Phytochemicals as inhibitors of NF-κB for treatment of Alzheimer's disease.

Background
Traditional Chinese medicinal herbs Cortex Moutan and Radix Salviae Milthiorrhizaeare are prescribed together for their putative cardioprotective effects in clinical practice. However, the rationale of the combined use remains unclear. The present study was designed to investigate the cardioprotective effects of paeonol and danshensu (representative active ingredient of Cortex Moutan and Radix Salviae Milthiorrhizae, respectively) on isoproterenol-induced myocardial infarction in rats and its underlying mechanisms.

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Cardioprotective effect of paeonol and danshensu combination on isoproterenol-induced myocardial injury in rats.

Chemical profiling of Radix Paeoniae evaluated by ultra-performance liquid chromatography/photo-diode-array/quadrupole time-of-flight mass spectrometry.

Paeoniflorin (PF), the principal component of Paeoniae Radix prescribed in traditional Chinese medicine, has been reported to exhibit many pharmacological effects including protection against ischemic injury. However, the mechanisms underlying the protective effects of PF on cerebral ischemia are still under investigation. The present study showed that PF treatment for 14 days could significantly inhibit transient middle cerebral artery occlusion (MCAO)-induced over-activation of astrocytes and microglia, and prevented up-regulations of pro-inflamamtory mediators (TNFα, IL-1β, iNOS, COX(2) and 5-LOX) in plasma and brain. Further study demonstrated that chronic treatment with PF suppressed the activations of JNK and p38 MAPK, but enhanced ERK activation. And PF could reverse ischemia-induced activation of NF-κB signaling pathway. Moreover, our in vitro study revealed that PF treatment protected against TNFα-induced cell apoptosis and neuronal loss. Taken together, the present study demonstrates that PF produces a delayed protection in the ischemia-injured rats via inhibiting MAPKs/NF-κB mediated peripheral and cerebral inflammatory response. Our study reveals that PF might be a potential neuroprotective agent for stroke.

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Paeoniflorin protects against ischemia-induced brain damages in rats via inhibiting MAPKs/NF-κB-mediated inflammatory responses.

Stable adhesion of leukocytes to endothelium is crucial for transendothelial migration (TEM) of leukocytes evoked during inflammatory responses, immune surveillance, and homing and mobilization of hematopoietic progenitor cells. The basis of stable adhesion involves expression of intercellular adhesion molecule-1 (ICAM-1), an inducible endothelial adhesive protein that serves as a counter-receptor for beta(2)-integrins on leukocytes. Interaction of ICAM-1 with beta(2)-integrins enables leukocytes to adhere firmly to the vascular endothelium and subsequently, to migrate across the endothelial barrier. The emerging paradigm is that ICAM-1, in addition to firmly capturing leukocytes, triggers intracellular signaling events that may contribute to active participation of the endothelium in facilitating the TEM of adherent leukocytes. The nature, duration, and intensity of ICAM-1-dependent signaling events may contribute to the determination of the route (paracellular vs. transcellular) of leukocyte passage; these aspects of ICAM-1 signaling may in turn be influenced by density and distribution of ICAM-1 on the endothelial cell surface, the source of endothelial cells it is present on, and the type of leukocytes with which it is engaged. This review summarizes our current understanding of the "ICAM-1 paradigm" of TEM with an emphasis on the signaling events mediating ICAM-1 expression and activated by ICAM-1 engagement in endothelial cells.

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Hug Tightly and Say Goodbye: Role of Endothelial ICAM-1 in Leukocyte Transmigration

Paeonol suppresses intercellular adhesion molecule-1 expression in tumor necrosis factor-alpha-stimulated human umbilical vein endothelial cells by blocking p38, ERK and nuclear factor-kappaB signaling pathways.

The aim of this study was to investigate the effects of paeoniflorin (PF) and paeonol (PN), the main active compounds of the Paeonia albiflora Pallas, on myocardial ischemia and reperfusion (I/R)-induced injury in Sprague-Dawley rats IN VIVO. Under anesthesia, the rats were subjected to 25 min of ischemia by ligation of the left anterior descending coronary artery (LAD) followed by 6 h (Western blot analysis) or 24 h (hemodynamics and infarct size) of reperfusion. When the infarct size was measured as the percentage of the area at risk, both PF (25.0 % +/- 7.0 %) and PN (24.1 % +/- 5.5 %) significantly (P < 0.05) reduced it compared to I/R control (54.8 % +/- 2.6 %). Administration of 10 mg/kg PF or PN 1 h prior to I/R injury also resulted in a significant improvement of the hemodynamic parameters. Furthermore, both PF and PN decreased the caspase-3 and Bax expressions but up-regulated Bcl-2 in the left ventricles. The results show that both PF and PN reduced myocardial damage in rat through protection from apoptosis, suggesting that Paeonia albiflora Pallas might be useful in treating myocardial infarction.

Paeonol and paeoniflorin, the main active principles of Paeonia albiflora, protect the heart from myocardial ischemia/reperfusion injury in rats.

A new monoterpene glucoside, 1-O-β-D-glucopyranosyl-8-O-benzoylpaeonisuffrone (1), was isolated from the roots of Paeonia lactiflora cultivated in Korea, together with two known compounds 1-O-β-D-glucopyranosylpaeonisuffrone and paeonidanin (2). Their structures were established on the basis of chemical and spectroscopic methods.

A New Monoterpene Glucoside from the Roots of Paeonia lactiflora

A new megastigmane glucoside, simplicifloranoside (1), and three new flavonol glycosides, prunifolianosides A–C (2–4, resp.), were isolated from the aerial parts of Spiraea prunifolia var. simpliciflora. In addition, fifteen known compounds, including five phenolic acids, three lignans, four flavonoids, one eugenol glycoside, and two alkyl-primeverosides, were also identified. Their structures were elucidated on the basis of detailed spectroscopic analyses and acid hydrolysis.

A New Megastigmane Glucoside and Three New Flavonoid Glycosides from Spiraea prunifolia var. simpliciflora

A new 2,7`-cyclolignan named lonicerinol (1) along with eight known lignans, (-)-epipinoresinol (2), (-)-pinoresinol (3), 9α-hydroxypinoresinol (4), 7R,8S-dihydrodehydrodiconiferyl alcohol (5), (±)-neo-olivil (6), (+)-isolariciresinol (7), 3-methoxy-8,4`-oxyneoligna-3`,4,7,9,9`-pentol (8), and (-)-pinoresinol 4-O-glucoside (9), were isolated from the caulis of Lonicera japonica THUNB. (Caprifoliaceae). All of these constituents except for (-)-pinoresinol (3) and 9α-hydroxypinoresinol (4) are reported for the first time from the genus Lonicera. The structures and absolute configurations of these compounds were determined on the basis of spectroscopic analysis, including CD and 1D- and 2D-NMR techniques and chemical methods.

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Min Hye Yean

Papers

Paeonol suppresses intercellular adhesion molecule-1 expression in tumor necrosis factor-alpha-stimulated human umbilical vein endothelial cells by blocking p38, ERK and nuclear factor-kappaB signaling pathways.

Paeonol and paeoniflorin, the main active principles of Paeonia albiflora, protect the heart from myocardial ischemia/reperfusion injury in rats.

A New Monoterpene Glucoside from the Roots of Paeonia lactiflora

A New Megastigmane Glucoside and Three New Flavonoid Glycosides from Spiraea prunifolia var. simpliciflora

Lignans from Lonicerae caulis.