Tran Minh Ngoc

Anti-inflammatory activity of flavonoids from Populus davidiana.

Anin vitro bioassay-guide revealed that the methanol (MeOH) extract of the stem bark ofPopulus davidiana showed considerable inhibitory activity against cyclooxygenase (COX-1, COX-2). Continuous phytochemical study of the MeOH extract of this plant led to the isolation of ten flavonoids; sakuranetin (1), rhamnocitrin (2), 7-O-methylaromadendrin (3), naringenin (4), eriodictyol (5), aromadendrin (6), kaempferol (7), neosakuranin (8), sakuranin (9) and sakurenetin-5,4′-di-β-D-glucopyranoside (10). Their structures were identified on the basis of their physicochemical and spectroscopic analyses. The isolated compounds,1–10, were tested for their inhibitory activities against COX-1 and COX-2. Compound7 was found to have potent inhibitory effect on COX-1 and a moderate effect on COX-2, meanwhile, compounds1–6 showed moderate inhibition against COX-1 only. Moreover, compounds5–8 exhibited suppressive effects on xanthine oxidase (XO). These results may explain, in part, the traditional uses ofP. davidiana in ethnomedicine.

Antioxidant activities of coumarins from Korean medicinal plants and their structure-activity relationships.

The aim of this work was to study the structure–activity relationships of the antioxidant activity of natural coumarins isolated from four Korean medicinal plants (1–17) and four purchased coumarins (18–21). The free radical scavenging and lipid peroxidation assays revealed that five phenolic coumarins, scopoletin (1), aesculetin (2), fraxetin (3), umbelliferone (18) and daphnetin (19), possessed considerable antioxidant activities. The coumarins having a catechol group, 2, 3 and 19, showed significant free radical scavenging activity and inhibitory effects on lipid peroxidation, indicating that the catechol group significantly contributed to the antioxidant activities of coumarins. In contrast, the sugar moiety markedly reduced the activities of coumarin glycosides. The results also demonstrate that the α‐pyrone ring of coumarins significantly enhanced the capacity of inhibiting oxidative reactions of coumarins. Copyright

Antioxidant and lipoxygenase inhibitory activity of oligostilbenes from the leaf and stem of Vitis amurensis.

ETHNOPHARMACOLOGICAL RELEVANCE The root and stem of Vitis amurensis (Vitaceae) have popularly used as traditional medicine for treatment of cancer and various pains in Korea and Japan. Recent studies, its root and stem possess anti-inflammatory, anti-tumor activities, and protective effects against beta-amyloid-induced oxidative stress. AIM OF THE STUDY This study deals with the isolation, structural identification of the potent bioactive compounds from the leaf and stem, and their antioxidant capacity, as well as anti-inflammatory effect via lipoxygenase inhibitory assay. MATERIALS AND METHODS All isolated compounds yielded after using column chromatography were identified base on the physico-chemical properties and 1D, 2D NMR spectra. The scavenge ability against DPPH and ABTS(+) radicals, and to inhibit lipid peroxidation, as well as lipoxygenase type I inhibitory activity of all isolates were performed using in vitro assays. RESULTS Eleven resveratrol derivatives (1-11), including a new oligostilbene cis-amurensin B (9), whose structures were determined on the basis of extensively spectral analyses, were isolated from the leaf and stem of Vitis amurensis. The isolates (1-11) were examined for their antioxidant activities by evaluating scavenge ability against DPPH and ABTS(+) radicals, and to inhibit lipid peroxidation. Stilbenes 1 and 4, and oligostilbenes 5-10 displayed moderate anti-lipid peroxidation activities, but all the isolates exhibited strong ABTS(+) radical scavenging activity in the dose-dependent manner. In addition, the isolates showed stronger inhibitory capacity against soybean lipoxygenase type I than that of baicalein, a positive control. Of the isolates, r-2-viniferin (8) exhibited the strongest scavenging activity against ABTS(+) radical with TEAC value of 5.57, and the most potential inhibitory effect on soybean lipoxygenase with the IC(50) value of 6.39 microM. CONCLUSION This is the first report on the potential antioxidant and LOX-1 inhibitory effects of oligostilbenes isolated from the leaf and stem of Vitis amurensis. In addition, chemical compositions isolated from the leaf and stem are almost similar to those isolated from the root of Vitis amurensis. Therefore, the results may explain, in part, the uses of the leaf and stem, as well as the root of Vitis amurensis in the Korean traditional medicine.

Stilbenes and oligostilbenes from leaf and stem of Vitis amurensis and their cytotoxic activity

Chromatographic separation of the EtOAc fraction from the leaf and stem of Vitis amurensis led to the isolation of six oligostilbenoids (i.e., r-2-viniferin (1), trans-amurensin B (2), trans-ɛ-viniferin (3), gnetin H (4), amurensin G (5), (+)-ampelopsin A (8)) and four stilbenoids (i.e., trans-resveratrol (6), (+)-ampelopsin F (7), piceatannol (9), and trans-piceid (10)). The structures have been identified on the basis of spectroscopic evidence and physicochemical properties. The isolates were investigated for cytotoxic activity against three cancer cell lines in vitro using the MTT assay method. Amurensin G (5) and trans-resveratrol (6) showed significant cytotoxic activity against L1210, K562 and HTC116 cancer cell lines with IC50 values ranging from 15.7 ± 2.1 to 30.9 ± 1.8 μM. (+)-Ampelopsin A (8) and trans-piceid (10) exhibited considerable cytotoxic activity against L1210 (IC50 values of 30.6 ± 4.1 and 28.7 ± 2.81 μM, respectively) and K562 (IC50 values of 38.6 ± 0.82 and 24.6 ± 0.76 μM, respectively). Gnetin H (4) showed only weak cytotoxic activity against L1210 with an IC50 value of 40.1 ± 4.23 μM. On the other hand, r-2-viniverin (1), trans-amurensin B (2), trans-ɛ-viniferin (3), (+)-ampelopsin F (7), and piceatannol (9) exhibited no activity on three cancer cell lines.

Cholinesterase inhibitory and anti-amnesic activity of alkaloids from Corydalis turtschaninovii.

In the course of screening plants used in Korean folk medicine as memory enhancers, a 70% ethanol extract of tuber from Corydalis turtschaninovii Besser (Papaveraceae) showed significant acetylcholinesterase (AChE) inhibitory activity. Repeated column chromatography led to the isolation of a new aporphine alkaloid, oxoglaucidaline (9), and a new protoberberine, pseudodehydrocorydaline (13) together with 14 known compounds (1-8, 10-12, and 14-16). The chemical structures of isolated compounds were elucidated base on extensive 1D and 2D NMR spectroscopic data. Compounds 1-16 were investigated in vitro for their anti-cholinesterase activity using the mice cortex AChE enzyme. In further study, the anti-amnesic activities of pseudoberberine (16) in mice on the learning and memory impairments induced by scopolamine (1.0 mg/kg, i.p.) were examined. This alkaloid (5.0 mg/kg, p.o.) administration significantly reversed cognitive impairments in mice by passive avoidance test (P<0.05). It also reduced escape latencies in training trials and prolonged swimming times in the target quadrant during the probe trial in the water maze task (P<0.05). These results indicated that Corydalis turtschaninovii due to its alkaloids have anti-cholinesterase activity and pseudoberberine and other alkaloids have anti-amnesic activities that may be useful for cognitive impairment treatment.

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.

Lipoxygenase inhibitory constituents from rhubarb.

Phytochemical study on the ethanol extract of rhubarb led to the isolation of fifteen compounds, including five anthraquinones: chrysophanol (1), physcion (2), emodin (7), chrysophanol-8-O-β-d-glucopyranoside (9) and emodin-8-O-β-d-glucopyranoside (15), and ten stilbenes: desoxyrhaponticin (3), rhaponticin (4), resveratrol (5), desoxyrhapotigenin (6), rhapontigenin (8), piceatannol-3′-O-β-d-glucopyranoside (10), piceid (11), ε-viniferin (12), ampelopsin B (13) and isorhaponticin (14). Their structures were identified by comparing the physicochemical data with those of published papers. Among the isolated compounds, stilbene derivatives (3–6, 8 and 10–14) showed remarkable inhibitory effect on lipoxygenase with IC50 values ranging from 6.7 to 74.1 μM. The inhibition kinetics analyzed by Lineweaver-Burk plots found that they were competitive inhibitors with the linoleic acid at the active site of lipoxygenase. In addition, stilbenes exhibited significantly free radical scavenging activity against ABTS·+ with trolox equivalent activity capacity (TEAC) values ranging from 1.16 to 4.64. Whereas, anthraquinone derivatives (1–2, 7, 9 and 15) neither inhibited lipoxygenase nor scavenged free radical ABTS·+. These results indicated that stilbene derivatives were considerate to be mainly lipoxygenase inhibitor and free radical scavenger constituents of rhubarb.

Palbinone and triterpenes from Moutan Cortex (Paeonia suffruticosa, Paeoniaceae) stimulate glucose uptake and glycogen synthesis via activation of AMPK in insulin-resistant human HepG2 Cells

Moutan Cortex is a well-known herb in traditional Korean, Chinese, and Japanese anti-diabetic formulae. In the current study, we investigated the metabolic effects of isolated triterpenes (1-7) in HepG2 cells under high glucose conditions. These compounds remakably stimulated AMP-activated protein kinase (AMPK), GSK-3beta, and ACC phosphorylation. The compounds also increased glucose uptake and enhanced glycogen synthesis. Among these, compound 1 displayed the greatest potential anti-diabetic activity though the AMPK activation pathway. Compound 1 significantly increased the levels of phospho-AMPK, phospho-ACC, and phospho-GSK-3beta and stimulated glucose uptake and glycogen synthesis in a dose-dependent manner. In conclusion, our results suggest that these compounds, especially compound 1, may have beneficial roles in glucose metabolism via the AMPK pathway.

Acetylcholinesterase inhibitory effect of lignans isolated from Schizandra chinensis.

The hexane extract of the fruit ofSchizandra chinensis (Schisandraceae) was found to show significant inhibition of the activity of acetylcholinesterase enzyme (AChE). In further studies, fourteen lignans were isolated, and evaluated for their inhibitory effect on AChE. The compounds having both aromatic methylenedioxy and hydroxyl groups on their cyclooctadiene ring, such as gomisin C (6), gomisin G. (7), gomisin D (8), schisandrol B (11) and gomisin A (13), entirely inhibited AChE in dose dependent manners, with IC50 values of 6.71 ± 0.53, 6.55 ± 0.31, 7.84 ± 0.62, 12.57 ± 1.07 and 13.28 ± 1.68 ¼M, respectively. These results indicate that the lignans could potentially be a potent class of AChE inhibitors.

Inhibitors of aldose reductase and formation of advanced glycation end-products in moutan cortex (Paeonia suffruticosa).

The methanol extract of Moutan cortex (Paeonia suffruticosa) afforded two new compounds, 8-O-benzoylpaeonidanin (1) and 5-hydroxy-3S-hydroxymethyl-6-methyl-2,3-dihydrobenzofuran (2), in addition to 4-O-butylpaeoniflorin (3) as an artifact of the separation, seven monoterpene glycosides (4-10), two monoterpenes (11, 12), four acetophenones (13-16), and two triterpenes (17, 18). The structures of the compounds were determined by spectroscopic methods, and the compounds were evaluated for inhibitory effects against rat lens aldose reductase (RLAR) and advanced glycation end-product (AGEs) formation. Compounds 17 and 18 showed the most potent inhibitory activity against RLAR, with IC(50) values of 11.4 and 28.8 microM, respectively. Compounds 3 and 6 also inhibited RLAR with IC(50) values of 36.2 and 44.6 microM, respectively. The positive control, 3,3-tetramethyleneglutamic acid, had an IC(50) value of 31.8 microM. Compounds 3 and 6 inhibited AGE formation with IC(50) values of 10.8 and 11.3 microM, respectively. Compound 2 had an IC(50) value of 177.0 microM, whereas the positive control, aminoguanidine, had an IC(50) value of 1026.8 microM.