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.
Verma S and Pandey AK