Molecular Docking Approach of Bryophyllum Pinnatum Compounds as Atherosclerosis Therapy By Targeting Adenosine Monophosphate-Activated Protein Kinase and Inducible Nitric Oxide Synthase.

Background: Bryophyllum pinnatum is a herbal medicine from Indonesia which has an anti-inflammatory effect. Adenosine monophosphate-activated protein kinase (AMPK) and inducible nitric oxide synthase (iNOS) play a function in thickening and inflammation in atherosclerosis disease. Objective: This research aims conducted to know the potential of Bryophyllum pinnatum as a therapy for atherosclerosis by targeting AMPK and iNOS. Methods: We employed a molecular docking technique to interact active compounds of Bryohyllum pinnatum with AMPK and iNOS, which were retrieved on the protein databank. Molecular docking analysis utilizing tools such as Pyrx 9.5, Pymol, and Discovery Studio, to support the interaction between the compound and protein. Molecular Dynamic (MD) simulation also performed using CABS-FLEX 2.0 server to know the stability interaction. Results: Bryophillin B was an active compound that possesses significant binding to AMPK and iNOS. It had same binding pocket as native ligand, and Bryophyllin B has a stronger interaction with AMPK. Based on the RMSF, the interaction biding complex Bryophyllin B with AMPK and iNOS were stable. Conclusion: Bryophillin B was predicted to have potential therapy for atherosclerosis disease.

Direct comparison of non-vitamin K antagonist oral anticoagulant versus warfarin for stroke prevention in non-valvular atrial fibrillation: a systematic review and meta-analysis of real-world evidences.

BACKGROUND: To overcome the several drawbacks of warfarin, non-vitamin K antagonist oral anticoagulants (NOACs) were developed. Even though randomized controlled trials (RCTs) provided high-quality evidence, the real-world evidence is still needed. This systematic review and meta-analysis proposed to measure the safety and efficacy profile between warfarin and NOACs in non-valvular atrial fibrillation (NVAF) patients in preventing stroke. RESULTS: We collected articles about the real-world studies comparing warfarin and NOACs for NVAF patients recorded in electronic scientific databases such as Embase, ProQuest, PubMed, and Cochrane. The pooled hazard ratio (HR) and 95% confidence interval (CI) were estimated using the generic inverse variance method. A total of 34 real-world studies, including 2287288 NVAF patients, were involved in this study. NOACs effectively reduced the stroke risk than warfarin (HR 0.77; 95% CI 0.69 to 0.87; p < 0.01). Moreover, NOACs effectively lowered all-cause mortality risk (HR 0.71; 95% CI 0.63 to 0.81; p < 0.01). From the safety aspect, compared to warfarin, NOACs significantly reduced major bleeding risk (HR 0.68; 95% CI 0.54 to 0.86; p < 0.01) and intracranial bleeding risk (HR 0.54; 95% CI 0.42 to 0.70; p < 0.01). However, NOACs administration failed to decrease gastrointestinal bleeding risk (HR 0.78; 95% CI 0.58 to 1.06; p = 0.12). CONCLUSIONS: In NVAF patients, NOACs were found to be more effective than warfarin at reducing stroke risk. NOACSs also lowered the risk of all-cause mortality, cerebral hemorrhage, and severe bleeding in NVAF patients compared to warfarin.