Berberine modulates cardiovascular diseases as a multitarget-mediated alkaloid with insights into its downstream
Sanaa Almowallad1, Rehab Al-Massabi1
1Assistant Professor of Medical Biochemistry, Department of Biochemistry, Faculty of Sciences, University of Tabuk, Tabuk 71491, Saudi Arabia.
Insights
Berberine chloride shows potential in treating atherosclerosis by targeting multiple pathways. This computational study confirms its ability to restore cardiac function and combat cardiovascular disease complications.
Area of Science:
- Biochemistry
- Pharmacology
- Computational Biology
Background:
- Atherosclerosis is linked to oxidative stress, inflammation, and endothelial dysfunction.
- Berberine, a natural alkaloid, exhibits therapeutic potential against atherosclerosis.
- Cardiovascular diseases (CVDs) present significant health challenges globally.
Purpose of the Study:
- To computationally evaluate berberine chloride's multitarget restorative effects against atherosclerosis and associated CVDs.
- To investigate berberine's binding interactions with key CVD-related targets.
- To predict the drug-likeness and pharmacokinetic properties of berberine.
Main Methods:
- In silico screening and molecular docking simulations were employed.
- QSAR/ADMET and Lipinski's Rule of Five analyses were performed for drug-likeness.
- Binding affinities, modes, and interactions with CVD targets were evaluated.
Main Results:
- Berberine chloride demonstrated potent binding to multiple CVD-related targets.
- Computational analyses predicted favorable drug-likeness and pharmacokinetic profiles for berberine.
- Berberine chloride was shown to alleviate ER stress, apoptosis, oxidative stress, and inflammation.
Conclusions:
- Berberine chloride holds significant therapeutic promise for atherosclerotic CVDs.
- It acts through diverse mechanisms including autophagy activation and improved metabolic parameters.
- This study supports berberine chloride as a potential agent for cardiovascular health.
Abstract:
Atherosclerosis is potentially correlated with several cardiac disorders that are greatly associated with cellular oxidative stress generation, inflammation, endothelial cells dysfunction, and many cardiovascular complications. Berberine is a natural isoquinoline alkaloid compound that widely modulates pathogenesis of atherosclerosis through its different curative potentials. This in silico screening study was designed to confirm the potent restorative properties of berberine chloride as a multitarget-mediated alkaloid against the CVDs and their complications through screening, identifying, visualizing, and evaluating its binding models, affinities, and interactions toward several CVDs-related targets as direct and/or indirect-mediated signals via inhibiting cellular ER stress and apoptotic signals and activating autophagy pathway. The drug-likeness properties of berberine were predicted using the computational QSAR/ADMET and Lipinski's RO5 analyses as well as in silico molecular docking simulations. The potent berberine-binding modes, residues-interaction patterns, and free energies of binding scores towards several CVDs-related targets were estimated using molecular docking tools. Furthermore, the pharmacokinetic properties and toxicological features of berberine were clearly determined. According to this in silico virtual screening study, berberine chloride could restore cardiac function and improve pathogenic features of atherosclerotic CVDs through alleviating ER stress and apoptotic signals, activating autophagy, improving insulin sensitivity, decreasing hyperglycemia and dyslipidemia, increasing intracellular RCT signaling, attenuating oxidative stress and vascular inflammation, and upregulating cellular antioxidant defenses in many cardiovascular tissues. In this in silico study, berberine chloride greatly modulated several potent CVDs-related targets, including SIGMAR1, GRP78, CASP3, BECN1, PIK3C3, SQSTM1/p62, LC3B, GLUT3, INSR, LDLR, LXRα, PPARγ, IL1β, IFNγ, iNOS, COX-2, MCP-1, IL10, GPx1, and SOD3.
More Related Videos
11:06Network Pharmacology Prediction and Metabolomics Validation of the Mechanism of Fructus Phyllanthi against Hyperlipidemia
Published on: April 7, 2023
07:58Behavioral and Network Pharmacology-Based Analyses for the Traditional Mongolian Medicine Zadi-5 in a Rat Model of Depression
Published on: February 24, 2023
Related Concept Videos
01:26Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
01:25Antianginal Drugs: Calcium Channel Blockers and Ranolazine
CCBs, a diverse class that includes dihydropyridines (nifedipine) and diphenylalkylamines (verapamil and diltiazem), exert their effect by blocking calcium channels in cardiac and smooth muscle cells. This...
01:26Targets for Drug Action: Overview
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...
01:31Adrenergic Antagonists: ɑ and β-Receptor Blockers
01:27Transducer Mechanism: Enzyme-Linked Receptors
Major types that are helpful drug targets include:
01:27Adrenergic Antagonists: Pharmacological Actions of β-Receptor Blockers