The protective effects of Polygonum multiflorum stilbeneglycoside preconditioning in an ischemia/reperfusion model of HUVECs

Abstract

Aim: To investigate the protective effects of preconditioning human umbilical vein endothelial cells (HUVECs) with Polygonum multiflorum stilbeneglycoside (PMS) under anoxia/reoxygenation (A/R), and the mechanism of protection. Methods: Prior to A/R, HUVECs were incubated with PMS (0.6×10 , or 2.4×10 -11 mol/L) for 3 h. Cell injury was subsequently evaluated by measuring cell viability with an MTT assay and lactate dehydrogenase (LDH) release, whereas lipid peroxidation was assayed by measuring malondialdehyde (MDA) content. Antioxidant capacity was quantified by superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity. Nitric oxide (NO) production was determined by nitrite accumulation. Endothelial NO synthase (eNOS) and inducible NOS (iNOS) protein expression was detected by Western blotting. Guanylate cyclase activity and cyclic GMP (cGMP) activity were assessed by an enzyme immunoassay kit. Results: PMS incubation attenuated A/R-induced injury in a concentration-dependent manner, as evidenced by a decrease in LDH activity and an increase in cell viability. PMS exerted its protective effect by inhibiting the A/R-mediated elevation of MDA content, as well as by promoting the recovery of SOD and GSH-Px activities. Additionally, PMS incubation enhanced NO and cGMP formation by increasing iNOS expression and guanylate cyclase activity. The protective effects of PMS were markedly attenuated by NOS inhibitor L-NAME, soluble guanylate cyclase inhibitor ODQ or PKG inhibitor KT5823.Conclusion: PMS preincubation resulted in the enhancement of antioxidant activity and anti-lipid peroxidation. The NO/cGMP/cGMPdependent protein kinase (PKG) signaling pathway was involved in the effect of PMS on HUVECs.

cGMP-Phosphodiesterase Inhibition Prevents Hypoxia-Induced Cell Death Activation in Porcine Retinal Explants

“…PDE inhibition significantly ameliorated antioxidant response and reduced superoxide radical formation in the ONL. Our results suggest that cGMP-PKG pathway mediated these protective effects by increasing SOD activity and reducing superoxide radical formation as observed in other ischemic situations [77]. …”

Pharmacokinetics and tissue distribution of 2,3,5,4′-tetrahydroxystilbene-2-O-β-d-glucoside from traditional Chinese medicine Polygonum multiflorum following oral administration to rats

“…PM-SG has attracted intense interest for its therapeutic activities (Ip et al, 1997;X. Li et al, 2005;Yang et al, 2005;Liu et al, 2010) and for the quality control of its parent herb (Zhang et al, 2008). However, to our knowledge, no study of plasma pharmacokinetics and tissue distribution of this bioactive compound in any herb extract has hitherto been published.…”

“…Since PM-SG has been reported to possess various beneficial and therapeutic effects in vitro and in vivo (Ip et al, 1997;X. Li et al, 2005;Yang et al, 2005;China Pharmacopoeia Committee, 2010;Liu et al, 2010), it would be very useful and meaningful to obtain its pharmacokinetic information for better understanding on when, where and how this bioactive compound can be effective. Thus, the present pharmacokinetic study is considered to support the clarification of PM-SG's mechanism of action, which can provide a deeper understanding of the pharmacology of PM-SG.…”

“…This herb possesses many effects, such as lipid lowering, antioxidation, toxin detoxification, anti-tumor, and lubricating intestine, to treat cardiovascular disorders, neurological disorders, and other diseases commonly associated with aging (Ip et al, 1997;X. Li et al, 2005;Yang et al, 2005;China Pharmacopoeia Committee, 2010;Liu et al, 2010). Modern chromatographic separation studies have demonstrated that many bioactive compounds in Polygonum multiflorum, e.g.…”

“…stilbene glycosides, are responsible for its medicinal activities (Yao et al, 2006;Yi et al, 2007;Han et al, 2009). 2,3,5,4 -Tetrahydroxystilbene-2-O-ˇ-d-glucoside (structure in Fig. 1), a major active stilbene glycoside in Polygonum multiflorum, has been reported to possess antioxidative, anti-inflammatory, endothelial protective, and oncogenic enzyme inhibitory activities (Ryu et al, 2002;Li-Shuang et al, 2006;Lv et al, 2007;Wang et al, 2008;Kwon et al, 2009;Liu et al, 2010). These medicinal functions of the Polygonum multiflorum stilbene glycoside (PM-SG) has attracted much attention and generated great interest of researchers for its further investigation and therapeutic application.…”