Role of Oxidative Stress and Genetic Polymorphism of Matrix Metalloproteinase-2 and Tissue Inhibitor of Metalloproteinase-2 in COPD.

Chronic obstructive pulmonary disease (COPD), a complaint described by progressive and inadequately reversible limitation in lungs with systemic inflammation, is largely current in India. There's no remedy available so far it is, thus, imperative to understand the underpinning pathogenesis of the complainant. A set of proteases known as Matrix metalloproteinase (MMPs) are especially involved in the process of alveolar destruction and mucus hypersecretion. There are responsible factors in an inheritable position to control COPD like MMPs and TIMPs (Tissue Inhibitor of Metalloproteinases). MMPs degrade extracellular matrix and lead to the pathogenesis of COPD [1]. TIMPs proteins that help to inhibit the Matrix metalloproteinases. [2]. This review summarizes the implicit part of crucial MMP-2 and TIMP-2 in COPD disease. Though the concept seems promising, limited knowledge about the exact functions of a particular MMP in COPD and the complications of MMP in substrate affinity makes this a grueling task. MMP2 and TIMP2 both are directly or indirectly regulated by oxidative stress and epigenetic mechanism which regulates their expressions. COPD is a seditious response to factors like dust, smoke, etc., and triggers extra-pulmonary goods which cause inflammation. [3]. This review explains the relationship between MMP2 and TIMP2 in COPD patients with oxidative stress, its impact on COPD pathogenesis, and gene expression of TIMP2 and MMP2 with their downstream effects. This also gives some insights into therapeutic interventions for targeting these enzymes. MMP2 and TIMP2 both play a role in the development of COPD and they need to be studied with the utmost focus.

Protective effects of novel diazepinone derivatives in snake venom induced sterile inflammation in experimental animals.

Snake envenomation leads to the formation of damage-associated molecular patterns (DAMPs), which are mediated by endogenous intracellular molecules. These are recognized by pattern-recognition receptors (PRRs) and can induce sterile inflammation. AIMS: In the present study, we aim at understanding the mechanisms involved in DAMPs induced sterile inflammation to unravel the novel therapeutic strategies for treating snake bites. The potential of benzodiazepinone derivatives to act against snake venom induced inflammation has been explored in the present investigation. MAIN METHODS: Three compounds VA 17, VA 43 and PA 03 were taken from our library of synthetic compounds. Oxidative stress markers such as lipid peroxidation, superoxide and nitric oxide were measured along with the analysis of DAMPs (IL6, HMGB1, vWF, S100b and HSP70). These compounds have been docked using molecular docking against the snake venom PLA2 structure (PDB code: 1OXL). KEY FINDINGS: The compounds have been found to effectively neutralize viper and cobra venoms induced lethal activity both ex vivo and in vivo. The compounds have also neutralized the viper venom induced hemorrhagic, coagulant, anticoagulant reactions as well as inflammation. The fold of protection have always been found to be higher in case of ex vivo than in in vivo. These compounds have neutralized the venom induced DAMPs as exhibited by IL6, HMGB1, vWF, S100b and HSP70. The fold of neutralization is found to be higher in VA 43. SIGNIFICANCE: The identified compounds could be used as potential candidates for developing treatment of snakebites in areas where antiserums are not yet available.

Bioactive Compounds and Traditional Herbal Medicine: Promising Approaches for the Treatment of Dementia.

Dementia is a term that encompasses a group of clinical symptoms affecting memory, thinking and social abilities, characterized by progressive impairment of memory performance and cognitive functions. There are several factors involved in the pathogenesis and progression of dementia, such as old age, brain ischemia, toxin exposure, and oxidative stress. There are extensive similarities between dementia and Alzheimer's disease (AD) either in clinical manifestations or experimental animal models. AD is the most dominant form of dementia, characterized by the accumulation of beta-amyloid protein and cholinergic neurotransmission deficits in the brain. Currently available medications for the treatment of dementia, such as choline esterase inhibitors, N-methyl-D-aspartate (NMDA) antagonists (memantine), have short-term efficacy and only relieve symptoms rather than targeting the main underlying pathogenesis. Several animal studies and clinical trials are being conducted to provide a rational approach to these medicinal plants in the prevention or treatment of memory deficits. This review highlights the potential effects of medicinal plants and their derived lead molecules, and explains the related mechanisms and effects reviewed from published literature as major thrust aspects and hopeful strategies in the prevention or treatment of dementia.