Exploring the Molecular Mechanism of Niuxi-Mugua Formula in Treating Coronavirus Disease 2019 via Network Pharmacology, Computational Biology, and Surface Plasmon Resonance Verification.

BACKGROUND: In China, Niuxi-Mugua formula (NMF) has been widely used to prevent and treat coronavirus disease 2019 (COVID-19). However, the mechanism of NMF for treating COVID-19 is not yet fully understood. OBJECTIVE: This study aimed to explore the potential mechanism of NMF for treating COVID-19 by network pharmacology, computational biology, and surface plasmon resonance (SPR) verification. METHODS: The NMF-compound-target network was constructed to screen the key compounds, and the Molecular Complex Detection (MCODE) tool was used to screen the preliminary key genes. The overlapped genes (OGEs) and the preliminary key genes were further analyzed by enrichment analysis. Then, the correlation analysis of immune signatures and the preliminary key genes was performed. Molecular docking and molecular dynamic (MD) simulation assays were applied to clarify the interactions between key compounds and key genes. Moreover, the SPR interaction experiment was used for further affinity kinetic verification. RESULTS: Lipid and atherosclerosis, TNF, IL-17, and NF-kappa B signaling pathways were the main pathways of NMF in the treatment of COVID-19. There was a positive correlation between almost the majority of immune signatures and all preliminary key genes. The key compounds and the key genes were screened out, and they were involved in the main pathways of NMF for treating COVID-19. Moreover, the binding affinities of most key compounds binding to key genes were good, and IL1B-Quercetin had the best binding stability. SPR analysis further demonstrated that IL1B-Quercetin showed good binding affinity. CONCLUSION: Our findings provided theoretical grounds for NMF in the treatment of COVID19.

Comprehensive analysis of the chemical constituents in sulfur-fumigated Lonicerae Japonicae Flos using UHPLC-LTQ-Orbitrap mass spectrometry.

Lonicerae Japonicae Flos (LJF), a kind of traditional Chinese medicines (TCMs), has functions of detoxifying and evacuating heat. In the study, a method based on ultra-high performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometry (UHPLC-LTQ-Orbitrap MS) was developed for the chemical constituent analysis of organic acids, flavonoids, iridoids and new-generated compounds in sulfur-fumigated LJF (SF-LJF). Based on the accurate mass measurement (< ± 5 ppm), chromatographic behavior and diagnostic product ions (DPIs), 113 constituents were unambiguously or tentatively characterized from SF-LJF extract, including 46 chlorogenic acids, 19 flavonoids, 29 iridoid glycosides and 19 newly-generated compounds (including 17 sulfur-containing derivatives). In addition, 5-CQA (5-caffeoylquinic acid, chlorogenic acid) was chosen to be sulfur-fumigated for the result validation. It was found that the most significant change of LJF after sulfur fumigation was the occurrence of sulfate or sulfite esterification reactions, which resulted in the emergence of many new sulfur-containing components. Our results demonstrated that the established method was a useful and efficient analytical tool to comprehensively characterize the material basis of SF-LJF, and also an excellent guidance of quality control about LJF.

Adefovir Dipivoxil plus Chinese Medicine in HBeAg-Positive Chronic Hepatitis B Patients: A Randomized Controlled 48-Week Trial.

OBJECTIVE: To evaluate the effects of a 48-week course of adefovir dipivoxil (ADV) plus Chinese medicine (CM) therapy, namely Tiaogan Jianpi Hexue () and Tiaogan Jiedu Huashi () fomulae, in hepatitis B e antigen (HBeAg)-positive Chinese patients. METHODS: A total of 605 HBeAg-positive Chinese CHB patients were screened and 590 eligible participants were randomly assigned to 2 groups in 1:1 ratio including experimental group (EG, received ADV plus CM) and control group (CG, received ADV plus CM-placebo) for 48 weeks. The major study outcomes were the rates of HBeAg and HBV-DNA loss on week 12, 24, 36, 48, respectively. Secondary endpoints including liver functions (enzymes and bilirubin readings) were evaluated every 4 weeks at the beginning of week 24, 36, and 48. Routine blood, urine, and stool analyses in addition to electrocardiogram and abdominal B scan were monitored as safety evaluations. Adverse events (AEs) were documented. RESULTS: The combination therapy demonstrated superior HBeAg loss at 48 weeks, without additional AEs. The full analysis population was 560 and 280 in each group. In the EG, population achieved HBeAg loss on week 12, 24, 36, and 48 were 25 (8.90%), 34 (12.14%), 52 (18.57%), and 83 (29.64%), respectively; the equivalent numbers in the CG were 20 (7.14%), 41 (14.64%), 54 (19.29%), and 50 (17.86%), respectively. There was a statistically significant difference between these group values on week 48 (P<0.01). No additional AEs were found in EG. Subgroup analysis suggested different outcomes among treatment patterns. CONCLUSION: Combination of CM and ADV therapy demonstrated superior HBeAg clearance compared with ADV monotherapy. The finding indicates that this combination therapy may provide an improved therapeutic effect and safety profile (ChiCTR-TRC-11001263).

Chinese Herbal Medicine Combined with Entecavir for HBeAg Positive Chronic Hepatitis B: Study Protocol for a Multi-Center, Double-Blind Randomized-Controlled Trial.

BACKGROUND: The domestic prevalence of chronic hepatitis B (CHB) in China is 7.18% in 2006, imposing great societal healthcare burdens. Nucleot(s)ide analogues (NUCs) anti-hepatitis B virus (HBV) therapies are widely applied despite the relatively low rate of seroconversion and high risk of drug-resistant mutation. More effective treatments for CHB deserve further explorations. Combined therapy of NUCs plus Chinese herbal medicine (CHM) is widely accepted in China, which is recognized as a prospective alternative approach. The study was primarily designed to confirm the hypothesis that Tiaogan-Yipi Granule (, TGYP) or Tiaogan-Jianpi-Jiedu Granule (, TGJPJD) plus entecavir tablet (ETV) was superior over ETV monotherapy in enhancing HBeAg loss rate. METHODS: The study was a nationwide, large-scale, multi-center, double-blind, randomized, placebo-controlled trial with a designed duration of 108 weeks. A total of 16 hospitals and 596 eligible Chinese HBeAg positive CHB patients were enrolled from November 2012 to September 2013 and randomly allocated into 2 groups in 1:1 ratio via central randomization system: experimental group (EG) and control group (CG). Subjects in EG received CM formulae (TGYP or TGJPJD, 50 g per dose, twice daily) plus ETV tablet (or ETV placebo) 0.5 mg per day in the first 24 weeks (stage 1), and CHM granule plus ETV tablet (0.5 mg per day) from week 25 to 108 (stage 2). Subjects in CG received CHM Granule placebo plus ETV tablet (0.5 mg per day) for 108 weeks throughout the trial. The assessments of primary outcomes (HBV serum markers and HBV-DNA) were conducted by a third-party College of American Pathologists (CAP) qualified laboratory. Adverse effects were observed in the hospitals of recruitment. DISCUSSION: The study was designed to compare the curative effect of CM plus ETV and ETV monotherapy in respect of HBeAg loss, which is recognized by the European Association for the Study of the Liver as "a valuable endpoint". We believe this trial could provide a reliable status for patients' "journey" towards durable responses after treatment discontinuation. The trial was registered before recruitment on Chinese Clinical trial registry (No. ChiCTR-TRC-12002784, Version 1.0, 2015/12/23).