Fast repair of DNA radicals.

This tutorial review highlights the mechanism of a novel non-enzymatic fast repair of DNA damage, which refers exclusively to repair DNA radicals including DNA-OH* adducts, DNA radical cations and anions by various endogenous, natural and synthetic compounds. The repair rate constants are as high as 10(9) M(-1) s(-1). In cells, when the enzymatic repair system was inhibited or before the enzymatic repair mechanism was initiated, DNA oxidative damage was significantly reduced by natural polyphenols. This decrease of DNA damage is assigned to the fast repair. Fast repair takes place through an electron transfer process, and docking of polyphenol into the DNA minor groove could be the essential step.

Sesquiterpenoids from Lactuca tatarica.

A new guaianolide and a new eudesmanolide were isolated from Lactuca tatarica, as well as eight known sesquiterpenoids. The new compounds were elucidated on the basis of spectroscopic methods including IR, HRESIMS, 1D and 2D NMR, and the known compounds were established by comparing their physical data with those of the corresponding compounds in the literature.

Non-enzymatic fast repair of DNA oxidative damage might also exist in cells.

Many studies have shown that in a chemical system natural polyphenols can rapidly repair DNA oxidative damage. In this paper we report that in a cellular system the non-enzymatic fast repair activities of two natural polyphenols might also exist. The viability of a Chinese hamster ovary cell line (AA8) highly expressing the XRCC1 gene (a DNA repairing protein) treated with H2O2 is significantly higher than that of a normal Chinese hamster ovary cell line (CHO). Following inhibition of the enzymatic repair system by different inhibitors--methoxyamine (MX), 3-aminobenzamide (3AB) or nicotinamide (NIC)--DNA oxidative damage by H2O2 increased 2-5-fold in both cell lines. However, when natural polyphenols--rosmarinic acid (RA) or verbascoside (VER)--were added, DNA oxidative damage was significantly reduced. This decrease of DNA oxidative damage by RA or VER is not due to their scavenging activity for reactive oxygen species (ROS) because cells suffered from heavy ROS throughout the whole experimental process. Therefore, the decrease of DNA damage might be due to their non-enzymatic fast repair mechanisms. Further investigation showed that H2O2 induced a drop in the mitochondrial membrane potential (MMP), and that RA and VER were able to attenuate the drop. Previous studies have shown that H2O2 initiates a chain of events in cells, involving mtDNA damage, a drop in MMP and loss of repair activity. These results, taken together with our present results, suggest that the non-enzymatic fast repair mechanism exists not only in chemical systems but also might exist in cells.

Four new terpenoids from the roots of Ligularia narynensis.

Four new oplopane and guaiane type sesquiterpenoids (1-3), and a monoterpenoid (4) together with three known monoterpenoids (5-7), have been isolated from the roots of Ligularia narynensis. The structures of 1-4 were elucidated as 3beta,4-diacetoxy-8alpha-(2-methylbutyryloxy)-9alpha-(4-methylsenecioyloxy)-11alpha,12-epoxyoplop-10 (14)-ene (1), 3beta,4-diacetoxy-9alpha-(4-acetoxy-4-methylsenecioyloxy)-2beta,8alpha-di (2-methylbutyryloxy)-11alpha,12-epoxyoplop-10 (14)-ene (2), 2alpha-hydroxy-1betaH,7alphaH,10alphaH-guai-4,11 (12)-dien-3-one (3) and 1alpha,2beta,3alpha,6alpha-tetrahydroxy-p-menthane (4) by spectroscopic methods. 1 and 2 were evaluated for their in vitro cytotoxic activity against cultured SMMC-7721 (human hepatoma), L02 (human hepatocyte), and HL-60 (human promyelocytic leukaemia) cell lines.

Natural antioxidant pedicularioside G inhibits angiogenesis and tumourigenesis in vitro and in vivo.

Pedicularioside G is a new compound of phenylpropanoid glycosides, isolated from Pedicularis striata in our laboratory. Pedicularioside G inhibited two major angiogenic responses, human umbilical vein endothelial cell proliferation and migration, as well as neovascularization in a chicken embryo chorioallantoic membrane model. In addition, pedicularioside G inhibited human hepatoma cells proliferation and migration in vitro along with transplanting tumour formation and growth in a chicken embryo chorioallantoic membrane model. So pedicularioside G has anti-angiogenic, antitumour growth, antimetastatic and antitumoural effects. Pedicularioside G also remarkably reduced reactive oxygen species level in both vein endothelial cells and hepatoma cells in a concentration-dependent manner. These results suggest that the anti-angiogenic and antitumoural effects of pedicularioside G might partially attribute to its antioxidative activity.

Fast repair of oxidative DNA damage by phenylpropanoid glycosides and their analogues.

The repair activities and reaction mechanisms of phenylpropanoid glycosides (PPGs) and their analogues, isolated from Chinese folk medicinal herbs, towards oxidative DNA damage were studied with pulse radiolytic technique. On pulse irradiation of nitrogen-saturated 4 mM poly C aqueous solution containing one of the tested polyphenols, 40 mM K2S2O8 and 200 mM t-BuOH, the transient absorption spectrum of the oxidative radical of poly C decays with the concurrent formation of the phenoxyl radical of the tested polyphenols within several tens of microseconds after the electron pulse irradiation. The result indicated that there was a repair reaction between oxidative radical of poly C and the tested polyphenols. The repair activities also were observed for the tested polyphenols towards the radical cations of single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA). The rate constants were determined to be 3.7-6.4 x 10(9), 4.8-5.5 x 10(8) and 8.8-10.3 x 10(8) M(-1).sec(-1) for the repair reactions of oxidative radical of poly C and radical cations of ssDNA and dsDNA, respectively. The result of this study together with those of our previous studies demonstrates that PPGs and their analogues can fast repair not only the damage of deoxynucleoside and deoxynucleotide but also the damage of integral DNA, with the latter being closer to a cellular condition.

Effects of phytoestrogens and 17beta-estradiol on vasoconstriction elicited by reactive oxygen species.

To study the effects of different reactive oxygen species (ROS) on the resting tension of porcine coronary artery rings and to identify the effects of genistein (GEN), resveratrol (RES) and 17beta-estradiol (EST) on ROS-elicited vasoconstriction, porcine coronary rings were prepared and mounted in an organ bath and, after an equilibration period, the changes induced by the drugs were observed. Rings with intact endothelium showed an obvious but slow contraction after treatment with xanthine (100 microM)/xanthine oxidase (20 mU x mL(-1)) (X/XO) whereas endothelium-denuded rings showed no effects. H2O2 (200 microM) induced a fast and transient contraction in endothelium-denuded rings and failed to do so in intact-endothelium rings. Like superoxide dismutase (SOD, 200 U x mL(-1)), GEN (1 microM) and RES (1 microM) significantly inhibited contractile response evoked by X/XO, however in contrast to GEN and RES, EST (1 microM) had no obvious effect. GEN (30 microM) and RES (30 microM), like catalase (CAT, 800 U x mL(-1)), markedly attenuated the contraction elicited by H2O2. The results demonstrate that GEN and RES have distinct inhibitory effects on vasoconstriction induced by O2*- generated by X/XO and H2O2, and their actions are clearly greater than to that of EST.

New weakly cytotoxic eremophilane sesquiterpenes from the roots of Ligularia virgaurea.

Six new eremophilane sesquiterpenes, including a novel nortrieremophilane carbon skeleton, were isolated from the roots of Ligularia virgaurea. Their structures were elucidated as 3 alpha,4 alpha-epoxy-6 alpha-(2'-methylacryloyl)oxy-8 alpha-methoxyeremophil-7(11)-en-8 beta,12-olide (1), 3 alpha,4 alpha-epoxy-6 alpha-(2'-methylacryloyl)oxy-8 alpha-ethoxyeremophil-7(11)-en-8 beta,12-olide (2), 1 beta,10 beta-epoxy-6 beta-(2'-methylacryloyl)oxy-8 beta-methoxyeremophil-7(11)-en-8 alpha,12-olide (3), 1 beta,10 beta-epoxy-6 beta-angeloyloxy-8 beta-methoxyeremophil-7(11)-en-8 alpha,12-olide (4), 6 beta-methoxyeremophil-7(11)-en-8 beta,12-olide (5), and 5 beta-angeloyloxy-3a,4,5,6,7,7a-hexahydro-3a beta-methyl-1 H-indene-2,4 beta-dioic acid methyl ester (6) by spectral methods, including IR, HR-ESI-MS, 1D and 2D NMR techniques. All of compounds were evaluated for their in vitro cytotoxic activities against human hepatoma (SMMC-7721), human promyelocytic leukemia (HL-60), and human hepatocyte (L-02) cells.

A new iridoid and other chemical constituents from Pedicularis kansuensis forma albiflora Li.

A new iridoid (1) and thirteen known compounds 2-14 were isolated from Pedicularis kansuensis forma albiflora Li., and their structures were elucidated by spectroscopic methods including 2D-NMR techniques.

Cytotoxic germacranolides and acyclic diterpenoides from the seeds of Carpesium triste.

Four new highly oxygenated germacranolides (1, 4, 6, and 7) and four new acyclic diterpenes (8-11), along with three known germacranolides (2, 3, and 5), were isolated from the seeds of Carpesium triste. The structures of the new compounds were elucidated by spectroscopic methods including IR, HRESIMS, and 1D and 2D NMR experiments, and the absolute configurations of compounds 1 and 8-10 were established by CD and Mosher's methods, respectively. Compounds 1, 2, and 4-10 were evaluated for their in vitro cytotoxic activity against cultured SMMC-7721 (human hepatoma), HL-60 (human promyelocytic leukemia), and L02 (human hepatocyte) cell lines. Compounds 1, 2, and 4-7 exhibited significant cytotoxicity against HL-60 cells, and compound 10 exhibited cytotoxicity against SMMC-7721 cells.

A new tricyclic-alpha,beta-unsaturate ketone and a new delta-hexano lactone glycoside from Adenocaulon himalaicum.

Two new compounds, a tricyclic-alpha,beta-unsaturate ketone (adenocaulone) (1) and a delta-hexanolactone glycoside (adenocaulolide) (2), along with 10 known compounds 3-12 were isolated from Adenocaulon himalaicum Edgew. Their structures were elucidated by spectroscopic methods (IR, MS, 1H, 13C and 2D NMR). In addition, the antibacterial activity of compounds 2, 3 and 4 were tested.

Labdane diterpenoid glycosides from Aster veitchianus.

Four new labdane-type rhamnopyranosides derived from 13-epimanool, compounds 1-4, with differently acetylated sugar moieties, were isolated from A. veitchianus. Their structures and absolute configurations were elucidated by chemical transformation, spectroscopic and mass-spectrometric analyses (IR, 1D- and 2D-NMR, HR-ESI-MS), as well as by single-crystal X-ray diffraction (compound 1). The isolates 2-4 were investigated for their cytotoxic properties against cultured human hepatoma (SMMC-7721), ovarian neoplasm (HO-8910), and leukemia (HL-60) cells, and for their antibacterial activities against Escherichia coli, Bacillus subtilis, and Staphylococcus aureus.

The effect of 17 sesquiterpenes on cell viability and telomerase activity in the human ovarian cancer cell line HO-8910.

Using the MTT assay and the telomeric repeat amplification protocol (TRAP)-based PCR-ELISA assay, the cytotoxicity and telomerase inhibiting ability of 17 sesquiterpenes (extracted from Chinese herbs) were tested in the human ovarian cancer cell line HO-8910. The results indicated that seven sesquiterpenes inhibited cell proliferation without having an effect on telomerase activity; two sesquiterpenes inhibited neither cell proliferation nor telomerase activity; and the other eight sesquiterpenes inhibited both cell proliferation and telomerase activity to a certain extent. Without exception, none of these 17 sesquiterpenes could only inhibit telomerase activity without inhibiting cell proliferation. This indicated that the telomerase inhibiting activity is not a universal mechanism for all anticancer drugs but is only one of several possible mechanisms. The structure-activity relationships of 5 groups of sesquiterpenes are also discussed. This study may help to develop anticancer drugs.

Three new triterpenoids from Potentilla multicaulis.

Three new triterpenoids, 19-hydroxy-2,3-secours-12-ene-2,3,28-trioic acid 3- methyl ester (1), 19-hydroxy-1-oxo-2-nor-2,3-secours-12-ene-3,28-dioic acid (2), and (3beta,18alpha,19alpha)-3,28-dihydroxy-20,28-epoxyursan-24-oic acid (3), were isolated from the roots of Potentilla multicaulis. Their structures were elucidated on the basis of spectroscopic methods (IR, HR-ESI-MS, and 1D- and 2D-NMR). Compound 2b exhibited moderate cytotoxic activity against human promyelocytic leukemia (HL-60) cells.

Five new iridoids from Patrinia rupestris.

Five new iridoids, namely rupesin A-E (1-5, resp.), together with six known iridoids, 6-11, were isolated from the roots of Patrinia rupestris. Their structures were elucidated by spectroscopic methods including IR, UV, MS, and 1D- and 2D-NMR experiments, and comparison with data of known analogues. Compounds 4 and 11, compounds 1, 2, 5, 6, 8, 9, and 10, and compounds 3, 4, and 8 showed significant antibacterial activities against Bacillus subtilis, Escherichia coli, and Staphylococcus aureus, respectively.

New bisabolane sesquiterpenes and coumarin from Leontopodium longifolium.

From the roots of Leontopotium longifolium, three new bisabolane sesquiterpenes, rel-(1S,4R,5S,6R)-4,5-diacetoxy-6-[(R)-1,5-dimethylhexa-3,5-dienyl]-3-methylcyclohex-2-enyl (Z)-2-methylbut-2-enoate (1), rel-(1S,4R,5S,6R)-4,5-diacetoxy-6-[(R)-5-hydroxy-1,5-dimethylhex-3-enyl]-3-methylcyclohex-2-enyl (Z)-2-methylbut-2-enoate (2), rel-(1R,2S,4R,5S)-4-acetoxy-2-[(R)-5-hydroxy-1,5-dimethylhex-3-enyl]-5-methylcyclohexyl (Z)-2-methylbut-2-enoate (3), and a new coumarin, 2,3-dihydro-5-hydroxy-2-(1-methylethenyl)-7H-pyrano[2,3-g][1,4]benzodioxin-7-one (4) together with nine known compounds have been isolated. The structures of these compounds were established by spectroscopic methods. Compounds 1 and 2 exhibited moderate cytotoxic activities against human promyelocytic leukemia (HL-60) cells.

Eudesmane sesquiterpenoids from the Asteraceae family.

This review covers the structures and biological activities of eudesmane-type sesquiterpenoids from the plants of the Asteraceae family. Biosynthetic studies or chemical syntheses leading to the revision of structures or stereochemistries have also been included, and 593 references are cited.

Two new benzofurans and other constituents from Ligularia przewalskii.

Two new benzofurans, 2-(1,2-dihydroxyisopropyl)-5,6-dimethoxybenzofuran (1) and 2-(1-O-feruloyl-2-hydroxyisopropyl)-5,6-dimethoxybenzofuran (2), along with eleven known compounds (3-13) were isolated from the roots of Ligularia przewalskii. Their structures were established on the basis of spectroscopic methods. The antibacterial activity of compounds 1 and 3-5 was tested.

Triterpenoids and Sesquiterpenes from Mulgedium tataricum.

The chemical investigation of Mulgedium tataricum afforded six new compounds which were identified as lanost-9(11),23 Z(24)-diene-3beta,25-diol (1), lanost-9(11),25-diene-3beta,24beta-diol (2), ursane-20-ene-3beta,22alpha-diol (3), 4 E,10 E-3beta,11beta-dihydroxygermacra-4(5),10(1)-dien-12,6alpha-olide (4), 4 E-1beta-hydroperoxy-3beta,11beta-dihydroxygermacra-4(5),10(14)-dien-12,6alpha-olide (5) and lactucin-8-O-P-methoxyphenyl acetate (6) by using a combination of MS and NMR techniques. Compound 6 exhibited significant cytotoxicity against cultured human hepatoma cells (SMMC-7721) and human acute promyelocytic leukemia cells (HL60). The antibacterial activity study indicated that 1 and 2 strongly inhibited the growth of Escherichia coli.

Differential mechanisms involved in effects of genistein and 17-beta-estradiol on porcine coronary arteries.

The purpose of this work was to examine the differential mechanisms involved in relaxation induced by genistein and 17-beta-estradiol in isolated porcine coronary arteries. Similar to 17-beta-estradiol, genistein could dose-dependently relax 30 mM KCI-precontracted coronary artery rings. The pD2 values of genistein and 17-beta-estradiol were 4.91 +/- 0.13 and 4.98 +/- 0.12 respectively. Incubation with N-L-nitroarginine (L-NNA), endothelium removal or in the presence of a potent inhibitor of protein tyrosine phosphatase sodium orthovanadate did not affect the relaxation induced by genistein, but could partially reduce the vasorelaxation induced by 17-beta-estradiol. The relaxations induced by genistein and 17-beta-estradiol were unaffected by the estrogen receptor antagonist tamoxifen, the inhibitor of prostanoid synthesis indomethacin and the protein synthesis inhibitor, cycloheximide. In addition, both of genistein and 17-beta-estradiol could decrease the contractile responses of KCI, 5-HT and CaCl2, and shift their cumulative concentration-response curves rightward in a parallel manner. These findings suggest that the relaxant effects induced by genistein and 17-beta-estradiol are probably mainly due to inhibition of Ca2+ influx through voltage-dependent calcium channels (VDCCs), and are not related to sex hormone receptor and classical genomic activities. Also there is an interesting finding that the relaxing response of 17-beta-estradiol is partially endothelium-dependent, but that of genistein is not.