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This study investigates the renal protective effects of cinnamic acid (CA) in a Type 2 diabetes mellitus (T2DM) rat model induced by high-fat diet (HFD) and streptozotocin (STZ), with a focus on its potential as a natural hypoglycemic agent and SGLT2 inhibitor. In a randomized design, five groups of rats (n = 8) were administered different treatments for 8 weeks: Control, Control + CA (40 mg/kg), T2DM, T2DM + CA (20 mg/kg), and T2DM + CA (40 mg/kg). CA treatment (20 and 40 mg/kg) significantly improved the glomerular and tubular structure in T2DM group, with normal features observed at the highest dose. In a dose-dependent manner, CA doses also reduced fasting glucose, HbA1c, and HOMA-IR in T2DM group, alongside enhanced total antioxidant capacity (TAC). Notably, renal function was significantly improved with CA treatment at both doses, as evidenced by reduced urine volume, serum BUN, creatinine, and urinary albumin. Furthermore, CA markedly reduced glomerular injury markers (NAG, A1M, F-LAP) and tubular injury biomarkers (transferrin, fibronectin, ceruloplasmin). Additionally, mRNA expression of SGLT, TLR4, and NF-kB was significantly reduced in CA-treated T2DM group. These findings suggest that CA exerts a multifaceted protective effect against renal dysfunction in T2DM by acting as an SGLT2 inhibitor.
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http://dx.doi.org/10.1002/mnfr.70164 | DOI Listing |
Genes Brain Behav
October 2025
Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
Major depressive disorder is a prevalent and debilitating psychiatric illness that produces significant disability. Clinical data suggest that the pathophysiology of depression is due, in part, to a dysregulation of inflammation and glutamate levels in the brain. The systemic administration of lipopolysaccharide (LPS) has been shown to induce depressive-like behaviors in mice.
View Article and Find Full Text PDFDiabetes Obes Metab
September 2025
Department of Pharmacology, Kagawa University, Kagawa, Japan.
Aim: Sodium-glucose cotransporter 2 (SGLT2) inhibitors consistently demonstrate renal protection against progressive kidney disease. We hypothesised that SGLT2 inhibition reduces blood glucose levels in peri-proximal tubular capillaries by limiting reabsorption from the tubular filtrate, thereby safeguarding the renal microvasculature from hyperglycaemic stress.
Materials And Methods: In anaesthetised streptozotocin-induced type 1 and Otsuka-Long Evans fatty (OLETF) type 2 diabetic rats, we measured the arterial-to-renal venous glucose ratio (RV/A) to evaluate the effects of canagliflozin, a SGLT2 inhibitor.
Ren Fail
December 2025
Department of Nephrology, National Clinical Key Specialty Construction Program (2023); Institute of Nephrology; Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-communicable Diseases; Key Laboratory of Prevention and Management of Chronic Kidney Disease of Zhanjiang City, Affil
Sodium-glucose cotransporter 2 inhibitors reduced proteinuria in patients with IgA nephropathy; however, their efficacy in patients at high risk of progression receiving immunosuppressive agents and renin angiotensin-aldosterone system inhibitors remains unclear. After 3 months of low-dose steroid alone or combined with mycophenolate mofetil, as well as renin angiotensin-aldosterone system inhibitors treatment, 105 biopsy-proven IgA nephropathy patients with proteinuria greater than 0.5 g/d were included in this study.
View Article and Find Full Text PDFG Ital Nefrol
August 2025
UO Nefrologia e Dialisi, Ospedale di Cassino, Italia.
SGLT-2 inhibitors are a relatively new class of antidiabetic drugs. They activate a transcriptional response similar to calorie restriction characterized by the up-regulation of sensors involved in nutrient deprivation, such as SIRT1 and AMPK, and the down-regulation of mTOR, a molecule involved in nutritional excess signaling. The purpose of this review is to illustrate the main pathways of nutrient deprivation: a complex mechanistic framework partly responsible for the cardio-renal benefits that makes these drugs unique.
View Article and Find Full Text PDFCardiovasc Diabetol
September 2025
Computational Biomedicine, Center for Thrombosis and Hemostasis (CTH), Mainz, Germany.
Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors, such as Empagliflozin, are antidiabetic drugs that reduce glucose levels and have emerged as a promising therapy for patients with heart failure (HF), although the exact molecular mechanisms underlying their cardioprotective effects remain to be fully elucidated. The EmDia study, a randomized, double-blind trial conducted at the University Medical Center of Mainz, has confirmed the beneficial effects of Empagliflozin in HF patients after both one and twelve weeks of treatment. In this work, we aimed to assess whether changes in lipid profiles driven by Empagliflozin use in HF patients in the EmDia trial could assist in gaining a better understanding of its cardioprotective mechanisms.
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