Exploring the anxiolytic mechanism of Fructus gardeniae based on metabolomics, network pharmacology, and molecular docking.

OBJECTIVE: To explore the effect and anxiolytic mechanism of a natural remedy called Fructus gardeniae (FG). METHODS: The elevated-plus maze (EPM) test was used to confirm the anxiolytic effect of FG. The potential and anxiolytic components, targets, and route processes of FG were investigated using the network pharmacology method in conjunction with metabolomics and molecular docking technologies. RESULTS: FG could greatly enhance the proportion of time and times of opening arms, according to the EPM data. As to the metabolomics findings, a total of 61 distinct metabolites were found, mainly involved in glycine, serine, and threonine metabolism as well as alanine, aspartate, and glutamate metabolism. The primary active ingredients of FG, nicotiflorin, jasminodiol, and crocetin, demonstrated substantial binding affinities with monoamine oxidase A (MAOA), monoamine oxidase A (ACHE), malate dehydrogenase 2 (MDH2), glutamate decarboxylase 2 (GAD2), glutamate decarboxylase 1 (GAD1), and nitric oxide synthase (NOS1), according to the findings of network pharmacology and molecular docking. CONCLUSION: FG exerts an anxiolytic action via targeting MAOA, ACHE, MDH2, GAD2, GAD1, and NOS1, and regulating the metabolism of glycine, serine, and threonine as well as alanine, aspartic acid, and glutamic acid.

Pharmacodynamic and targeted amino acid metabolomics researches on the improvement of diabetic retinopathy with Fufang Xueshuantong component compatibility.

The Fufang Xueshuantong capsule (FXT) has significant preventive and therapeutic effects on diabetic retinopathy(DR), but the compatibility of its active components remains to be thoroughly explored. In this study, a zebrafish diabetic retinopathy model was established using high-mixed sugars, and the optimal ratios of notoginseng total saponins, total salvianolic acid, astragaloside, and harpagide were selected through orthogonal experiments. Furthermore, we used UPLC-QqQ/MS to detect the changes in amino acid content of DR zebrafish tissues after administration of FXT and its compatible formula to analyze the effects of FXT and its compatible formula on amino acid metabolites. The results showed that the final compatibility ratios of the components were 8: 5: 1: 6.6 by comprehensive evaluation of the indicators. FXT and its compatibility formula had beneficial effects on retinal vasodilatation, lipid accumulation in the liver, total glucose, and VEGF levels in DR zebrafish, and all of them could call back some amino acid levels in DR zebrafish. In this research, we determined the compatible formulation of the active ingredients in the FXT and investigated their efficacy in DR zebrafish for further clinical applications.

Antithrombotic pharmacodynamics and metabolomics study in raw and processed products of Whitmania pigra Whitman.

Objective: As a traditional Chinese medicine, leech has obvious pharmacological activities in anticoagulantion and antithrombosis. Whitmania pigra Whitman (WP) is the most commonly used leech in the Chinese market. It is often used in clinical applications after high-temperature processing by talcum powder to remove the fishy taste and facilitate crushing. The anticoagulant and thrombolytic active ingredients are protein and polypeptide, which may denaturate and lose activity after high-temperature processing. The rationality of its processing has been questioned in recent years. This study aims to investigate the effect of talcum powder scalding on the antithrombotic activity of WP in vivo and to discuss its pharmacodynamic mechanism in vivo. Methods: Raw and talcum-powdered processed WP were administered intragastrically for 14 days, and carrageenan was injected intraperitoneally to prepare a mouse model of tail vein thrombosis. The incidence rate of tail vein thrombosis and the thrombus area under pathological tissue sections were calculated to evaluate the antithrombotic effect between raw and processed WP. Non-targeted metabolomics was conducted using UPLC-Q-TOF/MS technology to analyze the changes of small molecule metabolites in the body after administration of WP. Results: After intragastric administration, both the raw product and the processed product of WP could inhibit the thrombosis induced by carrageenan, and the processed product had a more apparent antithrombotic effect than the raw product. The administration of WP could regulate the changes of some small molecular metabolites, such as amino acids, lipids, and steroids, in Sphingolipid metabolism and Glycerophospholipid metabolism. Conclusions: Based on the results of pharmacodynamics and metabolomics, processed WP will not reduce the antithrombotic activity of WP. This study provided a scientific basis for the rational use of leeches.

Nephrotoxicity assessment of podophyllotoxin-induced rats by regulating PI3K/Akt/mTOR-Nrf2/HO1 pathway in view of toxicological evidence chain (TEC) concept.

Adverse reactions to traditional Chinese medicine have hindered the healthy development and internationalization process of the traditional Chinese medicine industry. The critical issue that needs to be solved urgently is to evaluate the safety of traditional Chinese medicine systematically and effectively. Podophyllotoxin (PPT) is a highly active compound extracted from plants of the genus Podophyllum such as Dysosma versipellis (DV). However, its high toxicity and toxicity to multiple target organs affect the clinical application, such as the liver and kidney. Based on the concurrent effects of PPT's medicinal activity and toxicity, it would be a good example to conduct a systematic review of its safety. Therefore, this study revolves around the Toxicological Evidence Chain (TEC) concept. Based on PPT as the main toxic constituent in DV, observe the objective toxicity impairment phenotype of animals. Evaluate the serum biochemical indicators and pathological tissue sections for substantial toxic damage results. Using metabolomics, lipidomics, and network toxicology to evaluate the nephrotoxicity of PPT from multiple perspectives systematically. The results showed that PPT-induced nephrotoxicity manifested as renal tubular damage, mainly affecting metabolic pathways such as glycerophospholipid metabolism and sphingolipid metabolism. PPT inhibits the autophagy process of kidney cells through the PI3K/Akt/mTOR and Nrf2/HO1 pathways and induces the activation of oxidative stress in the body, thereby causing nephrotoxic injury. This study fully verified the feasibility of the TEC concept for the safety and toxicity evaluation of traditional Chinese medicine. Provide a research template for systematically evaluating the safety of traditional Chinese medicine.

Integration of non-targeted metabolomics with network pharmacology deciphers the anxiolytic mechanisms of Platycladi Semen extracts in CUMS mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Platycladi Semen was recorded in Shen Nong's Herbal Classic and was considered a herbal medicine with low toxicity after long-term medication. Multiple traditional Chinese medicine prescriptions containing Platycladi Semen have been used to treat insomnia. Modern clinical practitioners commonly use Platycladi Semen to treat anxiety disorders, but there are few studies on its composition and anxiolytic mechanisms. AIM OF THE STUDY: To describe the main components of Platycladi Semen and investigate its anxiolytic effects and mechanisms. MATERIALS AND METHODS: The main components of Platycladi Semen were characterized by liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS). The anxiolytic effects of oral Platycladi Semen were evaluated in chronic unpredictable mild stress (CUMS) induced mice. To explore the anxiolytic mechanisms of Platycladi Semen, serum non-targeted metabolomics combined with network pharmacology and molecular docking was performed. RESULTS: Fourteen compounds were identified in the 50% methanol extract and 11 fatty acid derivatives were identified in the methyl-esterified fatty oil of Platycladi Semen. In CUMS mice, both the aqueous extract and fatty oil of Platycladi Semen had anxiolytic effects, which were shown by the increase in the time and frequency of mice entering the open arm in the elevated plus maze (EPM) experiment. Through serum non-targeted metabolomics, 34 differential metabolites were identified, and lipid metabolic pathways such as sphingolipid metabolism, steroidogenesis, alpha-linoleic acid, and linoleic acid metabolism were enriched. Through network pharmacology, 109 targets of the main components in Platycladi Semen were identified, and the 'neuroactive ligand-receptor interaction' and 'lipid metabolism' were enriched. The molecular docking results showed that the main components in Platycladi Semen could bind to the key targets such as peroxisome proliferator-activated receptor delta (PPARD), peroxisome proliferator-activated receptor alpha (PPARA), fatty acid binding protein 5 (FABP5), fatty acid binding protein 3 (FABP3), peroxisome proliferator-activated receptor gamma (PPARG), arachidonate 5-lipoxygenase (ALOX5) and fatty acid amide hydrolase (FAAH). CONCLUSION: This study indicated that Platycladi Semen has anxiolytic effects, and the anxiolytic mechanisms may be the regulation of lipid metabolism and the neuroactive ligand-receptor interaction.

Serum metabolomics study of anxiety disorder patients based on LC-MS.

BACKGROUND: In the current environment of increasing social pressure, anxiety disorder has become a kind of health problem that needs to be solved urgently. However, the pathological mechanism of anxiety is still unclear, the classification of clinical diagnosis and symptoms is complex, and there is still a lack of biomarkers that can be identified and judged. METHODS: This study used LC-MS and non-targeted metabolomics to analyze the clinically collected plasma of 18 samples from anxiety disorder patients and 31 samples from healthy people to screen differential metabolites and perform subsequent metabolic pathway analysis. Binary Logistic regression was used to construct the anxiety disorder diagnosis prediction model and evaluate the prediction efficacy. RESULTS: The results showed that 22 metabolites were disturbed in the plasma of anxiety patients compared with healthy people. These metabolites mainly participate in 6 metabolic pathways. The combined diagnostic factors 4-Acetamidobutanoate, 3-Hydroxysebacic acid, and Cytosine were used to construct the diagnosis prediction model. The prediction probability of the model is 91.8%, the Youden index is 0.889, the sensitivity is 0.889, and the specificity is 1.000, so the prediction effect is good. CONCLUSIONS: This study preliminarily analyzed and explored the differences between plasma samples from patients with anxiety disorder and healthy individuals, increased the types of potential biomarkers for anxiety disorder, and provided a valuable reference for subsequent research related to anxiety disorder.

[Nucleic acid aptamer-based traditional Chinese medicine application:therapy,targeting and diagnosis].

Nucleic acid aptamers, broad-spectrum target-specific single-stranded oligonucleotides, serve as molecules in targeted therapy, targeted delivery and disease diagnosis for the treatment of tumor or microbial infection and clinical detection. Due to the existence of components in the use of traditional Chinese medicine(TCM), the target is difficult to concentrate and the specificity of treatment is poor. The effective components of TCM are toxic components, so a highly sensitive detection method is urgently needed to reduce the toxicity problem at the same time. The combined application of TCM and modern medical treatment strategy are difficult and cannot improve the therapeutic effect. Aptamers, advantageous in biosensors, aptamer-nanoparticles for targeted drug delivery, and aptamer-siRNA chimeras, are expected to connect Chinese medicinals with nanotechnology, diagnostic technology and combined therapies. We summarized the preparation, screening, and modification techniques of nucleic acid aptamers and the biomedical applications and advantages in therapy, targeting, and diagnosis, aiming at providing a reference for the in-depth research and development in TCM.