Cephalotaxus Harringtonia Research Articles

Anti-aging potential of Cephalotaxus harringtonia extracts: the role of harringtonine and homoharringtonine in skin protection

Photoaging damages the skin layers. The tumor necrosis factor-alpha (TNF-α) plays a crucial role in the central mechanism of photoaging. TNF-α production leads to direct damage to skin cells and facilitates the degradation of vital extracellular matrix (ECM) proteins. TNF-α stimulates matrix metalloproteinase-1 (MMP-1) activation This accelerates the loss of skin elasticity and wrinkle formation. Thus, preventing photoaging and delaying the skin aging process are important research objectives, and the development of new anti-aging substances that target the TNF-α and MMP-1 pathways is promising. In this context, the efficacies of four extracts derived from two types of Cephalotaxus harringtonia (CH) buds (CH-10Y-buds, CH-200Y-buds) and leaves (CH-10Y-leaves, CH-200Y-leaves) were investigated, exhibiting a significant reduction in reactive oxygen species (ROS). Among the four extracts, CH-10Y-buds was the most effective in reducing ROS and exhibited the highest amounts of harringtonine and homoharringtonine. The activities of harringtonine, homoharringtonine, and ginkgetin were evaluated; harringtonine exhibited a high efficacy in inhibiting TNF-α-induced inflammatory responses and MMP-1 activation, thereby reducing collagen degradation. These findings suggest that CH-10Y-buds and their components herringtonin are promising candidates for preventing damage caused by photoaging. Our results can facilitate the development of new methods for maintaining skin health and inhibiting the skin aging process. Further research is necessary to comprehensively evaluate the potential efficacy of these candidate substances and investigate their applicability to actual skin. Such studies will aid in the development of more effective anti-aging strategies in the future.

Inhibition of G protein-coupled receptor 68 using homoharringtonine attenuates chronic kidney disease-associated cardiac impairment

Chronic kidney disease (CKD) induces cardiac inflammation and fibrosis and reduces survival. We previously demonstrated that G protein-coupled receptor 68 (GPR68) promotes cardiac inflammation and fibrosis in mice with 5/6 nephrectomy (5/6Nx) and patients with CKD. However, no method of GPR68 inhibition has been found that has potential for therapeutic application. Here, we report that Cephalotaxus harringtonia var. nana extract and homoharringtonine ameliorate cardiac inflammation and fibrosis under CKD by suppressing GPR68 function. Reagents that inhibit the function of GPR68 were explored by high-throughput screening using a medicinal plant extract library (8,008 species), and we identified an extract from Cephalotaxus harringtonia var. nana as a GPR68 inhibitor that suppresses inflammatory cytokine production in a GPR68 expression-dependent manner. Consumption of the extract inhibited inflammatory cytokine expression and cardiac fibrosis and improved the decreased survival attributable to 5/6Nx. Additionally, homoharringtonine, a cephalotaxane compound characteristic of C. harringtonia, inhibited inflammatory cytokine production. Homoharringtonine administration in drinking water alleviated cardiac fibrosis and improved heart failure and survival in 5/6Nx mice. A previously unknown effect of C. harringtonia extract and homoharringtonine was revealed in which GPR68-dependent inflammation and cardiac dysfunction were suppressed. Utilizing these compounds could represent a new strategy for treating GPR68-associated diseases, including CKD.

Bioecology, landscape use, and breeding technology of ephalotaxus drupacea sieb. Et zucc.

According to the UN Convention on Biological Diversity, 34,000 plant species are in danger of going extinct. Environmental issues including climate change provide difficulties for landscaping, plant selection, and environment aesthetics. In addition to employing landscape trees, adding lovely blooming shrubs may improve the landscaping's aesthetic value. In this article Cephalotaxus drupacea Sieb. et Zucc. The bioecology, decorativeness and breeding technology of Danakbosh zarnab are discussed, as well as practical experiences. The results of studying the morphobiological characteristics of Cephalotaxus drupacea seeds are presented. It has been shown that the size, shape, and texture of the seeds serve as a diagnostic feature. These features of Cephalotaxus drupacea indicate a high level of adaptation to environmental factors. It is an evergreen ornamental shrub, 10-15 m tall, belonging to the Cephalotaxaceae family. Homeland - Central China, Korea, East India, Japan. Shade-loving, cold-resistant. According to AL Takhtadjian, Cephalotaxaceae family, Cephalotaxus genus consists of 6 species, which were widespread in the Northern Hemisphere in ancient geological times. Currently, this species is distributed only in Asia, namely: East India, Central and South China, Taiwan Islands, Korea and Japan.

Biosynthesis of novel metallic silvers on kraft papers using cephalotaxus harringtonia fruit extract as a sustainable stabilizing agent (KP@AgNP).

Greenly synthesized silver nanoparticles (AgNPs) on different cellulosic materials show tremendous potential for colorful, biocidal, and reasonably strong products by replacing the traditional chemical-based synthesis protocols. This study reports on a novel in situ synthesis protocol for synthesizing green and sustainable AgNPs over cellulosic kraft paper substrates using a bio-based stabilizing agent (Cephalotaxus harringtonia fruit extract). The protocol could play a significant role in packaging industries. The aqueous extracts of Cephalotaxus harringtonia fruits have been used to synthesize the metallic silver. The deposited AgNPs values were investigated through XRF (X-ray fluorescence) analysis. The number of deposited nanoparticles (NPs) was 268 ± 7, 805 ± 14, and 1,045 ± 16 PPM, respectively for 0.5, 1.5, and 2.5 mm silver precursors. The developed products were tested with SEM (scanning electron microscopy), SEM-mediated elemental mapping, EDX (energy disruptive X-ray), FTIR (Fourier transform infrared spectroscopy), and XRD (X-Ray diffraction). XRD analysis further confirmed the presence of peaks for elemental AgNP on the deposited papers. Colorimetric values were measured to confirm the colorful appearances of the developed metallic silvers. Mechanical properties were tested in terms of the tensile index and bursting index. Moreover, the statistical analysis of coefficient of variations (R2) and a post-hoc ANOVA test that adopted the Newman-Keul methodology also confirm the significance of developed nanoparticles in the papers. The shielding capacity against UV light was also investigated; all the AgNPs-treated products provided values higher than 40, demonstrating the strong UV resistance capability of the kraft paper material. Overall, the study confirms a successful development of green AgNPs on paper materials.

Photoaffinity Probe Reveals the Potential Target of Harringtonolide for Cancer Cell Migration Inhibition.

Harringtonolide (HO, 1) is a bioactive diterpenoid tropone isolated from Cephalotaxus harringtonia with antiproliferation activity. Until now there have been no reports to elucidate its anticancer mechanism. Herein we report the synthesis of HO-derived probes (10, 11, and 12) to identify the possible target of HO. As a result, the application of a novel photoaffinity alkyne-tagged probe from HO (compound 12) showed direct engagement between HO and receptor for activated C kinase 1 (RACK1). Furthermore, HO could suppress the epithelial-mesenchymal transition (EMT) process and inhibit activation of the FAK/Src/STAT3 signaling pathway in A375 cells. This study provides a groundwork for HO as an effective antitumor agent that targets RACK1 to suppress cancer cell migration.

Homoharringtonine inhibits the progression of hepatocellular carcinoma by suppressing the PI3K/AKT/GSK3β/Slug signaling pathway.

Homoharringtonine (HHT), was first isolated from the bark of Cephalotaxus harringtonia (Knight ex J. Forbes) K. Koch and Cephalotaxus fortunei Hook trees. The bark extract is used to treat leukemia and in recent years has also been used in traditional Chinese medicine (TCM) to treat solid tumors. However, the inhibitory mechanism of HHT in the progression of hepatocellular carcinoma (HCC) is rarely studied. We aimed to evaluate the antitumor efficacy of HHT on HCC in vitro and in vivo and elucidate the underlying molecular mechanism(s). HCC cell lines, including HCCLM3, HepG2, and Huh7, were used to evaluate the antitumor efficacy of HHT in vitro. Cytotoxicity and proliferative ability were evaluated by MTT and colony formation assays. Cell cycle progression and apoptosis in HHT-treated HCC cells were evaluated by flow cytometry. To determine the migration and invasion abilities of HCC cells, wound-healing and Transwell assays were used. Finally, western blot analysis was used to reveal the proteins involved. We also established a xenograft nude mouse model for in vivo assessments of the preclinical efficacy of HHT, mainly using hematoxylin and eosin staining, immunohistochemistry, ultrasound imaging (USI), and magnetic resonance imaging (MRI). HHT suppressed the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of HCC cells, and induced cell cycle arrest at the G2 phase and apoptosis. In the HCC xenograft model, HHT showed an obvious tumor-suppressive effect. Surprisingly, Slug expression was also decreased by HHT via the PI3K/AKT/GSK3β signaling pathway at least partially suppressed the growth of HCC via the PI3K/AKT/GSK3β/Slug signaling pathway.

Cephalotaxine inhibits Zika infection by impeding viral replication and stability

The Zika virus (ZIKV) is a mosquito-borne flavivirus that has reemerged as a serious public health problem around the world. Syndromes of infected people range from asymptomatic infections to severe neurological disorders, such as Guillain-Barré syndrome and microcephaly. Screening anti-ZIKV drugs derived from Chinese medicinal herbs is one method of identifying antiviral agents. In this paper, we report that (1) Cephalotaxine (CET), an alkaloid isolated from Cephalotaxus drupacea, was effective in inhibiting ZIKV activity in vitro (i.e., in Vero and A549 cell lines) and (2) the mechanisms which underlie these effects involve virucidal activity and a decrease in viral replication. Specifically, CET was found to decrease ZIKV RNA and viral protein expression, inhibit ZIKV replication, and inhibit ZIKV mRNA/protein production. We also determined that CET is effective in inhibiting dengue virus 1–4 (DENV1-4). Taken together, our findings indicate that CET could be an effective lead compound in the treatment of ZIKV and also suggest that further investigation and development of CET-derived drugs may lead to a new class of anti-Flavivirus medications.

Effect of ethanol plant extracts on Staphylococcus Epidermidis, Staphylococcus Aureus

The emergence of multiresistant strains of Staphylococcus epidermidis, Staphylococcus aureus that are difficult to antibiotics and cause severe lesions of soft tissues, sepsis, and complicated surgical pathology are recognized as the one of problems of current infectious diseases of animals and humans. One of challenges in pharmacognosy is the search for alternative sources of antibacterial substances with an exhaustive resource of antibiotics of fungal origin. The use of raw medicinal plants is quite promising in this regard. The tendency of scientific research of recent decade reveals a promising range of plants of a number of families, which typically contents certain active substances (phytoncides, saponins, alkaloids, glycosides, tannins, essential oils etc.).
 The goal of the work was to establish the antibacterial effect of plant infusions on reference cryogenic strains of Staphylococcus epidermidis, Staphylococcus aureus in vitro.
 Herbal material of 50 species (seeds, grass, shoots, leaves, compound fruit, peel) obtained at different periods of the growing season was used for investigation. The material was classified, dried, and grounded. Samples of 1 g were poured with 5 cm3 of 96 % ethanol and were kept it over three weeks in a dry cold place. The obtained alcohol infusion was filtered with sterile multi-layer gauze disc filters. Before the discs were put on the surface of agar with inoculation of the corresponding culture, they were dried in a sterile laminar box under ultraviolet rays. Antibacterial activity of various tinctures was determined by the disk diffusion method in agar with the measurement of the diameter of the growth suppression zone of the culture using a template ruler.
 Concerning the above mentioned point, herein, we report the results of the use of tinctures Staphylococcus epidermidis, Staphylococcus aureus in vitro. Obtained data has been systematized, summarized and evaluated.
 The paper presents the results of the effectiveness of phytopreparations on Staphylococcus epidermidis, Staphylococcus aureus in vitro. The antibacterial effect of plant tinctures of Cephalotaxus harringtonia, Hedera helix, Geranium sanguineum on cryogenic strains Staphylococcus epidermidis, Staphylococcus aureus. We consider it possible to recommend the investigated extracts of Cephalotaxus harringtonia, Hedera helix, Geranium sanguineum for further research in the fight against polyresistant strains of the above-mentioned microorganisms.
 The obtained results give grounds to recommend herbal tinctures to combat multi-resistant strains of Staphylococcus epidermidis, Staphylococcus aureus.

An Integrative Approach to Decipher the Chemical Antagonism between the Competing Endophytes Paraconiothyrium variabile and Bacillus subtilis.

An integrative approach combining traditional natural products chemistry, molecular networking, and mass spectrometry imaging has been undertaken to decipher the molecular dialogue between the fungus Paraconiothyrium variabile and the bacterium Bacillus subtilis, which were isolated as endophytes from the conifer Cephalotaxus harringtonia and are characterized by a strong and mutual antibiosis. From this study, we highlight that bacterial surfactins and a fungal tetronic acid are involved in such competition and that the fungus is able to hydrolyze surfactins to fight against the bacterial partner.

A Phenylpropanoid and Biflavonoids from the Needles of Cephalotaxus harringtonia var. harringtonia

A phenylpropanoid [2-(3-methoxy-4-hydroxyphenyl)-propane-1,3-diol] (1) together with four known biflavonoids namely 7, 4′, 7′″, 4′″-tetra- O-methyl amentoflavone (2); 7, 4′, 7″-tri- O-methyl amentoflavone (3); ginkgetin (4); sequoiaflavone (5) were isolated from the acetone soluble extract of needles of Cephalotaxus harringtonia var. harringtonia. Their structures were elucidated mainly on the basis of interpretation of 1D and 2D NMR spectroscopy and X-ray diffraction studies. The detailed spectral data of phenylpropanoid have been described for the first time. Ginkgetin (4) exhibited significant hepatoprotective activity in rat at 6 mg/kg oral dose level.

The spatial distributions of understory trees in relation to dwarf bamboo cover in a cool-temperate deciduous broadleaf forest in Japan

Dwarf bamboo is a major understory vegetation in Japanese forests, and is recognized to be an ecological filter for the seedlings of overstory tree species. However, the effects of dwarf bamboo cover on the entire understory tree community, including shrubs, have not been fully assessed. Using spatial analysis by distance indices (SADIE), we analyzed the spatial distributions of, and the spatial associations between, Sasa palmata cover and understory trees (diameter at breast height <2 cm, height ≥50 cm) in a cool-temperate deciduous broadleaf forest dominated by Fagus crenata. In a 20 m × 240 m area, we found 49 total species, among 11,686 stems. Cephalotaxus harringtonia var. nana, plus Lindera umbellata and F. crenata stems accounted for about 50 % of the overall total. The SADIE analysis based on 5 m × 5 m quadrats demonstrated that most species, among the 20 tree species we examined, showed significantly aggregated distributions (P < 0.05) and/or significant spatial dissociations (P < 0.05) with S. palmata cover. However, for C. harringtonia var. nana, L. umbellata, Meliosma tenuis, and Ligustrum tschonoskii, their spatial distributions were independent, or significantly associated (P < 0.05) with S. palmata cover. Our results indicates that dwarf bamboo acts as an ecological filter, not only for the seedlings of overstory tree species but also for other understory trees, in the cool-temperate deciduous broadleaf forest.

Leaf anatomy and its implications for phylogenetic relationships in Taxaceae s. l.

The comparative study on leaf anatomy and stomata structures of six genera of Taxaceae s. l. was conducted. Leaf anatomical structures were very comparable to each other in tissue shape and their arrangements. Taxus, Austrotaxus, and Pseudotaxus have no foliar resin canal, whereas Amentotaxus, Cephalotaxus, and Torreya have a single resin canal located below the vascular bundle. Among them, Torreya was unique with thick-walled, almost round sclerenchymatous epidermal cells. In addition, Amentotaxus and Torreya were comprised of some fiber cells around the vascular bundle. Also, Amentotaxus resembled Cephalotaxus harringtonia and its var. nana because they have discontinuous fibrous hypodermis. However, C. fortunei lacked the same kind of cells. Stomata were arranged in two stomatal bands separated by a mid-vein. The most unique stomatal structure was of Taxus with papillose accessory cells forming stomatal apparatus and of Torreya with deeply seated stomata covered with a special filament structure. Some morphological and molecular studies have already been discussed for the alternative classification of taxad genera into different minor families. The present study is also similar to these hypotheses because each genus has their own individuality in anatomical structure and stomata morphology. In conclusion, these differences in leaf and stomata morphology neither strongly support the two tribes in Taxaceae nor fairly recognize the monogeneric family, Cephalotaxaceae. Rather, it might support an alternative classification of taxad genera in different minor families or a single family Taxaceae including Cephalotaxus. In this study, we would prefer the latter one because there is no clear reason to separate Cephalotaxus from the rest genera of Taxaceae. Therefore, Taxaceae should be redefined with broad circumscriptions including Cephalotaxus.

Cost effective quantification of camptothecin and a comparative study of its content in Nothapodytes foetida and Ophiorrhiza mungos sourced from selected geographical locations

Abstract High-performance liquid chromatography is theprevalent method used to estimate Camptothecin quantita-tively. In the present study thin layer chromatography andUV spectrophotometric method was established as a sensi-tive, economical and accurate method of detection and esti-mation of Camptothecin. The method was developed onTLCaluminumplates(60F 254 fromE-MerckLtd.)precoatedwith silica gel using solvent system ethyl acetate: methanol(7.5:2.5, v/v) which gives a dark blue spot of Camptothecinat 254 nm (Rf value 0.46 cm). Spectrometric analysis ofCamptothecin was carried out at the absorbance of 254 nm.Leaves and stems of Nothapodytes foetida and Ophiorrhizamungos were extracted, subjected to TLC and UV spectro-photometric analysis and maximum absorption of CPT inethyl acetate was observed at 254 nm. The quantification bythis method was comparable to data obtained by HPLC. Theoptimized method was simple, repeatable, precise and costeffective, useful when there is large number of crude sam-ples.Inthepresentstudythismethodwasusedtoscreenhighyielding lines of CPT producing plants.Keywords Camptothecin .Nothapodytesfoetida .Ophiorrhizamungos .ThinlayerchromatographyAbbreviationsCPT CamptothecinTLC Thin layer chromatographyHPLC High performance liquid chromatographyIntroductionCamptothecin (CPT) is a cytotoxic quinoline alkaloid(Fig. 1), first isolated by Wall and Wani (1996) fromCamptotheca acuminate belonging to family Nyssaceae.Camptothecin and its derivatives was found to inhibit DNAtopoisomerase activity and at present the semi syntheticwater soluble CPT analogs known as topotecan andirinotecan are used as anti-cancer agents (Aimi et al. 1989;Arisawa et al. 1981; Hsiang et al. 1985; Yasuyo Yamazakiet al. 2003). Among the various plant sources for anti-tumorcompounds like Vinca alkaloid Vincristine (Noble 1990),Etoposide derived from Podophyllum peltatum (Thurstonet al. 1989), Flavopiridol a synthetic flavone derived fromthe plant alkaloid rohitukine which was isolated from theleaves and stems of Amoora rohituka and later fromDysoxylum binectariferum (Kelland 2000). A number ofadditional plant derived agents are currently under investi-gation. Homoharringtonine is an alkaloid isolated from theChinese tree, Cephalotaxus harringtonia has shown efficien-cyagainstvariousleukemia,4-Ipomoeaonolisapneumotoxicfuran derivative isolated from sweet potato Ipomoea batatas(Rehm and Devor 1993). It is believed that CPT is thethird most important alkaloid sought after by pharma-ceutical companies around the world which was initiallyisolated from the bark and wood of Camptotheca acu-minate (Nyssaceae) and act by inhibiting topoisomerase

Geographic locality greatly influences fungal endophyte communities in Cephalotaxus harringtonia

Although endophytes of conifers have been extensively studied, few data are available on Cephalotaxaceae. We examined foliar and stem endophytes of Cephalotaxus harringtonia, within its natural range in Japan and outside its natural range in France to study the effect of geography on endophyte community composition. In Japan, rapidly growing endophytes were dominant and may have masked the real diversity, in comparison to France where most endophytes were growing slowly. Analyses of ITS rDNA revealed 104 different Blast Groups among 554 isolates. Almost no overlap between endophyte assemblages of C. harringtonia from the two countries was observed. It seems that Japanese C. harringtonia trees, which should be well adapted to their native site, would host a specific, endemic endophyte community, while trees that have been introduced recently to a foreign site, in France, should have captured existing cosmopolitan and more generalist taxa. In Japan the majority of xylariaceous taxa, which dominated the communities, were unknown and, although closely related to Asian taxa, may be new to science. Dothideomycetes were more prevalent in France. Locally, urban environment, particularly in Japan, may have introduced some perturbations in the native endophyte community of C. harringtonia, with an abundance of generalist fungi such as Nigrospora and Colletotrichum.

Chemical Communication between the Endophytic Fungus Paraconiothyrium Variabile and the Phytopathogen Fusarium oxysporum

Paraconiothyrium variabile, one of the specific endophytic fungi isolated from the host plant Cephalotaxus harringtonia, possesses the faculty to inhibit the growth of common phytopathogens, thus suggesting a role in its host protection. A strong antagonism between the endophyte P. variabile and Fusarium oxysporum was observed and studied using optic and electronic microscopies. A disorganization of the mycelium of F. oxysporum was thus noticed. Interestingly, the biological effect of the main secondary metabolites isolated from P. variabile against F. oxysporum did not account for this strong antagonism. However, a metabolomic approach of pure fungal strains and confrontation zones using the data analysis tool XCMS were analyzed and pointed out a competition-induced metabolite production by the endophyte in the presence of the phytopathogen. Subsequent MS/MS fragmentations permitted to identify one of the induced metabolites as 13-oxo-9,11-octadecadienoic acid and highlighted a negative modulation of the biosynthesis of beauvericin, one of the most potent mycotoxin of F. oxysporum, during the competition with the endophyte.

Guaiane Sesquiterpenes from Biscogniauxia nummularia Featuring Potent Antigerminative Activity

Xylaranone, a previously unreported guaiane sesquiterpene along with the known terpenoid xylaranol B and the two mellein derivatives 3,5-dimethyl-8-methoxy-3,4-dihydroisocoumarin and 3,5-dimethyl-8-hydroxy-3,4-dihydroisocoumarin were isolated from Biscogniauxia nummularia. Pogostol was also isolated from this fungus, and in light of our spectroscopic data, its structure was revised and corrected. This fungus, which was isolated as an endophyte from the plum yew Cephalotaxus harringtonia, is also suspected of being a pathogen. Interestingly, we report here the potent antigerminative activity of xylaranone and xylaranol B against seeds of Raphanus sativus at concentrations comparable to glyphosate, a commonly used herbicide. This effect suggests a role for these metabolites in the latent fungal pathogenesis of B. nummularia.

Cephastigiamide A, and Antiplasmodial Activity of Cephalotaxus Alkaloids from Cephalotaxus harringtonia Forma Fastigiata

A new Cephalotaxus alkaloid, cephastigiamide A (1), has been isolated from the leaves of Cephalotaxus harringtonia forma fastigiata and the structure was elucidated by 2D NMR analysis and chemical degradation. Harringtonine, deoxyharringtonine, and homodeoxyharringtonine showed pronounced antiplasmodial activity against Plasmodium falciparum 3D7 but not against Leishmania major. Structure-activity relationship for antiplasmodial activity of isolated Cephalotaxus alkaloids was also discussed.

Further Studies of the Norditerpene (+)-Harringtonolide Isolated fromCephalotaxus harringtoniavar.drupacea: Absolute Configuration, Cytotoxic and Antifungal Activities

Harringtonolide (= hainanolide) is a complex polycyclic fused norditerpene isolated from CEPHALOTAXUS HARRINGTONIA var. DRUPACEA. In spite of its appealing biological properties - we measured an IC (50) of 43 nM on KB cells and a significant antifungal activity - its absolute configuration has not yet been firmly established. This was done herein using X-ray anomalous scattering after bromination of the tropone ring, unambiguously giving the stereochemistry 5 R,6 R,7 S,13 S,14 S,15 R,16 R. Detailed IN VITRO biological measurements are provided.

Homoharringtonine inhibits the AKT pathway and induces in vitro and in vivo cytotoxicity in human multiple myeloma cells

Involvement of phosphatidylinositol 3-kinase/Akt-1 in cell survival and proliferation of multiple myeloma (MM) has been well established. In this study, we demonstrate that homoharringtonine (HHT), an antileukemic drug first isolated from the Chinese evergreen Cephalotaxus harringtonia, induces significant cytotoxicity in dexamethasone-sensitive and -resistant and chemotherapy-sensitive MM cell lines in a time and dose-dependent manner. HHT also triggers apoptosis in chemotherapy-resistant patient's myeloma cells. Contrary to dexamethasone, the cytotoxicity of HHT on myeloma is independent of interleukin-6. The mechanism of HHT cytotoxicity is related to down-regulation of Akt phosphorylation/activation and various target genes of Akt including nuclear factor κ B, XIAP, cIAP and cyclin D1. Moreover, in vivo antitumor activity of HHT is demonstrated in RPMI8226 myeloma xenograft model. Importantly, an additive effect of antitumor is confirmed in the myeloma cells treated with HHT and bortezomib concomitantly with inhibition of phosphorylated Akt. Together, these findings obtained with HHT should give useful insights into a novel antimyeloma chemotherapy.

New Biflavonoids from Cephalotaxus harringtonia var. fastigiata (Cephalotaxaceae)

Three new biflavonoids 1 (2,3-dihydro-6-methylginkgetin), 2 (2,3-dihydro-6-methylbilobetin) and 3 (2,3-dihydro-6-methylsequoiaflavone) have been isolated from the leaves of Cephalotaxus harringtonia K. Koch var. fastigiata Rehder (Cephalotaxaceae) and their structures were elucidated by spectral analysis.