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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.

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.

The perivascular adipose tissue (PVAT) refers to an ectopic local deposit of connective tissue that anatomically surrounds most of the blood vessels. While it was initially known only as a structural support for vasculature, the landmark findings of Soltis and Cassis (1991), first demonstrating that PVAT reduces the contractions of norepinephrine in the isolated rat aorta, brought the potential vascular role of PVAT into the limelight. This seminal work implied the potential ability of PVAT to influence vascular responsiveness. Several vasoactive/vasocrine substances influencing vascular homeostasis were successively shown to be released from PVAT that include both adipocyte-derived relaxing and contracting factors. The PVAT is currently recognized as a metabolically active endocrine organ and is eventually considered as the 'protagonist' in vascular homeostasis. It plays prominent defending and opposing roles in vascular function, while the actual vascular influences of PVAT vary with an increase in adiposity. Recent studies have presented compelling evidence implicating the pivotal role of PVAT in the local activation of the renin-angiotensin system (RAS), which substantially impacts vascular physiology and physiopathology. Current findings have advanced our understanding of the role of PVAT in favorably or adversely modulating the vascular function through differential RAS activation. Given that adipocytes also produce major RAS components locally to influence vascular function, this review provides a scientific basis to distinctly understand the key role of PVAT in regulating the autocrine and paracrine functions of vascular RAS components and its potential as an emerging therapeutic target for mitigating cardiovascular complications.

Ageratum conyzoides Linn. ( Asteraceae) is a soft hairy annual weed with powerful traditional uses. A queous, ethyl acetate and ethanolic extracts were prepared from the whole plant of A. conyzoides ( L.). Urolithiasis was induced by using 5 % ethylene glycol in wistar albino rats. Rats were treated with different extra cts of A. conyzoides ( L.) at a dose level of 500 mg /kg bwt while C alcuri at same dose level was used as standard. The results of the study proved that all the plant extracts significantly reduced calcium and oxalate concentration in the excreted urine and the deposition of the same in the kidney , while the highest reduction in the calcium and oxalate in the urine and kidney was noted with the ethanol extract. Preliminary phytochemical analysis revealed the presence of a number of phytochemical constituents in different extracts which may help in the identification of plant. The pre sent result advocates the anti urolithiatic activities of different extracts of the plant.

Aminoglycoside antibiotics are employed clinically because of their potent bactericidal activities, less bacterial resistance, post-antibiotic effects and low cost. However, drugs belong to this class are well-known to cause nephrotoxicity, which limits their frequent clinical exploitation. Gentamicin, a commonly used aminoglycoside, is associated with an induction of tubular necrosis, epithelial oedema of proximal tubules, cellular desquamation, tubular fibrosis, glomerular congestion, perivascular edema and inflammation, which ultimately show the way to renal dysfunction. It is a matter of debate whether we have promising agents to prevent the incidence of gentamicin-induced nephrotoxicity. The present review critically discussed the pathogenesis of gentamicin-induced nephrotoxicity. In addition, based on the experimental and clinical studies, the possible therapeutic approach to prevent gentamicin-induced nephrotoxicity has been discussed.

Thiamine, known as vitamin B(1), plays an essential role in energy metabolism. Benfotiamine (S-benzoylthiamine O-monophoshate) is a synthetic S-acyl derivative of thiamine. Once absorbed, benfotiamine is dephosphorylated by ecto-alkaline phosphatase to lipid-soluble S-benzoylthiamine. Transketolase is an enzyme that directs the precursors of advanced glycation end products (AGEs) to pentose phosphate pathway. Benfotiamine administration increases the levels of intracellular thiamine diphosphate, a cofactor necessary for the activation transketolase, resulting in the reduction of tissue level of AGEs. The elevated level of AGEs has been implicated in the induction and progression of diabetes-associated complications. Chronic hyperglycemia accelerates the reaction between glucose and proteins leading to the formation of AGEs, which form irreversible cross-links with many macromolecules such as collagen. In diabetes, AGEs accumulate in tissues at an accelerated rate. Experimental studies have elucidated that binding of AGEs to their specific receptors (RAGE) activates mainly monocytes and endothelial cells and consequently induces various inflammatory events. Moreover, AGEs exaggerate the status of oxidative stress in diabetes that may additionally contribute to functional changes in vascular tone control observed in diabetes. The anti-AGE property of benfotiamine certainly makes it effective for the treatment of diabetic neuropathy, nephropathy and retinopathy. Interestingly, few recent studies demonstrated additional non-AGE-dependent pharmacological actions of benfotiamine. The present review critically analyzed the multifaceted therapeutic potential of benfotiamine.