Caffeic acid phenethyl ester suppresses intestinal FXR signaling and ameliorates nonalcoholic fatty liver disease by inhibiting bacterial bile salt hydrolase activity.

Propolis is commonly used in traditional Chinese medicine. Studies have demonstrated the therapeutic effects of propolis extracts and its major bioactive compound caffeic acid phenethyl ester (CAPE) on obesity and diabetes. Herein, CAPE was found to have pharmacological activity against nonalcoholic fatty liver disease (NAFLD) in diet-induced obese mice. CAPE, previously reported as an inhibitor of bacterial bile salt hydrolase (BSH), inhibited BSH enzymatic activity in the gut microbiota when administered to mice. Upon BSH inhibition by CAPE, levels of tauro-ß-muricholic acid were increased in the intestine and selectively suppressed intestinal farnesoid X receptor (FXR) signaling. This resulted in lowering of the ceramides in the intestine that resulted from increased diet-induced obesity. Elevated intestinal ceramides are transported to the liver where they promoted fat production. Lowering FXR signaling was also accompanied by increased GLP-1 secretion. In support of this pathway, the therapeutic effects of CAPE on NAFLD were absent in intestinal FXR-deficient mice, and supplementation of mice with C16-ceramide significantly exacerbated hepatic steatosis. Treatment of mice with an antibiotic cocktail to deplete BSH-producing bacteria also abrogated the therapeutic activity of CAPE against NAFLD. These findings demonstrate that CAPE ameliorates obesity-related steatosis at least partly through the gut microbiota-bile acid-FXR pathway via inhibiting bacterial BSH activity and suggests that propolis enriched with CAPE might serve as a promising therapeutic agent for the treatment of NAFLD.

Fruit, vegetable, and fruit juice consumption and risk of gestational diabetes mellitus: a systematic review and meta-analysis : List of all authors.

BACKGROUND: Fruit, vegetable, and fruit juice intake is associated with the risk of gestational diabetes mellitus (GDM). However, the conclusion is limited and conflicted. The purpose of this systematic review and meta-analysis is to investigate the association between fruit, vegetable, and fruit juice consumption and the risk of GDM. METHODS: To find relevant studies, we searched PubMed, The Cochrane Library, Web of Science, Embase, ScienceDirect, PsycINFO, CINAHL, Ovid, EBSCO, CBM, CNKI, Wanfang Data, and VIP for the report on prospective cohort studies published from inception to April 8, 2022. Summary relative risks (RR) and 95% confidence intervals (Cis) were estimated using a random-effects model. RESULTS: A total of 12 studies with 32,794 participants were included in the meta-analysis. Total fruit consumption was associated with a lower risk of GDM (RR = 0.92, 95% CI = 0.86-0.99). Whereas an increasing the consumption of vegetable, including all vegetable (RR = 0.95, 95% CI = 0.87-1.03), starchy vegetable (RR = 1.01, 95% CI = 0.82-1.26), and fruit juice (RR = 0.97, 95% CI = 0.91-1.04) was not associated with a reduction in the risk of GDM. In a dose‒response analysis of eight studies, a 3% reduction in risk of GDM for a 100 g/d increase in fruit consumption (RR = 0.97, 95% CI = 0.96-0.99). CONCLUSIONS: The findings suggest that higher fruit consumption may reduce the risk of GDM, with a 3% reduction in the risk of GDM for every 100 g/d increase in fruit intake. Higher-quality prospective studies or randomized clinical trials are required to validate the effect of different variations of fruits, vegetables, and fruit juice consumption on the risk of GDM.

Anti-Inflammatory Phomalones from the Deep-Sea-Derived Fungus Trichobotrys effuse FS522.

Four new phomalones A-D (1-4), together with five known analogues (5-9) were isolated from the deep-sea-derived fungus Trichobotrys effuse FS522. Their structures of the new compounds established by analysis of their NMR and HR-ESI-MS spectroscopic data, and the absolute configurations of 2 was determined by electronic circular dichroism (ECD) calculations. compounds 4, 6 and 8 substantially inhibited the production of nitric oxide (NO) with IC50 values of 4.64, 13.90, and 34.07 µM.

[Characterization and phylogenetic analysis of complete chloroplast genome of cultivated Qinan agarwood].

"Tangjie" leaves of cultivated Qinan agarwood were used to obtain the complete chloroplast genome using high-throughput sequencing technology. Combined with 12 chloroplast genomes of Aquilaria species downloaded from NCBI, bioinformatics method was employed to determine the chloroplast genome characteristics and phylogenetic relationships. The results showed that the chloroplast genome sequence length of cultivated Qinan agarwood "Tangjie" leaves was 174 909 bp with a GC content of 36.7%. A total of 136 genes were annotated, including 90 protein-coding genes, 38 tRNA genes, and 8 rRNA genes. Sequence repeat analysis detected 80 simple sequence repeats(SSRs) and 124 long sequence repeats, with most SSRs composed of A and T bases. Codon preference analysis revealed that AUU was the most frequently used codon, and codons with A and U endings were preferred. Comparative analysis of Aquilaria chloroplast genomes showed relative conservation of the IR region boundaries and identified five highly variable regions: trnD-trnY, trnT-trnL, trnF-ndhJ, petA-cemA, and rpl32, which could serve as potential DNA barcodes specific to the Aquilaria genus. Selection pressure analysis indicated positive selection in the rbcL, rps11, and rpl32 genes. Phylogenetic analysis revealed that cultivated Qinan agarwood "Tangjie" and Aquilaria agallocha clustered together(100% support), supporting the Chinese origin of Qinan agarwood from Aquilaria agallocha. The chloroplast genome data obtained in this study provide a foundation for studying the genetic diversity of cultivated Qinan agarwood and molecular identification of the Aquilaria genus.

[Research progress of circadian rhythm].

Circadian rhythm disorder is a common society issue caused by jet lag,shift work,sleep disruption and changes in food consumption. Light is the major factor affecting the circadian rhythm system. Disruption of the circadian rhythm system can cause damage to the body,leading to some diseases. Maintaining a normal circadian system is of great importance for good health. Ideal therapeutic effect can not only alleviate symptoms of the diseases,but also recovery the disturbed circadian rhythm to normal. The paper summarizes the modeling methods of animal circadian rhythm disorder,diseases of circadian rhythm abnormality,regulation of circadian clock genes and medicine which are related to circadian rhythm to diseases of circadian rhythm disorder.

Metabolic profiling of RB-2 and RB-4, two analogs of polyacetylene from Bupleurum.

RB-2 and RB-4 are two structural analogs of polyacetylene from Radix Bupleuri that show antidepressant effects. However, no metabolic data are available to elucidate their systemic homeostasis. Mass spectrometry combined with liver microsomes and recombinant drug-metabolizing enzymes were performed to profile the biotransformations of RB-2/RB-4 in vitro and in vivo. Oxidation should be the major metabolic pathways for them in phase I, while CYP2C9 and CYP2E1 was the major contributor. In phase II, conjugational groups usually combined with the metabolites from phase I. This study provides an important reference basis for the safety evaluation and rational application of RB-2/RB-4.

[Advances in research of traditional Chinese medicine for promoting bile secretion and excretion].

Cholagogic traditional Chinese medicines refer to those that can promote bile secretion and excretion, strengthen gallbladder contraction and promote gallbladder emptying. They are mainly used to treat cholecystitis, gallstones, cholestasis, biliary tract infection, jaundice hepatitis and other diseases in clinical application. As a traditional medicine in our country, Chinese herbal medicines have many advantages, such as extensive resources, low cost, little or no toxic and side effects, and in addition, it is not easy for animals to produce drug resistance. With the progress of science and technology and the rapid development of traditional Chinese medicine, many achievements have been made in the research of cholagogic traditional Chinese medicines. Traditional Chinese medicine plays a cholagogic role mainly by promoting bile secretion, regulating SCP2 mRNA, FXR, BSEP and efflux transporter protein, dissolving cholesterol, promoting the relaxation of Oddi's sphincter and changing the composition of bile, etc. Traditional Chinese medicine decoction, traditional Chinese medicine preparation, Chinese medicine combined with acupuncture, ear acupoint pressing, soaking bath, western medicine and alike are often used to treat biliary system diseases in clinical practice. The effective rate of combination of traditional Chinese medicine and other methods was significantly higher than that of compound prescription, western medicine, acupuncture and soaking bath alone. General attack therapy and new therapies are also used in clinical treatment. The clinical effect of traditional Chinese medicine is remarkable. By means of literature review, the pharmacological effects, mechanism and clinical application of Chinese herbal medicines and compound prescriptions with gallbladder-promoting effect in the past 15 years were summarized in this paper. At the same time, some existing problems were found and prospects were expected.

[Study on difference of chemical compositions of Guilingji before and after alchemy based on mass spectrometry and multivariate statistical analysis].

UPLC-Q-Orbitrap MS/MS and ICP-MS coupled with multivariate statistical analysis was employed to explore the differences in chemical compositions of Guilingji(GLJ) before and after alchemy.The changes in organic chemical compositions and inorganic elements were observed and 39 differential organic compositions were found in GLJ after alchemy, 24 compounds of which were identified. The differential compositions of GLJ included violet ketones, chalcones, amides, and fatty acids whose contents were increased after alchemy, as well as flavones, isoflavones, dihydroflavones, flavonoid glycosides, and coumarins whose content were decreased after alchemy. This study showed 6 inorganic elements filtered out as markers for distinguishing GLJ before and after alchemy, including B, Si, Mg, K, Cr, and Ni.The contents of Mg, K, Cr and Ni were increased while the contents of B and Si were decreased after alchemy.The difference of the contents after alchemy changed the cold and hot properties of the compound, showing the decrease of dryness, and the hot property was changed to warm and neutral properties; in addition, the membrane permeability and absorption of the compound compositions were improved. In this study, we preliminarily investigated the changes of chemical compositions in GLJ before and after alchemy as well as the effects of alchemy on physical and chemical properties and cold-heat nature of GLJ, laying a foundation for further clarifying the scientific connotation of alchemy process.

Chromone-Derived Polyketides from the Deep-Sea Fungus Diaporthe phaseolorum FS431.

Five new chromone-derived polyketides phaseolorins A-F (1⁻5), together with nine known compounds, were isolated from the deep-sea derived fungus Diaporthe phaseolorum FS431. The structures of new compounds were determined by analysis of their NMR and high-resolution electrospray ionization mass spectroscopy (HRESIMS) spectroscopic data. The absolute configurations were confirmed by chemical transformations, extensively experimental electron capture detection (ECD) calculations, or X-ray crystallography. Among them, compound 2 represented the first example for a new family of chromone derivative possessing an unprecedented recombined five-member γ-lactone ring. Moreover, the new compounds (1⁻5) were evaluated for in vitro cytotoxic activities against a panel of human cancer cell lines.

Highly Substituted Benzophenone Aldehydes and Eremophilane Derivatives from the Deep-Sea Derived Fungus Phomopsis lithocarpus FS508.

Five new benzophenone derivatives named tenellones D⁻H (1⁻5), sharing a rare naturally occurring aldehyde functionality in this family, and a new eremophilane derivative named lithocarin A (7), together with two known compounds (6 and 8), were isolated from the deep marine sediment-derived fungus Phomopsis lithocarpus FS508. All of the structures for these new compounds were fully characterized and established on the basis of extensive spectroscopic interpretation and X-ray crystallographic analysis. Compound 5 exhibited cytotoxic activity against HepG-2 and A549 cell lines with IC50 values of 16.0 and 17.6 µM, respectively.

[Quantitative analysis of eight polyacetylenes derived from Bupleuri Radix by ultra-performance liquid chromatography coupled with photodiode array detector].

To establish quantitative methods for determination of polyacetylenes in Bupleuri Radix, an ultra-performance liquid chromatography method coupled with photodiode array detector (UPLC-PDA) was developed. The analysis was performed on a Waters BEH C18 column (2.1 mm×100 mm, 1.7 µm) using a gradient system of methanol and water. The flow rate was 0.3 mL•min⁻¹ and the detection wavelength was 315 nm. Eight polyacetylenes were prepared using traditional extraction and isolation method, of which compounds 7 and 8 were two new polyacetylenes. All calibration curves showed good linearity (r>0.999 0) within the concentration range. Both the intra- and inter-day precisions for eight analytes were less than 1.9%, respectively, with the mean recovery at the range of 93.21%-108.4%. Meanwhile, 17 bupleurum samples were examined with this process. The results showed a variety either the chemotaxonomic or content of polyacetylenes. The method indicated good linearity, limit of detection and quantification, precision, accuracy and recovery. The developed method allows quantitative assessment and quality control of polyacetylenes, and might be a good alternative according to detection levels in polyacetylenes from Bupleurum Radix.

[Sesquiterpenoids of endophytic fungus Cerrena sp. from Pogostemon cablin and their cytotoxic activities].

The secondary metabolites of endophytic fungus Cerrena sp.A593 from Pogostemon cablin and their cytotoxic activities were investigated. Eight sesquiterpenoids were isolated from the fermentation broth of the strain A593 by silica gel, reverse phase silica gel, Sephadex LH-20, HPLC and so on. Their structures were identified as chloriolin B(1), chloriolin C(2), pleurocybellone A(3), dihydrohypnophilin(4), cucumin F(5), antrodin A(6), 10α-hydroxyamorphan-4-en-3-one(7), and connatusin A(8). Compounds 1- 8 were firstly found from the genus Cerrena. All isolated sesquiterpenoids were evaluated for in vitro cytotoxic activities against HepG-2, SF-268, MCF-7 and NCI-H460 tumor cell lines. Compounds 1-3 showed inhibitory activities against the four tumor cell lines with IC50 values ranging from 20.33 to 63.13 µmol•L⁻¹.

[Analysis and evaluation of chemically induced artificial agarwood].

In this study,the content of ethanol extraction of agarwood were performed following the method of Chinese Pharmacopoeia(ChP 2015 edition). The chromatographic fingerprints were established by GC-MS. Similarity Evaluation System for Chromatographic Fingerprint of traditional Chinese medicine（TCM）(version 2012) was employed to calculate the similarity of each chromatogram of agarwood. The ratios of sum peak area in the range of 170-270 min and 0-100 min of individual chromatogram were calculated using square peaks to normalization. AMDIS and RI were employed to identify the common and different peaks. Correlation coefficient P(corr) combined with Variable important in projection(VIP) value was employed to screen the different representative components based on OPLS-DA analysis. Grey related degree and TOPSIS were used to evaluate the quality of artificial agarwoods. The results showed that more than 10.0% of the ethanol extract content was found in 15 batches of artificial agarwoods among the total 18. The similarity of 18 batches artificial agarwoods was 0.439-0.779. The peak area ratios of two intervals were in the range of 0.307-13.254. The 9 common components and 8 different components were identified. Meanwhile, 2% salicylic acid is the best inducer based on grey related degree and TOPSIS. Grey related degree and TOPSIS can be used to evaluate the quality of artificial agarwoods rapidly. These results provide a reference data to evaluate the qualityof artificial agarwood.

[Effect of Grade and Steaming Time on Quality of Cultivated Cistanche deserticola].

Objective: To study the correlation between chemical component content and grades of Cistanche deserticola,and then to determine the optimum steaming time of different grades of Cistanche deserticola. Methods: Morphological indexes of postharvest stems of Cistanche deserticola were analyzed by principal component analysis and K-mean cluster analysis to determine a grading standard. Concentrations of phenylethanoid glycosides,polysaccharides,dilute ethanol-soluble extracts and total ashes in dried stems of Cistanche deserticola were determined using high performance liquid chromatography and ultraviolet spectrophotometer. Results: There was no significant relationship between grades and chemical component content. The effect of steaming time was stronger than that of grades on chemical component content. Moreover, the optimum steaming time of grade Ⅰwas 30 min,of grade Ⅱ and Ⅲ were both 20 min. Conclusion: It is suggested that postharvest Cistanche deserticola should be divided into three grades and steamed for a certain time.

[Variation and correlation analysis on phenotypic traits of Scutellaria baicalensis from different strains].

To research the differences and correlation between Scutellaria baicalensis about phenotypic traits of different strains, 10 aboveground traits and 6 root traits of S. baicalensis in two-year-transplanted plants from 14 different strains were compared respectively, and the SPSS 17.0 statistical software was used for data analysis. It showed that phenotypic traits variation of different S. baicalensis strains was rich and the F value ranged from 3.169 to 71.58. The difference was significant between each other and germplasm 15 performs the most outstanding characters. Correlation analysis showed that there existed a significant correlation between the characters except for lateral root number, root diameter and length. The correlation coefficient between the fresh weight of root and the reed head diameter was up to 0.877. Principal component analysis showed that the average of overall yield per plant and root diameter could be used as the comprehensive reference index for germplasm evaluation. The differences and correlations in phenotypic traits of different S. baicalensis strains, provide theoretical basis for distinguishing germplasm and breeding good varieties of S. baicalensis.

[An exploration in the action targets for antidepressant bioactive components of Xiaoyaosan based on network pharmacology].

The present study aims to predict the action targets of antidepressant active ingredients of Xiaoyaosan to understand the "multi-components, multi-targets and multi-pathways" mechanism. Using network pharmacology, the reported antidepressant active ingredients in Xiaoyaosan (saikosaponin A, saikosaponin C, saikosaponin D, ferulic acid, Z-ligustilide, atractylenolide I, atractylenolide II, atractylenolide III, paeoniflorin, albiflorin, liquiritin, glycyrrhizic acid and pachymic acid), were used to predict the targets of main active ingredients of Xiaoyaosan according to reversed pharmacophore matching method. The prediction was made via screening of the antidepressive drug targets approved by FDA in the DrugBank database and annotating the information of targets with the aid of MAS 3.0 biological molecular function software. The Cytoscape software was used to construct the Xiaoyaosan ingredients-targets-pathways network. The network analysis indicates that the active ingredients in Xiaoyaosan involve 25 targets in the energy metabolism-immune-signal transmutation relevant biological processes. The antidepressant effect of Xiaoyaosan reflects the features of traditional Chinese medicine in multi-components, multi-targets and multi-pathways. This research provides a scientific basis for elucidation of the antidepressant pharmacological mechanism of Xiaoyaosan.

[Anti-depressive mechanism of Fufang Chaigui prescription based on neuroendocrine hormone and metabolomic correlation analysis].

To elucidate the anti-depressive effect of Fufang Chaigui prescription and its mechanism and investigate its effect on neuroendocrine hormone, rats were included into a chronic unpredictable mild stress (CUMS) model for 28 d, and drugs were administered at the same time. During the period, rats' behaviors were observed and the blood was collected by using ELISA to determine representative hormone concentrations of HPAA, HPTA and HPGA. The changes in endogenous metabolites were analyzed by using H NMR metabolomics to seek the potential biomarkers. Results showed Fufang Chaigui prescription could improve the behaviors of CUMS rats obviously, increase contents of ACTH, CORT, T3and decrease contents of TSH and TESTO and regulate the levels of lactate, α-glucose, choline, N-acetylglycoprotein, trimethylamine oxide and leucine to get closer to the contents of control group. The results of correlation analysis indicated that HPTA was associated with glycometabolism, amino acid metabolism and choline metabolism. And HPAA was related to glycometabolism and amino acid metabolism. However, HPGA was only correlated with glycometabolism. In conclusion, Fufang Chaigui prescription could show an obvious anti-depressive effect and its underlying mechanism might involve regulations of neuroendocrine function and pathways of glycometabolism, amino acid metabolism and choline metabolism.

[Effects of agarwood formation induced by Fusarium sp. A2 on distribution and community composition of endophytic fungi in leaves of Aquilaria sinensis].

The aim of the paper is to observe the distribution of the endophytic fungi in leaves of Aquilaria sinensis by using permanent paraffin-cut section, optical microscope photography and histochemistry. Total DNA was extracted with modified CTAB method and rDNA ITS regions of plant and endophytic fungi were amplified with eukaryotic universal primers. The rDNA ITS amplicon was characterized by RFLP analysis, sequencing of rDNA ITS library and phylogenetic analyses using PAUP by maximum parsimony. Fusarium sp. A2 was used to induce the formation of resinous in A. sinensis trees. As a result, endophytic fungi mainly distributed in spongy and phloem in leaf. Endophytic fungi distributed in the phloem in agarwood-producing tree and had a relatively high abundance. Phoma sp. and Collectrotrichum sp. were the absolute advantage species in the leaf tissues of non-resinous and agarwood-producing tree, respectively. Collectrotrichum sp. was the only fungal species detected both in the two types of A. sinensis with different levels of abundance. The culture-independent molecular method can be used to identify fungal species directly and rapidly from the plant tissues. Endophytic fungal communities in non-resinous and agarwood-producing A. sinensis leaf tissues were quite different.

[Study on supercritical CO2 extraction of xiaoyaosan and its GC-MS fingerprint].

To determine the optimum conditions of supercritical CO2 extraction of Xiaoyaosan, and establish its fingerprint by gas chromatography-mass spectrometry (GC-MS), the yield of extract were investigated, an orthogonal test was used to quantify the effects of extraction temperature, pressure, CO2 flow rate and time, and fingerprint analysis of different batches of extracts were by GC-MS. The optimal extraction conditions were determined as follows: extraction pressure 20 MPa, extraction temperature 50 degrees C, CO2 flow rate 25 kg x h(-1), extraction time 3 h, and average yield 2.2%. The GC-MS fingerprint was established and 27 common peaks were found, whose contents add up to 81.89% of the total peak area. Among them, 21 compounds were identified, accounting for 53.20% of the total extract. The extraction process is reasonable and favorable for industrial production. The GC-MS method is accurate, reliable, reproducible, and can be used for quality control of supercritical CO2 extract from Xiaoyaosan.

[Anti-depressant effect and mechanism of supercritical CO2 extract from Compound Chaigui Fang].

The tail suspension test (TST), forced swimming test (FST) and chronic unpredictable mild stress (CUMS) model were used to evaluate the anti-depressant effect of supercritical CO2 extract from Compound Chaigui Fang (FFCGF). A nuclear magnetic resonance (NMR)-based metabonomics combined with multivariate statistical analysis was performed to explore the mechanism of FFCGF. Rats were conducted by CUMS procedure for 28 days and drugs were administrated at the same time. The body weight, sucrose preference, crossings and rearings in open-field tests were evaluated and the urine was collected simultaneously. The metabonomic profiles of rats' urine were analyzed by NMR and potential biomarkers were searched by multivariate statistical analysis. The results showed that administration of FFCGF significantly decreasing the immobility time in FST and TST and improving rats' body weight, sucrose preference, crossings and rearings in CUMS, which were indication that the anti-depressant effect of FFCGF was abvious. Significant differences in the metabolic profile of the CUMS treated group and the control group were observed, which were consistent with the results of behavioral tests. Decreased levels of acetic acid, succinic acid, 2-oxidation glutaric acid and citric acid and increased glycine and pyruvic acid in urine were significantly affected by the CUMS procedure and the 6 biomarkers were reversed evidently after administration of FFCGF. These changes were suggestion that the anti-depressant mechanism of FFCGF was associated with energy metabolism, lipid metabolism and amino acid metabolism.