Jie Su

Luteolin Ameliorates Hypertensive Vascular Remodeling through Inhibiting the Proliferation and Migration of Vascular Smooth Muscle Cells

Objectives. Preliminary researches showed that luteolin was used to treat hypertension. However, it is still unclear whether luteolin has effect on the hypertensive complication such as vascular remodeling. The present study was designed to investigate the effect of luteolin on the hypertensive vascular remodeling and its molecular mechanism. Method and Results. We evaluated the effect of luteolin on aorta thickening of hypertension in spontaneous hypertensive rats (SHRs) and found that luteolin could significantly decrease the blood pressure and media thickness of aorta in vivo. Luteolin could inhibit angiotensin II- (Ang II-) induced proliferation and migration of vascular smooth muscle cells (VSMCs). Dichlorofluorescein diacetate (DCFH-DA) staining result showed that luteolin reduced Ang II-stimulated ROS production in VSMCs. Furthermore, western blot and gelatin zymography results showed that luteolin treatment leaded to a decrease in ERK1/2, p-ERK1/2, p-p38, MMP2, and proliferating cell nuclear antigen (PCNA) protein level. Conclusion. These data support that luteolin can ameliorate hypertensive vascular remodeling by inhibiting the proliferation and migration of Ang II-induced VSMCs. Its mechanism is mediated by the regulation of MAPK signaling pathway and the production of ROS.

Effects of an Enriched Extract of Paeoniflorin, a Monoterpene Glycoside used in Chinese Herbal Medicine, on Cholesterol Metabolism in a Hyperlipidemic Rat Model

Background Paeoniflorin is a monoterpene glycoside extracted from the roots of Paeonia lactiflora and is used in Chinese herbal medicine to treat hyperlipidemia. The aim of this study was to evaluate the effects of an enriched extract of paeoniflorin on cholesterol levels, hemodynamics, and oxidative stress in a hyperlipidemic rat model. Material/Methods Male Sprague-Dawley rats were fed high-cholesterol diets and treated with three different doses of paeoniflorin for 12 weeks. The effects of paeoniflorin treatment were assessed on cholesterol levels, cholesterol metabolism, red blood cell vascular flow using hemorheology, antioxidant enzymes, and expression of the rate-limiting enzyme in the mevalonate pathway, 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR). Rat liver histology and immunohistochemical analysis were performed to evaluate the expression of nuclear factor erythroid 2–related factor 2 (Nrf2), cytochrome P450 7A1 (CYP7A1), and peroxisome proliferator-activated receptors (PPAR)-α. Protein expression HMG-CoAR, low-density lipoprotein receptor (LDLR), PPAR-α and CYP7A1 was measured by Western blotting. Antioxidant activity in rat liver was determined by measuring superoxide dismutase (SOD) and malondialdehyde (MDA). Results Serum and hepatic cholesterol, hepatic steatosis and the products of cholesterol metabolism were reduced by paeoniflorin treatment, which also reduced the activity of HMG-CoAR and upregulated the expression of LDLR, PPAR-α, and CYP7A1 expression, increased SOD, decreased MDA, and upregulated Nrf2 expression. Conclusions The findings of this study in a rat model of hyperlipidemia have shown that paeoniflorin regulates hepatic cholesterol synthesis and metabolism and may also protect the liver from oxidative stress.

Combined Antihypertensive Effect of Paeoniflorin Enriched Extract and Metoprolol in Spontaneously Hypertensive Rats

Background: Hypertension is a great global health challenge and it mostly requires drug combination therapy with the various advantages. Metoprolol (MP) and paeoniflorin are both commonly used for the treatment of hypertension. However, whether they exert synergistic effects on antihypertension or not remains unclear, especially on vascular endothelial function. Objective: The purpose of the study is to investigate the advantages of the combined antihypertensive effects of paeoniflorin enriched extract from Radix Paeoniae Alba (RE) and MP in spontaneously hypertensive rats (SHR). Materials and Methods: SHR divided into six groups (n = 8 each group), animals in each group were administrated orally with distilled water, MP (6 and 20 mg/kg), RE (30 and 90 mg/kg), and MP (6 mg/kg) combined with RE (30 mg/kg) (MP + RE), respectively, daily for 6 weeks. Blood pressure (BP) and microcirculation were assessed. The organ bath experiment and hematoxylin and eosin staining were, respectively, performed for the functional and pathological vascular function analysis. Immunohistochemistry was applied to detect endothelial nitric oxide synthase (eNOS) expression in aorta, heart, and kidney. Further, high-performance liquid chromatography was employed to quantitatively determine paeoniflorin in RE and MP + RE sample solvent, as well as in plasma of Sprague-Dawley rats (SD) after single-dose administration of them. Results: The results showed that MP + RE significantly reduced BP, increased microcirculation, improved vascular function and pathological changes, and upregulated eNOS expression. MP was also found to increase the blood concentration of paeoniflorin in SD. Conclusion: The combination of RE and MP could be used for the treatment of hypertension and could improve microcirculation, upregulate eNOS expression, and mitigate endothelial dysfunction in SHR. Abbreviations used: RE: Paeoniflorin enriched extract from Radix Paeoniae Alba, MP: Metoprolol, MP + RE: MP combined with RE, NC: Normal control, MC: Model control, SHR: Spontaneously hypertensive rats, SD: Sprague-Dawley rats, H and E: Hematoxylin and eosin, BP: Blood pressure, SBP: Systolic blood pressure, DBP: Diastolic blood pressure, MBP: Mean arterial blood pressure, NA: Norepinephrine, ACh: Acetylcholine, SNP: Nitroprusside, NO: Nitric oxide, eNOS: Endothelial nitric oxide synthase, RPA: Radices Paeoniae Alba, IHC: Immunohistochemistry, Cmax: Peak concentration, Tmax: The time to reach Cmax, t½: Half-life, AUC0-t: Area under the curve of 0-t time; MRT0-t: Mean residence of 0-t time; CL: Clearance rate.

Gypenosides Inhibits Xanthine Oxidoreductase and Ameliorates Urate Excretion in Hyperuricemic Rats Induced by High Cholesterol and High Fat Food (Lipid Emulsion)

Background The aim of this study was to study the effects of gypenosides (GPS) on lowering uric acid (UA) levels in hyperuricemic rats induced by lipid emulsion (LE) and the related mechanisms. GPS are natural saponins extracted from Gynostemma pentaphyllum. Material/Methods Forty-eight male SD rats were randomly divided into six groups: normal, model, two positive controls, and two GPS treated groups (two different doses of GPS). The normal group rats were fed a basic diet, and the other rats were orally pretreated with LE. Urine and blood were collected at regular intervals. Full automatic biochemical analyzer was used to detect the concentration levels of serum UA (SUA), serum creatinine (SCr), BUN, and urine UA (UUA), and urine creatinine (UCr) and fractional excretion of UA (FEUA). ELISA kits were used to detect enzymes activities: xanthine oxidase (XOD), adenosime deaminase (ADA), guanine deaminase (GDA), and xanthine dehydrogenase (XDH). Immunohistochemistry was used to observe kidney changes and protein (URAT1, GLUT9, and OAT1) expression levels. RT-PCR was used to detect the relevant mRNA expression levels. Results Treatment with GPS significantly reduced the SUA, prevented abnormal weight loss caused by LE, and improved kidney pathomorphology. Treatment with GPS also decreased the levels of XOD, ADA, and XDH expression, increased the kidney index and FEUA, downregulated URAT1 and GLUT9 expression and upregulated OAT1 expression in the kidney. Conclusions GPS may be an effective treatment for hyperuricemia via a decrease in xanthine oxidoreductase through the XOD/XDH system; and via an increase in urate excretion through regulating URAT1, GLUT9, and OAT1 transporters.

Beneficial Effects of Paeoniflorin Enriched Extract on Blood Pressure Variability and Target Organ Damage in Spontaneously Hypertensive Rats

Blood pressure variability (BPV) is associated with the development and progression of severe target organ damage (TOD). This study aims to evaluate the protective effect of paeoniflorin enriched extract from Radix Paeoniae Alba (PG) on BPV and TOD in spontaneously hypertensive rats (SHR). All SHR were orally treated with distilled water, metoprolol (MP, 20 mg/kg), and PG (PG-H, 90 mg/kg or PG-L, 30 mg/kg) for a single time or daily for 7 weeks. The 24-hour dynamic blood pressure was monitored and then calculated BPV including long- and short-term systolic blood pressure variability (SBPV), diastolic blood pressure variability (DBPV), mean blood pressure variability (MBPV), and heart rate variability (HRV) as well as the 24-hour-SBP, 24-hour-DBP, and 24-hour-MBP. The protective effects of PG on TOD were observed by histopathologic and biochemical detection. The results indicated that long- and short-term SBPV, DBPV, MBPV, and HRV as well as 24-hour-SBP, 24-hour-DBP, and 24-hour-MBP showed no significant changes after single-dose administration of PG and significantly decreased after administration with PG for 7 weeks. PG could also markedly improve the damage of aorta, heart, kidney, and brain. This study suggested that PG could notably reduce BPV, stabilize blood pressure, and mitigate TOD in SHR.