Lignans from stems and leaves of Cephalotaxus fortunei (Ⅱ) / 中国中药杂志

The present study aimed to explore the chemical constituents from the stems and leaves of Cephalotaxus fortunei. Seven lignans were isolated from the 75% ethanol extract of C. fortunei by various chromatographic methods, including silica gel, ODS column chromatography, and HPLC. The structures of the isolated compounds were elucidated according to physicochemical properties and spectral data. Compound 1 is a new lignan named cephalignan A. The known compounds were identified as 8-hydroxy-conidendrine(2), isolariciresinol(3), leptolepisol D(4), diarctigenin(5), dihydrodehydrodiconiferyl alcohol 9'-O-β-D-glucopyranoside(6), and dihydrodehydrodiconiferyl alcohol 4-O-β-D-glucopyranoside(7). Compounds 2 and 5 were isolated from the Cephalotaxus plant for the first time.

Effect of Homoharringtonine as a Combined Regimen for Acute Myeloid Leukemia

Homoharringtonine (HHT), a cephalotaxus alkaloid has shown promising results in the treatment of several hematological disorders such as chronic myeloid leukemia, acute myeloid leukemia (AML), and myelodysplastic syndrome. It is known for its unique mechanism of action by which it prevents the initial elongation step of protein biosynthesis. Hence, it is used in hematological malignancies where it synergistically potentiates the action of other drugs and induces apoptosis. The relevant studies published were searched using an electronic database from 2002 to 2019. The articles published in English were only considered. Search engines such as PubMed, MEDLINE, Google Scholar, and Semantic scholar were used. In this review, we have discussed the effect of HHT in combination with other chemotherapeutic agents for AML with or without genetic mutation specification and the future perspective of these regimens. Although standard treatment options exist for most of these diseases, still cure rates are low with reported morbidity and the drug resistance emergence is pervasive. Thus, novel treatment approaches are crucial for better outcome. Alternative regimens together with HHT have not been a standard practice, although they have shown a very good potential in AML patients. Many of the combinations were also proved to be safe and effective with very low toxic potential. All these data outcomes of various combinations under different scenarios exhibit that HHT has promising results in the treatment of AML which may lead to its approval in the upcoming years.

Ethnopharmacology, chemodiversity, and bioactivity of Cephalotaxus medicinal plants / 中国天然药物

Cephalotaxus is the only genus of Cephalotaxaceae family, and its natural resources are declining due to habitat fragmentation, excessive exploitation and destruction. In many areas of China, folk herbal doctors traditionally use Cephalotaxus plants to treat innominate swollen poison, many of which are cancer. Not only among Han people, but also among minority ethnic groups, Cephalotaxus is used to treat various diseases, e.g., cough, internal bleeding and cancer in Miao medicine, bruises, rheumatism and pain in Yao medicine, and ascariasis, hookworm disease, scrofula in She medicine, etc. Medicinal values of some Cephalotaxus species and compounds are acknowledged officially. However, there is a lack of comprehensive review summarizing the ethnomedicinal knowledge of Cephalotaxus, relevant medicinal phytometabolites and their bioactivities. The research progresses in ethnopharmacology, chemodiversity, and bioactivities of Cephalotaxus medicinal plants are reviewed and commented here. Knowledge gaps are pinpointed and future research directions are suggested. Classic medicinal books, folk medicine books, herbal manuals and ethnomedicinal publications were reviewed for the genus Cephalotaxus (Sanjianshan in Chinese). The relevant data about ethnobotany, phytochemistry, and pharmacology were collected as comprehensively as possible from online databases including Scopus, NCBI PubMed, Bing Scholar, and China National Knowledge Infrastructure (CNKI). "Cephalotaxus", and the respective species name were used as keywords in database search. The obtained articles of the past six decades were collated and analyzed. Four Cephalotaxus species are listed in the official medicinal book in China. They are used as ethnomedicines by many ethnic groups such as Miao, Yao, Dong, She and Han. Inspirations are obtained from traditional applications, and Cephalotaxus phytometabolites are developed into anticancer reagents. Cephalotaxine-type alkaloids, homoerythrina-type alkaloids and homoharringtonine (HHT) are abundant in Cephalotaxus, e.g., C. lanceolata, C. fortunei var. alpina, C. griffithii, and C. hainanensis, etc. New methods of alkaloid analysis and purification are continuously developed and applied. Diterpenoids, sesquiterpenoids, flavonoids, lignans, phenolics, and other components are also identified and isolated in various Cephalotaxus species. Alkaloids such as HHT, terpenoids and other compounds have anticancer activities against multiple types of human cancer. Cephalotaxus extracts and compounds showed anti-inflammatory and antioxidant activities, immunomodulatory activity, antimicrobial activity and nematotoxicity, antihyperglycemic effect, and bone effect, etc. Drug metabolism and pharmacokinetic studies of Cephalotaxus are increasing. We should continue to collect and sort out folk medicinal knowledge of Cephalotaxus and associated organisms, so as to obtain new enlightenment to translate traditional tips into great therapeutic drugs. Transcriptomics, genomics, metabolomics and proteomics studies can contribute massive information for bioactivity and phytochemistry of Cephalotaxus medicinal plants. We should continue to strengthen the application of state-of-the-art technologies in more Cephalotaxus species and for more useful compounds and pharmacological activities.

Lignans from stems and leaves of Cephalotaxus fortunei / 中草药

Objective: To study chemical constituents of Cephalotaxus fortunei. Methods: The chemical constituents were separated and purified by preparative thin-layer chromatography, silica gel, ODS, HP20 macroporous resin and Sephadex LH-20 gel column chromatography, and semi-preparative HPLC. Their structures were determined by NMR and ESI-MS spectroscopic techniques. Results: Seventeen lignans were isolated from the ethanol extracts of C. fortunei and their structures were identified as shonanin (1), arctigenin (2), α-conidendrin (3), matairesinol (4), nortrachelogenin (5), epinortrachelogenin (6), (7'S)- hydroxymatairesinol (7), (7'R)-hydroxymatairesanol (8), (7'S)-hydroxyarctigenin (9), secoisolariciresinol (10), 4,4'-di-O-methylcephafortin A (11), 5-(3″,4″-dimethoxyphenyl)-3-hydroxy-3-(4'-hydroxy-3'-methoxybenzyl)-4-hydroxymethyl-dihydrofuran-2-one (12), cephafortin B (13), dihydrodehydrodiconiferyl alcohol (14), 7R,8S-4,7,9,9'-tetrahydroxy-3,3'-dimethoxy-8-O-4'-neolignan (15), 7R,8R-4,7,9,9'- tetrahydroxy-3,3'-dimethoxy-8-O-4'-neolignan (16), and threo-1,2-bis-(4-hydroxy-3-methoxyphenyl)-1,3-propanediol (17). Conclusion: Compounds 3, 6, 10 and 17 were isolated from genus Cephalotaxus for the first time, and compounds 4, 5, 7-9, 12 and 14 were isolated from C. fortunei for the first time.

Chemical constituents of alkaloids part of Cephalotaxus hainanensis / 中草药

Objective To study the alkaloids constituents from Cephalotaxus hainanensis. Methods The column chromatography Sephadex LH-20 and ODS were used to isolate and purify the compounds of alkaloids part of C. hainanensis. The chemical structures were identified on basis of physicochemical properties and spectral data. Results Thirteen compounds were isolated and identified as cephalotaxine (1), isocephalotaxinone (2), cephalotaxinone (3), cephalezomine G (4), (2R,3S,4S,5S)-2,3-dihydroxycephalotaxane (5), acetylcephalotaxine (6), deoxyharringtonine (7), (R)-fortunine (8), (S)-fortunine (9), isomer of 3-epi-schellhammericine (10), 1,4 (PrINH)2-anthraquinone (11), 2-ethyl-n-hexyl benzoate (12), and β-sitosterol (13). Conclusion Compounds 3-6 and 10-13 are isolated from this plant for the first time.

Effect of L-tryptophan and its derivatives on cephalotaxine production in Cephalotaxu mannii suspension cells / 中草药

Objective: To investigate the effects of L-tryptophan and its derivative 5-methyl-DL-tryptophan (5-MT) on suspension cells growth and cephalotaxine production of Cephalotaxu mannii. Methods: The cell suspension cultures were treated with L-tryptophan and 5-MT on day 15, respectively. Then the cell growth, cephalotaxine production, and activity of key enzymes in the metabolism pathway were determined. Results: L-tryptophan and 5-MT could enhance cephalotaxine production. The cultures treated with 5 mg/L L-tryptophan showed the highest cephalotaxine yield (2.944 mg/L). While treated with 10 mg/L L-tryptophan and 5 mg/L 5-MT, the cephalotaxine yields were 1.947 and 2.192 times of the control culture (1.343 mg/L); The biomass of suspension cultures were decreased by 9.35% and 18.04%, respectively, less than those in the control group (2.406 g/L); The activity of 3-deoxy-D-arabino- heptulosonate-7-phosphate synthase was decreased by 12.4% and 5.57% compared with the control (0.67 U/mg); The activity of phenylalanine ammonium-lyase activity increased by 37.72% and 28.02% and the total phenolics content increased by 19.14% and 9.61% compared with the control (78.21 U/mg and 0.36 mg/mL). Conclusion: L-tryptophan and its derivative 5-MT can inhibit the L-tryptophan biosynthetic pathway and promote the accumulation of cephalotaxus alkaloids.

Sesquiterpenoids from branches and leaves of Cephalotaxus lanceolata / 中草药

Objective: To isolate and identify the chemical constituents from the branches and leaves of Cephalotaxus lanceolata. Methods: The compounds were separated and purified by column chromatography with silica gel, Sephadex LH-20, MPLC, and HPLC. Their structures were elucidated on the basis of spectroscopic methods. Results: Eleven sesquiterpenoids were isolated from 95% ethanol extract of the branches and leaves of C. lanceolata and identified as lanceoloside A (1), lanceoloside B (2), lanceoloside C (3), 9-hydroxy-4,7-megastigmadien-3-one (4), corchoionol C (5), 9,10-dihydroxy-4,7-megastigmadien-3-one (6), 5,12-epoxy-9- hydroxy-7-megastigmen-3-one (7), 5,12-epoxy-6,9-hydroxy-7-megastigmen-3-one (8), loliolide (9), (3S,5R,8S)-5,8-epoxy-6- megastigmadien-3,9-diol (10), and clovandiol (11) respectively. Conclusion: Compounds 1 is identified as a new sesquiterpenoid, while compounds 2-3 are two new natural products. Compounds 4-11 are isolated from this plant for the first time.

Isolation, identification and antimicrobial activities of endophytic fungi from Cephalotaxus fortunei / 中国药学杂志

OBJECTIVE: To isolate and identify endophytic fungi from Cephalotaxus fortunei and to investigage their antibiotic activities, in order to obtain the strains with good antimicrobial activity. METHODS: Endophytic fungi were isolated by tissue-culture method and preliminarily identified by morphological method, and the antimicrobial activities of endophytic fungi were determined against six kinds of bacteria by fungus cake method and paper sheet method. RESULTS: sixty-one strains of endophytic fungi were isolated from the seed coats, stems and leaves of Cephalotaxus fortunei. By morphological identification, 52sporulated strains were classified into 9 genera, 5 families and 3 orders. Fifty strains (81.97%) showed antimicrobial activity against one or more of the tested microbes, and the secondary metabolites of 40 strains (65.57%) presented antibacterial activities against one or more of the tested microbes. CONCLUSION: There are abundant and multiple endophytic fungi in Cephalotaxus fortunei, and most of them have strong anti-bacterial activities.

Antitumor activities of chemical constituents of Cephalotaxus fortunei in Guizhou province / 中国药科大学学报

Aim: To study the antitumor activities of the constituents of Cephalotaxus fortunei distributed in Guizhou province. Methods: The constituents were isolated by column chromatography and identified by physical and spectral analysis. Meanwhile, the anti-tumor activities of some compounds were evaluated by sulforhodamine B( SRB) and MTT assay. Results: Eleven compounds were isolated and identified as apigenin (Ⅰ), β-sitosterol (Ⅱ), acetylcephalotaxine (Ⅲ), chrysoeriol (Ⅳ), drupacine ( Ⅴ), 1-hentriacontanol ( Ⅵ), 7, 3', 4' -trihydroxyfla-vone (Ⅶ), sugiol ( Ⅷ), cephalotaxine (Ⅸ), wllsonine (Ⅹ), and hainanolide (Ⅺ), respectively. Biological screening results demonstrated that some of the tested compounds exhibited the antitumor activities in vitro. Conclusion: Compounds Ⅱ, Ⅵ-Ⅷ were isolated from this plant for the first time. Compound Ⅺ has a better inhibitory activity on cell line A549 and K562 .

Screening of Antitumor and Antimicrobial Activities of the Endophytic Fungi Isolated from Cephalotaxus hainanensis Li / 微生物学通报

Seventy-two endophytic fungi isolated from Cephalotaxus hainanensis Li were screened for antitumor and antimicrobial activities. The results showed that 9 strains presented cytotoxic activities to at least one of the tested tumor cells, five strains exhibited strong antimicrobial activity against Staphylococcus aureus, one strain had inhibitory effect on Phytophthora parasitica. It was evidently that the endophytic fungi of C. hainanensis are potential resources to find valuable bioactive components.

Isolation and Primary Identification of Endophytic Fungi from Cephalotaxus hainanensis L / 微生物学通报

Seventy-two strains of endophytic fungi were isolated from the healthy bark, branches and leaves of Cephalotaxus hainanensis L.. Sixty-eight of them were morphologically classified into Fungi Imperfecti, thirty-three sporulated were identified to five genera. For those did not sporulate, one was identified to Rhizoctonia sp., the rest were tentatively classified into Mycelia Sterilia. Four were identified to Basidiomycetes. The result indicated the endophytic fungi of C. hainanensis show a degree of tissue specificity. There were significant differences about the quantity, genera and composition between the fungi isolated from bark and those from branches and leaves.