Ki Hwan Bae

Anti-inflammatory effects of schisandrin isolated from the fruit of Schisandra chinensis Baill

Schisandrin is the main active ingredient isolated from the fruit of Schisandra chinensis Baill. Recent studies have demonstrated that schisandrin exhibits anti-oxidative effects in vivo. In the present study, the effect of schisandrin on plasma nitrite concentration in lipopolysaccharide (LPS)-treated mice was evaluated. It also significantly inhibited carrageenan-induced paw edema and acetic acid-induced vascular permeability in mice. Furthermore, schisandrin had a protective effect on lipopolysaccharide (LPS)-induced sepsis. In vitro, our results are the first that show that the anti-inflammatory properties of schisandrin result from the inhibition of nitric oxide (NO) production, prostaglandin E(2) (PGE(2)) release, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression, which in turn results from the inhibition of nuclear factor-kappaB (NF-kappaB), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) activities in a RAW 264.7 macrophage cell line.

Antifungal activity of magnolol and honokiol.

Two neolignan compounds, magnolol (5,5′-diallyl-2,2′-dihydroxybiphenyl,1) and honokiol (5,5′-diallyl-2,4′-dihydroxybiphenyl,2), were isolated from the stem bark ofMagnolia obovata and evaluated for antifungal activity against various human pathogenic fungi. Compound1 and2 showed significant inhibitory activities againstTrichophyton mentagrophytes, Microsporium gypseum, Epidermophyton floccosum, Aspergillus niger, Cryptococcus neoformans, andCandida albicans with minimum inhibitory concentrations (MIC) in a range of 25–100 μg/ml. Therefore, compound1 and2 could be used as lead compounds for the development of novel antifungal agents.

2-Methoxycinnamaldehyde from Cinnamomum cassia reduces rat myocardial ischemia and reperfusion injury in vivo due to HO-1 induction

ETHNOPHARMACOLOGICAL RELEVANCE Cinnamomum cassia Blume has been used as a traditional Chinese herbal medicine for alleviation of fever, inflammation, chronic bronchitis, and to improve blood circulation. AIM OF THE STUDY We addressed whether 2-methoxycinnamaldehyde (2-MCA), one of active ingredients of Cinnamomum cassia, reduces vascular cell adhesion molecule-1 (VCAM-1) expression in tumor necrosis factor-alpha (TNF-α)-activated endothelial cells and protects ischemia/reperfusion (I/R)-injury due to heme oxygenase (HO)-1 induction. MATERIALS AND METHODS Adult male rats were subjected to 30 min of ischemia by occlusion of the left anterior descending coronary artery followed by 24h of reperfusion. Rats were randomized to receive vehicle or 2-MCA (i.v.) 10 min before reperfusion. RESULTS Administration of 2-MCA significantly improved I/R-induced myocardial dysfunction by increasing the values of the first derivative (±dp/dt) of left ventricular pressure and decreased infarct size. In addition, 2-MCA reduced the expression of high mobility group box 1 (HMGB1), an activator of the inflammatory cascade when released into the extracellular space, and VCAM-1 in I/R myocardium along with increase of HO-1 induction. The reduced injury was accompanied by significantly reduction of neutrophils infiltration and increased SOD activity in ischemic tissues and reduced serum level of cardiac troponin I (cTnI). Furthermore, 2-MCA significantly increased HO-1 induction by translocation of Nrf-2 from cytosol to nucleus in endothelial cells. Inhibition of VCAM-1 expression by 2-MCA was reversed both by SnPPIX, a HO-1 inhibitor and siHO-1 RNA trasfection in TNF-α-activated cells. In addition, 2-MCA significantly inhibited NF-κB luciferase activity in TNF-α-activated endothelial cells. As expected, 2-MCA significantly inhibited monocyte (U937) adhesion to endothelial cells. CONCLUSION We concluded that 2-MCA protects of myocardial I/R-injury due to antioxidant and anti-inflammatory action possibly by HO-1 induction which can be explained why Cinnamomum cassia has been used in inflammatory disorders.

Cytotoxic coumarins from the root of Angelica dahurica.

Ten coumarins were isolated from the root ofAngelica dahurica by repeated silica gel column chromatography. Their chemical structures were elucidated on the basic of physicochemical and spectroscopic data. Among them, oxypeucedanin hydrate acetonide (7) was isolated for the first time from this plant. Cytotoxicity of coumarins isolated were determinedin vitro against L1210, HL-60, K562, and B16F10 tumor cell lines by MTT method. Pangelin (5) and oxypeucedanin hydrate acetonide (7) showed a potent cytotoxic activity with the IC50 values of 8.6 to 14.6 μg/mL against four kinds of tumor cell lines. Other compounds showed the moderate cytotoxic activity or no activity against the tumor cell lines.

Two new lignans fromLindera obtusiloba blume

Two new furanolignans (3, 5), together with three known lignans (1, 2, 4), were isolated from the stem ofLindera obtusiloba (Lauraceae). The structures of the compounds were determined as actifolin (1), pluviatilol (2), 5,6-dihydroxymatairesinol (3), (+)-syringaresinol (4), and (+)-9′-O-trans-feruloyl-5,5′-dimethoxylariciresinol (5) on the basis of physicochemical and spectroscopic evidences. Compounds1, 2, 3, and5 showed cytotoxicity against a small panel of human tumor cell lines with ED50 values of 3.40∼19.27 μg/ml.

Anti-human immunodeficiency virus-type 1 activity of constituents fromJuglans mandshurica

Three naphthalene glycosides (1-3), four flavonoids (4-7), and two galloyl glycosides (8-9) were isolated from the stem-bark ofJuglans mandshurica (Juglandaceae). Their structures were determined by chemical and spectral means, including to 2D-NMR (COSY, HMQC, and HMBC) experiments. Amongst the isolated compounds, taxifolin (4) showed the most potent HIV-induced cytopethic activity against MT-4 cells with complete inhibitory concentration (IC100) value of 25 μg/ml and maximum cytotoxic concentration (CC100) value of above 100 μg/ml. However, naphthalene glycosides (1-3), flavonoids (5-7)), and galloyl tannins (8-9) were inactive against anti-HIV-1 activity.

Screening of Korean plants against human immunodeficiency virus type 1 protease.

With the aim of finding novel anti‐human immunodeficiency virus agents from natural products, 93 MeOH extracts of Korean plants were screened for their inhibitory activities against HIV‐1 protease. The most potent inhibition was shown by the root of Rodiola rosea with 70.4% inhibition at a concentration of 100 µg/mL. Copyright

Anti-Apoptotic Effect of Magnolol in Myocardial Ischemia and Reperfusion Injury Requires Extracellular Signal-Regulated Kinase1/2 Pathways in Rat In Vivo

Magnolol, an active component extracted from Magnolia officinalis, has been reported to have protective effect on ischemia and reperfusion (I/R)-induced injury in experimental animals. The aim of the present investigation was to further evaluate the mechanism(s) by which magnolol reduces I/R-induced myocardial injury in rats in vivo. Under anesthesia, left anterior descending (LAD) coronary artery was occluded for 30 min followed by reperfusion for 24 h (for infarct size and cardiac function analysis). In some experiments, reperfusion was limited to 1 h or 6 h for analysis of biochemical and molecular events. Magnolol and DMSO solution (vehicle) were injected intra-peritoneally 1 h prior to I/R insult. The infarct size was measured by TTC technique and heart function was monitored by Millar Catheter. Apoptosis related events such as p-ERK, p-Bad, Bcl-xl and cytochrome c expression were evaluated by Western blot analysis and myocardial caspase-3 activity was also measured. Magnolol (10 mg/kg) reduced infarct size by 50% (P < 0.01 versus vehicle), and also improved I/R-induced myocardial dysfunction. Left ventricular systolic pressure and positive and negative maximal values of the first derivative of left ventricular pressure (dP/dt) were significantly improved in magnolol-treated rats. Magnolol increased the expression of phosphor ERK and Bad which resulted in inhibition of myocardial apoptosis as evidenced by TUNEL analysis and DNA laddering experiments. Application of PD 98059, a selective MEK1/2 inhibitor, strongly antagonized the effect of magnolol. Taken together, we concluded that magnolol inhibits apoptosis through enhancing the activation of ERK1/2 and modulation of the Bcl-xl proteins which brings about reduction of infarct size and improvement of cardiac function in I/R-induced injury.

Constituents of the roots ofPueraria lobata inhibit formation of advanced glycation end products (AGEs)

Two isoflavoneC-glucosides, puerarin (1) and PG-3 (2), a but-2-enolide, (±)-puerol B (3), two isoflavoneO-glucosides, daidzin (4) and genistin (5), and three pterocarpans, (−)-medicarpin (6), (−)-glycinol (7) and (−)-tuberosin (8), were isolated from a MeOH extract of the roots ofPueraria lobata, using anin vitro bioassay based on the inhibition of the formation of advanced glycation end products (AGEs) to monitor chromatographic fractionation. The structures of1–8 were determined by spectroscopic data interpretation, particularly by 1D- and 2D-NMR studies, and by comparison of these data with values in the literature. All of the isolates (1–8) were evaluated for their inhibitory activity on AGEs formationin vitro. Of these, puerarin (1), PG-3 (2), and (±)-puerol B (3) exhibited more potent inhibitory activity than the positive control aminoguanidine.

Manassantin a and b isolated fromSaururus chinensis inhibit TNF-α-induced Cell adhesion molecule expression of human umbilical vein endothelial cells

Leukocyte adhesion to the vascular endothelium is a critical initiating step in inflammation and atherosclerosis. We have herein studied the effect of manassantin A (1) and B (2), dineolignans, on interaction of THP-1 monocytic cells and human umbilical vein endothelial cells (HUVEC) and expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin in HUVEC. When HUVEC were pretreated with1 and2 followed by stimulation with TNF-α, adhesion of THP-1 cells to HUVEC decreased in dose-dependent manner with IC50 values of 5 ng/mL and 7 ng/mL, respectively, without cytotoxicity. Also,1 and2 inhibited TNF-α-induced up-regulation of ICAM-1, VCAM-1 and E-selectin. The present findings suggest that1 and2 prevent monocyte adhesion to HUVEC through the inhibition of ICAM-1, VCAM-1 and E-selectin expression stimulated by TNF-α, and may imply their usefulness for the prevention of atherosclerosis relevant to endothelial activation.