Piperazine Ferulate

Piperazine ferulate exerts antihypertensive effect and improves endothelial function in vitro and in vivo via the activation of endothelial nitric oxide synthase.[Pubmed:30942165]

Cell Mol Biol (Noisy-le-grand). 2019 Mar 31;65(3):119-124.

To investigate the effect of Piperazine Ferulate (PF) on hypertension and endothelial function, and to assess the possible underlying mechanism. Human umbilical vein endothelial cells (HUVEC), adult male Wistar Kyoto (WKY) rats aged 12 to 14 weeks, and spontaneously hypertensive (SH) and Sprague Dawley (SD) rats were used for this study. Cell viability, activities of angiotensin-converting enzyme (ACE) and heme oxygenase-1 (HO-1), in vivo NO synthesis, arterial systolic blood pressure, vascular function, expressions of endothelial NO synthase (eNOS) and phosphorylated-eNOS (p-eNOS) were determined or assessed as appropriate. The results of MTT assay showed the number of viable cells were significantly increased with increase in PF concentration (p < 0.05). The level of expression of ACE was significantly reduced with increase in PF concentration (p < 0.05), while the level of HO-1 expression significantly increased (p < 0.05). Results of DAF-FM fluorescent staining showed that the amounts of NO synthesized in vivo was significantly higher in aortic rings of SH and SD rats treated with PF than in the corresponding control groups (p < 0.05). Treatment with PF in vivo significantly improved impaired acetylcholine-induced aortic relaxation in SH rats. Total eNOS expression was significantly increased after treatment with PF (p < 0.05). The expressions of total eNOS and p-eNOS in both groups were not affected by PF when compared to the control group. These results indicate that PF exerts antihypertensive effect and improves endothelial function in vitro and in vivo via the activation of eNOS.

Piperazine ferulate ameliorates the development of diabetic nephropathy by regulating endothelial nitric oxide synthase.[Pubmed:30664213]

Mol Med Rep. 2019 Mar;19(3):2245-2253.

Diabetic nephropathy (DN) is among the most common complications of diabetes mellitus. The disorder is associated with a decrease in the activity of the nitric oxide synthase/nitric oxide system. Piperazine Ferulate (PF) is widely used for the treatment of kidney disease in China. The aim of the present study was to examine the effects of PF on streptozotocin (STZ)induced DN and the underlying mechanism of this process. STZinduced diabetic mice were intragastrically administered PF (100, 200 and 400 mg/kg/body weight/day) for 12 weeks. At the end of the treatment period, the parameters of 24h albuminuria and blood urea nitrogen, creatinine and oxidative stress levels were measured. Hematoxylin and eosin staining, periodic acidSchiff staining and electron microscopy were used to evaluate the histopathological alterations. mRNA and protein expression of endothelial nitric oxide synthase (eNOS) were measured by quantitative polymerase chain reaction and western blotting, respectively. PF significantly decreased blood urea nitrogen and creatinine levels and 24h albuminuria, and it alleviated oxidative stress, improved glomerular basement membrane thickness and caused an upregulation in eNOS expression and activity levels in diabetic mice. In addition, high glucose decreased eNOS expression levels, whereas PF caused a reversal in the nitric oxide (NO) levels of glomerular endothelial cells. The present results suggested that PF exhibited renoprotective effects on DN. The mechanism of its action was associated with the regulation of eNOS expression and activity.

Clinical effects of perazine ferulate tablets combined with eucalyptol limonene pinene enteric soft capsules for treatment of children with IgA nephropathy.[Pubmed:27347034]

Exp Ther Med. 2016 Jul;12(1):169-172.

The clinical effects of Piperazine Ferulate tablets combined with eucalyptol limonene pinene enteric soft capsules for treatment of children with IgA nephropathy were investigated. Sixty children with IgA nephropathy were included in the study and were randomly divided into the control (n=30) and observation (n=30) groups. The patients in the control group were treated with conservative or hormone therapy while patients in the observation group were treated with Piperazine Ferulate tablets combined with eucalyptol-limonene-pinene enteric soft capsules. Clinical effects were observed and compared. The total effective rate of the observation group was significantly higher than that of the control group, while the incidence of complications was significantly lower than that of the control group (p<0.05). Serum IgA and fibronectin levels of the observation group were significantly lower than those of the control group, while the level of C3 was significantly higher than that of the control group (p<0.05). In conclusion, Piperazine Ferulate tablets combined with eucalyptus enteric soft capsule constituted a safe and effective for the treatment of children with IgA nephropathy. The treatment was superior to conservative or hormone therapy, and thus worthy of clinical promotion.

General acteoside of Rehmanniae leaves in the treatment of primary chronic glomerulonephritis: a randomized controlled trial.[Pubmed:24146510]

Afr J Tradit Complement Altern Med. 2013 May 16;10(4):109-15. eCollection 2013.

The objective of the study was to investigate the effectiveness and efficacy of the randomized, parallel, and controlled trial of Traditional Chinese Medicine, general acteoside of Rehmanniae leaves, compared with Piperazine Ferulate in the treatment of primary chronic glomerulonephritis. Rehmanniae leaves and Piperazine Ferulate can reduce proteinuria and erythrocyturia effectively in the treatment of primary chronic glomerulonephritis. A total of 400 patients diagnosed with primary chronic glomerulonephritis were recruited from outpatient clinics and were randomly assigned to the treatment group (general acteoside of Rehmanniae leaves, two 200mg tablets, bid) or the control group (Piperazine Ferulate, four 50-mg tablets, bid ). The primary outcome was 24-h urinary protein. Secondary outcome measures included estimated glomerular filtration rate (eGFR), erythrocyturia, and electrolytes. After 8 weeks of treatment, the treatment group and the control group showed a mean reduction in 24-h proteinuria of 34.81% and 37.66%. The 95% CI of difference of the mean reduction in 24-h proteinuria between the two groups was [-11.50%, 5.80%]. No significant differences were found between the two groups in the erythrocyturia reduction. Neither group showed obvious changes between baseline and 8 weeks in eGFR or electrolytes. Adverse events occurred at a similarly low rate in the treatment group (1.5%) and control group (2.5%, P = 0.7238). Both general acteoside of Rehmanniae leaves and Piperazine Ferulate can reduce proteinuria and erythrocyturia effectively in the treatment of primary chronic glomerulonephritis.

Rapid analysis of piperazine ferulate tablets by optic-fiber sensing technology and the similarity of ultraviolet spectra.[Pubmed:29403759]

J Pharm Anal. 2012 Aug;2(4):310-313.

A rapid analysis method of Piperazine Ferulate tablets by optic-fiber sensing technology with UV-vis absorption spectrum was established. Qualitative and quantitative data were obtained and compared by maximum and minimum wavelength, absorbance and contrast spectra. Similarity method was used to identify authenticity of drugs. The difference of contents measured by this method and UV determination method in China Pharmacopoeia showed no statistical significance (P>0.05), while the similarity can be used as a parameter to identify the authenticity of drugs.

[Effects of piperazine ferulate on TGF-beta1-induced renal interstitial fibroblast activation].[Pubmed:19024302]

Sichuan Da Xue Xue Bao Yi Xue Ban. 2008 Sep;39(5):736-9, 762.

OBJECTIVE: To investigate the effects of Piperazine Ferulate (PF) on TGF-beta1-induced renal interstitial fibroblast activation, and to explore the mechanism of PF in the prevention of renal tubulointerstitial fibrosis. METHODS: In cultured normal rat renal kidney fibroblast (NRK-49F), the effect of PF on the TGF-beta1-induced cell vitality was observed by MTT. The protein expression levels of a-smooth muscle actin (alpha-SMA), connective tissue growth factor (CTGF) induced by TGF-beta1 were evaluated by immunocytochemistry. The levels of a-SMA, CTGF mRNA expression induced by TGF-beta1, were determined by quantitative real time fluroscent polymerase chain reaction. The levels of collagen type I (Col I) and fibronectin (FN) protein expression were examined by Enzyme Linked Immunosorbent Assay(ELISA). RESULTS: TGF-beta1 may markedly increase the cell vitality, alpha-SMA and CTGF expression, FN and Col I protein expression (P < 0.05). Compared with TGF-beta1-induced group, PF can partly decrease the cell vitality, level of alpha-SMA and CTGF expression and extracellular matrix(ECM) synthesis induced by TGF-beta1 (P < 0.05). CONCLUSION: PF may inhibit TGF-beta1-induced fibrosis in the renal fibroblast to a certain extent.

[Effects of piperazine ferulate on connective tissue growth factor and extracellular matrix in TGF-beta1 induced mesangial cells].[Pubmed:19024301]

Sichuan Da Xue Xue Bao Yi Xue Ban. 2008 Sep;39(5):732-5.

OBJECTIVE: To observe the effects of Piperazine Ferulate (PF) on synthesis of extracellular matrix and expression of connective tissue growth factor (CTGF) in transforming growth factor-betal (TGF-beta1) induced rat glomerular mesangial cells (GMC), and to investigate its mechanism on the prevention of glomerulosclerosis. METHODS: Rat HBZY-1 GMCs were cultured in vitro and divided into 5 groups: Normal control group, TGF-beta1-stimulated group, TGF-beta1 plus 50, 100, 200 ng/mL PF group. The level of CTGF protein expression induced by TGF-beta1 was measured by immunocytochemistry, The mRNA expression of CTGF was evaluated by quantitative real time fluroscent polymerase chain reaction. The expressions of fibronectin and collagen I were analyzed by enzyme linked immunosorbent assay (ELISA). RESULTS: With the stimulation of TGF-beta1, the expression of of CTGF protein and mRNA, as well as fibronectin and collagen I were markly increased (P < 0.05), which then were decreased by the treatment of PF. (P < 0.05). CONCLUSION: PF can partly inhibit synthesis of the extracellular matrix and CTGF. PF may take part in the prevention of glomerulosclerosis through the inhibition of CTGF expression.