Comparison of the molecular mechanisms of Fuzi Lizhong Pill and Huangqin decoction in the treatment of the cold and heat syndromes of ulcerative colitis based on network pharmacology.

OBJECTIVE: The aim of this study was to illuminate the similarities and differences of two prescriptions as "cold" and "heat" drugs for treating ulcerative colitis (UC) with the simultaneous occurrence of heat and cold syndrome via network pharmacology. METHODS: (1) Active compounds of Fuzi-Lizhong Pill (FLP) and Huangqin Decoction (HQT) were retrieved from the TCMSP database, and their common active compounds were compared using the Venn diagram. (2) Potential proteins targeted to three sets of compounds either (i) shared by FLP and HQT, (ii) unique to FLP or (iii) unique to HQT were screened from the STP, STITCH and TCMSP databases, and three corresponding core compound sets were identified in Herb-Compound-Target (H-C-T) networks. (3) Targets related to UC were identified from the DisGeNET and GeneCards databases and compared with the FLP-HQT common targets to identify potential targets of FLP-HQT compounds related to UC. (4) Three potential target sets were imported into the STRING database for protein‒protein interaction (PPI) analysis, and three core target sets were defined. (5) The binding capabilities and interacting modes between core compounds and key targets were verified by molecular docking via Discovery Studio 2019 and molecular dynamics (MD) simulations via Amber 2018. (6) The target sets were enriched for KEGG pathways using the DAVID database. RESULTS: (1) FLP and HQT included 95 and 113 active compounds, respectively, with 46 common compounds, 49 FLP-specific compounds and 67 HQT-specific compounds. (2) 174 targets of FLP-HQT common compounds, 168 targets of FLP-specific compounds, and 369 targets of HQT-specific compounds were predicted from the STP, STITCH and TCMSP databases; six core compounds specific to FLP and HQT were screened in the FLP-specific and HQT-specific H-C-T networks, respectively. (3) 103 targets overlapped from the 174 predicted targets and the 4749 UC-related targets; two core compounds for FLP-HQT were identified from the FLP-HQT H-C-T network. (4) 103 FLP-HQT-UC common targets, 168 of FLP-specific targets and 369 of HQT-specific targets had shared core targets (AKT1, MAPK3, TNF, JUN and CASP3) based on the PPI network analysis. (5) Molecular docking demonstrated that naringenin, formononetin, luteolin, glycitein, quercetin, kaempferol and baicalein of FLP and HQT play a critical role in treating UC; meanwhile, MD simulations revealed the stability of protein‒ligand interactions. (6) The enriched pathways indicated that most targets were related to anti-inflammatory, immunomodulatory and other pathways. Compared with the pathways identified using traditional methods, FLP-specific pathways included the PPAR signaling pathway and the bile secretion pathway, and HQT-specific pathways included the vascular smooth muscle contraction pathway and the natural killer cell-mediated cytotoxicity pathway etc. CONCLUSION: In this study, we clarified the common mechanisms of FLP and HQT in treating UC and their specific mechanisms in treating cold and heat syndrome in UC through compound, target and pathway distinction and a literature comparison based on network pharmacology; these results provide a new perspective on the detailed mechanism of "multidrugs and single-disease" thought in traditional Chinese medicine.

COVID-19 and adherence to biologic therapies for psoriasis: An analysis of nationwide pharmacy claims data.

BACKGROUND: Early after the onset of the COVID-19 pandemic, concerns were raised that the use of psoriasis treatments, particularly biologic therapies because of their immunosuppressant effects, could be associated with a poor prognosis in the case of COVID-19 infection. OBJECTIVE: To examine changes in adherence to systematic biologic therapies for psoriasis after the onset of the COVID-19 pandemic. METHODS: Using IQVIA medical and pharmacy claims data from January 1, 2018, to October 31, 2020, we identified patients aged 18 years or older who had a diagnosis of plaque psoriasis in 2018 and who received systemic biologic therapies for psoriasis, including both provider-administered and pharmacy-dispensed therapies. We calculated the incidence of 14-day gaps without therapy per 1,000 study participants for each 30-day interval. We constructed interrupted time series analyses to test changes in the incidence of outcomes after the pandemic declaration. RESULTS: The sample included 15,890 study participants: 45.4% were female and 15.2% were aged 65 years or older. For patients using biologic therapies dispensed from the pharmacy, there was a 13.1% decrease in the incidence of 14-day gaps without biologic therapy immediately after pandemic declaration, from 92.4 gaps per 1,000 patients to 80.2 gaps per 1,000 patients, but this decrease was not statistically significant. However, for patients using provider-administered therapies, the incidence of 14-day gaps without biologic therapy increased by 55.1% after pandemic declaration, from 29.0 gaps per 1,000 patients to 44.9 gaps per 1,000 patients (P < 0.01). CONCLUSIONS: Following the onset of the COVID-19 pandemic, we found an increased incidence of gaps in biologic therapy for psoriasis among users of provider-administered treatments but not among users of pharmacy-dispensed therapies. DISCLOSURES: Dr Hernandez reports personal fees from Bristol Myers Squibb and personal fees from Pfizer outside the submitted work. Dr Hernandez is funded by the National Heart, Lung and Blood Institute (grant K01HL142847). The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. The statements, findings, conclusions, views, and opinions expressed in this publication are based on data obtained under license from IQVIA as part of the IQVIA Institute's Human Data Science Research Collaborative.