en Cardiovascular Physiology/Pharmacology Cardiovascular Physiology/Pharmacology Experimental research article Experimental research article <span style="line-height:2;"><span style="font-size:12px;"><span style="font-family:Arial;"><b>Introduction:</b><b> </b>In diabetic patients, high blood sugar levels provoke sustained inflammation in cardiac tissue and impair normal cardiac activity. Considering the anti-diabetic characteristics of endurance training and Urtica Dioica (UD) extract, this study evaluated their potential in modulating TLR-4 levels and the inflammatory condition of cardiac tissue in diabetic Wistar rats.<b><span lang="AR-SA" dir="RTL" style="font-family:"Arial",sans-serif"></span></b><br /> <b>Methods: </b>In the present study, a total of 50 male Wistar rats were randomly allocated into 5 equal groups: Healthy-Control (H-C), Diabetic-Control (D-C), Diabetic-Exercise (D-Ex), Diabetic-Urtica Dioica (D-UD), and Diabetic-Exercise-Urtica Dioica (D-Ex-UD). Diabetes was induced by an intraperitoneal injection of streptozotocin (STZ) (45 mg/kg). Two weeks post-STZ injection, a moderate-intensity treadmill running regimen (five days/week) performed, and UD extract (50 mg/kg) was given per day by gavage for 6 weeks.<span lang="AR-SA" dir="RTL" style="font-family:"Arial",sans-serif"></span><br /> <b>Results: </b>A six-week regimen of exercise and UD extract improve diabetes-induced weight loss. They also resulted in a significant decrease in blood glucose of the D-Ex (P = 0.001), D-UD (P = 0.001), and D-Ex-UD (P = 0.001) groups relative to D-C. Moreover, these interventions alone and in interaction resulted in a decrease in TLR-4 and TNF-&alpha; levels, as well as an increase in IL-10 levels in cardiac tissue. However, the D-Ex-UD group indicated the most excellent effectiveness in reducing TLR-4 levels and improving the cardiac inflammatory profile (IL-10/TNF-&alpha; ratio).<b><span lang="AR-SA" dir="RTL" style="font-family:"Arial",sans-serif"></span></b><br /> <b>Conclusion: </b>EX and UD extract reduce myocardial inflammation by modulating the TLR-4 pathway and restoring the balance of inflammatory cytokines, such that the combined intervention, through simultaneous targeting of inflammatory pathways, exerts a stronger effect than either intervention alone.<br /> &nbsp;</span></span></span> Endurance exercise,Urtica Dioica,Inflammation,cardiac tissue,Diabetes 0 0 http://ppj.phypha.ir/browse.php?a_code=A-10-2622-1&slc_lang=en&sid=1 setareh amiri se.amiri@urmia.ac.ir 3200319475328460039074 3200319475328460039074 No M.A. in Exercise Physiology, Department of Exercise Physiology and Corrective Exercises, Faculty of Sport Sciences, Urmia University, Urmia, Iran Mohammadreza Zolfaghardidani m.didani@urmia.ac.ir 3200319475328460039075 3200319475328460039075 Yes Associate Professor of Exercise Physiology, Department of Exercise Physiology and Corrective Exercises, Faculty of Sport Sciences, Urmia University, Urmia, Iran masoud rahmati rahmati.mas@lu.ac.ir 3200319475328460039076 3200319475328460039076 No Professor of Exercise Physiology, Department of Exercise Physiology, Faculty of Literature and Humanities, Lorestan University, Khorramabad, Iran ghafour ghaffari gh.ghaffari@urmia.ac.ir 3200319475328460039077 3200319475328460039077 No Ph.D. in Exercise Physiology, Department of Exercise Physiology and Corrective Exercises, Faculty of Sport Sciences, Urmia University, Urmia, Iran