances and nuclear accumulation of P65 protein in BMDMs as well as the conversion of LX-2 cells to fibroblasts. LWWL inhibited the proliferation of HepG2 and Huh7 cells, including the initiation of apoptosis and the reduction of stemness gene expression. Importantly, LWWL regulates the PI3K/AKT/NF-κB pathway, which affects hepatic inflammation and cancer progression. CONCLUSION: LWWL inhibited the occurrence and development of HCC by modulating the severity of hepatitis and liver fibrosis, indicating the potential clinical relevance of LWWL in preventing and treating HCC.

Quality markers of Guchang Zhixie pills based on multicomponent qualitative and quantitative analysis combined with network pharmacology and chemometric analysis.

Traditional Chinese medicine Guchang Zhixie pills(GCZX) is one of the famous varieties of "Qin medicine" that has been extensively applied to treating irritable bowel syndrome(IBS). However, despite the acknowledged clinical advantages of GCZX there are significant constraints on its quality control and evaluation. The present study utilized UHPLC-Q-Exactive-Orbitrap-MS to analyze the chemical composition of GCZX. Additionally, network pharmacology approaches were utilized to explore the underlying mechanism by which blood components exert therapeutic effects in the treatment of IBS. Furthermore, the GCZX samples were evaluated for their quality on the basis of the qualitative results obtained from 25 batches of GCZX samples using fingerprinting; subsequently, multivariate statistical analysis methods were employed for further analysis. The results indicated the presence of 198 individual components. Among them, 17 prototype compounds were detected in the serum of rats that were administered with GCZX. The potential therapeutic mechanism of GCZX in the treatment of IBS may be associated with the modulation of the neurological system, the immunological system, and the inflammatory response. Moreover, a total of seven prominent peaks were identified after fingerprint analysis. The range of fingerprint similarity among the 25 batches of samples varied from 0.843 to 1.000. The application of chemometrics analysis successfully facilitated the categorical classification of 25 batches of GCZX into three distinct groups. Seven components hold significant importance and should be duly considered during the quality control process of GCZX. The present study can establish the Q-Markers of GCZX for IBS, thereby providing a foundation for investigating the theoretical underpinnings and elucidating the mechanisms underlying the therapeutic effects of GCZX in the treatment of IBS.

Steerable Microneedles Enabling Deep Delivery of Photosensitizers and CRISPR/Cas9 Systems for Effective Combination Cancer Therapy.

Although gene therapy has shown prospects in treating triple-negative breast cancer, it is insufficient to treat such a malignant tumor. Herein, nanoparticles (NPs)-embedded dissolving microneedles (IR780-PL/pFBXO44@MNs) with steerable and flectional property were developed to achieve the codelivery of FBXO44-targeted CRISPR/Cas9 plasmids (pFBXO44) and hydrophobic photosensitizers. For improved NP penetration in tumor tissue, collagenase@MNs were preapplied to degrade the tumor matrix. Under light irradiation, IR780 exhibited remarkable phototherapy, while the escape efficiency of NPs from lysosomes was improved. pFBXO44 was subsequently released in tumor cell cytoplasm via reducing the disulfide bonds of NPs, which could specifically knock out the FBXO44 gene to inhibit the migration and invasion of tumor cells. As a result, tumor cells were eradicated, and lung metastasis was effectively suppressed. This micelle-incorporated microneedle platform broadens the potential of combining gene editing and photo synergistic cancer therapy.

[Hot water washing processing technology of Euodiae Fructus based on change laws of active components and tastes].

In order to establish the standardized processing technology of the hot water washing of Euodiae Fructus, this study, based on the traditional processing method of hot water washing of Euodiae Fructus recorded in ancient works and modern processing specifications of traditional Chinese medicine decoction pieces, took the yield of decoction pieces and the content of main components as the indicators and optimized the processing conditions by orthogonal test based on the results of single factor investigation. At the same time, electronic tongue technology was used to analyze the change law of the taste index of Euodiae Fructus during the hot water washing. The results of the single factor investigation showed that the content of the main components in Euodiae Fructus showed some regular changes during the processing. Specifically, the content of chlorogenic acid, hyperin, isorhamnetin-3-O-rutinoside, isorhamnetin-3-O-galactoside, and dehydroevodiamine decreased significantly, with average decreases of-23.75%,-27.80%,-14.04%,-14.03%, and-13.11%, respectively. The content of limonin increased significantly with an average increase of 19.83%. The content of evodiamine, rutaecarpine, evocarpine, and dihydroevocarpine showed fluctuating changes and generally increased, with average variation amplitudes of 0.54%,-3.78%, 2.69%, and 5.13%, respectively. The orthogonal test results showed that the optimum processing parameters for the hot water washing of Euodiae Fructus were as follows: washing time of 2 min, the solid-to-liquid ratio of 1∶10 g·mL~(-1), washing temperature of 80 ℃, washing once, and drying at 50 ℃. After the hot water washing processing, the average yield of Euodiae Fructus pieces was 94.80%. The content of limonin, evodiamine, and rutaecarpine was higher than those of raw pro-ducts, and the average transfer rates were 102.56%, 103.15%, and 105.16%, respectively. The content of dehydroevodiamine was lower than that of the raw products, and the average transfer rate was 83.04%. The results of taste analysis showed that the hot water washing could significantly reduce the salty, astringent, and bitter tastes of Euodiae Fructus. This study revealed the influence of the hot water washing on the content of main components and taste of Euodiae Fructus, and the processing technology of the hot water was-hing of Euodiae Fructus established in this study was stable, feasible, and suitable for industrial production, which laid a foundation for clarifying its processing principle and improving the quality standard and clinical application value of decoction pieces.

[Medicinal evolution and modern research progress on Mume Fructus].

Prunus mume is an edible and medicinal material, and Mume Fructus is its processed product, which was first recorded in Shennong's Classic of Materia Medica(Shen Nong Ben Cao Jing). It is an effective drug for stopping diarrhea with astringents and promoting fluid production to quiet ascaris. By consulting the ancient herbal works of the past dynasties, modern codes, and other rela-ted literature, this paper sorted out the medicinal evolution of Mume Fructus, examined the ancient efficacy of Mume Fructus and the main indications, and summarized the inclusion of Mume Fructus in national and provincial standards. It is recorded in the ancient herbal works of the past dynasties that Mume Fructus can be processed by various methods such as roasting, stir-frying or micro-frying, stir-frying with charcoal, single steaming, steaming with wine, and steaming after soaking in wine or vinegar, and prepared into pills, powders, and ointments, which are used in the treatment of fatigue, diabetes, malaria, dysentery, ascariasis, and other diseases. Mume Fructus has been included in nine editions of Chinese Pharmacopoeia and 19 provincial and municipal preparation specifications. The processing method of Mume Fructus is determined, namely, clean P. mume should be softened by moistening in water or steaming and pitted. By reviewing the effects of processing on its chemical composition, pharmacological effects, and its modern clinical application, this paper identified the following issues. The ancient application methods of Mume Fructus are diverse but less commonly used in modern times, there is a lack of standardized research on the processing, and the research on the changes caused by the difference in Mume Fructus before and after processing is not deep. Therefore, it is necessary to further investigate the change pattern of its chemical composition before and after processing and its correlation between its medicinal activity to standardize the processing technology and provide a solid basis for the use of Mume Fructus in parts and its quality control.

[Regional differences analysis of Alismatis Rhizoma based on UPLC characteristic chromatogram and determination of eight terpenoids].

An ultra-performance liquid chromatography(UPLC) method integrating characteristic chromatogram and eight terpenoids determination has been established for comparing the differences of Alismatis Rhizoma(Zexie) from different product areas. Thirty-seven batches of crude drugs and thirty batches of prepared slices of Alismatis Rhizoma were analyzed. The obtained data were analyzed by similarity evaluation, principal components analysis(PCA) and partial least squares discriminant analysis(PLS-DA). There were three main characteristic peaks in the characteristic chromatograms, and alisol B 23-acetate(S) was selected as the reference. Compared with the S peak, the relative retention times of the other two characteristic peaks were 0.55(alisol) and 0.77(alisol B), respectively. Peak areas and the ratio of alisol B to alisol B 23-acetate could be used to distinguish Alismatis Rhizoma from different geographical origins. The samples were divided into three groups by PCA and PLS-DA based on the content determination results, and they were "Jian Zexie"(Fujian and Jiangxi provinces), "Chuan Zexie"(Sichuan and Hubei provinces), and "Guang Zexie"(Guangxi province). The contents of chemical components in samples from different producing areas were notably different. For example, the contents of alisol A and alisol A 24-acetate were significantly higher in "Guang Zexie" compared with "Jian Zexie" and "Chuan Zexie"(P<0.000 1). The contents of alisol B and alisol C were significantly higher in "Chuan Zexie" compared with "Jian Zexie"(P<0.000 1). Combining the characteristic chromatograms and quantitative analysis of eight terpenoids, this study showed that the relative contents of components and their ratios were notable different in samples from different regions, but types and numbers of chemical compositions were basically similar. The results of this study illustrated the regional differences of Alismatis Rhizoma and their components characteristics, and provided references for authentication and quality control of Alismatis Rhizoma.

[Recommendations on quality standards of Alismatis Rhizoma in Chinese Pharmacopoeia(2020 edition)].

The present research was launched to improve the quality standards of Alismatis Rhizoma and supply scientific evidence and recommendations for the quality control of Alismatis Rhizoma in Chinese Pharmacopoeia(Ch. P) 2020 edition. The contents of water, total ash, heavy metals and deleterious element, pesticide residues and alcohol-soluble extract were analyzed according to the methods listed in the volume Ⅳ of Ch. P 2015 edition. Alisol B 23-acetate, alisol C 23-acetate and reference herbs were used to identify Alismatis Rhizoma by TLC method, which was developed by using a mixture of dichloromethane-methanol(15∶1) as developing solvent on silica gel GF_(254 )precoated plates. In HPLC method, alisol B 23-acetate and alisol C 23-acetate were separated with acetonitrile-water as the mobile phase and detected at 208 nm and 246 nm, respectively. Thirty-seven batches of crude drugs, thirty batches of prepared slices and nineteen batches of salt prepared slices of Alismatis Rhizoma were determined according to the methods established. The quality standards established based on the research results were specific and repeatable, and suitable for the quality evaluation of Alismatis Rhizoma. We recommended that the botanical sources, TLC examination, alcohol-soluble extract of salt prepared slices and content determination should be revised in the Ch. P 2020 edition.

[Studies on quality standards of Poria].

In order to provide scientific recommendations for the revision of the quality standards of Poria in Chinese Pharmacopoeia(Ch. P) 2020 edition, a series of experiments were carried out to improve the quality standards of Poria. TLC methods were established to identify Poria by using pachymic acid, dehydrotumulosic acid and reference herbs as reference substances. The contents of water, total ash, pesticide residues, heavy metals and deleterious element, mycotoxins, sulfur dioxide residues and ethanol-soluble extract of herbal materials and decoction pieces of Poria were determined according to the methods recorded in the volume Ⅳ of Ch. P 2015 edition. An HPLC method was developed for the determination of pachymic acid and dehydropachymic acid. The contents of polysaccharide were determined by spectrophotometry using D-glucose as reference substance. The quality standards were established on the basis of the research results, in which the [assay] were added, and the [identification] and [tests] were revised when compared with Ch. P 2015 edition. The established methods are simple, specific, repeatable, and suitable for the quality evaluation of Poria.

[Preliminary screening of biomarkers for curcumin's antidepressant effect based on metabonomics method].

To screen potential biomarkers of curcumin related to treating depression rats by using metabolomics means, so as to explore the antidepressant action mechanism of curcumin. The healthy male SD rats were randomly divided into four groups. Chronic unpredictable mild stress (CUMS) stimulation was conducted for modeling for 2 weeks, and then curcumin (200 mg•kg⁻¹) or venlafaxine (40 mg•kg⁻¹) was given by gavage administration. The blank group and model group rats were given with the same volume of 1% CMCNa normal saline, once per day for two weeks. The rats serum for each group was collected and LC/MS-IT-TOF method was used to characterize the metabolic differences. Also multivariate statistical analysis was used to screen possible potential biomarkers and analyze the possible metabolic pathways. After administration of curcumin and venlafaxine respectively, the depression indexes of CUMS model rats were all improved significantly (P<0.05), but there were no significant differences between curcumin and venlafaxine groups. In PCA and PLS-DA analysis after curcumin or venlafaxine intervention on CUMS model group rats, the small molecule metabolites level reflects a normal trend, and particularly for the curcumin group. Through metabonomics technology, 11 biomarkers associated with curcumin antidepressant effect were screened, and at the same time seven metabolic pathways were involved. The results showed that curcumin had antidepressant effects, which was evident in both macro and micro levels, comparable with positive drug of venlafaxine. The antidepressant effect of curcumin may be associated with the glycerol phospholipid metabolism, linoleic acid metabolism, pentose and glucuronic acid ester and ether lipid metabolism, but still need further exploration in the future.

[Preliminary research on effect of licorice-processed Tripterygium wilfordii on reducing liver toxicity].

To explore the effect of the licorice-processed Tripterygium wilfordii on reducing the liver toxicity. In animal experiments, the liver toxicity of T. wilfordii was evaluated both before and after processing, and the differences in liver tissue biopsy, serum biochemical indexes and inflammatory cell factor among blank group, T. wilfordii group and licorice-processed T. wilfordii group were observed. Liver tissue biopsy results showed that liver tissue injury was obvious in T. wilfordii group, and no obvious injury was found in licorice-processed T. wilfordii group. As compared with the blank group, the levels of AST, ALT and CRE were significantly increased (P<0.01), UREA was increased (P<0.05), and ALB level was significantly decreased (P<0.01) in the T. wilfordii group. As compared with T. wilfordii group, the levels of AST, ALT, CRE, and UREA were decreased (P<0.01), while ALB was increased (P<0.01) in the licorice-processed T. wilfordii group. The results of inflammatory factors in rats showed that the levels of IL-1ß, IL-6, and TNF-α in T. wilfordii group were significantly higher than those in blank group (P<0.01); the levels of IL-1ß, IL-6, and TNF-α in licorice-processed T. wilfordii group were significantly lower than those in T. wilfordii group (P<0.01). Overall, licorice processing of T. wilfordii can effectively reduce the liver toxicity and reduce the liver injury caused by T. wilfordii. The experiment can provide reference for the clinical rational use of the T. wilfordii, and provide data support for the studies on reducing the liver toxicity of T. wilfordii by licorice processing.

[Preliminary study on effective components of Tripterygium wilfordii for liver toxicity based on spectrum-effect correlation analysis].

In this paper, the spectrum-effect correlation analysis method was used to explore the main effective components of Tripterygium wilfordii for liver toxicity, and provide reference for promoting the quality control of T. wilfordii. Chinese medicine T.wilfordii was taken as the study object, and LC-Q-TOF-MS was used to characterize the chemical components in T. wilfordii samples from different areas, and their main components were initially identified after referring to the literature. With the normal human hepatocytes (LO2 cell line)as the carrier, acetaminophen as positive medicine, and cell inhibition rate as testing index, the simple correlation analysis and multivariate linear correlation analysis methods were used to screen the main components of T. wilfordii for liver toxicity. As a result, 10 kinds of main components were identified, and the spectrum-effect correlation analysis showed that triptolide may be the toxic component, which was consistent with previous results of traditional literature. Meanwhile it was found that tripterine and demethylzeylasteral may greatly contribute to liver toxicity in multivariate linear correlation analysis. T. wilfordii samples of different varieties or different origins showed large difference in quality, and the T. wilfordii from southwest China showed lower liver toxicity, while those from Hunan and Anhui province showed higher liver toxicity. This study will provide data support for further rational use of T. wilfordii and research on its liver toxicity ingredients.

[Investigation of metabolites of Triptergium wilfordii on liver toxicity by LC-MS].

In this paper, biomarkers of liver toxicity of Triptergium wilfordii based on metabolomics was screened, and mechanism of liver toxicity was explored to provide a reference for the clinical diagnosis for liver toxicity of Triptergium wilfordii. MS method was carried on the analysis to metabolic fingerprint spectrum between treatment group and control group. The potential biomarkers were compared and screened using the multivariate statistical methods. As well, metabolic pathway would be detailed description. Combined with PCA and OPLS-DA pattern recognition analysis, 20 metabolites were selected which showed large differences between model group and blank group (VIP > 1.0). Seven possible endogenous biomarkers were analyzed and identified. They were 6-phosphate glucosamine, lysophospholipid, tryptophan, guanidine acetic acid, 3-indole propionic acid, cortisone, and ubiquinone. The level changes of above metabolites indicated that the metabolism pathways of amino acid, glucose, phospholipid and hormone were disordered. It is speculated that liver damage of T. wilfordii may be associated with the abnormal energy metabolism in citric acid cycle, amino acid metabolism in urea cycle, and glucose metabolism. It will be helpful to further research liver toxicity ingredients of Triptergium wilfordii.

[Development of Silymarin nanocrystals lyophilized power applying nanosuspension technology].

OBJECTIVE: To prepare silymarin nanosuspension and lyophilized power for enhancing the dissilution of poorly soluble drugs. METHOD: The precipitation technique was adapted to produce the silymarin nanosuspensions respectivly applying Tween 80, SDS and Poloxamer188 as stabilizers. The lyophilized formula contained 5% mannitol as cryoprotectant. Particle size, Polydispersity index and Zeta potential were detected by Mastersizer nano ZS (Malvern England). Morphological character was observed with Transmission Electron Microscopy. The product's structure was performed with X-ray diffractometer. RESULT: The silymarin nanosuspension was successfully prepared, in which the drug particle size was about 100-300 nm,and the particles had ball-like shape and good dispersive properties. CONCLUSION: This study provided potential for the neotype dosage form development of the Chinese Traditional Medicine.

[Comparative study on in vitro drug-release between Tuizhang ophthalmic gel and Tuizhang oculentum].

OBJECTIVE: To prepare tuizhang gel to cure cataract, the characteristics of Tuizhang gel on the drug-releasing in vitro were evaluated by compared with Tuizhang oculentum. METHOD: The emodin and chrysophanol in the releasing mediator were determined by HPLC, and the drug releasing characteristics of Tuizhang gel and Tuizhang oculentum were studied by bag filter method. RESULT: The emodin and chrysophanol in Tuizhang gel released (98.3, 1.1)%, (95.8, 1.8)% within 24 hours, respectively, while those in tuizhang oculentum released (10.62, 0.7)%, (10.46, 0.4)%, respectively. The emodin and chrysophanol in Tuizhang gel released more quickly and completely than in Tuizhang oculentum, so Tuizhang gel has enhanced the bioavailability. CONCLUSION: The Tuizhang gel is characterized by slow-release to some degree, and it shows a promising future on ophthalmic drug delivery.

[Studies on preparation technology of Flos Magnoliae essential oil-beta-cyclodextrin inclusion complex].

OBJECTIVE: To find the best condition of the preparation technology of Flos Magnoliae essential oil-beta-cyclodextrin inclusion complex. METHOD: L9(3(4)) table was used to examine the effects of 4 factors, and the inclusion rate of each test was determined of orthogonal test. RESULT: The best condition was:oil:beta-cyclodextrin:water = 1:8:60 (mL:g:mL), stirring for 1 hour at 80 degrees C. CONCLUSION: The complex prepared on the condition aforementioned is stable and stirring has a highest inclusion rate.

[Study on in vitro dissolution rate of geniposide in huangqin qingfei dispersible tablet].

OBJECTIVE: To study in vitro dissolution rate of geniposide in Huangqin Qingfei dispersible tablet. METHOD: A reversed-phase HPLC method was developed for determination of geniposide. In vitro dissolution rates were compared between Huangqin Qingfei dispersible tablet and conventional tablet in the dissolution medium of pH 1.0, 2.85, 4.5, 6.8, and 8.0 accordingly. Zero-class model, single-index model, logarithm normal school model, and Weibull distributing model were used to simulate the dissolution curve. RESULT: The dissolution rate of two tablets is not affected by pH so much, and they can dissolve within 5 to 10 minutes. Weibull distributing model is the best simulation for in vitro dissolution. Comparing with conventional tablet, dispersible tablet dissolve quickly and completely. CONCLUSION: The in vitro dissolution rate of geniposide in Huangqin Qingfei dispersible tablet conforms to Weibull distributing model. The dispersible tablet is able to release rapidly.