Systems Pharmacology and Molecular Docking Reveals the Mechanisms of Nux Vomica for the Prevention of Myasthenia Gravis.

Background: Myasthenia gravis (MG) is a rare autoimmune disease with clinical symptoms of fluctuating muscle weakness. Due to the side effects of current therapies, there is an urgent need for a new medication for MG treatment. Nux vomica is a traditional Chinese medicine used in various diseases. However, the mechanism of action of Nux vomica against MG remains unclear. Methods: Network pharmacology was used to explore the underlying mechanisms of Nux vomica in MG treatment, which was validated using molecular docking and in vivo experiments in mice. Results: Twelve bioactive compounds and 72 targets in Nux vomica were screened. Seventy-nine myasthenia-related targets were obtained from the GENECARD and DisGeNET databases. PPI networks of Nux vomica- and myasthenia-related targets were constructed using Bisogenet, and these two networks were subsequently merged into an intersection to establish a core-target PPI network that consisted of 204 nodes and 4,668 edges. KEGG enrichment analysis indicated that 132 pathways were enriched in 204 core targets. In addition, we obtained 50 docking pairs via molecular docking. In vivo experiments revealed that Nux vomica can improve the symptoms of MG. Conclusion: Nux vomica is involved in the pathogenesis of MG through the "multicomponent-target-pathway" mechanism.

Investigation of Invigorating Qi and Activating Blood Circulation Prescriptions in Treating Qi Deficiency and Blood Stasis Syndrome of Ischemic Stroke Patients: Study Protocol for a Randomized Controlled Trial.

Ischemic stroke (IS) is characterized by high morbidity and high mortality. The integration of Traditional Chinese medicine (TCM) and western medicine has shown promising benefits in relieving symptoms, promoting neurological recovery, and improving the quality of life of patients with IS. In TCM, Qi-deficiency along with blood-stasis (QDBS) syndrome is one of the common types of IS that is treated by invigorating Qi and activating blood circulation. In TCM theory, improving the corresponding degree of prescription-syndrome correlation (PSC) is helpful to improve clinical efficacy. In this study, we intend to use similar prescriptions that invigorate Qi and activate blood circulation: Buyang Huanwu granules (BHG), Naoxintong capsules (NXTC), and Yangyin Tongnao granules (YTG). The goal is to evaluate their level of PSC inpatients with IS with QDBS syndrome and find relevant biomarkers to provide an objective basis for precise treatment of TCM and improve the clinical therapeutic effects. A multicenter, randomized, double-blinded, and placebo-controlled intervention trial will be conducted in IS patients with QDBS syndrome, followed by an add-on of Chinese patent medicine. A total of 160 subjects will be randomly assigned to the BHG, NXTC, YTG, and placebo groups in a 1:2:1:1 allocation ratio. All subjects will undergo 28 days of treatment and then followed for another 180 days. The primary outcome is the changes in the National Institutes of Health Stroke Scale score after 28 days of medication. The secondary outcomes include the modified Rankin scale score, activity of daily living scale score, and TCM symptom score. Data will be analyzed in accordance with a predefined statistical analysis plan. Ethical approval of this trial has been granted by the Research Ethics Committee of the First Affiliated Hospital of Zhejiang Chinese Medical University (ID: 2017-Y-004-02). Written informed consent of patients will be required. This trial is registered in the Chinese Clinical Trial Registry (ChiCTR1800015189), and the results will be disseminated to the public through peer-reviewed journals and academic conferences.

Zhengtian Capsule versus flunarizine in patients with migraine: a multi-center, double-blind, double-dummy, randomized controlled, non-inferior clinical trial.

BACKGROUND: The primary objective of this study was to assess whether Zhengtian Capsule was non-inferior to flunarizine in efficacy and safety profile for prevention of migraine in adults. METHODS: This was a double-dummy, double-blind, multicenter, positive drug (flunarizine), parallel randomized controlled, non-inferior clinical trial. Patients (n = 360) were randomized in a 1:1 to receive either Zhengtian Capsule or flunarizine, including 12 weeks' intervention and 4 weeks' follow-up. The primary outcome measure was responder rate (defined as the percentage of subjects in a treatment group with 50 % or greater reduction in attack frequency during treatment compared with the baseline period). The secondary outcome measures included migraine attack frequency, the number of migraine days, pain evaluated by visual analogue scale (VAS) score, duration of migraine attacks, the times of using analgesics, patient-reported outcome (PRO) measure of migraine and the scores of short-form 36 Health Survey Scale (SF-36). Weight variation in both groups was also evaluated. Adverse events were monitored throughout the trial. RESULTS: Zhengtian Capsule was non-inferior to flunarizine in responder rate at week 12 and follow-up period (P = 0.002, P < 0.001). There was fewer migraine days in Zhengtian Capsule group at follow-up period compared with flunarizine (P = 0.001). For the total duration of migraine attacks, there was significant group difference at week 4 which favored the control group (P = 0.009). For the total score of PRO scale, there was statistical difference between the two groups at follow-up period (P = 0.021). There were also group differences between the two groups in the dimensions of somatization symptoms at week 4 (P = 0.022) and functional status at week 12 and follow-up period (P < 0.001, P < 0.001). However, there were no significant differences between the two groups in migraine attack frequency, VAS scores reduction, consumption of acute pain drugs and the dimension scores of SF-36 at any time interval of the treatment period (P > 0.05). No severe adverse events occurred in the trial. Flunarizine was found associated with a weight gain. CONCLUSION: Zhengtian Capsule was non-inferior to flunarizine with regard to the primary endpoint. In addition, it could reduce migraine days and improve the functional status and somatization symptoms of migraine patients with good safety profile. TRIAL REGISTRATION: This trial was registered at Chinese Clinical Trial Register (ChiCTR), ChiCTR-TRC-13004412.

[Studies on the chemical constituents of ethyl acetate extraction from Reineckea carnea].

OBJECTIVE: To study the chemical constituents of Reineckea carnea. METHODS: The compounds were isolated by extraction, silica gel and reversed phase silica gel column chromatography. The structures were identified by various spectroscopic methods including 1D and 2D-NMR spectrum, MS, IR, etc. RESULTS: Six compounds were isolated and identified as beta-sitosterol (1), isorhodeasapogenin (2), isorhodeasapogenin (3), (25S)-1beta,3beta,4beta-trihydroxyspirotan-5beta-yl-O-beta-D-glucopyranoside (4), kitigenin-5-O-beta-D-glucopyranoside (5) and nicotianoside B (6). CONCLUSION: Compounds 4, 6 are obtained from this plant for the first time.