Effect of exposure to interleukin-21 at various time points on human natural killer cell culture.

BACKGROUND AIMS: Interleukin-21 (IL-21) can enhance the effector function of natural killer (NK) cells but also limits their proliferation when continuously combined with IL-2/IL-15. Paradoxically, membrane-bound (mb)-IL-21 has been shown to improve human NK cell proliferation when cultured with IL-2/mb-IL-15. To clarify the role of IL-21, we investigated the effect of the timing of IL-21 addition to NK cell culture. METHODS: IL-2/IL-15-activated NK cells were additionally treated with IL-21 according to the following schedules; (i) control (without IL-21); (ii) first week (day 0 to day 7); (iii) intermittent (the first 3 days of each week for 7 weeks); (iv) after 1 week (day 8 to day 14); and (v) continuous (day 0 to day 49). The expression of NK receptors, granzyme B, perforin, CD107a, interferon-γ, telomere length and NK cell death were measured by flow cytometry. RESULTS: Compared with the control (2004.2-fold; n = 10 healthy donors) and intermittent groups (2063.9-fold), a strong proliferative response of the NK cells on day 42 was identified in the "first week" group (3743.8-fold) (P < 0.05). NK cells treated with IL-21 in the "first week" group showed cytotoxicity similar to that in control cells. On day 28, there was a significant increase in cytotoxicity of "first week" NK cells that received IL-21 treatment for an additional 2 days compared with the "first week" NK cells (P < 0.05). CONCLUSIONS: These data suggest that controlling temporal exposure of IL-21 during NK cell proliferation can be a critical consideration to improve the yields and cytotoxicity of NK cells.

Suppression of inflammatory responses by handelin, a guaianolide dimer from Chrysanthemum boreale, via downregulation of NF-κB signaling and pro-inflammatory cytokine production.

The anti-inflammatory activity of handelin (1), a guaianolide dimer from Chrysanthemum boreale flowers, was evaluated in vivo, and the effects on mediators nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß) and the nuclear factor-κB (NF-κB) and ERK/JNK signaling pathways were investigated in vitro. Compound 1 inhibited lipopolysaccharide (LPS)-induced production of NO and PGE2 in cultured mouse macrophage RAW 264.7 cells. The suppression of NO and PGE2 production by 1 was correlated with the downregulation of mRNA and protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Compound 1 also suppressed the induction of pro-inflammatory cytokines TNF-α and IL-1ß in LPS-stimulated RAW 264.7 cells. To further clarify the transcriptional regulatory pathway in the expression of iNOS and COX-2 by 1, the role of NF-κB was determined in RAW 264.7 cells. Compound 1 inhibits the binding activity of NF-κB into the nuclear proteins. The transcriptional activity of NF-κB stimulated with LPS was also suppressed by 1, which coincided with the inhibition of IκB degradation. Compound 1 also suppressed the activation of mitogen-activated protein kinases, including ERK and JNK signaling. In addition, the LPS-stimulated upregulation of miRNA-155 expression was suppressed by 1. The oral administration of 1 inhibited acute inflammation in carrageenan-induced paw and 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced ear edema models. The serum level of IL-1ß was also inhibited by 1 in a carrageenan-induced paw edema model. These findings suggest that the suppression of NF-κB activation and pro-inflammatory cytokine production may be a plausible mechanism of action for the anti-inflammatory activity of handelin.

Glycosides from the aerial parts of Patrinia villosa.

An investigation of the Korean medicinal plant Patrinia villosa (THUNB.) JUSS. (Valerianaceae) led to the isolation of two new flavonoid glycosides, patrivilosides 1 (1) and 2 (2), a new iridoid glycoside, patrinovalerosidate (3), and two new saponins, patrinovilosides A (4) and B (5), along with six known compounds including three flavonoid glycosides and three iridoid glycosides. The structures of the new compounds were elucidated based on analysis of their one dimensional (1D)- and 2D-NMR spectra along with their mass spectrometric data and the results of acid hydrolysis.

Sesquiterpenes and other constituents from Dendranthema zawadskii var. latilobum.

Six new germacranolides, zawadskinolides A-F (1-6), and a new eudesmane glucoside, chrysantiloboside (7) were isolated from the aerial parts of Dendranthema zawadskii var. latilobum, along with thirteen known constituents. Their structures were elucidated by means of spectroscopic evidence. Bioassay showed that flavonoids such as apigenin (9), (-)-eriodictyol (10) and nepetin (12), as well as the sesquiterpene lactone, zawadskinolide F (6), inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells with IC50 values of 66.15, 132.55, 35.44, and 91.32 µM, respectively.

A new polyoxygenated triterpene and two new aeginetic acid quinovosides from the roots of Rehmannia glutinosa.

A new minor polyoxygenated triterpene named glutinolic acid (1) and two new aeginetic acid quinovosides (2, 3) were isolated from the roots of Rehmannia glutinosa LIBOSCH. (Scrophulariaceae) cultivated in Gunwi-gun, Korea. The structures of these compounds were established as 3α,19α,20ß,24,30-pentahydroxyurs-12-en-28-oic acid (1, glutinolic acid), aeginetic acid 5-O-ß-D-quinovoside (2) and aeginetoyl ajugol 5″-O-ß-D-quinovoside (3) on the basis of chemical and spectroscopic evidence.

Effect of Repetitive Transcranial Magnetic Stimulation in Post-stroke Patients with Severe Upper-Limb Motor Impairment.

Repetitive transcranial magnetic stimulation (rTMS) has been known to improve the motor function through modulation of excitability in the cerebral cortex. However, most studies with rTMS were limited to post-stroke patients with mild to moderate motor impairments. The effect of rTMS on severe upper-limb motor impairment remains unclear. Therefore, this study investigated the effects of rTMS on the upper extremity function in post-stroke patients with severe upper-limb motor impairment. Subjects were divided into 3 groups, low-, high-frequency rTMS and control group were received stimulation 10 times for 2 weeks. The motor scale of Fugl-Meyer Assessment (FMA) and cortical excitability on the unaffected hemisphere were measured before and after performing 10 rTMS sessions. The motor scale of upper extremity FMA (UE-FMA) and shoulder component of the UE-FMA were significantly improved in both low- and high-frequency rTMS groups. However, no significant improvement was observed in the wrist and hand components. No significant differences were noted in low- and high-frequency rTMS groups. The amplitude of motor evoked potential on the unaffected hemisphere showed a significant decrease in the low- and high-frequency stimulation groups. rTMS may be helpful in improving upper extremity motor function even in post-stroke patients with severe upper-limb motor impairment.

Comprehensive pharmacogenomic characterization of gastric cancer.

BACKGROUND: Gastric cancer is among the most lethal human malignancies. Previous studies have identified molecular aberrations that constitute dynamic biological networks and genomic complexities of gastric tumors. However, the clinical translation of molecular-guided targeted therapy is hampered by challenges. Notably, solid tumors often harbor multiple genetic alterations, complicating the development of effective treatments. METHODS: To address such challenges, we established a comprehensive dataset of molecularly annotated patient derivatives coupled with pharmacological profiles for 60 targeted agents to explore dynamic pharmacogenomic interactions in gastric cancers. RESULTS: We identified lineage-specific drug sensitivities based on histopathological and molecular subclassification, including substantial sensitivities toward VEGFR and EGFR inhibition therapies in diffuse- and signet ring-type gastric tumors, respectively. We identified potential therapeutic opportunities for WNT pathway inhibitors in ALK-mutant tumors, a significant association between PIK3CA-E542K mutation and AZD5363 response, and transcriptome expression of RNF11 as a potential predictor of response to gefitinib. CONCLUSIONS: Collectively, our results demonstrate the feasibility of drug screening combined with tumor molecular characterization to facilitate personalized therapeutic regimens for gastric tumors.

Hyperoside prevents oxidative damage induced by hydrogen peroxide in lung fibroblast cells via an antioxidant effect.

We elucidated the cytoprotective effects of hyperoside (quercetin-3-O-galactoside) against hydrogen peroxide (H2O2)-induced cell damage. We found that hyperoside scavenged the intracellular reactive oxygen species (ROS) detected by fluorescence spectrometry, flow cytometry, and confocal microscopy. In addition, we found that hyperoside scavenged the hydroxyl radicals generated by the Fenton reaction (FeSO4)+H2O2) in a cell-free system, which was detected by electron spin resonance (ESR) spectrometry. Hyperoside was found to inhibit H2O2-induced apoptosis in Chinese hamster lung fibroblast (V79-4) cells, as shown by decreased apoptotic nuclear fragmentation, decreased sub-G(1) cell population, and decreased DNA fragmentation. In addition, hyperoside pretreatment inhibited the H2O2-induced activation of caspase-3 measured in terms of levels of cleaved caspase-3. Hyperoside prevented H2O2-induced lipid peroxidation as well as protein carbonyl. In addition, hyperoside prevented the H2O2-induced cellular DNA damage, which was established by comet tail, and phospho histone H2A.X expression. Furthermore, hyperoside increased the catalase and glutathione peroxidase activities. Conversely, the catalase inhibitor abolished the cytoprotective effect of hyperoside from H2O2-induced cell damage. In conclusion, hyperoside was shown to possess cytoprotective properties against oxidative stress by scavenging intracellular ROS and enhancing antioxidant enzyme activity.

Cholinesterase and BACE1 inhibitory diterpenoids from Aralia cordata.

Fourteen diterpenes were isolated from the n-hexane fraction of the roots of Aralia cordata (syn. = A. continentalis). Through spectroscopy, the chemical structures were determined as: ent-pimara-8(14),15-diene-19-oic acid (1); ent-kaur-16-en-19-oic-acid (2); 18-nor-ent-pimara-8(14),15-diene-4beta-ol (3); 18-nor-ent-kaur-16-ene-4beta-ol (4); ent-pimara-8(14),15-diene-19-ol (5); 7alpha-hydroxy-ent-pimara-8(14),15-diene-19-oic acid (6); 7beta-hydroxy-ent-pimara-8(14),15-diene-19-oic acid (7); ent-pimar-15-en-8alpha,19-diol (8); 7-oxo-ent-pimara-8(14),15-diene-19-oic acid (9); 16alpha-hydroxy-17-isovaleroyloxy-ent-kauran-19-oic acid (10); 17-hydroxy-ent-kaur-15-en-19-oic acid (11); 15alpha,16alpha-epoxy-17-hydroxy-ent-kauran-19-oic acid (12); 16alpha,17-dihydroxy-ent-kauran-19-oic acid (13); and 16alpha-methoxy-17-hydroxy-ent-kauran-19-oic acid (14). Compounds 4, 5, 8, 12, and 14 were first isolated from this plant. The anti-Alzheimer and antioxidant effects of ent-pimarane-type diterpenes 1, 3, 5, 8, and 9, as well as ent-kaurane-type diterpenes 2, 4, and 10-13, were evaluated via beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), peroxynitrite (ONOO(-)), and nitric oxide (NO*) assays. Of the compounds tested, 8 exerted the most effective BChE inhibition with an IC(50) value of 7.58 microM, followed by 3, 13, 11, 2, and 10. Compounds 9-11 exhibited good BACE1 inhibitory activities with IC(50) values of 18.58-24.10 microM. However, 11 showed marginal AChE inhibitory effect, and all compounds tested showed no scavenging activities on ONOO(-) and NO* at a concentration of 100 microM.

Selective colony area method for heterogeneous patient-derived tumor cell lines in anti-cancer drug screening system.

We aimed to establish a fluorescence intensity-based colony area sweeping method by selecting the area of highest viability among patient-derived cancer cells (PDC) which has high tumor heterogeneity. Five gastric cancer cell lines and PDCs were screened with 24 small molecule compounds using a 3D micropillar/microwell chip. 100 tumor cells per well were immobilized in alginate, treated with the compounds, and then stained and scanned for viable cells. Dose response curves and IC50 values were obtained based on total or selected area intensity based on fluorescence. Unlike homogeneous cell lines, PDC comprised of debris and low-viability cells, which resulted in an inaccurate estimation of cell viability using total fluorescence intensity as determined by high IC50 values. However, the IC50 of these cells was lower and accurate when calculated based on the selected-colony-area method that eliminated the intensity offset associated with the heterogeneous nature of PDC. The selected-colony-area method was optimized to accurately predict drug response in micropillar environment using heterogeneous nature of PDCs.

Rat growth-hormone release stimulators from fenugreek seeds.

Bioassay-guided fractionation of MeOH extract from fenugreek (Trigonella foenum-graecum L.) seeds resulted in the isolation of two rat growth-hormone release stimulators in vitro, fenugreek saponin I (1) and dioscin (9), along with two new, i.e., 2 and 3, and five known analogues, i.e., 4-8. The structures of the new steroidal saponins, fenugreek saponins I, II, and III (1-3, resp.), were determined as gitogenin 3-O-beta-D-xylopyranosyl-(1-->6)-beta-D-glucopyranoside, sarsasapogenin 3-O-beta-D-xylopyranosyl-(1-->6)-beta-D-glucopyranoside, and gitogenin 3-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranoside, respectively. Fenugreek saponin I (1) and dioscin (9) caused ca. 12.5- and 17.7-fold stimulation of release, respectively, of rat growth hormone from rat pituitary cells, whereas gitogenin (5) showed moderate activity. To our knowledge, this is the first study to demonstrate that steroidal saponins stimulate rat growth-hormone release in rat pituitary cells.

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 (2'-hydroxy-4'-methoxyacetophenone), the main active compound of the traditionally used Chinese herb Paeonia lactiflora Pallas, has anti-inflammatory, antioxidant and cardiovascular protective activities. We studied how the levels of intercellular adhesion molecule-1 (ICAM-1), one of the key molecules in the development of atherosclerosis, might be affected by paeonol in tumor necrosis factor-alpha (TNF-alpha)-activated human umbilical vein endothelial cells (HUVECs). Paeonol concentration-dependently inhibited the production of ICAM-1; it inhibited nuclear factor-kappaB (NF-kappaB) p65 translocation into the nucleus and the phosphorylation of inhibitory factor kappaBalpha (IkappaBalpha). It also blocked the TNF-alpha-induced phosphorylation of p38 and extracellular signal-regulated kinase (ERK), which are involved in regulating ICAM-1 production by TNF-alpha. Paeonol inhibited U937 monocyte adhesion to HUVECs stimulated by TNF-alpha, suggesting that it may inhibit the binding of monocytes to endothelium by regulating the production of critical adhesion molecules by TNF-alpha. The inhibitory effect of paeonol on ICAM-1 production might be mediated by inhibiting p38, ERK and NF-kappaB signaling pathways, which are involved in TNF-alpha-induced ICAM-1 production. Thus, paeonol may be beneficial in the treatment of cardiovascular disorders such as atherosclerosis.

Induction of growth hormone release by glycyrrhizae radix on rat.

Induction of growth hormone (GH) by Glycyrrhizae Radix (GR), one of the most popular herbal medicine, and its major ingredients were studied in rat pituitary cells in vitro and in vivo assay. The MeOH extract and the n-hexane (HX) fraction of GR induced rat GH (rGH) release up to 1.89 times (0.34 +/- 0.04 nM) and 4.59 times (0.83 +/- 0.03 nM), compared to the basal level (p < 0.05). Among many ingredients isolated and purified from GR both glycyrrhetinic acid and glycyrrhizin induced significantly rGH release compared to the control (p < 0.05). After an intravenous injection of rat growth hormone releasing hormone (rGHRH) (10 microg/kg) as positive control, in SD rats, Tmax of plasma rGH level was 10 min, C(max) was 3.84 +/- 0.01 nM (n = 3), and enhanced plasma rGH level returned to the baseline in 90 min. Both AUC(0-90) (area under the curve) of plasma rGH level after HX fraction and that after rGHRH administration were increased significantly from the basal level, respectively (p < 0.01). In conclusions, HX fraction is the most active fraction of MeOH extract of GR in rGH induction.

Norditerpenoid and dianthramide glucoside alkaloids from cultivated Aconitum species from korea.

A new norditerpene alkaloid named 8-O-methylhypaconine (1) was isolated along with twelve known alkaloids from the underground parts of an unknown species of Aconitum plant culti vated in Korea. Among the known alkaloids, two dianthramide glucosides, N-(2'-beta-glucopyra nosyl-5'-hydroxysalicyl)-5-hydroxyanthranilic acid methyl ester (2) and N-(2'-beta-glucopyranosyl-5'-hydroxysalicyl)-5-hydroxy-6-methoxyanthranilic acid methyl ester (3), were isolated from Aconitum plants for the first time. The structures were established on the basis of chemical and spectroscopic methods.

The Impact of Cetuximab Plus AKT- or mTOR- Inhibitor in a Patient-Derived Colon Cancer Cell Model with Wild-Type RAS and PIK3CA Mutation.

Background: Anti-EGFR therapies have been recommended for advanced colorectal cancer (CRC) with wild-type RAS and PIK3CA mutation. However, PIK3CA mutations are a poor prognostic marker and a negative predictor of response to anti-EGFR therapies in RAS wild-type CRC. Therefore, new and advanced treatment strategies are needed for personalized medical treatment of patients with wild-type RAS and PIK3CA mutation. Methods: Patient-derived tumor cells were collected from the ascites of a refractory colon cancer patient with wild-type RAS and PIK3CA mutation. We performed a cell viability assay for cetuximab, AZD5363 (AKT inhibitor), and everolimus (mTOR inhibitor) using PDCs. We also evaluated combinations of cetuximab plus AZD5363 or everolimus in a cell viability assay. Results: Based on cellular proliferation by MTT assay, tumor cells were significantly inhibited by 1uM cetuximab (control vs. cetuximab, mean growth = 100.0% vs 58.07%, p = 0.0103), 1uM AZD5363 (control vs. AZD5363, mean growth = 100.0% vs 58.22%, p = 0.0123), and 1uM everolimus (control vs. everolimus, mean growth = 100.0% vs 52.17%, p = 0.0011). Tumor cell growth was more profoundly reduced by combinations of cetuximab plus AZD5363 (control vs. cetuximab plus AZD5363, mean growth = 100.0% vs 25.00%, p < 0.0001) or everolimus (control vs. cetuximab+everolimus, mean growth = 100.0% vs 28.24%, p < 0.0001). Conclusions: Taken together, these results indicate that RAS wild-type and PIK3CA mutant PDCs originating from CRC are considerably inhibited by treatment with cetuximab plus AZD5363 or everolimus, with downregulation of the AKT and ERK pathways. These combinations may be considered as new options for advanced CRC patients with wild-type RAS and PIK3CA mutation in the context of clinical trials.

Effects of ADAM10 and ADAM17 Inhibitors on Natural Killer Cell Expansion and Antibody-dependent Cellular Cytotoxicity Against Breast Cancer Cells In Vitro.

BACKGROUND/AIM: The inhibition of a disintegrin and metalloproteinase (ADAM) has the potential to become a novel approach for natural killer (NK) cell-based cancer immunotherapy. Thus, the aim of this study was to investigate the influence of ADAM10 and ADAM17 inhibitors on expanded NK cell to enhance antibody-dependent cellular cytotoxicity (ADCC) in breast cancer cell lines. MATERIALS AND METHODS: NK cells were expanded in medium supplemented with an ADAM10 or ADAM17 inhibitor to prevent the shedding of soluble CD16/FcγRIII. The expression level of CD16 and production of interferon-gamma (IFN-γ) was detected by flow cytometry using specific antibodies. ADCC activity of expanded NK cells was estimated in trastuzumab treated breast cancer cell lines such as MCF-7, MDA-MB-231, SKBR3, and BT-474 cells. RESULTS: The ADAM17 inhibitor increased the purity of expanded NK cells to 90% after 14 days at 5 and 10 µM in vitro (p=0.043). However, the expansion rate of NK cells was decreased at 10 µM of the ADAM 17 inhibitor (p=0.043). Inhibition of ADAM10 suppressed the expansion of NK cells, although the NK purity was increased at 1 µM of the inhibitor. The expression of CD16 was significantly increased at 1 and 5 µM of the ADAM17 inhibitor (p=0.046, 0.028, respectively) during the culturing period. Inhibition of ADAM10 reduced the expression of CD16 on NK cells. The cytotoxic activity of the ADAM17 inhibitor treated NK cells against MCF-7 (p=0.039) and BT-474 (p=0.027) cells was significantly elevated. The ADCC activity of NK cells treated with 5 µM of ADAM17 inhibitor was significantly increased against SKBR-3 and BT-474 (p=0.027). Inhibition of ADAM17 increased the production of IFN-γ in expanded NK cells. CONCLUSION: The inhibition of ADAM17 enhanced the purity of expanded NK cells and the ADCC activity of these cells against trastuzumab treated breast cancer cell lines.

Trichotomoside: a new antioxidative phenylpropanoid glycoside from Clerodendron trichotomum.

The structure and antioxidant properties of a new natural glycoside, trichotomoside (1), isolated from Clerodendron trichotomum, were investigated. Trichotomoside was identified as 2-(3-hydroxy-4-methoxyphenyl)ethyl 3-O-(2,3-di-O-acetyl-alpha-L-rhamnopyranosyl)-4-O-[(2E)-3-(3-hydroxy-4-methoxyphenyl)prop-2-enoyl]-beta-D-glucopyranoside. The compound was active towards intracellular reactive oxygen species (ROS) and exhibited DPPH-radical-scavenging effects. The radical-scavenging activity of 1 was found to protect the viability of Chinese hamster lung fibroblasts (V79-4 cells) exposed to H2O2 and gamma-irradiation.

Constituents from the fruiting bodies of Ganoderma applanatum and their aldose reductase inhibitory activity.

Eight compounds were isolated from the fruiting bodies of Ganoderma applanatum, and were identified as 2-methoxyfatty acids (1), 5-dihydroergosterol (2), ergosterol peroxide (3) 3beta,7beta, 20,23xi-tetrahydroxy-11,15-dioxolanosta-8-en-26-oic acid (4), 7beta,20,23xi-trihydroxy-3,11,15-trioxolanosta-8-en-26-oic acid (5), cerevisterol (6), 7beta,23xi-dihydroxy-3,11,15-trioxolanosta-8,20E (22)-dien-26-oic acid (7), and 7beta-hydroxy-3,11,15,23-tetraoxolanosta-8,20E(22)-dien-26-oic acid methyl ester (8) by spectral analysis. All compounds were isolated for the first time from this fruiting bodies, and their effect on rat lens aldose reductase (RLAR) activity was tested. Among these eight compounds, ergosterol peroxide (3) was found to exhibit potent RLAR inhibition, its IC50 value being 15.4 microg/mL.

Chemical constituents of the root of Dystaenia takeshimana and their anti-inflammatory activity.

In our ongoing search for bioactive compounds originating from the endemic species in Korea, we found that the hexane and EtOAc fractions of the MeOH extract from the root of Dystaenia takeshimana (Nakai) Kitagawa (Umbelliferae) showed cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) dual inhibitory activity by assessing their effects on the production of prostaglandin D2 (PGD2) and leukotriene C4 (LTC4) in mouse bone marrow-derived mast cells. By activity-guided fractionation, five coumarins, viz. psoralen (2), xanthotoxin (3), scopoletin (4), umbelliferone (5), and (+)-marmesin (6), together with beta-sitosterol (1), were isolated from the hexane fraction, and two phenethyl alcohol derivatives, viz. 2-methoxy-2-(4'-hydroxyphenyl)ethanol (7) and 2-hydroxy-2-(4'-hydroxyphenyl)ethanol (8), three flavonoids, viz. apigenin (9), luteolin (10), and cynaroside (11), as well as daucosterol (12) were isolated from the EtOAc fraction using silica gel column chromatography. In addition, D-mannitol (13) was isolated from the BuOH fraction by recrystallization. Two of the coumarins, scopoletin (4) and (+)-marmesin (6), the two phenethyl alcohol derivatives (7, 8) and the three flavonoids (9-11) were isolated for the first time from this plant. Among the compounds isolated from this plant, the five coumarins as well as the three flavonoids showed COX-2/5-LOX dual inhibitory activity. These results suggest that the anti-inflammatory activity of D. takeshimana might in part occur via the inhibition of the generation of eicosanoids.

Antioxidant activity of isoacteoside from Clerodendron trichotomum.

The antioxidant properties of isoacteoside, isolated from Clerodendron trichotomum (Verbenaceae), were investigated. This compound scavenged intracellular reactive oxygen species (ROS) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, and prevented lipid peroxidation. This radical scavenging activity of isoacteoside protected cell viability of Chinese hamster lung fibroblast (V79-4) cells exposed to hydrogen peroxide (H2O2). Furthermore, isoacteoside reduced the apoptotic cells formation induced by H2O2, as demonstrated by the decreased number of sub-G1 hypo-diploid cells and apoptotic cell body formation. However, isoacteoside increased the activities of cellular antioxidant enzymes, superoxide dismutase (SOD) and catalase (CAT). Taken together, these findings suggest that isoacteoside, isolated from C. trichotomum, possesses antioxidant properties.