Comparative evaluation of four Lycium barbarum cultivars on NaIO3-induced retinal degeneration mice via multivariate statistical analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: The fruit of Lycium barbarum L. (goji berry) is a traditional Chinese medicine and is often used to improve vision. While various goji cultivars may differentially treat retinal degeneration, however their comparative effectiveness remains unclear. AIM OF THE STUDY: To evaluate the protective effects of four goji cultivars on NaIO3-induced retinal degeneration mouse model and identify the most therapeutically potent cultivar. MATERIALS AND METHODS: The principal compounds in the extracts of four goji cultivars were characterized by UPLC-Q-TOF/MS. A retinal degeneration mouse model was established via NaIO3 injection. Dark-light transition and TUNEL assays were used to assess visual function and retinal apoptosis. The levels of antioxidative, inflammatory, and angiogenic markers in serums and eyeballs were measured. Hierarchical cluster analysis, principal component analysis and partial least squares-discriminant analysis were used to objectively compare the treatment responses. RESULTS: Sixteen compounds were identified in goji berry extracts. All goji berry extracts could reverse NaIO3-induced visual impairment, retinal damage and apoptosis. The samples from the cultivar of Ningqi No.1 significantly modulated oxidative stress, inflammation, and vascular endothelial growth factor levels, which are more effectively than the other cultivars based on integrated multivariate profiling. CONCLUSION: Ningqi No.1 demonstrated a stronger protective effect on mouse retina than other goji cultivars, and is a potential variety for further research on the treatment of retinal degeneration.

Comparative Analysis of Pharmacokinetics and Metabolites of Three Main Terpenoids before and after Compatibility of Frankincense and Myrrh in Rats by UHPLC-MS.

BACKGROUND: 3-acetyl-11-keto-beta-boswellic acid (AKBA) and 11-keto-boswellic acid (KBA) are the main active components of frankincense as pentacyclic triterpenoids, which are designated by the European Pharmacopoeia 8.0 as the quality standard for the evaluation of Indian frankincense, 2-methoxy-8,12-epoxygermacra- 1(10),7,11-trien-6-one (MCS134) is a non-volatile sesquiterpene compound in myrrh. OBJECTIVE: In this paper, the absorption pharmacokinetics and metabolites of AKBA, KBA and MCS134 after frankincense, myrrh and their compatibility were analyzed, elaborated their absorption and metabolism mechanism and provided the ideas for the research on the bioactive components of frankincense and myrrh compatibility in vivo. METHODS: The area under the blood concentration time curve (AUC), half-life (t_1/2) and drug clearance (CL) of AKBA, KBA and MCS134 in rats were analyzed by LC-TQ / MS. The metabolites of AKBA, KBA and MCS134 in rats were analyzed by ultra-high pressure liquid chromatography with a linear ion trap-high resolution Orbitrap mass spectrometry system (UHPLC-LTQ-Orbitrap-MS). RESULTS: The results showed that AKBA, KBA and MCS134 reached the maximum plasma concentration at about 2 h, 2 h and 15 min, respectively. AUC_0-t and t_1/2 of the three components increased in varying degrees after compatibility, and the clearance/ bioavailability (CL/F) decreased. AKBA, KBA and MCS134 were metabolized in phase I and phase II in rats, and there represented differences before and after compatibility. CONCLUSION: After the compatibility of frankincense and myrrh, the absorption of effective components was improved to some extent, and there were some differences in the metabolites in rats. The results provide ideas for elucidating the in vivo effect mechanism of frankincense and myrrh.

[Structure-activity relationship of Lycium barbarum polysaccharides].

As a traditional Chinese herb and functional food, the fruits of Lycium barbarum has been widely used for thousands of years in China. L. barbarum polysaccharides(LBPs) are predominant active components, which have immunomodulatory, antioxidant, hypoglycemic, neuroprotective, anti-tumor, and prebiotic activities. The molecular weight, monosaccharide composition, glycosidic bond, branching degree, protein content, chemical modification, and spatial structure of LBPs are closely related to their biological activity. Based on the previous studies of this research team, this paper systematically combed and integrated the research progress of structure, function, and structure-activity relationship of LBPs. At the same time, some problems restricting the clarification of the structure-activity relationship of LBPs were considered and prospected, hoping to provide references for the high value utilization of LBPs and in-depth exploration of their health value.

[Preparation of Huoluo Xiaoling gel plaster and its transdermal penetration in vitro].

Huoluo Xiaoling Dan is a classical prescription commonly used for blood circulation and pain relief in clinic with obvious effects. To make it directly treat lesion and improve the effect, this research optimized the preparation process of Huoluo Xiaoling gel paste and further evaluated its in vitro transdermal absorption performance, so as to provide a scientific basis for its development and utilization. Using primary viscosity, holding viscosity, and sensory score as evaluation indexes, the matrix amount of gel paste was determined by the single factor test and Box-Behnken response surface method. The ultra-performance liquid chromatography(UPLC) method was established to determine the content of eight active ingredients, including Danshensu, ferulic acid, salvianolic acid B, salvianolic acid A, ligustilide, tanshinone Ⅱ_A, 11-keto-ß-boswellic(KBA), and 3-acetyl-11-keto-ß-boswellic acid(AKBA). A mo-dified Franz diffusion cell method was used to evaluate and compare the absorption properties of the gel paste without volatile oil and with volatile oil microemulsion. The results showed that the optimal prescription for Huoluo Xiaoling gel paste matrix was NP700(1.35 g), glycerol(7.00 g), micropowder silica gel(1.25 g), sodium carboxymethyl cellulose(0.20 g), tartaric acid(0.06 g), and glyceryl aluminum(0.04 g). The mass fractions of eight active ingredients in the paste were successively 0.48, 0.014, 0.95, 0.39, 0.57, 0.055, 0.35, and 0.97 mg·g~(-1). The results of the in vitro transdermal absorption test showed that the addition of the volatile oil or the volatile oil microemulsion promoted the transdermal absorption of the active ingredients, and the law of drug penetration conformed to the zero equation or the Higuchi equation. The gel paste prepared by the optimal prescription has good appearance and adhesion, with no residue, and has the characteristics of skeletal slow-release preparation, which is easy to reduce the number of administration, la-ying a foundation for the development of new external dosage forms of Huoluo Xiaoling Dan.

Investigation of the material basis of Xiexin Tang to alleviate type 2 diabetes mellitus based on spectrum-effect analysis by UPLC-Q-TOF/MS.

Xiexin Tang (XXT) is a classic prescription for treating diabetes in clinical practices for thousands of years in China, which has been also proved by a large number of modern pharmacological studies. However, due to its complex composition, the bioactive ingredients of XXT is still unclear. In present researches, spectrum-effect relationship analysis is widely used to explore the material basis of traditional medical herbs, so this method was adopted in this study. Firstly, the extract of XXT was separated and enriched into 5 fractions by macroporous adsorption resin. Then, UPLC-Q-TOF/MS method was used for qualitative identification of components in each eluting part, and efficacy of each fraction was assessed by the T2DM rat model. Based on grey relational analysis and pearson bivariate correlation analysis, it was found that the components such as berberine, gallic acid, catechin, epicatechin, acteoside, berberastine and 1-O-galloyl-ß-D-glucose might be the main effective basis of XXT to improve T2DM.

[Combination characteristics of frankincense and myrrh and progress and prospect of their combination efficacy and mechanism].

Herbal pair is formed based on the experience summary of doctors' deep understanding and perception of the medicinal nature in long-term clinical practice. It gradually becomes the exquisite structural unit for preparing traditional Chinese medicine(TCM) prescriptions, and often plays a core bridge role in the prescription combination. Frankincense and myrrh are raw resin materials of incense abroad, which are subsequently included as Chinese medicinal herbs and endowed with rich medicinal connotation. With the functions of relaxing Zang-fu organs, activating blood and relieving pain, they have definite clinical efficacy. From the perspective of herbal description and clinical application, this study systematically analyzed the combination of frankincense and myrrh as well as their combination proportion, efficacy characterization, diseases and syndromes, effective components and action mechanism. On this basis, the focus of in-depth research of frankincense-myrrh and the application prospects were proposed, in order to further reveal the potential meditation law of this herbal pair, thus contributing to clinical practice and drug innovation of traditional Chinese medicine, and providing reference for understanding of TCM medicinal nature and research of herbal pairs.

Evaluation and characterization of starch nanoparticles for adsorption of urea from dialysates.

Starch nanoparticles (SNPs) was produced from type-A, B and C native starches (corn, potato and Trichosanthes kirilowii pulp starches respectively), via the nanoprecipitation method. The SNPs showed different amylose contents, water contact angles, surface morphologies and urea clearance performances. In this work, to examine the parameters of SNPs that may change the urea adsorption capacity, urea adsorption performance in adsorption environments with different pH values, urea concentrations, and adsorption times was examined. Thereafter, the characteristics of SNPs were tested by water contact angle measurements (WCA), transmission electron microscopy, specific surface area measurements, gel permeation chromatography, and zeta potential analysis. The results showed that the Trichosanthes kirilowii pulp (C) SNPs show better adsorption than the corn (A) and potato (B) SNPs. The hydrophobicity of SNPs promotes the urea adsorption of the SNPs. Using grey relational analysis, it was found that WCA and Mn are the critical parameter affecting the adsorption performance, with WCA and Mn within the ranges of 31-33° and 1900-2100 kDa, respectively, were found to be the conditions for optimal urea adsorption.

[Identification of metabolites of Yiqi Baoyuan Prescription in rat plasma, bile, urine and feces after oral administration].

This study was designed to determine the metabolites of Yiqi Baoyuan Prescription(YQBYP) in rats. The ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry(UPLC-TOF-MS) and mass defect filter(MDF) were employed to analyze the metabolites of YQBYP in rat plasma, bile, urine and feces. Chromatographic separation was conducted on Acquity UPLC BEH C_(18) column(2.1 mm×100 mm, 1.7 µm) under gradient elution with 0.1% formic acid aqueous solution(A)-acetonitrile(B), and the column temperature was 30 ℃. Electrospray ion(ESI) source was used under positive and negative ion modes, with capillary voltage of 3.0 kV and mass scanning range of m/z 100-1 000. In this experiment, 9 prototype components and 36 metabolites were identified in rat plasma, bile, urine and feces samples. The results showed that the main metabolic pathways of YQBYP in rats involved methylation, demethylation, oxidation, and other phase Ⅰ reactions as well as glucuronidation, sulfation, and other phase Ⅱ reactions. This study provided scientific basis for clarifying the therapeutic material basis of YQBYP and product development.

Potential roles of gut microbiota and microbial metabolites in chronic inflammatory pain and the mechanisms of therapy drugs.

Observational findings achieved that gut microbes mediate human metabolic health and disease risk. The types of intestinal microorganisms depend on the intake of food and drugs and are also related to their metabolic level and genetic factors. Recent studies have shown that chronic inflammatory pain is closely related to intestinal microbial homeostasis. Compared with the normal intestinal flora, the composition of intestinal flora in patients with chronic inflammatory pain had significant changes in Actinomycetes, Firmicutes, Bacteroidetes, etc. At the same time, short-chain fatty acids and amino acids, the metabolites of intestinal microorganisms, can regulate neural signal molecules and signaling pathways, thus affecting the development trend of chronic inflammatory pain. Glucocorticoids and non-steroidal anti-inflammatory drugs in the treatment of chronic inflammatory pain, the main mechanism is to affect the secretion of inflammatory factors and the abundance of intestinal bacteria. This article reviews the relationship between intestinal microorganisms and their metabolites on chronic inflammatory pain and the possible mechanism.

Investigation of Enzymes in the Phthalide Biosynthetic Pathway in Angelica sinensis Using Integrative Metabolite Profiles and Transcriptome Analysis.

The roots of Angelica sinensis (Oliv.) Diels are well known for their efficacy in promoting blood circulation. Although many studies have indicated that phthalides are the main chemical components responsible for the pharmacological properties of A. sinensis, the phthalide biosynthetic pathway and enzymes that transform different phthalides are still poorly understood. We identified 108 potential candidate isoforms for phthalide accumulation using transcriptome and metabolite profile analyses. Then, six enzymes, including phospho-2-dehydro-3-deoxyheptonate aldolase 2, shikimate dehydrogenase, primary amine oxidase, polyphenol oxidase, tyrosine decarboxylase, and shikimate O-hydroxycinnamoyl transferase, were identified and proven to be involved in phthalide accumulation by heterologously expressing these proteins in Escherichia coli. We proposed a possible mechanism underlying phthalide transformation and biosynthetic pathways in A. sinensis based on our findings. The results of our study can provide valuable information for understanding the mechanisms underlying phthalide accumulation and transformation and enable further development of quality control during the cultivation of A. sinensis.

Elucidation of the Reinforcing Spleen Effect of Jujube Fruits Based on Metabolomics and Intestinal Flora Analysis.

Jujube (Ziziphus jujuba Mill.) fruit (JF) is widely consumed as food in Asian countries due to its potential effects for human health. As a traditional Chinese medicine, JF is often used to treat anorexia, fatigue and loose stools caused by spleen deficiency syndromes in China, but the mechanism underlying this effect has not been thoroughly elucidated. In this study, a rat model of spleen deficiency syndromes was adopted to investigate the therapeutic effect of JF extract and its possible mechanism by metabolomics analyses of plasma and urine as well as the intestinal flora analysis. The results showed that the changes in plasma and urine metabolites caused by spleen deficiency were reversed after administration of JF, and these changed endogenous metabolites were mainly involved in retinol metabolism, pentose and glucuronate interconversions, nicotinate and niacinamide metabolism pathways. The 16S rDNA sequencing results showed that JF could regulate intestinal flora imbalance caused by spleen deficiency. The covariance analysis of intestinal flora structure and metabolome indicated that Aerococcus may be a candidate strain for predicting and treating the metabolic pathways of spleen deficiency and related disorders. In summary, it can be revealed that spleen deficiency, which alters metabolic profiles and the intestinal flora, could be alleviated effectively by JF extract.

Evaluation of Anti-Inflammatory and Antioxidant Effectsof Chrysanthemum Stem and Leaf Extract on Zebrafish Inflammatory Bowel Disease Model.

Present studies have shown that Flos Chrysanthemi has anti-inflammatory and other effects and regulates intestinal function, while the chrysanthemum stem and leaf as non-medicinal parts of chrysanthemum have similar chemical components with chrysanthemum, but the activity and mechanisms are rarely elucidated. Therefore, this study used a DSS-induced zebrafish inflammatory bowel disease model to study the anti-inflammatory and antioxidant effects of chrysanthemum stem and leaf extracts. The results indicate that DSS induction leads to increased secretion of acidic mucin in the intestines of juvenile fish, enlargement of the intestinal lumen and the emergence of intestinal inflammation. Compared with the model group, each administration group differentially inhibited the expression of IL-1ß, IL-8 and MMP9 in DSS-induced zebrafish, while upregulating the activity of superoxide dismutase. The quantitative analysis results showed that the flavonoids (including Linarin, Diosmetin-7-glucoside, Tilianin, etc.) and phenolic acids (including Isochlorogenic acid C, Isochlorogenic acid A, 1,3-Dicaffeoylquinic acid, etc.) in the alcohol extract were closely related with both anti-inflammatory and antioxidant activity, while the polysaccharides were also shown a certain anti-inflammatory and antioxidant activity. In conclusion, this study suggests that the flavonoids, phenolic acids and polysaccharides from chrysanthemum stem and leaf extracts can improve inflammatory bowel disease of zebrafish by regulating the expressions of IL-1ß, IL-8 and MMP9.

[Determination of eight active components of Bufei Huoxue Capsules in rat plasma and their pharmacokinetics by UHPLC-MS/MS].

An ultra-high performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS) method was established to investigate the pharmacokinetic behaviors of psoralenoside, isopsoralenoside, calycosin-7-glucoside, ononin, psoralen, isopsoralen, methylnissolin, and neobavaisoflavone in rat plasma after oral administration of Bufei Huoxue Capsules. After SD rats were administered with Bufei Huoxue Capsules suspension by gavage, blood samples were collected from the inner canthus at different time points. After protein precipitation, plasma samples were separated on ACQUITY UPLC BEH C_(18) column(2.1 mm×100 mm, 1.7 µm). The mobile phase consisted of acetonitrile(A) and water(B) containing 0.1% formic acid in gradient elution. The positive and negative ions were measured simultaneously in the multi-reaction monitoring(MRM) mode. The pharmacokinetic parameters were calculated and fitted by DAS 3.2.8. Psoralenoside, isopsoralenoside, calycosin-7-glucoside, ononin, psoralen, isopsoralen, methylnissolin, and neobavaisoflavone were detected in the rat plasma after drug administration, with AUC_(0-t) of(3 357±1 348),(3 555±1 696),(3.03±0.88),(2.21±0.33),(1 787±522),(2 295±539),(5.69±1.41) and(3.40±0.75) µg·L~(-1)·h, and T_(max) of(1.56±0.62),(1.40±0.70),(0.21±0.05),(0.25±0.12),(0.26±0.11),(0.34±0.29),(0.74±0.59), and 0.25 h. The method is proved specific and repeatable and is suitable for the determination of psoralenoside, isopsoralenoside, calycosin-7-glucoside, ononin, pso-ralen, isopsoralen, methylnissolin, and neobavaisoflavone in the rat plasma, which can be applied to pharmacokinetic study.

[DNA methylation diversity analysis of Lycium barbarum samples from different cultivation areas based on MSAP].

Obvious epigenetic differentiation occurred on Lycium barbarum in different cultivation areas in China. To investigate the difference and change rule of DNA methylation level and pattern of L. barbarum from different cultivation areas in China, the present study employed fluorescence-assisted methylation-sensitive amplified polymorphism(MSAP) to analyze the methylation level and polymorphism of 53 genomic DNA samples from Yinchuan Plain in Ningxia, Bayannur city in Inner Mongolia, Jingyuan county and Yumen city in Gansu, Delingha city in Qinghai, and Jinghe county in Xinjiang. The MSAP technical system suitable for the methylation analysis of L. barbarum genomic DNA was established and ten pairs of selective primers were selected. Among amplified 5'-CCGG-3' methylated sites, there were 35.85% full-methylated sites and 39.88% hemi-methylated sites, showing a high degree of epigenetic differentiation. Stoichiometric analysis showed that the ecological environment was the main factor affecting the epigenetic characteristics of L. barbarum, followed by cultivated varieties. Precipitation, air temperature, and soil pH were the main ecological factors affecting DNA methylation in different areas. This study provided a theoretical basis for the analysis of the epigenetic mechanism of L. barbarum to adapt to the diffe-rent ecological environments and research ideas for the introduction, cultivation, and germplasm traceability of L. barbarum.

Mulberry leaves ameliorate diabetes via regulating metabolic profiling and AGEs/RAGE and p38 MAPK/NF-κB pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Mulberry leaves have been used as traditional hypoglycemic medicine-food plant for thousand years in China. According to traditional Chinese medicine theory, type 2 diabetes mellitus (T2DM) belongs to the category of XiaoKe. Presently, the research of mulberry leaf hypoglycemic and lipid-lowering direction is mature, but the curative effects of alkaloids, flavonoids, polysaccharides, and other bioactive ingredients and the related mechanism is still unclear. AIM OF THE STUDY: This paper aims to study the efficacy and mechanism of alkaloids, flavonoids, polysaccharides, and other bioactive components in mulberry leaves in the treatment of T2DM individually. MATERIALS AND METHODS: The determination of levels of fasting blood glucose (FBG), triglyceride (TG) and total cholesterol (T-Cho), and pyruvate kinase (PK), hexokinase (HK), and alanine aminotransferase (ALT/GPT) of in plasma of diabetic mice. Urine metabolomics was analyzed by UPLC-QTOF/MS to evaluate differential metabolites from multiple metabolic pathways. The glucose uptake of HepG2 cells and 3T3-L1 cells. Expression of Caspase-3 and caspase-9, inflammatory injury and p38MAPK/NF-κB signaling pathway in GLUTag cells. RESULTS: Our study revealed alkaloids, flavonoids, and polysaccharides in mulberry leaf could increase the levels of PK, HK, and ALT/GPT, and decrease the levels of TG and T-Cho significantly, and regulate glucose, amino acid, and lipid metabolism. Furthermore, 1-deoxynojirimycin (DNJ) and isoquercitrin (QG) both could increase glucose uptake and promote differentiation of HepG2 cells, increase PPARγ, C/EBPα and SREBP-l expression in 3T3-L1 cells, and inhibit AGEs-induced injury and apoptosis in GLUTag cells, reduce the expression of proteins related to AGEs/RAGE and p38MAPK/NF-κB pathway. Notably, isoquercitrin exhibited more pronounced anti-diabetic efficacy. CONCLUSIONS: The alkaloids, flavonoids, and polysaccharides from mulberry leaf exhibited hypoglycemic activity through the regulation of glucose, amino acid, and lipid metabolism. 1-DNJ and QG increased glucose uptake and promoted differentiation of HepG2 cells, increased PPARγ, C/EBPα and SREBP-l expression in 3T3-L1 cells, and inhibited AGEs-induced injury and apoptosis in GLUTag cells via the AGEs/RAGE and p38 MAPK/NF-κB pathway.

Synthesis of starch nanoparticles with controlled morphology and various adsorption rate for urea.

Starch nanoparticles (SNPs) with different morphology and particle size can be prepared by modulating the reaction conditions over SNPs preparation. This study was to synthesize various SNPs by using ultrasound assisted nanoprecipitation method, and characterized by particle size analysis, SEM and XRD performing. SNPs were successfully produced via nanoprecipitation and the particle size were controlled in the range of 95 to 150 nm. Moreover, variously different morphologies were obtained when using corn, potato or Trichosanthes kirilowii pulp (TKP) starch to produce nanoparticles, including fiber, flake and film. Results shown film TKP SNPs demonstrated an improved urea adsorption rate to 135.60 mg/g with the highest qm at 1.00 mg/mL. SNPs can be developed using ultrasound assisted nanoprecipitation method and the particle size together with surface morphology can be varied according to the source of starch and preparation method, while surface morphology is the key factor in altering adsorption performance.

[Effects and evaluation of different processing and drying methods on components in Paeoniae Radix Alba].

The present study evaluates different processing and drying methods and investigates their effects on the chemical components in Paeoniae Radix Alba via content determination. The fresh medicinal materials of Paeoniae Radix Alba collected from Bozhou of Anhui province were processed(boiled and peeled) and dried(hot air-dried, infrared-dried, and microwave-dried) at different temperatures(40, 50, 60 and 70 ℃), and the 11 components(monoterpene glycosides, polyphenols, tannin, and benzoic acid) in Paeoniae Radix Alba were determined by ultra-performance liquid chromatography coupled to triple quadrupole with electrospray tandem mass spectrometry(UPLC-TQ-MS). Then the compounds in processed and dried samples were analyzed by partial least squares discriminant analysis(PLS-DA) and orthogonal partial least squares discriminant analysis(OPLS-DA), and the contribution rates of differential components were evaluated by variable important in projection(VIP). The results indicated that the samples obtained by different processing and drying methods could be distinguished. Albiflorin, gallic acid, 1,2,3,4,6-pentakis-O-galloyl-ß-D-glucose, and benzoic acid were the common differential components in boiled Paeoniae Radix Alba. Benzoic acid was the common differential component in peeled Paeoniae Radix Alba. Gallic acid was the common differential component in Paeoniae Radix Alba dried by different methods. The samples could not be distinguished after drying at different temperatures due to the lack of common differential components. This study is expected to provide a reference for the selection of processing and drying methods and the optimization of processing parameters.

[Ant i-inflammatory mechanism of active components in Olibanum and Myrrha based on network pharmacology and cell experiments].

Two terpenes, 3-keto-tirucalla-8,24-dien-21-oic acid(KTDA) and 2-methoxy-5-acetoxy-furanogermacr-1(10)-en-6-one(FSA), are isolated from Olibanum and Myrrha respectively, which are characterized by high yield and easy crystallization during the preparation. The present study explored the regulatory targets and anti-inflammatory mechanism of KTDA and FSA based on network pharmacology and cell viability assay. First, the drug-likeness of KTDA and FSA was predicted by Swiss ADME. The target prediction of active components was carried out by Swiss Target Prediction and Pharmmapper. TTD, Drug Bank, and Gene Cards were searched for inflammation-related target genes of KTDA and FSA. Protein-protein interaction(PPI) analysis was performed on the inflammatory targets of KTDA and FSA by STRING, and Cytoscape was used to conduct topological analysis of the interaction results and construct the PPI network. GO function and KEGG pathway enrichment analyses of inflammatory targets of KTDA and FSA were carried out by DAVID, and a " component-target-pathway" network was constructed. Finally, lipopolysaccharide(LPS)-induced RAW264. 7 cells were treated with KTDA and FSA at different concentrations, and nitric oxide(NO) concentration and protein and m RNA expression levels were detected. The results showed that both KTDA and FSA showed good drug-likeness. A total of 157 and 142 inflammation-related targets of KTDA and FSA were screened out. PPI network analysis showed that MAPK1, AKT1, MAPK8, PIK3 CA,PIK3 R1, EGFR, etc. might be the key proteins for the anti-inflammatory effect. PI3 K/AKT and MAPK signaling pathways were obtained by KEGG and GO-BP enrichment. Cell experiment results showed that KTDA and FSA could exert anti-inflammatory effects by inhibiting NO production, reducing the phosphorylation levels of JNK, p38, and AKT proteins, and down-regulating the m RNA expression of interleukin(IL)-1ß and IL-6. Meanwhile, FSA could also inhibit ERK phosphorylation. The results indicated that KTDA and FSA had significant anti-inflammatory activity, which provided a scientific basis and important support for the further research,development, and utilization of Olibanum and Myrrha.

[Chemical constituents and pharmacological action of bile acids from animal:a review].

Bile of animal(mainly chicken, pig, snake, cow, and bear) has long been used as medicine. As the major active components of bile, bile acids mainly include cholic acid, deoxycholic acid, chenodeoxycholic acid, ursodeoxycholic acid, and taurochenodeoxycholic acid. They interact with intestinal microorganisms in enterohepatic circulation, thereby playing an important part in nutrient absorption and allocation, metabolism regulation, and dynamic balance. Bile acids have pharmacological effects such as protecting liver, kidney, heart, brain, and nerves, promoting bile secretion, dissolving gallstones, anti-cancer, relieving cough and dyspnea, dispelling phlegm, treating eye diseases, and regulating intestinal function and blood glucose, which are widely used in clinical practice. This study summarized and analyzed the research on the chemical constituents and pharmacological effects of bile acids from medicinal animals, in a bid to provide scientific basis and reference for the further development and utilization of bile acids.

Ziziphus jujuba Mill. var. spinosa (Bunge) Hu ex H. F. Chou Seed Ameliorates Insomnia in Rats by Regulating Metabolomics and Intestinal Flora Composition.

The seed of Ziziphus jujuba Mill. var. spinosa (Bunge) Hu ex H. F. Chou (ZSS) is often used as a traditional Chinese medicine for insomnia due to its sedative and hypnotic effects, but the mechanism underlying this effect has not been thoroughly elucidated. In this study, an insomnia model induced by intraperitoneal injection of DL-4-chlorophenylalanine suspension in Sprague-Dawley rats was adopted to investigate the therapeutic effect of ZSS extract. Metabolomics analyses of plasma and urine as well as 16S rRNA gene sequencing of the intestinal flora were performed. The relationships between the plasma and urine metabolites and the intestinal flora in insomnia rats were also analyzed. The results showed that changes in plasma and urine metabolites caused by insomnia were reversed after administration of ZSS, and these changes were mainly related to amino acid metabolism, especially phenylalanine metabolism. The results of 16S rRNA gene sequencing and short-chain fatty acid determination showed that the ZSS extract could reverse the imbalance of intestinal flora caused by insomnia and increase the contents of SCFAs in feces. All of these improvements are mainly related to the regulation of inflammation. Therefore, it is concluded that insomnia, which alters metabolic profiles and the intestinal flora, could be alleviated effectively by ZSS extract.