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1.
The present study demonstrated that the ethyl acetate extract and the isolated compound, parthenolide, from aerial parts of Tanacetum vulgare L. (Asteraceae), protected Vero cells from herpes simplex virus (HSV‐1) infection in vitro. The extract and parthenolide were assayed against HSV‐1 by the sulforhodamine B colorimetric assay and exhibited anti‐HSV‐1 activity with an EC50 of 40 µg/mL and 0.3 µg/mL, respectively. In order to determine which stage of the virus–cell interaction was affected by parthenolide, the pure compound was used. No effect was observed when both viruses and cells were pretreated, or during early stages of infection, suggesting that parthenolide interfered with virus replication after the penetration stage, inhibiting approximately 40% of plaques formed at a concentration of 2.5 µg/mL when compared with an untreated control. Copyright © 2009 John Wiley & Sons, Ltd.  相似文献   

2.
Medicinal plants are increasingly of interest as novel source of drugs for antiherpetic agents, because herpes simplex virus (HSV) might develop resistance to commonly used antiviral drugs. An aqueous extract of Melissa officinalis and the phenolic compounds caffeic acid, p‐coumaric acid and rosmarinic acid were examined for their antiviral activity against herpes simplex virus type 1 (HSV‐1) acyclovir‐sensitive and clinical isolates of acyclovir‐resistant strains in vitro. When drugs were added during the intracellular replication of HSV‐1 infected cells, no antiviral effect was observed by plaque reduction assay. However, Melissa extract interacted directly with free viral particles of two acyclovir‐resistant HSV strains at low IC50 values of 0.13 and 0.23 µg/mL and high selectivity indices of 2692 and 1522, respectively. The Melissa extract and rosmarinic acid inhibited HSV‐1 attachment to host cells in a dose‐dependent manner for acyclovir‐sensitive and acyclovir‐resistant strains. These results indicate that mainly rosmarinic acid contributed to the antiviral activity of Melissa extract. Penetration of herpes viruses into cells was inhibited by Melissa extract at 80% and 96% for drug‐sensitive and drug‐resistant viruses, respectively. Melissa extract exhibits low toxicity and affects attachment and penetration of acyclovir‐sensitive and acyclovir‐resistant HSVs in vitro. Copyright © 2014 John Wiley & Sons, Ltd.  相似文献   

3.
Mast cells play a critical role in the effector phase of immediate hypersensitivity and allergic reactions. Pinus radiata bark extract exerts multiple biological effects and exhibits immunomodulatory and antioxidant properties. However, its role in mast cell‐mediated anaphylactic reactions has not been thoroughly investigated. In this study, we examined the effects of proanthocyanidin‐rich water extract (PAWE) isolated from P. radiata bark on compound 48/80‐induced or antidinitrophenyl (DNP) immunoglobulin E (IgE)‐mediated anaphylaxis‐like reactions in vivo. In addition, we evaluated the mechanism underlying the inhibitory effect of PAWE on mast cell activation, with a specific focus on histamine release, using rat peritoneal mast cells. PAWE attenuated compound 48/80‐induced or anti‐DNP IgE‐mediated passive cutaneous anaphylaxis‐like reactions in mice, and it inhibited histamine release triggered by compound 48/80, ionophore A23187, or anti‐DNP IgE in rat peritoneal mast cells in vitro. Moreover, PAWE suppressed compound 48/80‐elicited calcium uptake in a concentration‐dependent manner and promoted a transient increase in intracellular cyclic adenosine‐3′,5′‐monophosphate levels. Together, these results suggest that proanthocyanidin‐rich P. radiata bark extract effectively inhibits anaphylaxis‐like reactions.  相似文献   

4.
Essential oils are complex natural mixtures, their main constituents, e.g. terpenes and phenylpropanoids, being responsible for their biological properties. Essential oils from eucalyptus, tea tree and thyme and their major monoterpene compounds α‐terpinene, γ‐terpinene, α‐pinene, p‐cymene, terpinen‐4‐ol, α‐terpineol, thymol, citral and 1,8‐cineole were examined for their antiviral activity against herpes simplex virus type 1 (HSV‐1) in vitro. These essential oils were able to reduce viral infectivity by >96%, the monoterpenes inhibited HSV by about >80%. The mode of antiviral action has been determined, only moderate antiviral effects were revealed by essential oils and monoterpenes when these drugs were added to host cells prior to infection or after entry of HSV into cells. However, both essential oils and monoterpenes exhibited high anti‐HSV‐1 activity by direct inactivation of free virus particles. All tested drugs interacted in a dose‐dependent manner with herpesvirus particles thereby inactivating viral infection. Among the analysed compounds, monoterpene hydrocarbons were slightly superior to monoterpene alcohols in their antiviral activity, α‐pinene and α‐terpineol revealed the highest selectivity index. However, mixtures of different monoterpenes present in natural tea tree essential oil revealed a ten‐fold higher selectivity index and a lower toxicity than its isolated single monoterpenes. Copyright © 2009 John Wiley & Sons, Ltd.  相似文献   

5.
Moringa oleifera Lam. is used as a nutritive vegetable and spice. Its ethanol extract has been previously shown to be significantly effective in alleviating herpetic skin lesions in mice. In this study, we evaluated the alleviation by the aqueous extract (AqMOL) and assessed the mode of its anti‐herpetic action in a murine cutaneous herpes simplex virus type 1 (HSV‐1) infection model. AqMOL (300 mg/kg) was administered orally to HSV‐1‐infected mice three times daily on days 0 to 5 after infection. AqMOL significantly limited the development of herpetic skin lesions and reduced virus titers in the brain on day 4 without toxicity. Delayed‐type hypersensitivity (DTH) reaction to inactivated HSV‐1 antigen was significantly stronger in infected mice administered AqMOL and AqMOL augmented interferon (IFN)‐γ production by HSV‐1 antigen from splenocytes of HSV‐1‐infected mice at 4 days post‐infection. AqMOL administration was effective in elevating the ratio of CD11b+ and CD49b+ subpopulations of splenocytes in infected mice. As DTH is a major host defense mechanism for intradermal HSV infection, augmentation of the DTH response by AqMOL may contribute to their efficacies against HSV‐1 infection. These results provided an important insights into the mechanism by which AqMOL activates cellular immunity. Copyright © 2016 John Wiley & Sons, Ltd.  相似文献   

6.
In the present study we report in vitro and in vivo inhibitory potential of crude aqueous extract of neem leaves and pure neem compound (Azadirachtin) on the replication of Dengue virus type-2. In vitro antiviral activity of aqueous neem leaves extract assessed in C(6/36) (cloned cells of larvae of Aedes albopictus) cells employing virus inhibition assay showed inhibition in dose dependent manner. The aqueous extract of neem leaves at its maximum non-toxic concentration of 1.897 mg/ml completely inhibited 100-10,000 TCID(50) of virus as indicated by the absence of cytopathic effects. The in vivo protection studies with neem leaves extract at its maximum non-toxic concentrations 120-30 mg/ml resulted in inhibition of the virus replication as confirmed by the absence of Dengue related clinical symptoms in suckling mice and absence of virus specific 511 bp amplicon in RT-PCR. The pure neem i.e. Azadirachtin did not reveal any inhibition on Dengue virus type-2 replication in both in vitro and in vivo systems.  相似文献   

7.
The limonoid 1‐cinnamoyl‐3,11‐dihydroxymeliacarpin (CDM) isolated from leaf extracts of Melia azedarach L, has potent antiherpetic effect in epithelial cells. Since Meliacine, the partially purified extract source of CDM, has therapeutic effect on murine genital herpes, the potential use of CDM as microbicide against herpetic infections was studied here. To determine the cytotoxic effect of CDM, the MTT assay and acridine orange staining of living cells were performed. The antiherpetic action of CDM was measured by plaque reduction assay, and the immunomodulatory effect was determined by measuring the cytokine production using a bioassay and ELISA method. The results presented here showed that CDM inhibited Herpes Simplex Virus type 2 (HSV‐2) multiplication in Vero cells but did not affect its replication in macrophages which were not permissive to HSV infection. In macrophages, levels of TNF‐α, IFN‐γ, NO, IL‐6 and IL‐10 were increased by CDM used alone or in combination with HSV‐2. Besides, CDM not only synergized TNF‐α production combined with IFN‐γ, but also prolonged its expression in time. Results indicate that CDM inhibits HSV‐2 multiplication in epithelial cells and also increases cytokine production in macrophages, both important actions to the clearance of infecting virus in the mouse vagina. Copyright © 2013 John Wiley & Sons, Ltd.  相似文献   

8.
Herpes simplex virus (HSV) infection is a major opportunistic infection in immunosuppressed persons. It is therefore a serious disease in high HIV/AIDS prevalence areas as in sub-Saharan Africa where infections due to HSV have risen significantly. The development of resistant strains of HSV to the available drugs for infection management, as is evident in the first drug of choice acyclovir, has further compounded this situation. There is therefore an urgent need to identify and develop new alternative agents for management of HSV infections, more so, for those due to resistant strains. We report here on an aqueous total extract preparation from the roots of Carissa edulis (Forssk.) Vahl (Apocynaceae), a medicinal plant locally growing in Kenya that has exhibited remarkable anti-HSV activity in vitro and in vivo for both wild type and resistant strains of HSV. The extract significantly inhibited formation of plaques in Vero E6 cells infected with 100PFU of wild type strains of HSV (7401H HSV-1 and Ito-1262 HSV-2) or resistant strains of HSV (TK(-) 7401H HSV-1 and AP(r) 7401H HSV-1) by 100% at 50 microg/ml in vitro with minimal cell cytotoxicity (CC(50)=480 microg/ml). When the extract was examined for in vivo efficacy in a murine model using Balb/C mice cutaneously infected with wild type or resistant strains of HSV, the extract at an oral dose of 250 mg/kg significantly delayed the onset of HSV infections by over 50%. It also increased the mean survival time of treated infected mice by between 28 and 35% relative to the infected untreated mice (p<0.05 versus control by Student's t-test). The mortality rate for mice treated with extract was also significantly reduced by between 70 and 90% as compared with the infected untreated mice that exhibited 100% mortality. No acute toxicity was observed in mice at the oral therapeutic dose of 250 mg/kg. These results suggest that this herbal extract has potent anti-viral agents against herpes simplex viruses that can be exploited for development of an alternative remedy for HSV infections.  相似文献   

9.
O. horridus is used as a folk medicine by natives in the Northern Pacific coast of North America. This experiment studied the antiproliferative effects of the extract of O. horridus root bark and its fractions chromatographed from Dianion HP20 resin column with water, 30, 50, 70 and 100% ethanol on human breast cancer MCF‐7 cells and non‐small cell lung cancer (NSCLC) cells. The role of O. horridus in the cell cycle and apoptosis of MCF‐7 cells was also investigated. The results showed that the 70% and 100% ethanol fractions demonstrated more potent antiproliferative effects than the total extract on both cell lines. The antiproliferative effects may result from the enrichment of active constituents detected by high performance liquid chromatography (HPLC). The IC50 of the total extract, 50, 70, and 100% ethanol fractions for antiproliferation on MCF‐7 cells were 248.4, 123.1, 44.0, and 31.5 μg/mL, respectively, and on NSCLC cells were 125.3, 271.1, 17.6, and 23.2 μg/mL, respectively. On the other hand, the water and 30% ethanol fractions significantly promoted cell proliferation on MCF‐7 cells at concentrations > 100 μg/mL, suggesting that the hydrophilic fractions should be removed from the extract when used for cancer chemoprevention in order to achieve desirable activities. The effects of the total extract on cell cycle and apoptosis were similar to that of the 100% ethanol fraction because of the similarity of their chemical composition. At higher concentrations, the apoptotic effects of the 70% ethanol fraction are more significant. Data from this study suggested that the 70% and 100% ethanol fractions are active antiproliferative fractions and that induction of apoptosis is the mechanism involved in the antiproliferative effect observed. Copyright © 2010 John Wiley & Sons, Ltd.  相似文献   

10.
In this study, 1,2,4,6‐tetra‐O‐galloyl‐β‐d ‐glucose (1246TGG), a polyphenolic compound isolated from traditional Chinese medicine Phyllanthus emblica L. (Euphorbiaceae), was found to inhibit herpes simplex virus type 1 (HSV‐1) and type 2 (HSV‐2) infection at different magnitudes of activity in vitro. Further studies revealed that 1246TGG directly inactivated HSV‐1 particles, leading to the failure of early infection, including viral attachment and penetration. 1246TGG also suppressed the intracellular growth of HSV‐1 within a long period post‐infection (from 0 h p.i. to 12 h p.i.), while it might exert an antiviral effect mainly before 3 h p.i. It inhibited HSV‐1 E and L gene expressions as well as viral DNA replication but did not affect the RNA synthesis of IE gene in our study. Also, in the presence of 1246TGG, the synthesis of viral protein was reduced. Taken together, it was suggested that 1246TGG might exert anti‐HSV activity both by inactivating extracellular viral particles and by inhibiting viral biosynthesis in host cells. These results warrant further studies on the antiviral mechanisms of 1246TGG and suggest that it might be a candidate for HSV therapy. Copyright © 2011 John Wiley & Sons, Ltd.  相似文献   

11.
The aim of the work is to investigate the effects of Bridelia grandis (Pierre ex Hutch) stem bark water extract on human HeLa cancer cells and normal monocytes treated in vitro, evaluating the morphological modifications with light and electron microscopy. The phytocomplex obtained from B. grandis caused a significant decrease in the mitotic index of both HeLa cancer cells and normal monocytes. In addition, a reduction of the typical aneuploid‐polyploid pattern has been observed in HeLa cells after treatment. Various alterations at fine structural level, both in neoplastic (HeLa cells) and normal (monocytes) cells have been observed. In particular, electron‐dense cells containing condensed mitochondria, autophagic vacuoles and dense spherical cytoplasmic inclusions have been observed. The results show that B. grandis water extracts have an antiproliferative effect on human cells, with a different effect on neoplastic and normal cells. The antiproliferative effect is accompanied by the appearance of various subcellular alterations. The morphological alterations observed are likely to represent the condition of ‘dark cell’ as a possible preliminary phase towards the autophagic and/or apoptotic cell death. Copyright © 2013 John Wiley & Sons, Ltd.  相似文献   

12.
ATP‐binding cassette transporter A1 (ABCA1) is a key mediator of cholesterol efflux to apoA‐I in lipid‐loaded macrophages, which is the first step of reverse cholesterol transport in vivo and a critical step in preventing atherosclerosis. Enhanced ABCA1 expression may inhibit foam cell formation and consequently reduce atherogenic risk. The purpose of this study was to investigate the effect of S‐allylcysteine (SAC), the most abundant organosulfur compound in aged garlic extract, on the expression of ATP‐binding cassette transporter A1 in human THP‐1 macrophages. The human monocyte THP‐1 cells were differentiated to macrophage cells in the presence of phorbol 12‐myristate13‐acetate (PMA). Macrophage cells were then treated with different concentrations (10, 20 and 40 mM) of SAC for 24 h. Total RNA of treated macrophages was extracted and analyzed with real‐time RT‐PCR. ABCA1 protein expression was also analyzed with western blotting. Results showed that SAC increased the ABCA1 mRNA (1.82‐, 2.07‐ and 2.23‐fold) and protein (1.37‐, 1.55‐ and 2.08‐fold) expression in macrophage THP‐1 cells compared with control (untreated cells). Results suggested that SAC can increase ABCA1 expression in macrophages and may be beneficial in promoting reverse cholesterol efflux. Copyright © 2012 John Wiley & Sons, Ltd.  相似文献   

13.
The thorns of Gleditsia sinensis are used as a medicinal herb in China and Korea. However, the mechanisms responsible for the antitumor effects of the water extract of Gleditsia sinensis thorns (WEGS) remain unknown. HCT116 cells treated with the WEGS at a dose of 800 μg/mL (IC50) showed a significant decrease in cell growth and an increase in cell cycle arrest during the G2/M‐phase. G2/M‐phase arrest was correlated with increased p53 levels and down‐regulation of the check‐point proteins, cyclinB1, Cdc2 and Cdc25c. In addition, treatment with WEGS induced phosphorylation of extracellular signal‐regulated kinase (ERK), p38 MAP kinase and JNK (c‐Jun N‐terminal kinases). Moreover, inhibition of ERK by treatment of cells with the ERK‐specific inhibitor PD98059 blocked WEGS‐mediated p53 expression. Similarly, blockage of ERK function in the WEGS‐treated cells reversed cell‐growth inhibition and decreased cell cycle proteins. Finally, in vivo WEGS treatment significantly inhibited the growth of HCT116 tumor cell xenografts in nude mice with no negative side effects, including loss of body weight. These results describe the molecular mechanisms whereby the WEGS might inhibit proliferation of colon cancer both in vitro and in vivo, suggesting that WEGS has potential as an anticancer agent for the treatment of malignancies. Copyright © 2010 John Wiley & Sons, Ltd.  相似文献   

14.
Prostate cancer (PC) is the most prevalent cancer and the leading cause of male cancer death. Azadirachta indica (neem tree) has been used successfully centuries to reduce tumors by herbalists throughout Southeast Asia. Here the present study indicated that an ethanolic extract of neem has been shown to cause cell death of prostate cancer cells (PC-3) by inducing apoptosis as evidenced by a dose-dependent increase in DNA fragmentation and a decrease in cell viability. Western blot studies indicated that treatment with neem extract showed decreased level of Bcl-2, which is anti-apoptotic protein and increased the level of Bax protein. So the neem extract could be potentially effective against prostate cancer treatment.  相似文献   

15.
A previous report indicated that the flavonoid‐rich extract of bergamot juice (BJe) exerts an anti‐inflammatory effect through the activation of SIRT1 in leukemic monocytes THP‐1 exposed to lipopolysaccharide (LPS). In this study, we deeply investigate the mode of action of BJe, along with its major flavonoids on SIRT1 through cell‐free, in silico, and in vitro experimental models. In the cell‐free assay, all the tested compounds as well as the whole BJe inhibited the deacetylase activity of SIRT1. This finding was reinforced by the results of the in silico study. In THP‐1 cells exposed to LPS, a reduction of SIRT1 activity was observed, effect that was reverted by the pre‐incubation with either BJe or its major flavonoids. This effect was also observed at gene level. Employing an activator and an inhibitor of AMP‐activated protein kinase (AMPK; AICAR and dorsomorphin, respectively), we discovered its involvement in the activation of SIRT1 elicited by BJe or its major flavonoids in whole cell. Our study indicates the dual role of BJe and its components, depending on the employed experimental model as well as reveals their mode of action on the AMPK/SIRT1 axis, suggesting their role as promising candidates in pathologies in which this axis is implied.  相似文献   

16.
Since natural products are considered powerful sources of novel drug discovery, a partially purified extract (meliacine) from the leaves of Melia azedarach L., a plant used in traditional medicine in India for the treatment of several diseases, has been studied. Meliacine exhibits a potent antiviral effect against several viruses without displaying cytotoxicity. The purpose of the present study was to evaluate the therapeutic effect of intravaginal administration of meliacine in a mouse model of genital herpetic infection. BALB/c female mice were infected with MS or G strains of Herpes Simplex Virus type 2 and then treated with meliacine topically. An overall protective effect was observed. Animal survival increased, the severity of the disease was reduced, life span was extended and virus shedding in vagina fluids was diminished. In addition, meliacine reduced the amount of virus that migrated to the brain and vaginal fluids presented higher levels of IFN‐γ and TNF‐α than untreated infected mice. These results indicate that meliacine could be an alternative therapeutic compound against HSV‐2 genital infection. Copyright © 2009 John Wiley & Sons, Ltd.  相似文献   

17.
Hawthorn (Crataegus oxyacantha L.), a plant used in traditional medicine, is a rich source of procyanidins which have been reported to exhibit antioxidant and anti‐carcinogenic activity. In this study, we assessed the effect of hawthorn bark extract (HBE) on Nrf2 pathway activation in THLE‐2 and HepG2 cells. Treatment with 1.1 µg/mL, 5.5 µg/mL and 11 µg/mL of HBE resulted in the translocation of Nrf2 from the cytosol to the nucleus in both cell lines; however, the accumulation of phosphorylated Nrf2 was observed only in THLE‐2. Accordingly, treatment of cells with HBE was associated with an increase in the mRNA and protein level of such Nrf2‐dependent genes as glutathione S‐transferases (GSTA, GSTP, GSTM, GSTT), NAD(P)H:quinone oxidoreductase 1 (NQO1) and heme oxygenase‐1 (HO‐1) (0.2–1.1‐fold change, p < 0.05), however, only in normal THLE‐2 hepatocytes. The induction of NQO1 correlated with an increased level of p53 (0.21–0.42‐fold change, p < 0.05). These effects may be related to induction of phosphorylation of upstream ERK and JNK kinases. Collectively, the results suggest that the Nrf2/ARE pathway may play an important role in the regulation of procyanidin‐mediated antioxidant/detoxifying effects in hepatocytes, and this may explain the hepatoprotective and chemopreventive properties of these phytochemicals. Copyright © 2013 John Wiley & Sons, Ltd.  相似文献   

18.
The present study is initially intended to evaluate antioxidant and β‐hydroxy‐β‐methylglutaryl‐CoA reductase (HMGR) inhibitory property of Ficus virens Ait., first by in vitro analyses followed by a corroboratory molecular informatics study. Our results show that of all the sequentially extracted fraction of F. virens bark and leaves extract, F. virens bark methanol extract exhibits strong radical scavenging, antioxidant and oxidative DNA damage protective activity, which is well correlated with its total phenolic content. In addition, F. virens bark methanol extract, which is non‐cytotoxic, significantly and non‐covalently inhibit the HMGR activity (IC50 = 3.45 ± 0.45 µg/ml) in comparison with other extracts. The mechanistic aspect of this inhibition activity is authenticated by molecular docking study of bioactive compounds as revealed from gas chromatography–mass spectrometry data, with HMGR. The analysis for the first time indicates that quinic acid (ΔG: ?8.11 kcal/mol) and paravastatin (ΔG: ?8.22 kcal/mol) exhibit almost same binding energy, while other compounds also showed good binding energy, suggesting that quinic acid alone or in combination with other major bioactive compound is probably responsible for HMGR inhibitory property of the extract and plausibly can be used in in vivo system for the management, prevention, and alleviation of hypercholesterolemia as well as hypercholesterolemia‐induced oxidative stress. Copyright © 2013 John Wiley & Sons, Ltd.  相似文献   

19.
Inflammatory cytokines such as interleukin‐1β, TNF‐α, and interferon‐γ are known to be involved in mediating β‐cells death in diabetes mellitus (DM). Thus, protecting from β‐cells death in patients with DM may be a useful target in alleviating symptoms of hyperglycemia. Traditional plant‐based remedies have been used to treat DM for many centuries and may play a role in protecting β‐cell from death. An example of these remedies is Gymnema sylvestre (GS) extract. In this study, we investigated the effect of this plant extract on β‐cells apoptosis. Om Santal Adivasi (OSA®) maintained cell membrane integrity in MIN6 cells and mouse islets. Om Santal Adivasi significantly protected MIN6 cells and mouse islets from cytokine‐induced apoptosis. In the presence of cytokines, OSA® significantly reduced the expression and activity of caspase‐3. The antiapoptotic effect of OSA® as shown by microarray analysis is largely mediated by activating pathways involved in cell survival (mainly casein kinase II pathway) and the free radical scavenger system (specifically superoxide dismutase and catalase). This study indicates that the GS isolate OSA® protects against cytokine‐induced apoptosis of β‐cells by increasing the expression of cell survival pathways and free radical scavenger system.  相似文献   

20.
Commiphora africana (A. Rich.) Endl. (Burseraceae) is a medicinal plant widely used in Nigerian ethnomedicine. The in vitro cytotoxicity of the stem bark extract of C. africana and isolated cytotoxic compounds was investigated. Three resveratrol derivatives: (E)‐resveratrol 3‐O‐rutinoside ( 1 ), 5‐methoxy‐(E)‐resveratrol 3‐O‐rutinoside ( 2 ), and pinostilbene ( 3 ), together with 3‐hydroxy‐5‐methoxybenzoic acid ( 4 ) were isolated from the methanol fraction of C. africana. Their structures were determined by extensive analysis of their HREIMS and NMR spectra. The cytotoxicity of the isolated compounds against four human carcinoma cells was determined using the MTT assay. Compound 1 displayed the highest antiproliferative effect on the cell lines, with IC50 values of 16.80, 21.74, 17.89, and 17.44 μM, against MCF7, A549, PC3, and HepG2 human cancer cell lines, respectively. In addition, compounds 1 – 3 showed low toxicity against normal human prostate cell line, with selectivity indices greater than five across the carcinoma cells, indicating that the compounds possess potential in the development of low‐toxicity chemotherapeutic agents. These results support the traditional use of this plant in the treatment of cancer.  相似文献   

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