Overuse and misuse of antibiotics are major factors in the development of antibiotic resistance in primary care institutions of rural China. In this study, the effectiveness of a Health Information System-based, automatic, and confidential antibiotic feedback intervention was evaluated. A randomized, cross-over, cluster-controlled trial was conducted in primary care institutions. All institutions were randomly divided into two groups and given either a three-month intervention followed by a three-month period without any intervention or vice versa. The intervention consisted of three feedback measures: a real-time pop-up warning message of inappropriate antibiotic prescriptions on the prescribing physician's computer screen, a 10-day antibiotic prescription summary, and distribution of educational manuals. The primary outcome was the 10-day inappropriate antibiotic prescription rate. There were no significant differences in inappropriate antibiotic prescription rates (69.1% vs. 72.0%) between two groups at baseline (P = 0.072). After three months (cross-over point), inappropriate antibiotic prescription rates decreased significantly faster in group A (12.3%, P < 0.001) compared to group B (4.4%, P < 0.001). At the end point, the inappropriate antibiotic prescription rates decreased in group B (15.1%, P < 0.001) while the rates increased in group A (7.2%, P < 0.001). The characteristics of physicians did not significantly affect the rate of antibiotic or inappropriate antibiotic prescription rates. A Health Information System-based, real-time pop-up warnings, a 10-day prescription summary, and the distribution of educational manuals, can effectively reduce the rates of antibiotic and inappropriate antibiotic prescriptions.
Polygonum capitatum as an ethnic medicine has been used to treat urinary tract infections, pyelonephritis and urinary calculi. In our previous study, P. capitatum was found to have anti-hyperuricemia effects. Nevertheless, the active constituents of P. capitatum for treating hyperuricemia were still unclear. In this study, an ultra-high-performance liquid chromatography coupled to quadrupole/orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) was used to comprehensively detect the chemical ingredients of P. capitatum and its absorbed constituents in the plasma of hyperuricemia rats for the first time. Xcalibur 3.0 and Compound Discoverer 2.0 software coupled to mzCloud and ChemSpider databases were utilized for qualitative analysis. A total of 114 chemical components including phenolics, flavonoids, tannins, phenylpropanoids, amino acids, amides and others were identified or tentatively characterized based on the exact mass, retention time and structural information. Compared to the previous P. capitatum study, an additional 66 different components were detected. Moreover, 68 related xenobiotics including 16 prototype components and 52 metabolites were found in the plasma of hyperuricemia rats. The metabolic pathways included ring fission, hydrolysis, decarboxylation, dehydroxylation, methylation, glucuronidation and sulfation. This work may provide important information for further investigation on the active constituents of P. capitatum and their action mechanisms for anti-hyperuricemia effects.
Acetaminophen (APAP) overdose is very common worldwide and has been widely recognized as the leading cause of drug-induced liver injury in the Western world. In our previous investigation, auriculatone, a natural product firstly obtained from Aster auriculatus, has demonstrated a potent protective effect against APAP-induced hepatotoxicity in HL-7702 cells. However, the poor water solubility and low bioavailability restrict its application. Auriculatone sulfate (AS) is a sulfated derivative of auriculatone with highly improved water-solubility. Hepatoprotective effects against APAP-induced liver injury (AILI) showed that intragastric pretreatment with AS at 50 mg/kg almost completely prevented mice against APAP-induced increases of serum alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase and ATPase. Histological results showed that AS could protect the liver tissue damage. In addition, AS pretreatment not only significantly retained hepatic malondialdehyde and the activities of glutathione, superoxide dismutase, and glutathione peroxidase at normal levels, but also markedly suppressed the increase of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 levels in mouse liver caused by overdose APAP. Immunohistochemical analysis showed that AS obviously attenuated the expression of CD45 and HNE in liver tissue. Further mechanisms of action investigation showed that inhibition of cytochrome P450 3A11 (CYP 3A11) and CYP2E1 enzymatic activities (but not that of CYP1A2) was responsible for APAP bioactivation. In conclusion, AS showed a hepatoprotective effect against AILI through alleviating oxidative stress and inflammation and inhibiting CYP-mediated APAP bioactivation. It may be an effective hepatoprotective agent for AILI and other forms of human liver disease.
Pseudostellaria heterophylla is used in China not only as a functional food but also as an herb to tonify the spleen, enhance immunity, and treat palpitation. Our previous investigation showed that a fraction enriched in glycosides obtained from the roots of P. heterophylla possessed pronounced protective effects on H9c2 cells against CoCl2-induced hypoxic injury. However, the active compounds responsible for the observed effects were still unknown. In the current investigation, pseudosterins A–C (1–3), three new alkaloids with a 1-ethyl-3-formyl-β-carboline skeleton, together with polydatin, have been isolated from the active fraction. Their structures were elucidated on the basis of spectroscopic analysis and quantum chemical calculations. The four compounds showed cardioprotective effects against sodium hydrosulfite-induced hypoxia-reoxygenation injury in H9c2 cells, with the three alkaloids being more potent. This is also the first report of alkaloids with a β-carboline skeleton isolated from P. heterophylla as cardioprotective agents.
Pulmonary fibrosis (PF) emerges as a significant pulmonary sequelae in the convalescent phase of coronavirus disease 2019 (COVID-19), with current strategies neither specifically preventive nor therapeutic. Geum japonicum var. chinense (GJC) is used as a traditional Chinese medicine to effectively treat various respiratory conditions. However, the protective effects of GJC against PF remains unclear. In the present study, the anti-PF effect of GJC aqueous extract was studied using a PF mouse model induced by bleomycin (BLM). To characterize the metabolite changes related to PF and reveal therapeutic targets for GJC aqueous extract, we performed metabolomic and network analysis on mice lungs. Finally, key targets were then validated by Western blotting. GJC aqueous extract effectively alleviated the onset and progression of lung fibrosis in PF mice by inhibiting inflammatory responses and regulating oxidative stress levels. Integrating serum metabolomics and network analyses showed the arachidonic acid (AA) pathway to be the most important metabolic pathway of GJC aqueous extract against PF. Further validation of AA pathway protein levels showed a significant rise in the levels of ALOX5, PTGS2, CYP2C9, and PLA2G2A in PF lungs. GJC aqueous extract treatment regulated the above changes in metabolic programming. In conclusion, GJC is a promising botanical drug to delay the onset and progression of PF mice. The primary mechanism of action is associated with the comprehensive regulation of metabolites and protein expression related to the AA metabolic pathway.