Phloretin: a comprehensive review of its potential against diabetes and associated complications.

OBJECTIVES: Phloretin is ubiquitous in apples (Malus domestica) and other fruits and has potential antidiabetic properties. Considering the preclinical potential of phloretin, its transition to clinical observations has unintentionally been neglected, particularly within the diabetic population. Furthermore, a comprehensive understanding of its pharmacokinetics remains elusive. This review seeks to offer valuable insights into phloretin's physical properties, pharmacokinetics, and pharmacodynamics, aiming to unveil opportunities for additional research on its therapeutic potential in the context of diabetes. KEY FINDINGS: All pharmacokinetic reports of phloretin confirm that the utilization of phloretin gets enhanced during diabetic conditions. Phloretin targets pathomechanisms such as glucose transporter 4 (GLUT4) and peroxisome proliferator's activity-activated receptor-γ (PPAR-γ) to decrease insulin resistance in diabetic conditions. Moreover, phloretin targets inflammatory, oxidative, and apoptotic signaling to minimize the progression of diabetes-associated macro- and microvascular complications. SUMMARY: The pleiotropic antidiabetic action of phloretin is mainly dependent on its pharmacokinetics. Nevertheless, further investigation into the altered pharmacokinetics of phloretin during diabetic conditions is essential. Additionally, the results derived from clinical studies utilized apples, apple extract, and supplements containing phloretin. Greater emphasis should be placed on future clinical studies to assess the potential of phloretin as a standalone compound.

Nutraceuticals and network pharmacology approach for acute kidney injury: A review from the drug discovery aspect.

Acute kidney injury (AKI) has become a global health issue, with ∼12 million reports yearly, resulting in a persistent increase in morbidity and mortality rates. AKI pathophysiology is multifactorial involving oxidative stress, mitochondrial dysfunction, epigenetic modifications, inflammation, and eventually, cell death. Hence, therapies able to target multiple pathomechanisms can aid in AKI management. To change the drug discovery framework from "one drug, one target" to "multicomponent, multitarget," network pharmacology is evolving as a next-generation research approach. Researchers have used the network pharmacology approach to predict the role of nutraceuticals against different ailments including AKI. Nutraceuticals (herbal products, isolated nutrients, and dietary supplements) belong to the pioneering category of natural products and have shown protective action against AKI. Nutraceuticals have recently drawn attention because of their ability to provide physiological benefits with less toxic effects. This review emphasizes the nutraceuticals that exhibited renoprotection against AKI and can be used either as monotherapy or adjuvant with conventional therapies to boost their effectiveness and lessen the adverse effects. Additionally, the study sheds light on the application of network pharmacology as a cost-effective and time-saving approach for the therapeutic target prediction of nutraceuticals against AKI.

Evaluating the potential of tauroursodeoxycholic acid as add-on therapy in amelioration of streptozotocin-induced diabetic kidney disease.

The bile acid tauroursodeoxycholic acid (TUDCA) is of natural origin and is used in traditional Chinese medicine for centuries. Earlier its use was limited to biliary disorders but owing to its pleiotropic effects dietary TUDCA supplementation is under clinical trials for diseases including type 1 and 2 diabetic complications. The current study aims to evaluate the potential and underlying molecular mechanism of the TUDCA as a monotherapy and as an add-on therapy to telmisartan, an angiotensin II type 1 receptor (AT1R) blocker against diabetic kidney disease (DKD). We employed both in-vitro and in-vivo approaches where NRK-52E cells were incubated with high glucose, and DKD was induced in Wistar rats using streptozotocin (55 mg/kg, i.p.). After 4 weeks, animals were administered with TUDCA (250 mg/kg, i.p.), telmisartan (10 mg/kg, p.o.), and their combination for 4 weeks. Plasma was collected for the biochemical estimation and kidneys were used for immunoblotting, PCR, and histopathological analysis. Similarly, for in-vitro experiments, cells were exposed to 1000 µM of TUDCA and 10 µM of telmisartan, and their combination, followed by cell lysate collection and immunoblotting analysis. We observed that the addition of TUDCA to conventional telmisartan treatment was more effective in restoring the renal function decline and suppressing the apoptotic and fibrotic signaling as compared to monotherapies of AT1R blocker and ER stress inhibitor. The results implicate the utility of traditionally used TUDCA as a potential renoprotective compound. Since, both TUDCA and telmisartan are approved for clinical usage, thus concomitant administration of them could be a novel therapeutic strategy against DKD.