A Unifying Perspective in Blunting the Limited Oral Bioavailability of Curcumin: A Succinct Look.

BACKGROUND: Curcumin is a polyphenolic compound derived from rhizomes of Curcuma longa, the golden spice. Curcumin has drawn much attention in recent years of biomedical research owing to its wide variety of biologic and pharmacologic actions. It exerts antiproliferative, antifibrogenic, anti-inflammatory, and antioxidative effects, among various imperative pharmacologic actions. In spite of its well-documented efficacies against numerous disease conditions, the limited systemic bioavailability of curcumin is a continuing concern. Perhaps, the poor bioavailability of curcumin may have curtailed its significant development from kitchen to clinic as a potential therapeutic agent. Subsequently, there have been a considerable number of studies over decades researching the scientific basis of curcumin's reduced bioavailability and eventually improvement of its bioavailability employing a variety of therapeutic approaches, for instance, in combination with piperine, the bio-active constituent of black pepper. Piperine has remarkable potential to modulate the functional activity of metabolic enzymes and drug transporters, and thus there has been a great interest in the therapeutic application of this widely used spice as alternative medicine and bioavailability enhancer. Growing body of evidence supports the synergistic potential of curcumin against numerous pathologic conditions when administered with piperine. CONCLUSION: In light of current challenges, the major concern pertaining to poor systemic bioavailability of curcumin, its improvement, especially in combination with piperine, and the necessity of additional research in this setting are together described in this review. Besides, the recent advances in the potential therapeutic rationale and efficacy of curcumin-piperine combination, a promising duo, against various pathologic conditions are delineated.

Unraveling the Differentially Articulated Axes of the Century-Old Renin-Angiotensin-Aldosterone System: Potential Therapeutic Implications.

Among numerous choices in cardiovascular therapies used for the management of hypertension and heart failure, drugs affecting the renin-angiotensin-aldosterone system (RAAS) hold substantial therapeutic roles. Therapies aimed at modifying the RAAS and its overactivation are employed for the management of various insidious disorders. In the pharmacologic perspective, RAAS is one of the frequently manipulated systems for the management of hypertension, heart failure, myocardial infarction, and renal disease. The RAAS pharmacologic interventions principally include the ACE inhibitors, the angiotensin II-AT1 receptor blockers, the mineralocorticoid receptor antagonists, and the direct renin inhibitors. In addition, therapeutic implication of ACE2/angiotensin (1-7)/Mas receptor activation using various ligands is being explored owing to their anti-inflammatory, anti-fibrotic, vasodilatory, and cardiovascular defensive roles. Moreover, being considered as the counter-regulatory arm of AT1 receptor, the potential role of AT2 receptor activation using selective AT2 receptor agonist is currently investigated for its efficacy in pulmonary complications. As an important regulator of fluid volume, blood pressure, and cardiovascular-renal function, the RAAS has been documented as a diversified intricate system with several therapeutic possibilities coupled with their fundamental structural and functional modulatory roles in cardiovascular, renal, and other systems. The RAAS possesses a number of regulatory, deregulatory, and counter-regulatory axes of physiopathologic importance in health and disease. The counter-regulatory arms of the RAAS might play an essential role in mitigating cardiovascular, renal, and pulmonary pathologies. In light of this background, we sought to explore the classical and counter-regulatory axes/arms of the RAAS and their imperative roles in physiologic functions and disease pathogenesis.

Detection of self-generated nanowaves on the interface of an evaporating sessile water droplet.

Evaporating sessile droplets have been known to exhibit oscillations on the air-liquid interface. These are generally over millimeter scales. Using a novel approach, we are able to measure surface height changes of 500 nm amplitude using optical trapping of a set of microscopic particles at the interface, particularly when the vertical thickness of the droplet reduces to less than 50 µm. We find that at the later stages of the droplet evaporation, particularly when the convection currents become large, the top air-water interface starts to spontaneously oscillate vertically as a function of time in consistency with predictions. We also detect travelling wave trains moving in the azimuthal direction of the drop surface which are consistent with hydrothermal waves at a different combination of Reynolds, Prandtl and Evaporation numbers than previously observed. This is the first time that wave-trains have been observed in water, being extremely challenging to detect both interferometrically and with infra-red cameras. We also find that such waves apply a force parallel to the interface along the propagation direction.