Abstract
Introduction: Cerebral ischemia arise due to insufficient/ interrupted blood supply to brain and is accompanied by pathologies like degradation of extracellular matrix resulting in blood brain barrier disruption, intra cranial haemorrhage, activation of astroglial cells and hence death of neurons. In addition, oxidative stress and inflammation is common to all neurodegenerative diseases enhancing the harmful consequences of diseases. Matrix Metalloproteinases (MMP) are normally involved in extracellular matrix remodelling and are regulated while injury and inflammation in tissue. Over expression of MMP2 and MMP9 results in progression of ischemic conditions by extracellular matrix degradation thus compromising the structural integrity of Blood Brain Barrier (BBB) proving them a potent targets for the disease. Violacein (source: Chromobacterium violaceum), purple pigment from microbial origin is a bisindole have high anti-inflammatory, anti-oxidant, anti-bacterial, anti-cancer and anti-parasitic properties. Present study is to study the effective potential of violacein against cerebral ischemia. Methods and findings: Violacein’s ADMET (Absorption, Distribution, Metabolism, Excretion, Toxicity), properties were calculated and structural inhibition of MMPs through molecular docking was evaluated. Violacein resulted six H-bonds with MMP2 with high binding energy of -11.83 kcal/mol and two H-bonds with MMP9 with binding energy of -9.889 kcal/mol. The Ki values of violacein with MMP2 and MMP9 were 2.12 nM and 56.14 nM respectively which proved high affinity of violacein towards the target. Conclusion: Violacein with its high antioxidant and anti-inflammatory property can be a potent all round treatment for cerebral ischemia and demands extensive research.
Highlights
Cerebral ischemia arise due to insufficient/ interrupted blood supply to brain and is accompanied by pathologies like degradation of extracellular matrix resulting in blood brain barrier disruption, intra cranial haemorrhage, activation of astroglial cells and death of neurons
Cerebral occlusion and haemorrhage are the leading cause of ischemic stroke resulting into an improper blood supply to brain causing reduction in oxygen and glucose level to meet the metabolic demand [32]
On the other hand the role of Matrix Metalloproteinases (MMP) in progression of ischemic conditions is well established and their increase in pathological conditions is reported by many researchers [3,5,6]
Summary
Cerebral ischemia arise due to insufficient/ interrupted blood supply to brain and is accompanied by pathologies like degradation of extracellular matrix resulting in blood brain barrier disruption, intra cranial haemorrhage, activation of astroglial cells and death of neurons. Over expression of MMP2 and MMP9 results in progression of ischemic conditions by extracellular matrix degradation compromising the structural integrity of Blood Brain Barrier (BBB) proving them a potent targets for the disease. Matrix Metalloproteinases (MMP) are Zn dependent proteolytic enzymes responsible for the remodelling of ECM in conditions of development, inflammation and tissue injury [6,7]. They are activated by cytokines and are reported to hamper the integrity of ECM in ischemic conditions due to there over expression [8].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
