peoniflorin and Kidney-Diseases

The monoterpene glycoside paeoniflorin (PF) is the principal active constituent of the traditional Chinese herbal medicines, Radix Paeoniae Alba and Radix Paeoniae Rubra, which have been used for millennia to treat cardiovascular diseases (eg, hypertension, bleeding, and atherosclerosis) and neurological ailments (eg, headaches, vertigo, dementia, and pain). Recent evidence has revealed that PF exerts inhibitory effects on inflammation, fibrosis, and apoptosis by targeting several intracellular signaling cascades. In this review, we address the current knowledge about the pharmacokinetic properties of PF and its molecular mechanisms of action. We also present results from recent preclinical studies supporting the utility of PF for the treatment of pain, cerebral ischemic injury, and neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases. Moreover, new evidence suggests a general protective role of PF in heart attack, diabetic kidney, and atherosclerosis. Mechanistically, PF exerts multiple anti-inflammatory actions by targeting toll-like receptor-mediated signaling in both parenchymal and immune cells (in particular, macrophages and dendritic cells). A better understanding of the molecular actions of PF may lead to the expansion of its therapeutic uses.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cardiovascular Diseases; Drugs, Chinese Herbal; Glucosides; Humans; Kidney Diseases; Monoterpenes; Nervous System Diseases

A method for screening nephroprotective compounds in cortex Moutan, a common traditional Chinese medicine (TCM) in treating diabetic nephropathy with renal mesangial cell extraction and ultra performance liquid chromatography technique was described in this paper. We hypothesize that the compounds which bind to cell membranes under pathological conditions may be the bioactive compounds in TCMs. Mesangial cells were cultured in medium containing 5 mM (physiological, NG) or 30 mM (pathological, HG) glucose for 48 h and then incubated with cortex Moutan extract. After the unbound substances were washed off, the cell membrane-bound compounds were dissociated and concentrated by an SPE column. By comparing the chromatograms of NG and HG cultured-cell extractions and cortex Moutan extract, three compounds bound to both NG and HG-cultured mesangial cells were identified as paeoniflorin, pentagalloylglucose (PGG) and paeonol. In vitro studies showed that paeoniflorin, PGG and paeonol reduced the activity of nicotinamide-adenine dinucleotide phosphate oxidase (NADPH) activity, and decreased the level of reactive oxygen species (ROS), transforming growth factor-β1 (TGF-β1) and fibronectin in high glucose cultured mesangial cells. The results indicate that paeonol, paeoniflorin and PGG may be the nephroprotective compounds from cortex Moutan. This study is expected to provide a more reliable and effective method for screening bioactive compounds from the complex TCM systems.

Topics: Acetophenones; Animals; Antioxidants; Cell Line; Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Fibronectins; Glucosides; Hydrolyzable Tannins; Kidney Diseases; Mesangial Cells; Mice; Monoterpenes; NADPH Oxidases; Paeonia; Reactive Oxygen Species; Solid Phase Extraction; Transforming Growth Factor beta1

Paeoniflorin (PF), the major active constituent of Paeonia lactiflora Pallas, has previously been reported to alleviate hepatic fibrosis. Whether and how it affects renal fibrosis was evaluated in the present study. The experimental renal fibrosis was induced by unilateral ureteral obstruction (UUO) operation in mice, and PF was orally administered for consecutive 7 days. Renal interstitial destruction and fibrosis degree were evaluated by histopathological examination and hydroxyproline assay. It was shown that PF treatment markedly ameliorated renal interstitial fibrotic lesions, attenuated synthesis of collagen and plasminogen activator inhibitor-1 (PAI-1), an important inhibitor of extracellular matrix degrading enzymes, in UUO mice. PF also suppressed epithelial-mesenchymal transition (EMT) by down-regulating TGF-β1 expression and maintaining BMP-7 mRNA expression, and inhibited Smad2/3 activation in fibrotic kidneys induced by UUO. These observations suggest that PF can effectively prevent renal interstitial fibrosis, and the underlying mechanisms are, at least in part, through blocking EMT via BMP-7 recovery and TGF-β/Smad signaling inhibition.

Topics: Animals; Benzoates; Bone Morphogenetic Protein 7; Bridged-Ring Compounds; Collagen; Down-Regulation; Epithelial-Mesenchymal Transition; Fibrosis; Gene Expression Regulation; Glucosides; Kidney Diseases; Male; Mice; Mice, Inbred ICR; Monoterpenes; Paeonia; Phosphorylation; Plasminogen Activator Inhibitor 1; Smad2 Protein; Transforming Growth Factor beta1; Ureteral Obstruction