Metformin demonstrates significant hypoglycemic efficacy, yet its clinical application is limited by gastrointestinal adverse reactions. The integration of Chinese and Western medicine through gut microbiota modulation provides a novel strategy for addressing metformin intolerance. Animal experiments were approved by the Animal Ethics Committee of Beijing Friendship Hospital, Capital Medical University (Approval No.: 23-2043). C57BL/6J mice were fed a high-fat diet (HFD) for 4 weeks, followed by 7 days of high-dose metformin administration (250 mg·kg^-1, bid) to establish a diarrhea model (HFDM). Additional groups included a normal chow diet group (NCD), HFD group, and combination group (HFDMB; co-administered baicalin while establishing the mouse model of diarrhea, 100 mg·kg^-1, bid). Observations of fecal morphology, diarrhea score, and fecal water content revealed that baicalin alleviated metformin-induced early diarrhea. Full-length 16S rRNA sequencing of fecal samples demonstrated that baicalin reduced the relative abundance of diarrhea-associated bacteria (Shigella sonnei, Enterococcus gallinarum, Enterococcus hirae) while increasing beneficial bacteria (Lactobacillus johnsonii, Ligilactobacillus murinus, Limosilactobacillus reuteri). Targeted bile acid quantification of colonic contents revealed elevated levels of primary bile acids (e.g., TCDCA, TCA) in the HFDM group, which were normalized by baicalin co-treatment. Histopathological analysis of colonic tissues via H&E staining and immunohistochemical labeling of tight junction proteins (ZO-1 and occludin) indicated that baicalin mitigated metformin-induced colonic damage and enhanced tight junction protein expression. In conclusion, this study elucidates that baicalin alleviates metformin-induced early diarrhea by modulating gut microbiota-bile acids-gut barrier, offering a scientifically grounded integrated therapeutic approach for clinical metformin intolerance.

In order to clarify the anti-fouling active components of the marine-derived fungal strain Aspergillus terreus GXIMD00546, its fermentation products of the rice medium were isolated by silica gel column chromatography and purified using HPLC. One new compound asperterrestide C (1) and 12 known compounds territrem B (2), methyl-3, 4, 5-trimethoxy-2-(2-(nicotinamido)benzamido)benzoate (3), butyrolactone Ⅰ (4), terrien (5), (1R, 2S)-2-hydroxy-5-oxo-3-((E)-prop-1-en-1-yl)cyclopent-3-en-1-yl acetate (6), (1S, 5R)-5-hydroxy-4-oxo-2-((E)-prop-1-en-1-yl)cyclopent-2-en-1-yl acetate (7), 4-hydroxykigelin (8), monacolin K (9), methyl ester of lactone ring-opened monacolin K (10), butyrolactone Ⅶ (11), aspernolide A (12), and epi-aszonalenin C (13) were identified by the detailed data analysis of NMR sepectra, high-resolution mass spectrometry spectra and the comparison with literatures. The new compound asperterrestide C (1) is a cyclopeptide with rare aminomethylation modifications. Compounds 1-3, 6, 7, 9, 11, 12 showed clear anti-fouling activities against the attachment of barnacle larvae in the EC₅₀ ranges of 0.12-12.5 μg·mL^-1 with low toxicity. Compounds 1, 2, 4, 9-12 also exhibited acetylcholinesterase inhibitory effects with EC₅₀ range of 17.16-55.77 μg·mL^-1. Compounds 4 and 11 have broad spectrum antibacterial activity against human pathogenic bacterium methicillin-resistant Streptococcus aureus (MRSA), and fouling bacteria Methanococcus janaschii (MJ), Vibrio pelagius (VP), and V. Rotiferianus (VR).

Nine flavonoid glycosides were isolated from water extract of the fruits of Lycium ruthenicum Murr. by using various chromatographic methods, including D-101 macroporous adsorption resin, silica gel, ODS, Sephadex LH-20 and semi-preparative HPLC. The structures of the isolated compounds were identified as laricetrin-3-O-β-D-glucopyranoside-7-O-[4′′′′-O-(E)-p-coumaroyl-α-L-rhamnopyranosyl-(1′′′′→6′′′)]-β-D-glucopyranoside (1), (2S)-naringenin-5-O-α-L-rhamnopyranosyl(1′′′→6′′)-β-D-glucopyranoside (2), kaempferol-3-O-robinobioside (3), quercetin-3-O-rutinose (4), isorhamnetin-3-rutinoside (5), kaempferol-3-β-D-glucopyranosyl(1→4)-α-L-rhamnopyranoside (6), prunin (7), (2S)-helichrysin A (8), 2′-O-β-D-glucopyranoside (9) by spectroscopy methods (1D NMR, 2D NMR, MS, etc.). Compounds 1 and 2 were new flavonoid glycosides, named lyciuflavonoid A and lyciuflavonoid B. Compounds 6 and 9 were isolated from L. ruthenicum for the first time. Compound 9 has an inhibitory effect on α-glucosidase with an IC₅₀ of (76.14 ± 4.64) μmol·L^-1.

The study aims to interpret the formula-syndrome correspondence of pacifying liver-subduing Yang and liver Yang hyperactivity from formulas containing Uncaria rhynchophylla based on metabolomics technology, and establish an efficacy evaluation method for these formulas. The rat model of hypertension with liver Yang hyperactivity syndrome was established by intragastrically administering Fuzi Decoction to spontaneously hypertensive rats. Animal experiments were approved by the Animal Ethics Committee of Shandong University of Traditional Chinese Medicine (Ethics No.: SDZYY20240304033). Tianma Gouteng Decoction, Lingjiao Gouteng Decoction, and Qingnao Jiangya Tablets were respectively administered. The blood pressure, appearance, pain threshold, facial temperature, level of irritability, and 24-hour water intake of the rats were observed. Ultra-high performance liquid chromatography-quadrupole-exactive orbitrap mass spectrometry and metabolomics were used to analyze differential metabolic markers in the serum of rats treated with formulas containing Uncaria rhynchophylla, and metabolic pathway analysis was carried out. Meanwhile the intervention effects of formulas containing Uncaria rhynchophylla were judged according to the changes in the ion intensity of differential metabolites combined with macroscopic data, and partial least squares (PLS) regression analysis was applied to screen significantly differential metabolites. The identified common differential metabolites were regarded as the core metabolic phenotypes of hypertension with liver Yang hyperactivity syndrome. By integrating macroscopic data and metabolic phenotypes, an evaluation method for the syndrome efficacy of Uncaria-based prescriptions was constructed. A total of 35 common differential metabolic markers were identified in this experiment. Among them, 24 differential metabolites decreased in the model group and increased after the intervention of formulas containing Uncaria rhynchophylla, while 11 differential metabolites showed the opposite trend. Metabolic pathway enrichment analysis showed that the intervention pathways were mainly associated with arachidonic acid metabolism, biosynthesis of unsaturated fatty acids, primary bile acid biosynthesis, and glycerophospholipid metabolism. Through PLS regression analysis, 14 significant differential metabolites were obtained, mainly involving three metabolic pathways: arachidonic acid metabolism, biosynthesis of unsaturated fatty acids and glycerophospholipid metabolism. The established efficacy evaluation method indicated that Tianma Gouteng Decoction showed the most significant intervention effect, which was consistent with the theory of traditional Chinese medicine. This study discovered the common factors of formulas containing Uncaria rhynchophylla in intervening hypertension with liver Yang hyperactivity syndrome, and revealed the metabolic basis of the correspondence between these formulas and liver Yang hyperactivity syndrome. The efficacy evaluation method was built to objectively quantify formulas containing Uncaria rhynchophylla, and offers evidence for clinical research.

In this study, LHCGR(-Ex10)-CRE-luc-HEK293 cell line and LHCGR-CRE-luc-HEK293 cell line were constructed according to the cAMP signaling pathway activated by luteinizing hormone (LH) binding to the receptor. The biological activity of LH was detected by luciferase detection system, and the relative titer of samples was calculated by four parameter fitting analysis. The method conditions were optimized, and the specificity, relative accuracy, precision and linearity of the method were verified. The results showed that there was a dose-response relationship between the concentration of LH and the expression of reporter gene, and it conformed to the four-parameter curve. After optimization, the conditions were determined as follows: the initial concentration of LH was 200 nmol·mL^-1, 6-fold serial dilution, 10 concentrations, the number of cells per well was 30 000, and the incubation time was 6 h. It is proved that the method has strong specificity, good accuracy, precision and linearity. This study successfully established and validated a reporter gene method to detect LH biological activity, which can be used for LH biological activity detection and quality control. With the increasing demand for the research and development of LH biosimilar drugs, the establishment of a stable and simple activity assay method to evaluate the biological activity of LH can provide technical support for the quality control of LH products and a powerful tool for the comparative study of similar products.

Forsythia suspensa is one of the great medicinal herbs. At present, research on the active ingredients of Forsythia suspensa mainly focuses on Forsythin, Forsythiaside and Phillygenol, etc. Polysaccharides show increasingly significant pharmacological functions, which may be associated with the efficacy of Forsythia suspensa in clearing heat and removing toxins and dispersing wind and heat. Therefore, it is important to study the green Forsythiae Fructus polysaccharide and ripe Forsythiae Fructus polysaccharide. In this paper, we have separated and purified green Forsythiae Fructus polysaccharides and ripe Forsythia Fructus polysaccharides by gel chromatography and comparatively analysed the structures of the two groups. Comparison of the anti-inflammatory activity of green and ripe Forsythiae Fructus polysaccharides by lipopolysaccharide (LPS)-induced macrophage hyperinflammation model in RAW264.7 mice, the mechanism of action of polysaccharides with powerful anti-inflammatory activity has also been preliminarily investigated using cellular metabolomics. It was determined that the weight average molecular weight of green Forsythiae Fructus polysaccharide was significantly higher than that of ripe Forsythiae Fructus polysaccharide. The type of monosaccharide that accounted for the largest proportion of the monosaccharide composition of both green and ripe Forsythiae Fructus polysaccharides was Gal-UA, followed by Glc methylation results indicate that the major linkage of both polysaccharides is 4-Gal(p)-UA. The results of the anti-inflammatory activity study demonstrated that both polysaccharides exhibited anti-inflammatory activity, with green Forsythiae Fructus polysaccharide displaying a more powerful anti-inflammatory effect. A metabolomic study identified 18 distinct metabolites in RAW264.7 cells following the action of the active ingredient of green Forsythiae Fructus polysaccharide, compared with the control group. These metabolites were primarily involved in arginine biosynthesis, alanine metabolism, and other pathways that are closely associated with oxidative stress and the inflammatory response. This paper compares the structure and activity of polysaccharides, one of the bases for the medicinal effects of green Forsythiae Fructus and ripe Forsythiae Fructus, and provides a solid foundation for further studies on green Forsythiae Fructus and ripe Forsythiae Fructus.

The objective of this study to explore the active components and action mechanisms of Tufuling Qiwei powder (TFLQW) in the treatment of ulcerative colitis (UC) based on serum migration components, network pharmacology and experimental validation. The UC mouse model was induced using dextran sulfate sodium (DSS), and TFLQW was administered at different concentrations via gavage. The inflammatory factors in mouse serum were detected using the ELISA, and the mouse colon tissues were evaluated with HE staining and pathological tissue scoring to confirm that TFLQW could alleviate the UC phenotype in UC mice. Subsequently, the HPLC-Q-Exactive-MS technology was used to analyze the serum migration components of TFLQW, and 20 serum migration components were identified through spectral library searching and mass spectrometry identification processes. The Swiss Target Prediction database was used to predict the target of the components, and UC targets were searched in disease databases GeneCards, OMIM, and DisGeNet. Venny 2.1.0 software was used to draw a Venn diagram to obtain 113 intersection targets. The "drug-components-targets-disease" network was constructed using Cytoscape 3.8.0 software, and the Centiscape 2.2 was used to screen for core components. Components such as palmatine, berberine, jatrorhizine, coptisine, chrysophanol, and resveratrol in TFLQW may be the active substances exerting the therapeutic effect. The String database was used to analyze protein-protein interaction (PPI) and to screen for key targets, suggesting that TFLQW exerts the therapeutic effect on UC by targeting STAT3, PIK3R1, SRC, PIK3CA, MAPK1, and AKT1, among others. The David database was used for GO enrichment analysis and KEGG pathway analysis of the intersection targets, and revealed that the pathways involved in TFLQW treatment of UC mainly include cancer, PI3K/AKT and C-type lectin receptor signaling pathways. Molecular docking was performed on key targets and core components, and PIK3CA binded well with various active components. Western blot was used to detect the protein expression of PI3K/AKT signaling pathway in mouse colon tissue. This study has confirmed the therapeutic effect of TFLQW on UC and preliminarily identified the potential active components and signaling pathways of TFLQW in treating UC. These findings provide a reference for in-depth research into the material basis and action mechanisms of the compound preparation, and also offer a theoretical basis for the clinical application of TFLQW. The animal welfare and experimental procedures were approved by the Medical Ethics Committee of Inner Mongolia Medical University (ethics approval number: YKD202302093).

To effectively determine the content of characteristic components in imported Dragon's Blood (DB) and domestic Chinese Dragon's Blood (CDB), this study established a multiple reaction monitoring (MRM) method based on ultra-high performance liquid chromatography-triple quadrupole-linear ion trap mass spectrometry (UHPLC-Q-Trap-MS). Chromatographic separation was achieved using an ACQUITY UPLC BEH C₁₈ column (2.1 mm × 100 mm, 1.7 μm) at 30 ℃ with a mobile phase consisting of 0.1% formic acid aqueous solution and acetonitrile at a flow rate of 0.3 mL·min^-1 under gradient elution. The method successfully separated and quantified six characteristic components in DB and eleven in CDB within 22 minutes. The developed approach demonstrated excellent specificity, enabling rapid and efficient determination of 17 components. All analytes exhibited strong linearity (R² > 0.99), and the average recovery rate was 93.58%-105.82%. Results revealed that imported Dragon's Blood contained higher levels of dracorhodin, (2S)-5-methoxyflavan-7-ol and (2S)-5-methoxy-6-methylflavan-7-ol, while domestic Chinese Dragon's Blood was rich in loureirin B, loureirin D and pterostilbene, albeit with significant variations among different batches. These findings provide critical references for quality control and standardization of DB and CDB, as well as the insights for distinguishing similar traditional Chinese medicines.

Using the heterobifunctional crosslinker 3-(2-pyridinedithio) propionate N-succinimidyl ester (SPDP) as a coupling agent, doxorubicin (DOX) was coupled with pamidronate sodium via a chemical cross-linking method to prepare bisphosphonate-modified doxorubicin (P-DOX). The obtained product was characterized by Fourier transform infrared spectroscopy and ultraviolet-visible spectroscopy. To evaluate the in vitro bone targeting of the drugs, the binding amount of drugs onto calcium phosphate was measured, and the in vitro drug release behavior was measured under different pH values and in the presence of cysteine. Finally, to evaluate the effect of phosphorylated doxorubicin on the cellular activity of normal bone tissue and its inhibitory ability on the growth of tumor cells, the drug was co-cultured with osteogenic precursor cells, prostate cancer cells, and osteosarcoma cells, respectively. Infrared spectra analysis showed that DOX/bisphosphonate complex was successfully synthesized. The drug adsorption experiments showed that the adsorption rate of modified doxorubicin onto hydroxyapatite was increased by about one time, and effective release was achieved in a cysteine-rich environment and acidic environment. Cell co-culture experiments showed that compared with traditional doxorubicin, phosphorylated doxorubicin accumulated less in osteogenic precursor cells, effectively reducing the toxicity of chemotherapeutic drugs to normal bone tissue cells. In addition, phosphorylated doxorubicin could be effectively taken up by tumor cells, which effectively inhibit the proliferation, migration, and invasion of tumor cells, and promote apoptosis and necrosis of tumor cells. Thus, the synthesis of doxorubicin-bisphosphonate conjugates provides a new solution for the treatment of malignant bone tumors and provides an important reference for the development of more targeted antitumor drugs.

This study investigates the effects of various curing methods on the dissolution, in vitro release, and pharmacokinetics of trans-cinnamaldehyde (CA). CA was cured and characterized using porous silica adsorption and β-cyclodextrin inclusion. The dissolution and release profiles were determined, followed by conducting comprehensive pharmacokinetic studies in SD rats. The successful preparation of the two cures was verified by analytical techniques such as differential scanning calorimetry, X-ray diffraction analysis, and Fourier transform infrared spectroscopy. Both curing methods significantly increased the cumulative dissolution and cumulative release of CA at pH 1.2, 4.5 and 6.8. In comparison to free CA, the use of porous silica adsorption not only enhanced the in vitro release of CA but also significantly increased its C_max and the AUC_0-∞ in rats. β-Cyclodextrin inclusion delays CA release in vitro, decreases C_max in vivo in rats and significantly increases AUC_0-∞. All animal experiments were approved by the Animal Ethics Committee of Jiangsu Province Hospital of Integrated Traditional Chinese and Western Medicine (Ethics Approval Number: AEWC-20220815-230). Our findings revealed that porous silica adsorption significantly enhanced both the in vitro release and the in vivo uptake rate of trans-cinnamaldehyde. Conversely, β-cyclodextrin inclusion of CA led to a noticeable retardation in its in vitro release and a moderate decrease in the in vivo uptake rate.