Protective effect of 3-n-butylphthalide against hypertensive nephropathy in spontaneously hypertensive rats

Abstract

Previous studies have demonstrated that a natural product of celery seeds, 3‑n‑butylphthalide (NBP), has significant antihypertensive effects that are widely utilized in Chinese traditional medicine. The present study aimed to investigate the effects of NBP on hypertensive nephropathy, as well as the mechanisms underlying this disease in spontaneously hypertensive rats (SHRs). SHRs were treated orally with saline, NBP (15 or 30 mg/kg) or losartan (10 mg/kg) daily for 20 weeks, during which time blood pressure was measured every four weeks. At the end of the 20‑week treatment, blood and urine samples were collected for biochemical analysis, and kidney tissues were obtained for histopathological analysis and immunohistochemistry. Enzyme‑linked immunosorbent assays and western blotting were used to analyze the expression of transforming growth factor (TGF)‑β1 in blood and kidney tissues, respectively. The results showed that NBP effectively attenuated progression of hypertensive nephropathy by decreasing urinary albumin excretion and blood urea nitrogen levels. It significantly decreased blood pressure (although less markedly than losartan) and the incidence of glomerulosclerosis. In addition, it alleviated tubular impairment and significantly decreased oxidative stress, as well as the expression of pro‑inflammatory cytokines and TGF-‑β1 in kidney tissues. In conclusion, the results suggested that NBP may slow the progression of hypertensive nephropathy by a variety of mechanisms.

Beneficial effects of celery (Apium graveolens) on metabolic syndrome: A review of the existing evidences

“…A chronic kidney disease model was employed to assess the effects of NBP against hypertensive nephropathy using spontaneously hypertensive rats. The obtained results of this study suggested a significant reduction in BP and development of hypertensive nephropathy that were attributed to the reduction of expression of interleukin 6 (IL‐6), tumor necrosis factor α (TNF‐α), and nuclear factor‐kappa B (NF‐κB) as well as oxidative stress (Zhu, Zhang, & Yang, ). Moreover, the exposure of male Wistar rats to 2% d‐limonene (an active compound in celery) diet for 4 weeks resulted in the reduction of BP through antioxidant capabilities (Santiago, Jayachitra, Shenbagam, & Nalini, ).…”

A Review of Recent Advances in Neuroprotective Potential of 3-N-Butylphthalide and Its Derivatives

“…Preliminary studies have been performed on the effect of NBP on various conditions with systemic cerebrovascular and cardiovascular repercussion such as diabetes, myocardial infarction, or hypertensive nephropathy [69–71]. The results showed several common neuroprotective mechanisms ranging from reduction of oxidative stress to prevention of apoptosis to induction of autophagy through suppression of the β -catenin signaling pathway [72] to promotion of angiogenesis.…”

“…The results showed several common neuroprotective mechanisms ranging from reduction of oxidative stress to prevention of apoptosis to induction of autophagy through suppression of the β -catenin signaling pathway [72] to promotion of angiogenesis. The converging points of NBP antioxidative [71], antiapoptotic, and proangiogenic effects on those conditions are believed to be through reduction of caspase-3 activity, upregulation of vascular endothelial growth factor (VEGF) expression, and elimination of ROS production [70, 73–75]. In addition, it has been indicated that l-NBP possesses additional properties such as the ability of increasing the Bcl-2 protein levels while decreasing cytochrome c levels.…”

Neuroprotective mechanisms of 3‑n‑butylphthalide in neurodegenerative diseases (Review)

“…NBP was reported to improve dyskinesia in a LPS-induced PD mouse model via a reduction in the loss of dopaminergic neurons, activation of mouse microglia, an increase in TNF-α levels and α-synuclein deposition in the black substantia of the mouse midbrain (16). Additionally, NBP-treatment reduces NF-κB activation following TBI (17), and NBP also inhibits the inflammatory reaction via the same pathway in spontaneously hypertensive rats (18). Notably, a number of studies have indicated that NBP inhibits the inflammatory reaction in other neuroassociated experimental models, such as an experimental model of autoimmune encephalomyelitis of microglia or autoimmune myositis in guinea pigs (19,20).…”