Ameliorative effects of Annona muricata Linn. (Annonaceae) against potassium dichromate-induced hypertension in vivo: involvement of Kim-1/p38 MAPK/Nrf2 signaling.

Abstract

Background Recently, the incidences of hypertension and environmental pollution have increased significantly. This study investigates the antihypertensive effect of Annona muricata extract against K2Cr2O7-induced hypertension. Methods Fifty rats were used for this study, which were divided into five groups of 10 rats each. Rats in Group A received normal saline, and those in Groups B, C, D, and E were treated with A. muricata extract alone at 250 mg/kg, K2Cr2O7 at 30 mg/kg, pretreated with the extract at 250 mg/kg, and pretreated with gallic acid at 60 mg/kg for 14 days, respectively, and thereafter administered with a single intraperitoneal injection of K2Cr2O7 at 30 mg/kg. Results Administration of K2Cr2O7 significantly increased systolic, diastolic, and mean arterial pressure and caused prolonged QT and QTc intervals. Further, pretreatment with the extract at 250 mg/kg and gallic acid at 60 mg/kg significantly reduced high blood pressure to near-normal values. K2Cr2O7 intoxication led to significant increases in serum advanced oxidative protein products, myeloperoxidase, and xanthine oxidase, while serum nitric oxide (NO) also reduced significantly. Immunohistochemistry of the renal kidney injury molecule (Kim-1) and p38 MAPK showed increased expressions following the administration of K2Cr2O7 together with the downregulation of nuclear factor erythroid 2-related factor 2 (Nrf2). Pretreatment with the extract at 250 mg/kg and gallic acid at 60 mg/kg also increased the expressions of Nrf2 and downregulated Kim-1 and p38. Conclusion Together, we found that pretreatment with the extract at 250 mg/kg and gallic acid at 60 mg/kg normalized the blood pressure, reduced the markers of oxidative stress, and improved the antioxidant defense system and serum NO bioavailability.