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Breast cancer is one of the most common cancers diagnosed among women worldwide. Estrogen receptor alpha (ER α ) is a transcriptional factor that plays an important role in the development and progression of breast cancer. Yuanhuatine, a natural daphnane-type diterpenoid extracted from Daphne genkwa , was reported to exhibit significant cytotoxicity against breast cancer cells. However, the underlying mechanism is still unclear. In this study, we evaluated the cytotoxicity of yuanhuatine on two breast cancer cell lines that are ER α -positive and -negative. The results show that yuanhuatine inhibits the growth of ER α -positive cells (MCF-7) with much stronger inhibitory activity (IC 50  = 0.62 µM) compared with positive control tamoxifen (IC 50  = 14.43 µM). However, no obvious cytotoxicity was observed in ER α -negative cells (MDA-MB-231). Subsequent experiment also indicated that yuanhuatine markedly induced mitochondrial dysfunction, leading to apoptosis in MCF-7 cells. Molecular docking studies suggest the potential interactions between yuanhuatine and ER α . Immunofluorescence staining and Western blot analysis indicated that yuanhuatine down-regulated the expression of ER α in MCF-7 cells. MPP, a specific ER α inhibitor, significantly enhanced yuanhuatine-induced mitochondrial dysfunction and apoptosis in MCF-7 cells. On the contrary, the treatment with yuanhuatine causes no apoptosis in MM231 cells. Altogether, in vitro and in silico results suggested that ER α down-regulation was involved in yuanhuatine-induced mitochondrial dysfunction and apoptosis in ER α -positive breast cancer cells. Thus, yuanhuatine could be a potential candidate for treating ER α -positive breast cancer., Competing Interests: The authors declare that they have no conflict of interest., (Georg Thieme Verlag KG Stuttgart · New York.)

Chikusetsusaponin IVa and calenduloside E were isolated from the whole plant of Alternanthera philoxeroides (Mart.) Griseb (Amaranthaceae) and evaluated for their antiviral activities. Chikusetsusaponin IVa showed antiviral activities against HSV-1, HSV-2, human cytomegalovirus, measles virus, and mumps virus with selectivity indices (CC (50)/IC (50)) of 29, 30, 73, 25, and 25, respectively. On the other hand, calenduloside E showed no antiviral effects against any of the viruses tested. The mode of HSV-2 action of chikusetsusaponin IVa was determined under different experimental conditions. The anti-HSV-2 target of the compound might be mainly related to direct inactivation of virus particles and to the inhibition of release of progeny viruses from infected cells, but it is not related to inhibition of viral attachment, cell penetration, and viral protein synthesis. This compound also provided in vivo efficacy in a mouse model of genital herpes caused by HSV-2. These results demonstrate that chikusetsusaponin IVa might be a candidate of antiherpetic agents.

In order to evaluate the potency of novel antiviral drugs, 11 natural sulfated polysaccharides (SPs) from 10 green algae ( Enteromorpha compressa, Monostroma nitidum, Caulerpa brachypus, C. okamurai, C. scapelliformis, Chaetomorpha crassa, C. spiralis, Codium adhaerens, C. fragille, and C. latum) and 4 synthetic sulfated xylans (SXs) prepared from the beta-(1,3)-xylan of C. brachypus, were assayed for anti-Herpes simplex virus type 1 (HSV-1) activity. Except for one from E. compressa, all SPs showed potent anti-HSV-1 activities with 50 % inhibitory concentrations (IC (50)) of 0.38 - 8.5 microg/mL, while having low cytotoxicities with 50 % inhibitory concentrations of >2900 microg/mL. Anti-HSV-1 activities of SXs were dependent on their degrees of sulfation. To delineate the drug-sensitive phase, 4 polysaccharides, which showed potent anti-HSV-1 activities, were applied to time-of-addition experiments. Among the polysaccharides tested, 3 polysaccharides (SX4, SP4 from C. brachypus, and SP11 from C. latum) showed strong anti-HSV-1 activities with IC (50) of 6.0, 7.5, and 6.9 microg/mL, respectively, even when added to the medium 8 h post-infection. These experiments demonstrated that some sulfated polysaccharides not only inhibited the early stages of HSV-1 replication, such as virus binding to and penetration into host cells, but also interfered with late steps of virus replication. These results revealed that some sulfated polysaccharides from green algae should be promising candidates of antiviral agents which might act on different stages in the virus replication cycle.

Sodium spirulan (Na-SP) is a sulfated polysaccharide isolated from the blue-green alga Spirulina platensis, which consists of two types of disaccharide repeating units, O-hexuronosyl-rhamnose (aldobiuronic acid) and O-rhamnosyl-3-O-methylrhamnose (acofriose) with sulfate groups, other minor saccharides and sodium ion. Vascular endothelial cells are present on the inner surface of blood vessels in a monolayer and have anticoagulant properties. To address the question whether Na-SP influences the maintenance of endothelial cell monolayers, we investigated the proliferation of cultured bovine aortic endothelial cells treated with Na-SP. It was found that Na-SP has an inhibitory activity on endothelial cell proliferation accompanied with suppression of whole protein synthesis but without non-specific cell damage. The inhibitory activity of Na-SP was the strongest when compared to that of heparan sulfate, heparin, dextran sulfate, dermatan sulfate, chondroitin sulfate A/C and hyaluronan. Furthermore, it was shown that the inhibitory activity of Na-SP disappeared by either desulfation or depolymerization. The present data suggest that Na-SP is a unique sulfated polysaccharide that strongly inhibits vascular endothelial cell proliferation, and the inhibitory activity requires polymerization of sulfated O-rhamnosyl-acofriose repeating units.

Magnolol is an 11beta-hydroxysteroid dehydrogenase (11beta-HSD) inhibitor contained in Magnolia officinalis which is used in Chinese remedies. We have reported that glycyrrhetinic acid, a strong 11beta-HSD inhibitor isolated from licorice, induces apoptosis of murine thymocytes via accumulation of corticosterone. In this paper, we report that magnolol inhibited 11beta-HSD without increases in the blood concentration of corticosterone and in thymocyte apoptosis in mice. Oxidative activities of the enzyme (from corticosterone to 11-dehydrocorticosterone) in liver, kidney and thymus in vitro were examined 24 h after a single administration of magnolol. Magnolol inhibited the enzyme activity in kidney (P < 0.0001) and thymus (P < 0.002), while the activity in liver was not affected. Blood concentrations of corticosterone in the magnolol-treated mice were unexpectedly lower than those in the control animals (P < 0.002). This means that the inhibition of 11beta-HSD by magnolol did not increase the systemic level of corticosterone which is relevant to thymocyte apoptosis. Accordingly, our flow cytometric analysis of thymocytes after magnolol treatment showed no change in the number of apoptotic cells. We concluded that unlike glycyrrhetinic acid, magnolol selectively inhibited 11beta-HSD in kidney and thymus but not in liver, so that the blood concentrations of corticosterone could not exceed the control level.

To define the anti-allergic components in Saiboku-To, a herbal medicine for bronchial asthma, we examined the effects of 11 compounds found in post-administrative urine of Saiboku-To on concanavalin A-induced human lymphocyte blastogenesis in vitro and picryl chloride (PC)-induced mouse ear swelling in vivo. The urinary products of Saiboku-To were flavonoids and lignans derived from the constitutional herbs and their hydrogenated metabolites. Medicarpin derived from Glycyrrhiza glabra, magnolol and 8,9-dihydroxydihydromagnolol from Magnolia officinalis, baicalein, wogonin and oroxylin A from Suctellaria baicalensis inhibited lymphocyte blastogenesis in dose-dependent fashion with IC50 values ranging from 3.0 to 7.7 micrograms/mL, which corresponded to 20-100 times that of prednisolone IC50 (0.08 microgram/mL). Davidigenin, dihydrowogonin and dihydrooroxylin A, which are hydrogenated metabolites of liquiritigenin, wogonin and oroxylin A, respectively, had no or little effects on lymphocyte blastogenesis. Oral administration of Saiboku-To, medicarpin, baicalein, magnolol and baicalin (100 mg/kg), inhibited PC-induced ear swelling significantly by 23.5, 40.1, 30.5, 23.6 and 20.9%, respectively, though the effects were weaker than that of 5 mg/kg of prednisolone (52.9%). The results suggested that flavonoids and lignans tested in the present study were implicated in anti-asthmatic effect of Saiboku-To through suppression of type IV allergic reaction.

The steam distillate prepared from fresh plants of Houttuynia cordata Thunb. (Saururaceae) was found to have direct inhibitory activity against herpes simplex virus type 1 (HSV-1), influenza virus, and human immunodeficiency virus type 1 (HIV-1) without showing cytotoxicity, but not against poliovirus and coxsackie-virus. The loss of viral infectivity was related to the duration of drug treatment. Three major components of the distillate, methyl n-nonyl ketone, lauryl aldehyde, and capryl aldehyde, also inactivated HSV-1, influenza virus, and HIV-1. These in vitro findings demonstrate that the essential oils provide virucidal activity against enveloped viruses by interfering with the function of virus envelope.

A partially purified extract (COL 1-6) from whole plant of Cordia salicifolia showed an inhibitory effect on herpes simplex virus type 1 (HSV-1). The activity of COL 1-6 on different steps of HSV-1 replication in HeLa cells was investigated. Under single-cycle replication conditions, COL 1-6 exerted a greater than 99.9% inhibition in virus yield when added to the cells 3 h or 1.5 h before infection, and even when added 8 h after infection the extract still caused a greater than 99% inhibition. The extract has been shown to have a direct virucidal activity. And also, analysis of early events following infection showed that COL 1-6 affected viral penetration in HeLa cells but did not interfere with adsorption to the cells.

A water extract of the Oriental crude drug "reishi", the fruit bodies of GANODERMA LUCIDUM, significantly decreased plasma sugar level in mice. Fractionation of the extract by monitoring the hypoglycemic activity afforded two glycans, ganoderans A and B. These glycans elicited remarkable hypoglycemic actions in normal and alloxan-induced hyperglycemic mice.