peoniflorin and Hyperlipidemias

Osteoporosis is linked to reduced bone mineral density (BMD) as a major risk factor for fragility fractures. Recent studies indicated an association between BMD and abnormally elevated lipid levels in blood as common indicators for hyperlipidemia. In this study, we assessed the protective effect of paeoniflorin, a phytochemical compound with multiple pharmacological activities, against hyperlipidemia-induced osteoporosis in rats fed a high-carbohydrate, high-fat diet (HCHF). The special diet-fed rats were subjected to an 8-week treatment with either paeoniflorin (20 mg/kg, daily) or vehicle. The control group received a normal diet during the entire study. At study conclusion, serum markers of lipid metabolism and bone turnover were measured. Bone strength was assessed by biomechanical testing, and femurs were scanned using micro-computed tomography to analyze trabecular and cortical bone structure. Interestingly, paeoniflorin controlled the serum lipid profile by significantly decreasing HCHF-induced high levels of total cholesterol, triglyceride, and low-density lipoprotein cholesterol. Paeoniflorin significantly improved trabecular and cortical parameters as well as femur length and width that were negatively affected by HCHF diet. Biomechanical strength testing showed that femurs of HCHF diet-fed rats endured significantly lower force but higher displacement and strain than those of control rats, whereas paeoniflorin reversed the negative effects. Moreover, paeoniflorin rescued osteoblast differentiation and cell spreading activities along with bone turnover markers. In conclusion, HCHF-induced hyperlipidemia caused adverse effects on the bone that were rescued by paeoniflorin treatment.

Topics: Animals; Biomechanical Phenomena; Bone Remodeling; Diet, High-Fat; Dietary Carbohydrates; Femur; Glucosides; Hyperlipidemias; Lipid Metabolism; Monoterpenes; Osteoporosis; Phytochemicals; Rats

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 AND 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.

Topics: Animals; Cholesterol; Cholesterol 7-alpha-Hydroxylase; Diet, High-Fat; Disease Models, Animal; Drugs, Chinese Herbal; Fatty Liver; Glucosides; Glycosides; Hyperlipidemias; Lipid Metabolism; Lipoproteins, LDL; Liver; Male; Monoterpenes; NF-E2-Related Factor 2; PPAR alpha; Rats; Rats, Sprague-Dawley; Triglycerides

Paeoniflorin (1), isolated from the methanol extract of Paeonia lactiflora, showed a lowering effect on cholesterol level in the experimentally-induced hyperlipidemic rats. Paeoniflorin showed a significantly lowering effect of total cholesterol, LDL and triglyceride levels compared with the control group at the dose of 200 and 400 mg/kg, p.o. once a day for 4 weeks.

Topics: Administration, Oral; Animals; Benzoates; Bridged-Ring Compounds; Cholesterol; Cholesterol, LDL; Dose-Response Relationship, Drug; Glucosides; Hyperlipidemias; Hypolipidemic Agents; Male; Monoterpenes; Paeonia; Phytotherapy; Plant Extracts; Plant Roots; Rats; Rats, Wistar; Triglycerides