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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., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

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., (Copyright 2010 Elsevier Ltd. All rights reserved.)

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., ((c) 2010 Elsevier Ltd. All rights reserved.)

Aqueous and alcoholic extracts of Vitis indica were tested for diuretic activity in rats. The parameters studied on individual rats were body weight before and after test period, total urine volume, urine concentration of Na+,Ka+ and Cr. In the present study, alcoholic and aqueous extracts of Vitis indica leaves (200 mg/kg body weight) shows increase in urine volume, cationic and anionic excretion. Fruosemide (100 mg/kg body weight) is used as a standard.