Shizao decoction for cirrhotic ascites: assessing potential targets based on network analysis combined with pharmacokinetics and metabolomics.

Introduction: Shizao decoction (SZD) is a traditional Chinese medicine decoction that has therapeutic effects on cirrhotic ascites (CAS). Because of the unclear treatment mechanism, in the current study, the anti-CAS activity of SZD and molecular mechanisms were analyzed by network analysis combined with pharmacokinetics and metabolomics. Methods: Firstly, we assessed the anti-CAS efficacy of SZD by hematoxylin-eosin (H&E), liver function tests, NO and ET-1 levels, and portal venous pressure. Secondly, network analysis was applied to dig out the metabolites, targets, and pathways related to SZD and CAS. Then, the pharmacokinetics of the pharmacokinetically relevant metabolites (PRM) were analyzed. Thirdly, the serum and urine metabolic biomarkers of rats with CAS were identified using metabolomics by comparing them with the SZD treatment group. In addition, MetaboAnalyst was utilized to conduct metabolic pathway analysis. Finally, the correlation analysis established a dynamic connection between absorbed PRM from SZD and CAS-associated endogenous metabolites. Results: Pharmacodynamic analysis indicated that SZD effectively mitigated liver injury symptoms by ameliorating inflammatory cell infiltration in CAS rats. The network analysis results indicated that twelve RPM contribute to the therapeutic efficacy of SZD against CAS; the key signaling pathways involved might be hepatitis B and PI3K-Akt. Pharmacokinetics results showed that the 12 RPM were efficiently absorbed into rat plasma, ensuring desirable bioavailability. The metabolomic analysis yielded 21 and 23 significantly distinct metabolites from the serum and urine, respectively. The 12 bioavailable SZD-PRM, such as luteolin, apigenin, and rutin, may be associated with various CAS-altered metabolites related to tryptophan metabolism, alpha-linolenic acid metabolism, glycine metabolism, etc. Discussion: A novel paradigm was provided in this study to identify the potential mechanisms of pharmacological effects derived from a traditional Chinese medicine decoction.

Molecularly imprinted polymers based on calcined rape pollen and deep eutectic solvents for efficient sinapic acid extraction from rapeseed meal extract.

Substances that possess hierarchical and interconnected porous features are ideal choices for acting as skeletons to synthesize surface molecularly imprinted polymers (MIPs). In this work, rape pollen, a waste of biological resources, was calcined and a porous mesh material with a high specific surface area was obtained. The cellular material was adopted as a supporting skeleton to synthesize high-performance MIPs (CRPD-MIPs). The CRPD-MIPs presented an ultrathin imprinted layered structure, with an enhanced adsorption capacity for sinapic acid (154 mg g-1) relative to the non-imprinted polymers. The CRPD-MIPs also exhibited good selectivity (IF = 3.24) and a fast kinetic adsorption equilibrium (60 min). This method exhibited a good linear relationship (R2 = 0.9918) from 0.9440 to 29.26 µg mL-1, and the relative recoveries were 87.1-92.3%. The proposed CRPD-MIPs based on hierarchical and interconnected porous calcined rape pollen may be a valid program for the selective extraction of a particular ingredient from complicated actual samples.

Study on the mechanism of anti-hepatic fibrosis of Glycyrrhiza Uralensis-Salvia miltiorrhiza prescription based on serum and urine metabolomics and network pharmacology.

Hepatic fibrosis (HF) is a kind of chronic epidemic liver disease. Glycyrrhiza Uralensis and Salvia Miltiorrhiza (GUSM), traditional Chinese medicine, has the obvious clinical treatment of liver fibrosis. This study aimed to investigate the mechanisms of GUSM against HF by an integrated strategy combining untargeted metabolomics with network pharmacology. The results showed that GUSM prescription can improve the morphology and structure of liver tissue, inhibit the proliferation of collagen fibers and reducing the inflammatory response of the liver and so on. Endogenous metabolites and HF-related potential biomarkers in serum and urine were detected by ultra-high-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF/MS). The metabolic pathways were enriched by MetaboAnalyst. GUSM prescription showed an antifibrotic effect on rats by regulating metabolic pathways, mainly pentose and glucuronate interconversions and arachidonic acid metabolism. Network pharmacology was then applied to find 42 overlapping targets of GUSM-HF. Quercetin was found to be the main active component and STAT3 was the main active target in GUSM prescription. Molecular docking showed high affinities between quercetin and STAT3. Therefore, GUSM has protective effects on HF by regulating the metabolism and different signaling pathways. The work also shows that the metabolomic and network pharmacology methods are promising tools to gain insight into the efficacy and mechanism research of traditional Chinese medicines.

Gut microbiota from patients with arteriosclerotic CSVD induces higher IL-17A production in neutrophils via activating RORγt.

The intestinal microbiota shape the host immune system and influence the outcomes of various neurological disorders. Arteriosclerotic cerebral small vessel disease (aCSVD) is highly prevalent among the elderly with its pathological mechanisms yet is incompletely understood. The current study investigated the ecology of gut microbiota in patients with aCSVD, particularly its impact on the host immune system. We reported that the altered composition of gut microbiota was associated with undesirable disease outcomes and exacerbated inflammaging status. When exposed to the fecal bacterial extracts from a patient with aCSVD, human and mouse neutrophils were activated, and capacity of interleukin-17A (IL-17A) production was increased. Mechanistically, RORγt signaling in neutrophils was activated by aCSVD-associated gut bacterial extracts to up-regulate IL-17A production. Our findings revealed a previously unrecognized implication of the gut-immune-brain axis in aCSVD pathophysiology, with therapeutic implications.

Preparation, structure and anticoagulant activity of a low molecular weight fraction produced by mild acid hydrolysis of sulfated rhamnan from Monostroma latissimum.

A low molecular weight fraction, designated LMWP, was prepared by mild acid hydrolysis of sulfated rhamnan from Monostroma latissimum and purified by anion-exchange and gel-permeation chromatography. Chemical and spectroscopic analyses showed that LMWP was mainly composed of rhamnose, and its molecular weight was about 33.6 kDa. The backbone of LMWP consists of 1,3-linked α-L-rhamnose units with partially sulfate groups at the C-2 position. Approximately 25% of 1,3-linked α-L-rhamnose units is substituted at C-2 by sulfated or non-sulfated 1,3-linked α-L-rhamnose and 1,2-linked α-L-rhamnose units. LMWP effectively prolonged clotting time as evaluated by the activated partial thromboplastin time assay and was a potent thrombin inhibitor mediated by heparin cofactor II. The investigation demonstrated that LMWP is a novel sulfated polysaccharide with anticoagulant activity.

[Observation on the therapeutic effect of scraping therapy on perimenopausal syndrome].

OBJECTIVE: To observe the clinical effects of scraping therapy on perimenopausal syndrome. METHODS: Twenty women with perimenopausal syndrome were treated with scraping therapy and the dorsal course of the Governor Vessell and the Urinary Bladder Meridian of Foot-Taiyang were scraped, especially on the Back-shu points and Ashi points. The clinical symptoms were observed and compared with a modified Kupperman score before and after treatment. RESULTS: In all the 20 patients, 3 cases were cured, 6 cases were markedly effective, 9 cases were effective, 2 cases were ineffective, and the total effective rate was 90.0%. The Kupperman total score after treatment of (10.4 +/- 7.5) was significantly lower than the score before treatment of (25.0 +/- 5.3) (P < 0.001), in which, hot flushes and sweating, insomnia, fatigue, paresthesia, anxiety/irritability, hypaphrodisia, urinary system infection, tinnitus, dizziness, memory deterioration and headache were eased significantly (P < 0.001, P < 0.05). CONCLUSION: The scraping therapy has a good clinical effect on perimenopausal syndrome and can significantly improve the clinical symptoms.