The Credible Role of Curcumin in Oxidative Stress-Mediated Mitochondrial Dysfunction in Mammals.

Oxidative stress and mitochondrial dysfunction are associated with the pathogenesis of several human diseases. The excessive generation of reactive oxygen species (ROS) and/or lack of adequate antioxidant defenses causes DNA mutations in mitochondria, damages the mitochondrial respiratory chain, and alters membrane permeability and mitochondrial defense mechanisms. All these alterations are linked to the development of numerous diseases. Curcumin, an active ingredient of turmeric plant rhizomes, exhibits numerous biological activities (i.e., antioxidant, anti-inflammatory, anticancer, and antimicrobial). In recent years, many researchers have shown evidence that curcumin has the ability to reduce the oxidative stress- and mitochondrial dysfunction-associated diseases. In this review, we discuss curcumin's antioxidant mechanism and significance in oxidative stress reduction and suppression of mitochondrial dysfunction in mammals. We also discuss the research gaps and give our opinion on how curcumin research in mammals should proceed moving forward.

Modulation of multiple cellular signalling pathways as targets for anti-inflammatory and anti-tumorigenesis action of Scopoletin.

OBJECTIVES: Scopoletin (6-methoxy-7-hydroxycoumarin) is a naturally occurring coumarin belonging to the category of secondary metabolites. Coumarins are commonly found in several herbs and play a prominent role in the defense mechanism of plants. Beneficial effects of scopoletin including antioxidant, anti-diabetic, hepatoprotective, neuroprotective and anti-microbial activity induced via numerous intracellular signalling mechanisms have been widely studied. However, anti-inflammation and anti-tumorigenesis properties of scopoletin are not well documented in the literature. Therefore, the primary focus of the present review was to highlight the plethora of research pertaining to the signalling mechanisms associated with the prevention of the progression of disease condition by scopoletin. KEY FINDINGS: Multiple signalling pathways like nuclear erythroid factor-2 (NEF2)-related factor-2 (NRF-2), apoptosis/p53 signalling, nuclear factor-κB (NF-κB) signalling, autophagy signalling, hypoxia signalling, signal transducer and activator of transcription-3 (STAT3) signalling, Wnt-ß signalling, Notch signalling are coupled with the anti-inflammation and anti-tumorigenesis potential of scopoletin. SUMMARY: Understanding crucial targets in these molecular signalling pathways may support the role of scopoletin as a promising naturally derived bioactive compound for the treatment of several diseases.

Autophagy markers as mediators of lung injury-implication for therapeutic intervention.

Lung injury is characterized by inflammatory processes demonstrated as loss of function of the pulmonary capillary endothelial and alveolar epithelial cells. Autophagy is an intracellular digestion system that work as an inducible adaptive response to lung injury which is a resultant of exposure to various stress agents like hypoxia, ischemia-reperfusion and xenobiotics which may be manifested as acute lung injury (ALI), acute respiratory distress syndrome (ARDS), chronic lung injury (CLI), bronchopulmonary dysplasia (BPD), chronic obstructive pulmonary disease (COPD), asthma, ventilator-induced lung injury (VILI), ventilator-associated lung injury (VALI), pulmonary fibrosis (PF), cystic fibrosis (CF) and radiation-induced lung injury (RILI). Numerous regulators like LC3B-II, Beclin 1, p62, HIF1/BNIP3 and mTOR play pivotal role in autophagy induction during lung injury possibly for progression/inhibition of the disease state. The present review focuses on the critical autophagic mediators and their potential cross talk with the lung injury pathophysiology thereby bringing to limelight the possible therapeutic interventions.

Oxidative stress responsive transcription factors in cellular signalling transduction mechanisms.

Oxidative stress results from the imbalances in the development of reactive oxygen species (ROS) and antioxidants defence system resulting in tissue injury. A key issue resulting in the modulation of ROS is that it alters hosts molecular, structural and functional properties which is accomplished via various signalling pathways which either activate or inhibit numerous transcription factors (TFs). Some of the regulators include Nuclear erythroid-2 related factors (Nrf-2), CCAAT/enhancer-binding protein delta (CEBPD), Activator Protein-1 (AP-1), Hypoxia-inducible factor 1(HIF-1), Nuclear factor κB (NF-κB), Specificity Protein-1 (SP-1) and Forkhead Box class O (FoxO) transcription factors. The expression of these transcription factors are dependent upon the stress signal and are sometimes interlinked. They are highly specific having their own regulation cellular events. Depending upon the transcription factors and better knowledge on the type of the oxidative stress help researchers develop safe, novel targets which can serve as efficient therapeutic targets for several disease conditions.