stilbenes and Shock--Septic

Resveratrol offers pleiotropic health benefits including a reported ability to inhibit lipopolysaccharide (LPS)-induced cytokine production. The aim of this work was to prepare, characterize, and evaluate a resveratrol nanoparticulate formulation based on zein. For this purpose, the oral bioavailability of the encapsulated polyphenol as well as its anti-inflammatory effects in a mouse model of endotoxic shock was studied. The resveratrol-loaded nanoparticles displayed a mean size of 307 ± 3 nm, with a negative zeta potential (-51.1 ± 1.55 mV), and a polyphenol loading of 80.2 ± 3.26 μg/mg. In vitro, the release of resveratrol from the nanoparticles was found to be pH independent and adjusted well to the Peppas-Sahlin kinetic model, suggesting a mechanism based on the combination of diffusion and erosion of the nanoparticle matrix. Pharmacokinetic studies demonstrated that zein-based nanoparticles provided high and prolonged plasma levels of the polyphenol for at least 48 h. The oral bioavailability of resveratrol when administered in these nanoparticles increased up to 50% (19.2-fold higher than for the control solution of the polyphenol). Furthermore, nanoparticles administered daily for 7 days at 15 mg/kg were able to diminish the endotoxic symptoms induced in mice by the intraperitoneal administration of LPS (i.e., hypothermia, piloerection, and stillness). In addition, serum tumor necrosis factor-alpha (TNF-α) levels were slightly lower (approximately 15%) than those observed in the control.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents; Biological Availability; Disease Models, Animal; Drug Carriers; Female; Humans; Male; Mice; Mice, Inbred C57BL; Nanoparticles; Rats; Rats, Wistar; Resveratrol; Shock, Septic; Stilbenes; Tumor Necrosis Factor-alpha; Zein

Anti-inflammatory effect of piceatannol, a naturally occurring polyphenol and a potent free radical scavenger, on ocular inflammation is not known. We examined the anti-inflammatory role of piceatannol in ocular inflammatory response due to endotoxin-induced uveitis (EIU) in rats. EIU was induced in Lewis rats by subcutaneous injection of lipopolysaccharide (LPS; 150 ug/rat). Piceatannol (30mg/kg body wt, i.p) was injected either 2h prior to or 1h post LPS induction. A significant increase in the number of infiltrating cells, total protein, and various cytokines and chemokines in AqH were observed in the EIU rat eyes as compared to control groups. However, pre- or post-treatment of piceatannol significantly blocked the LPS-induced changes. Further, piceatannol also suppressed the expression of cyclooxygenase-2 (Cox-2), inducible nitric oxide synthase (iNOS) and activation of NF-κB in the ciliary bodies as well as retina. Further, piceatannol also inhibited the expression of Cox-2, iNOS, and phosphorylation of NF-κB in primary human non-pigmented ciliary epithelial cells (HNPECs) treated with LPS. Similarly, piceatannol also diminished LPS-induced level of NO and prostaglandin E2 in HNPECs. Thus our results demonstrate an anti-inflammatory role of piceatannol in suppressing ocular inflammation induced by endotoxin in rats.

Topics: Animals; Aqueous Humor; Cells, Cultured; Cyclooxygenase 2; Cytokines; Disease Models, Animal; Free Radical Scavengers; Gene Expression Regulation; Humans; Male; NF-kappa B; Nitric Oxide Synthase Type II; Rats; Rats, Inbred Lew; Retina; Shock, Septic; Stilbenes; Uveitis

To study the effect of polydatin on phospholipase A(2) in lung tissues in rats with endotoxic shock.. Thirty-two healthy male Wistar rats were employed in this study. A total of 8 rats received normal saline intravenously (control group), 8 rats received 10 mg/kg of endotoxin (endotoxic shock group), 8 rats received 1 mg/kg of polydatin after endotoxin injection (polydatin treatment group), and 8 rats received 1 mg/kg of polydatin (polydatin prevention group) 30 minutes before endotoxin injection. Mean arterial pressure was measured once half an hour. Lung tissues were collected 6 hours later. Phospholipase A(2) activity was measured with acid titration. The gene expression of secretory phospholipase A(2) type IIA was detected with reverse transcription polymerase chain reaction. Meanwhile, the histological changes of the lungs among four groups were compared through microscopic examination.. Phospholipase A(2) activity and the gene expression of secretory phospholipase A(2) type IIA increased after endotoxin injection, but polydatin could inhibit these effects of endotoxin. Obvious morphological evidence could be found in the lung pathological sections and the protective effect of polydatin was most significant in the polydatin prevention group.. Polydatin has prophylactic and therapeutic effects (the former is more distinct than the latter) on acutely injured lungs in rats with endotoxic shock and which suggests that polydatin may be a phospholipase A(2) inhibitor.

Topics: Analysis of Variance; Animals; Glucosides; Lung; Male; Phospholipases A; Phospholipases A2; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; Shock, Septic; Stilbenes

Polydatin is extracted from a traditional Chinese herbal medicine, Polygonum cuspidatum, and has a special effect in shock treatment. The aim of this study is to explain the cellular and molecular basis of Polydatin in shock treatment. The fluorescent probe techniques, patch clamp method, and cellular flow chamber were used to test intracellular variables of vascular smooth muscle cells (VSMC), myocardial cells (MC), endothelial cells (EC), and white blood cell (WBC). It was shown that Polydatin could inhibit ICAM-1 expression in EC stimulated by lipopolysaccharide (LPS), attenuate WBC-EC adhesion, increase [Ca2+]i in MC with enhancement of MC contraction extent, activate KATP channels of VSMC, and decrease pHi value and [Ca2+]i of VSMC in shock. The study suggests that Polydatin has multiple effects on VSMC, MC, WBC and EC, which are related to the enhancement of heart function and improvement of microcirculatory perfusion in shock.

Topics: Animals; Calcium Channel Blockers; Calcium Signaling; Cell Adhesion; Cells, Cultured; Drug Evaluation, Preclinical; Endothelial Cells; Endothelium, Vascular; Fallopia japonica; Glucosides; Humans; Intercellular Adhesion Molecule-1; Leukocytes; Microcirculation; Muscle, Smooth, Vascular; Myocardium; Patch-Clamp Techniques; Phytotherapy; Plants, Medicinal; Potassium Channels; Rats; Shock, Hemorrhagic; Shock, Septic; Stilbenes; Verapamil