Inhibitors of soluble epoxide hydrolase minimize ischemia-reperfusion-induced cardiac damage in normal, hypertensive, and diabetic rats.

AIM: We designed a study to evaluate the cardioprotective effect of two soluble epoxide hydrolase (sEH) inhibitors, 1-(1-propanoylpiperidin-4-yl)-3-(4-trifluoromethoxy)phenyl)urea (TPPU) and trans-4-{4-[3-(4-trifluoromethoxyphenyl)-ureido]cyclohexyloxy}benzoic acid (t-TUCB), in ischemia-reperfusion (IR) model. METHODS: Cardioprotective effects of the sEH inhibitors were evaluated against IR-induced myocardial damage in hearts from normal, hypertensive, and diabetic rats using Langendorff's apparatus. In addition, the effect of sEH inhibitors on endothelial function was evaluated in vitro and ex vivo using isolated rat thoracic aorta. RESULTS: Ischemia-reperfusion (IR) increased the myocardial damage in hearts from normal rats. IR-induced myocardial damage was augmented in hearts isolated from hypertensive and diabetic rats. Myocardial damage as evident from increase in the activities of lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) in heart perfusate was associated with significant decrease in the heart rate and developed tension, and increase in the resting tension in isolated heart. Both sEH inhibitors protected the heart in normal, hypertensive, and diabetic rats subjected to IR injury. The sEH inhibitor t-TUCB relaxed phenylephrine precontracted aorta from normal rats. Relaxant effect of acetylcholine (ACh) was reduced in aortas from diabetic and hypertensive rats compared to normal rats. Pretreatment of sEH inhibitors to diabetic and hypertensive rats increased relaxant effect of ACh on aortas isolated from these rats. CONCLUSIONS: Prophylactic treatment with sEH inhibitors decreased myocardial damage due to IR, hypertension and diabetes, and decreased endothelial dysfunction created by diabetes and hypertension. Therefore, inhibitors of sEH are useful probes to study cardiovascular pathology, and inhibition of the sEH is a potential approach in the management of IR-induced cardiac damage and endothelial dysfunction-related cardiovascular disorders.

Effect of Cinnamomum cassia methanol extract and sildenafil on arginase and sexual function of young male Wistar rats.

INTRODUCTION: Herbs have been used as an aphrodisiac since ages. Cinnamomum cassia is an important ingredient of many Ayurvedic formulations to treat male sexual disorder including erectile dysfunction (ED). AIM: The objective of the present study was to evaluate erectogenic and aphrodisiac activity of methanol extract of C. cassia bark in young male rats. METHODS: Methanol extract of C. cassia was screened in vitro for arginase inhibition potential and IC50 was determined. Effect of the extract was observed in vitro on phenylephrine pre-contracted isolated rat corpus cavernosum smooth muscle (CCSM) at 0.1, 1, 10, and 100 µg/mL. Young male Wistar rats were dosed with extract at 100 mg/kg body weight for 28 days and its effects on sexual behavior and penile smooth muscle : collagen level were observed. MAIN OUTCOME MEASURE: Effect of C. cassia was studied on arginase activity in vitro and sexual behavior of young male rats. RESULTS: C. cassia inhibited arginase activity in vitro with an IC50 of 61.72 ± 2.20 µg/mL. The extract relaxed phenylephrine pre-contracted isolated rat CCSM up to 43% and significantly increased (P < 0.05) sexual function of young male rats. Treatment with the extract also increased smooth muscle level and decreased collagen level in rat penile tissue. CONCLUSION: The study proves usefulness of methanol extract of C. cassia bark for increasing sexual function.